REVIEW | doi:10.20944/preprints202202.0200.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibiotic resistance genes; antibiotic resistance gene database; annotation of antibiotic resistance genes
Online: 17 February 2022 (04:52:10 CET)
As the prevalence of antimicrobial resistance genes is increasing in microbes, we are facing the return of the preantibiotic era. Consecutively, the number of studies concerning antibiotic resistance and its spread in the environment is rapidly growing. Next generation sequencing technologies are widespread used in many areas of biological research and antibiotic resistance is no exception. For the rapid annotation of whole genome sequencing and metagenomic results considering antibiotic resistance, several tools and data resources were developed. These databases, however can differ fundamentally in the number and type of genes and resistance determinants they comprise. Furthermore, the annotation structure and metadata stored in these resources can also contribute to their differences. Several previous reviews were published on the tools and databases of resistance gene annotation, however, to our knowledge, no previous review focused solely and in depth on the differences in the databases. In this review, we compare the most well-known and widely used antibiotic resistance gene databases based on their structure and content. We believe that this knowledge is fundamental for selecting the most appropriate database for a research question and for the development of new tools and resources of resistance gene annotation.
ARTICLE | doi:10.20944/preprints201906.0019.v2
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibiotic cycling; antibiotic mixing; antibiotic resistance; diversity; entropy; heterogeneity
Online: 27 August 2020 (08:03:07 CEST)
Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden. Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.
REVIEW | doi:10.20944/preprints202306.0244.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: antibiotics; antibiotic therapy; antibiotic resistance; evolutionary medicine; ethics
Online: 5 June 2023 (05:32:00 CEST)
The first half of the 20th century was noteworthy for the introduction of a unique group of drugs – antibiotics. It drastically changed concepts of infectious diseases treatment, which for centuries remained a scourge of the human population. With improvement of the antibiotic treatment efficacy, humanity has faced the problem of a dramatic increase in antibiotic resistance in bacteria. The COVID-19 pandemic has only exacerbated the problem and posed a new challenge to the medical community in finding solutions, both clinical and organizational and methodological, to fight antibiotic resistance widespread all over the globe. This publication covers some aspects of evolutionary processes in either pathogens or diseases, including ethical perspective.
ARTICLE | doi:10.20944/preprints201806.0290.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: urine; resistance; antibiotic; nitrofurantoin; Mozambique
Online: 19 June 2018 (10:33:14 CEST)
Urinary tract infections are a major cause of morbidity and mortality in Mozambique. They are sometimes treated empirically with nitrofurantoin. However, little is known about this antibiotic’s performance and bacterial resistance in the country. This study analyzed the results of nitrofurantoin sensitivity tests requested in the Central Hospital of Maputo during 2012 and 2013. As result, 181 samples were tested and most cases (66.9%) showed absolute sensitivity but there were considerable cases of resistance (29.8%). Morganella morganii was the only bacteria presenting no absolute or intermediate resistance. The sensitivity was also high in the case of Escherichia coli (90%) and Gram-negative bacteria (66.7%). Serratia marcescens was mostly resistant (64.3%). The remaining bacteria showed inconclusive results. Thus they shall be subjected to a sensitivity test before prescription. Factors such as seasonality, patients’ sex and urine transparency did not seem to be reliable indicators of microbial resistance in the urine. Yet, a longer time span (over 5 years) might be sufficient for the sensitivity profile to change.
ARTICLE | doi:10.20944/preprints202006.0121.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: antibiotic usage; antibiotic resistance; poultry; KAP; Kwara; Nigeria
Online: 9 June 2020 (09:45:51 CEST)
There are overwhelming empirical evidences highlighting the contribution of indiscriminate antibiotic usage (ABU) in food animals to the overall burden of antibiotic resistance (ABR) in humans, thus making antibiotic use the main selective pressure driving antibiotic resistance. Social and behavioral perspective on antibiotic use and resistance in poultry is limited. Our study therefore aimed at obtaining information on antibiotic usage, awareness of ABR, and the attitude and perceptions towards prudent antibiotic usage and ABR. A cross-sectional survey using a structured questionnaire was conducted in 125 poultry farms in Kwara state in December 2019. Most farmers (69.6%, n=87/125) were aware of ABR and had satisfactory knowledge about ABR with a mean knowledge score of 3.16±1.47. The age, gender, level of education of farmers, and their flock size were significantly associated with a satisfactory knowledge of ABR (p<0.05). Tertiary education was significantly associated with ABR awareness (OR: 4.7; 95% CI: 0.0690, 0.654; p=0.007) and the ABR knowledge level (OR: 7.8269; 95% CI: 3.2693, 18.7381; p < 0.01). Higher flock size was significantly associated with a satisfactory knowledge of ABR (OR: 9.4551; 95%CI: 3.7928, 23.5707; p<0.01). Most of the poultry farmers (68%) had positive attitudes towards prudent antibiotic use with a mean score of 2.75±0.89. On the contrary, only 32.8% of poultry farmers had a good perception of ABR with a mean perception score of 4.95±1.12. The ABR knowledge level was significantly associated with the perceptions of farmers (p<0.05) but not their attitudes toward ABU and ABR (P=0.083). There was evidence of unprescribed use of antibiotics in poultry and a failure to observe antibiotic withdrawal periods. These constitute a risk of exposure to unacceptable levels of drug residues from poultry products and an increased risk of ABR. Improving education and communication on antibiotic stewardship programs are crucial to prevent the looming antibiotic apocalypse.
ARTICLE | doi:10.20944/preprints202012.0210.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: antibiotic resistance; antibiotic alternatives; heavy metals; essential oils
Online: 9 December 2020 (09:44:37 CET)
Antimicrobial resistance (AMR) represents a growing crisis in both human and veterinary medicine. We evaluated the use of two categories of antibiotic alternatives – heavy metals and essential oils – in beef cattle, and their effects on gram-negative and gram-positive bacteria. In this randomized controlled field trial, we measured the impact of supplemental zinc and menthol on antimicrobial resistance among commensal enteric bacteria of feeder cattle. Fecal suspensions were plated onto plain- and antibiotic-supplemented MacConkey and m-Enterococcus agar for quantification of total and antimicrobial-resistant Escherichia coli and Enterococcus spp., respectively. Temporal effects on overall E. coli growth were significant (P< 0.05); however, there were no significant effects on antibiotic-supplemented agar. Zinc was associated with significant increases in growth on erythromycin-supplemented m-Enterococcus agar. Cattle fed zinc exhibited significantly higher macrolide resistance among fecal enterococci isolates.
REVIEW | doi:10.20944/preprints202103.0050.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: antisense; antibiotic resistance; RNase P; RNase H; nucleotide analogs
Online: 2 March 2021 (09:17:47 CET)
Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.
HYPOTHESIS | doi:10.20944/preprints202310.1848.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: superbug; antibiotic resistance; generalist resistance; specialist resistance
Online: 30 October 2023 (09:56:48 CET)
Bacteria that have become resistant to antibiotics, also known as superbugs,pose a huge threat to the human population. This is because these developed resistance to antibiotics. Antibiotics are a type of medicine that fights bacteria by either killing it or preventing it from growing. Although antibiotics make the once deadly now easily treatable, they can become ineffective as bacteria develop resistance to the antibiotic, causing diseases to become potentially fatal once more. Thus, scientists are rushing to find solutions in this arms race against evolving bacteria by either evolving current antibiotics or discovering new stands to fight evolving bacteria. In order to discover whether bacteria can develop resistance to household antibiotics, a controlled experiment was conducted. This was done by growing bacteria on agar plates with antibiotic ointments applied (in dilution series) to see if antibiotic resistance could build. Theorizing that by lowering the concentration of over the counter antibiotics, resistant bacteria would be selected and my bacterial population would evolve antibiotic resistance.In conclusion of the experiment antibiotic resistance did appear as a trait, but the level of it was inconsistent across the different bacteria populations.
ARTICLE | doi:10.20944/preprints201808.0466.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibiotic; diarrhea; prevalence, shigella; shigellosis
Online: 27 August 2018 (15:08:52 CEST)
Infectious diarrhoea such as shigellosis causes considerable morbidity and mortality, especially in infants, immune-compromised individuals and those living with HIV/AIDS. It is endemic in developing countries and in Sub-Saharan Africa, including South Africa, where diarrhoeal disease remains a leading cause of morbidity and mortality. This study was undertaken to establish incidences of Shigella, its serotype and resistant pattern of isolates from human faeces from residence of Johannesburg, South Africa. All stools received between January to April from the private healthcare system were cultured on Xylose Lysine Deoxycholate and MacConkey Agar and Shigella was confirmed by standard biochemical reactions and a serological method. An antimicrobial sensitivity test was used. A total of 11 009 samples from patients between 22 days to 94 years old yielded 110 Shigella isolates, of which 47 (43%) were S. flexneri, 61 (55%) were S. sonnei, 1 (1%) was S. dysenteriae and 1 (1 %) was S. boydii. The majority of patients were children between < 1 to 5 years, 76 (69%), followed by those between 6 to 10 years 13 (12%). In children up to 10 years, S. sonnei was confirmed in 52 cases (59%) and S. flexneri in 36 cases (41%). Overall, 53 (48%) males and 57 (52%) females were infected.
REVIEW | doi:10.20944/preprints202301.0386.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Antibiotic resistance; bacteria; gene; developing countries
Online: 23 January 2023 (01:54:28 CET)
Antibiotic resistance is a major public health issue that requires a multifaceted approach. One potential source of antibiotic-resistant bacteria is wastewater in developing countries, which often lacks proper treatment infrastructure and can release high levels of antibiotics and antibiotic-resistant bacteria into the environment. This review article summarizes current knowledge on strategies to combat antibiotic resistance in wastewater in developing countries. Our review highlights the importance of improving wastewater treatment infrastructure to effectively remove antibiotics and antibiotic-resistant bacteria, implementing measures to reduce the release of antibiotics into the environment, and monitoring and surveillance to track the presence and spread of antibiotic-resistant bacteria in wastewater. We also discuss the potential challenges and barriers to implementing these strategies and the need for further research to determine their effectiveness in real-world settings. Overall, this review highlights the need for a comprehensive approach to address antibiotic resistance in wastewater in developing countries and underscores the importance of addressing this issue to protect public health.
ARTICLE | doi:10.20944/preprints202306.0434.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Staphylococcus equorum; antibiotic resistance; dairy microbiology; starters; adjunct cultures; cheese
Online: 6 June 2023 (09:52:40 CEST)
In this work, the resistance/susceptibility (R/S) profile of Staphylococcus equorum strains (n=30) from cheese to 16 antibiotics was determined by broth microdilution. The minimum inhibitory concentration (MIC) for all antibiotics was low in most strains, although higher MICs compatible with acquired genes were also noted. Genome analysis of 13 strains showed the S. equorum resistome to be composed of intrinsic mechanisms, acquired mutations, and acquired genes. However, the genetic data did not always correlate with the phenotype. As such, a cat gene providing resistance to chloramphenicol was found on a plasmid in one strain; this was able to provide resistance to Staphylococcus aureus after electroporation. An msr(A) polymorphic gene was identified in five strains. The Mrs(A) variants were associated with variable resistance to erythromycin. All strains harboured a polymorphic fosB/fosD gene, although only one acquired copy was associated with strong resistance to fosfomycin. Similarly, a plasmid-associated blaR1-blaZI operon encoding a penicillinase was identified in five ampicillin- and penicillin G-susceptible strains. Identified genes not associated with resistance further included mph(C) in two strains and norA in all strains. The antibiotic R/S status and gene content of S. equorum strains intended to be employed in food systems should be carefully determined.
ARTICLE | doi:10.20944/preprints201809.0255.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: metagenomics; antibiotic resistance; wastewater; environmental ecology
Online: 14 September 2018 (06:27:29 CEST)
Wastewater treatment plants (WWTPs) are thought to be potential incubators of antibiotic resistance. Persistence of commonly used antibiotics in wastewater may increase the potential for selection of resistance genes transferred between bacterial populations, some of which may pose a threat to human health. In this study, we measured the concentrations of ten antibiotics in wastewater plant influents and effluents, and in surface waters up- and downstream from two Charlotte area treatment facilities. We performed Illumina shotgun sequencing to assay the microbial community and resistome compositions at each site across four time points from late winter to mid-summer of 2016. Antibiotics are present throughout wastewater treatment, and elevated concentrations of multiple antibiotics are maintained in moving stream water downstream of effluent release. While some human gut and activated sludge associated taxa are detectable downstream, these seem to attenuate with distance while the core microbial community of the stream remains fairly consistent. We observe slight suppression of functional pathways in the downstream microbial communities, including amino acid, carbohydrate and nucleic acid metabolism as well as nucleotide and amino acid scavenging. Nearly all antibiotic resistance genes (ARGs) and potentially pathogenic taxa are removed in the treatment process, though a few ARG markers are elevated downstream of effluent release. Taken together, these results represent baseline measurements which future studies can utilize to help to determine which factors control the movement of antibiotics and resistance genes through aquatic urban ecosystems before, during and after wastewater treatment.
ARTICLE | doi:10.20944/preprints202005.0362.v1
Subject: Medicine And Pharmacology, Other Keywords: cross-sectional survey; antibiotic use; antimicrobial resistance; knowledge; brunei
Online: 23 May 2020 (05:54:43 CEST)
Background: Public misconception and demand for the indication of antibiotics could lead to inappropriate prescribing and consumption. Successful treatment can only be achieved when the public and industrial users have knowledge on antibiotic use and resistance. This survey is aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. Methods: A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from the World Health Organization (WHO) Antibiotic Resistance, Multi-country public awareness survey distributed online. Students at UBD were invited to participate in the online survey through internal email. The questionnaire consisted of 5 sections: demographic information, antibiotic usage, knowledge on antibiotics, antibiotic resistance (AMR) and use of antibiotics in agriculture. Data were analyzed descriptively and appropriate inferential statistics was used accordingly. Cronbach’s alpha was also done to determine the internal consistency. The section on antibiotic use and knowledge showed good internal consistency of Cronbach’s alpha 0.66 and 0.86 respectively. Research ethics approval was obtained from the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam (UBD). Results: A total of 145 students returned the complete questionnaire. The result of the study found that 50% of the students had good level of knowledge of antibiotic and antimicrobial resistance with a mean total knowledge score of 11.4 out of 14. Respondents reported the use of antibiotic in the past (69%). Many of the students could identify the use of antibiotics for the treatment of bacterial infection. However, there were also students who incorrectly thought that antibiotics can be used for cold and flu (43%) and fever (41%). Moreover, 76% of the respondents mistakenly believed that antibiotic resistance is the result of the body becoming resistant to antibiotics. Only 12% of the respondents were found to have poor knowledge in the study. Conclusions: Misconceptions in regards to the use of antibiotics for conditions related to viral illnesses was noticed among the respondents in our study. Thus, improving knowledge on antibiotics is crucial to address those beliefs.
ARTICLE | doi:10.20944/preprints202007.0104.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: Urinary tract infection; antimicrobial agents; antibiotic resistance; E. coli; uropathogens; aminoglycosides
Online: 6 July 2020 (10:30:47 CEST)
Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.
ARTICLE | doi:10.20944/preprints202203.0072.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: antibiotic resistance; Acinetobacter baumannii; severe pneumonia
Online: 4 March 2022 (03:15:35 CET)
Background: Patients hospitalized in the intensive care unit (ICU) have a higher susceptibility to infections. Respiratory infections are the most common nosocomial infections. Rising antibiotic resistance due to indiscriminate use of antibiotics and poor adherence to standard precaution in healthcare facilities compounds the problem. The main aim of this study is to assess microbial patterns and antibiotic resistance from bronchoalveolar lavage specimens in severe pneumonia patients. Methods: This retrospective study was conducted in an Indonesian tertiary care hospital from January 2016-December 2020. Written and verbal informed consent was obtained prior to bronchoscopy procedures. Patients were enrolled if they had severe community-acquired pneumonia (CAP) according to American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) criteria, had high-risk hospital-acquired pneumonia (HAP), late-onset ventilator-associated pneumonia (VAP), or pneumonia caused by Coronavirus disease (COVID-19). Respiratory specimens via bronchoscopy were inoculated on general semi-sloid thioglycolate media. Testing for antibiotic susceptibility was done using the disk diffusion method. Results: Two hundred and one patients’ data were analyzed. The majority of patients were males (65,17%) and above 60 years of age. The most common type of pneumonia was CAP (39,3%). Neurologic/cerebrovascular disease was the most common comorbidity (35,32%). Acinetobacter baumannii was the most frequently isolated microorganism. Ampicillin/sulbactam and amikacin were found to yield lower microbial resistance. Conclusion: Combination of ampicillin/sulbactam and amikacin appeared effective as initial empirical therapy in severe pneumonia patients. Further studies are needed to evaluate the feasibility and effectiveness of this combined therapy.
ARTICLE | doi:10.20944/preprints202306.1037.v1
Subject: Medicine And Pharmacology, Other Keywords: Antibiotic resistance; Biofilm; Pseudomonas aeruginosa; ofloxacin; tobramycin; ceftazidime; Antibiotic Sensitivity; Efflux transporters
Online: 14 June 2023 (09:51:58 CEST)
Pseudomonas aeruginosa is an antibiotic-resistant priority pathogen as listed by the World Health Organization. P. aeruginosa, a gram-negative, rod-shaped bacterium, is frequently encountered in hospital settings as an opportunistic pathogen in nosocomial infections. P. aeruginosa has shown high antibiotic resistance, which has been attributed to several mechanisms, such as intrinsic, acquired, and adaptive resistance. This study investigates several genes which may be attributed to the acquisition of antibiotic resistance in the bacteria P. aeruginosa, as it transitions from its planktonic form to the more threatening and resistant biofilm form. Subsequently, the study assesses the comparative efficacy of three antibiotics, Ofloxacin (OFX), Tobramycin (TOB), and Ceftazidime (CAZ), in altering the expression levels of the identified multidrug efflux pump genes associated with the ability to extrude antibiotics from the cell when in the biofilm form. Efflux transporter gene expression in P. aeruginosa was conducted via extraction of total RNA in planktonic and biofilm- both untreated and treated - with Tobramycin (TOB), Ofloxacin (OFX), and Ceftazidime (CAZ). Real-time quantitative reverse transcriptase PCR was employed to analyze alterations in expression levels of the Mex A, Mex B, Mex X, Mex Y, OprM, and RPSL genes in the collected samples. In samples where no antibiotics were administered, an increase in expression of the Mex B efflux pump gene was observed compared to all other efflux pump genes in the biofilm form, providing multidrug resistance when active. The gene of interest, Mex B, was assessed for antibiotic resistance by P. aeruginosa culturing in the planktonic and biofilm forms with simultaneous treatment with TOB, OFX, and CAZ. Of the three antibiotics used, OFX showed more effectiveness in preventing biofilm growth by reducing the expression level of the Mex B efflux pump gene in the biofilm form, making P. Aeruginosa more antibiotic sensitive to OFX. TOB has similar results compared to OFX but was slightly less effective in reducing the expression of Mex B. Conversely, CAZ was not effective in reducing expression of the Mex B gene in the biofilm form or the planktonic form and was determined to be ineffective at eradicating the organism.
ARTICLE | doi:10.20944/preprints202306.2193.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Helicobacter pylori; Antibiotic resistance; Mutation rates; American Indian
Online: 30 June 2023 (11:49:29 CEST)
Helicobacter pylori (H. pylori) is a common bacterial infection linked to gastric malignancies. While H. pylori infection and gastric cancer rates are decreasing, antibiotic resistance varies greatly by community. Little is known about resistance rates among rural Indigenous populations in the United States. From 2018 to 2021, 396 endoscopy patients were recruited from a Northern Arizona clinic, where community H. pylori prevalence is near 60%. Gastric biopsy samples positive for H. pylori (n=67) were sequenced for clarithromycin and metronidazole-associated mutations, 23S ribosomal RNA (23S), and oxygen-insensitive NADPH nitroreductase (rdxA) regions. Medical record data were extracted for endoscopic findings and prior H. pylori history. Data analysis was restricted to individuals with no history of H. pylori infection. Of 49 individuals, representing 64 samples that amplified in the 23S region, a clarithromycin-associated mutation was present in 38.8%, with T2182C the most common mutation, 90%. While prevalence of metronidazole resistance-associated mutations was higher, 93.9%, mutations were more variable, with D95N the most common, followed by L62V. No statistically significant sex differences were observed for either antibiotic. Given the risk of treatment failure with antibiotic resistance, there is a need to consider the resistance profile during treatment selection. The resistance rates in this population of American Indian patients undergoing endoscopy are similar to other high-risk populations. This is concerning given the high H. pylori prevalence and low rates of resistance testing in clinical settings. The mutations reported are associated with antibiotic resistance, but clinical resistance must be confirmed.
REVIEW | doi:10.20944/preprints202307.1236.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Copper; Mercury; Arsenic; Organic Acids; Antibiotic Resistance; Food Safety
Online: 19 July 2023 (03:31:51 CEST)
Antimicrobial resistance (AMR) has a significant global impact on human, animal, and environmental health. Misuse and overuse of antibiotics in clinical and animal production settings are the main drivers behind the emergence of antimicrobial resistant bacteria. However, other compounds with antimicrobial activity may also contribute to this global public health problem. The aim of this comprehensive review is to provide detailed insights into the impact of metals and organic acids on the emergence and spread of AMR in the food chain, for which their role is not fully understood. The review examines the widespread use of organic acids in the food industry as feed additives or disinfectants, the crucial role of copper in animal growth and the harmful effects of mercury and arsenic as pollutants in food-producing environments. Additionally, it explores the antimicrobial mechanisms of metals and organic acids, the tolerance mechanisms developed by bacteria, and the interplay between genes responsible for metal tolerance and AMR. The comprehensive and integrated data presented highlights the need to further explore and understand the role of metals and organic acids as drivers of AMR to develop well-defined strategies effectively mitigating the AMR crisis within the food chain context.
ARTICLE | doi:10.20944/preprints201811.0451.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibiotic resistance; urban wastewaters; natural waters Rostov-on-Don
Online: 19 November 2018 (10:42:07 CET)
Drug resistance has become an extremely serious problem worldwide. Antibiotic resistance genes (ARGs) entering the environment with wastewaters promote replenishment of the resistome of natural microbioms. Distribution of several clinically significant ARGs in wastewaters of Rostov-on-Don (Southern Russia), lower reaches of the Don River and natural waters of the neighboring region was investigated. Metagenomic DNA samples isolated from 250 ml of wastewaters or natural waters and 200 mg of surface sediments were used for the study. Identification of the ARGs was carried out with end-point detection PCR. Presence of NDM, OXA-48, CTX-M, VanA, VanB, ErmB, and TetM/TetO genes was detected in urban wastewaters. Samples of wastewater treatment plant (WWTP) sewage were enriched with ARGs in contrast to non-treated wastewaters from the sewage collector. NDM, VanA, ErmB, TetM/TetO genes were found only in wastewaters and were absent in samples of natural waters and surface sediments. Only OXA-48, VanB and CTXM genes were found in natural waters and surface sediments. The described ARGs are quite typical for urban and hospital wastewaters. The target ARGs were detected in the samples connected to the anthropogenous sources of pollution such as Rostov municipal WWTP or livestock enterprise effluents.
ARTICLE | doi:10.20944/preprints202306.0923.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: vascular access infections (VAIs); Staphylococcus aureus; antibiotic resistance; antibiotic resistance genes; multilocus sequence typing; molecular characterization
Online: 13 June 2023 (10:14:42 CEST)
Patients receiving hemodialysis are at risk of vascular access infections (VAIs) and particularly vulnerable to the opportunistic pathogen Staphylococcus aureus. Hemodialysis patients were also at increased risk of infection during the COVID-19 pandemic. Therefore, this study determined the change in the molecular and antibiotic resistance profiles of S. aureus isolates from VAIs during the pandemic compared with before. 102 S. aureus isolates were collected from VAIs between November 2013 and December 2021. Before the pandemic, 69 isolates were collected, 58%, 39.1%, and 2.9% from arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs), respectively. The prevalence of AVG and TCC isolates changed to 39.4% and 60.6%, respectively, of 33 isolates during the pandemic. Sequence type (ST)59 was the predominant clone in TCC-methicillin-resistant S. aureus (MRSA) and AVG-MRSA before the pandemic, whereas the predominant clone was ST8 in AVG-MRSA during the pandemic. ST59 carrying the ermB gene was resistant to clindamycin and erythromycin. By contrast, ST8 carrying the msrA gene was exclusively resistant to erythromycin. The ST distribution for different VAIs changed from before to during the pandemic. The change in antibiotic resistance rate for different VAIs was closely related to the distribution of specific STs.
ARTICLE | doi:10.20944/preprints202311.1291.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Antibiotic resistance; Dessie; Kombolcha; Prevalence; Salmonella species
Online: 21 November 2023 (10:45:42 CET)
Bacteria are the major pathogens affecting food safety and foods of animal origin are main vehicles of human illness since food animals are the main reservoirs for many food-borne pathogens. Moreover, emergence and spread of multidrug-resistant food-borne bacterial pathogens become a significant public health concern globally. A cross-sectional study was conducted from October 2019 to July 2021 to estimate the prevalence, identify associated factors, and determine antibiotic resistance pattern of Salmonella species from foods of bovine origin in Dessie and Kombolcha towns. A total of 384 samples were collected. Simple and systematic random sampling techniques were employed for sampling milking cows and carcasses among cattle slaughtered at abattoirs, respectively. Samples from milk tanks, milk products, and beef were also selected randomly. Salmonella species were isolated and identified according to recommended standard bacteriological protocols. All the detected Salmonella species isolates were screened for in vitro antimicrobial susceptibility using agar disc diffusion method against 12 antimicrobial disks. The collected raw data were analyzed using descriptive and inferential analysis techniques. The overall prevalence rate of Salmonella species was 7.0%. The highest prevalence rate of Salmonella species (16.7%) was obtained from milk tank samples but not detected in milk products. Multidrug resistance to three and more than three drugs was observed among all isolated Salmonella species. All Salmonella species isolates (100.0%) were found to be resistant to Erythromycin, Tetracycline, and Vancomycin. The majority of the isolates (96.3%) were also resistant to Doxycycline and Polymyxin B. On the other hand, all isolates (100.0%) were sensitive to Gentamicin and Ciprofloxacin. The detection of multidrug-resistant Salmonella species showed that foods of bovine origin produced in the study sites were not safe for consumption. Hence, preventive measures are required to reduce bacterial contamination, concurrently to improve the wholesomeness and safety of foods of bovine origin.
REVIEW | doi:10.20944/preprints202305.1510.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Antibiotic; antimicrobial resistance (AMR); One-Health; economic; nanotechnology; policy
Online: 22 May 2023 (10:55:31 CEST)
Antimicrobial resistance (AMR) is a growing public health concern worldwide, and it poses a significant threat to human, animal, and environmental health. The overuse and misuse of antibiotics have contributed significantly to the emergence and spread of antimicrobial resistance, which may lead to significant economic consequences like reduced productivity and increased healthcare costs. Nanotechnology offers a promising platform for addressing this challenge. Nanoparticles have unique properties that make them highly effective in combating bacterial infections by inhibiting the growth and survival of multidrug-resistant bacteria in three areas of health: human, animal, and environmental. To conduct an economic evaluation of surveillance in this context, it is crucial to have a comprehension of the connections to be addressed by several nations by implementing national action policies based on the One Health strategy. This review provides an overview of the progress made thus far and presents potential future directions to optimize the impact of nanobiotics on AMR.
ARTICLE | doi:10.20944/preprints201808.0435.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Respiratory tract infections (RTI); antibiotic; sensitivity; resistant; bacteria
Online: 24 August 2018 (11:46:41 CEST)
1) Background: Respiratory tract infections (RTI) has been known to be a significant health concern for mortality and morbidity since many years. This study was aimed at determining the prevalence of bacterial pathogen causing upper respiratory tract (URTIs) and the susceptibility patterns to frequently used antibiotics among patients attending Abusetta hospital in Tripoli district; 2) Methods: A total of 1,110 throat swabs were collected between Jan, 2011 to December, 2014 and inoculated onto Blood agar, MacCkonkey agar and Chocolate agar then incubated at 37 oC for 24 hours. Bacterial pathogens were determined by bacteriological culture methods and antibiotic susceptibility of the isolates was identified following Clinical Laboratory Standard Institute guidelines (CLSI); 3) Results: Of the 1,110 respiratory samples tested, 71.1% (n = 789) of specimens were positive cultures with the dominant bacterial pathogens being streptococcus pneumonia 43.3% (n = 342), followed by pseudomonas aeruginosa 22.8% (n = 180), staphylococcus aurous 13.8% (n = 109), Escherichia Coli 6.9% (n = 55), Enterobacter spp 6.2% (n = 49), Citrobacter 4.5% (n = 36), and Klebsiella 2.2% (n = 18). Most isolates exhibited resistance against the commonly used antibiotics and to at least one antibiotic; and 4) Conclusions: The level of antibiotic resistance in this study is alarming and brings to light the timely and suitable diagnosis of the common bacteria causes of URTIs and proper antibiotic administration based on susceptibility test.
REVIEW | doi:10.20944/preprints202308.1336.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibiotic; antimicrobial resistance; azithromycin; macrolide resistance; multidrug resistance; potentiation; adjuvants; macrolide potentiator
Online: 18 August 2023 (09:21:05 CEST)
Antibiotics were once called miracle drugs which hit the market with astounding impact as it was considered the ultimate cure for infectious diseases in the mid-20th century. However, today nearly all bacteria that afflict humankind have become resistant to these wonder drugs once developed to stop them, imperilling the foundation of modern medicine. During the COVID pandemic, there was a surge in macrolide use to treat secondary infections and this persistent use of macrolide antibiotics has provoked the emergence of macrolide resistance. In view of the current dearth of new antibiotics in the pipeline, it is essential to find an alternative way to combat drug resistance. Antibiotic potentiators or adjuvants are non-antibacterial active molecules that, when combined with antibiotics, increase their activity. Thus, potentiating the existing antibiotics is one of the promising approaches to tackle and minimize the impact of antimicrobial resistance. Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against MDR pathogens. The present review summarizes the different resistance mechanisms adapted by bacteria to resist macrolides and further emphasizes the major macrolide potentiators identified which could serve to revive the antibiotic and can be used for the reversal of macrolide resistance.
REVIEW | doi:10.20944/preprints202301.0180.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: antibiotic resistance; food chain; antimicrobial peptides; food safety; food pathogens
Online: 10 January 2023 (07:56:04 CET)
Antibiotic resistance (ABR) is concerning issue due to its direct and indirect repercusions on public health, since decreased therapeutic effect of certain antibiotic to treatment complications that can cause death. There are several mechanism as to how ABR can be transferred from one microoorganisms to another, and many of them are dependant many environmental factors. The food supply chain is a environment in which ABR gene transfer can occur is multiple pathways, which generate concerns regarding food safety. Here, we summarize relevant mechanisms which are implied in ABR in food supply chain but also we are addressing routes of transmission and prevalence of ABR, implications on public health, and the application of new alternatives to antibiotics such as antimicrobial peptides, mainly bacteriocins, in order to countermeasure ABR.
ARTICLE | doi:10.20944/preprints202101.0040.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Antibiotics; antibiotic resistance; rational drug use; community pharmacist
Online: 4 January 2021 (12:58:43 CET)
Antibiotic resistance (ABR) is an emerging global threat to public health. Substantial evidence has indicated that community pharmacists (CPs) can play a critical role in managing the ever-increasing threat of antibiotic resistance. The study aimed to determine the knowledge, attitude, and practices of CPs (n=180) towards antibiotics and antibiotic resistance as well as to improve the rational use of antibiotics. Two phases of mixed methods (quantitative and qualitative) online study were conducted in Pakistan from August 2019 to March 2020 by using validated questionnaires and semi-structured interview data. Different statistical methods were used to tabulate the quantitative data whereas inductive thematic analysis was conducted to categorize themes from the qualitative data and draw conclusions. Approximately 64.4% were male (mean: 29-33 years old). Overall, CPs had good knowledge of and were familiar with superbugs and their roles in ABR (65.6%, Median=1, IQR=1) although they were poor in differentiating some antibiotic groups with their respective ABR patterns (31.1%, Median=1, IQR=1). Most CPs have a positive attitude towards antibiotics with most (90.0%) having identified ABR as a critical issue in public health (Median=1, IQR=0). Overall, CPs' practices towards antibiotics were reasonable where they tend to educate patients about the rational use of antibiotics (52.8%, Median=1, IQR=1). Two main themes (antibiotics and counseling of patients) were related to self-medication with while educational interventions are the sub-theme. ABR is multifactorial where the subthemes related to budget, time constraints incompetent staff, the absence of CPs, the lack of training, enforcement of laws and regulations are the need of the hour in Pakistan. Effective antibiotic stewardship programs, patient education, and awareness campaigns about antibiotics and ABR along with training of the CPs are important factors that have to be addressed in a timely manner.
ARTICLE | doi:10.20944/preprints201911.0282.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Nile tilapia; pseudomonas; antibiotic resistance; biofilm formation; virulence genes
Online: 24 November 2019 (14:11:40 CET)
Pseudomonas aeruginosa (P. aeruginosa) produces a suite of virulence factors that are coordinated by Quorum Sensing (QS) contributing to its disease-causing ability in aquaculture. The present study is first of its kind to obtain information regarding the presence and distribution of five QS genes, three virulence genes viz: lasI, lasR, rhlI, rhlR, rhlAB, toxA, aprA and plcH and seven of the Extended-spectrum βlactamases (blaVEB, blaPER, blaTEM,, blaSHV, blaCTX-M1, blaCTX-M2 and blaCTX-M3) of Pseudomonas species isolated from fish meat by direct PCR. Bacterial identification was based mainly on conventional biochemical techniques using the Vitek 2, automated system. Phenotypic sensitivity of antibiotics was established by the agar disc diffusion technique through 16 various antimicrobial drugs. Quantification of their in vitro production of numerous virulence genes outside the cell that are QS dependent namely, pyocyanin, elastase, alkaline protease, biofilm and cytotoxicity of Vero cell was as well executed. Fifteen genes demonstrated an enormous variety in their association. The total number of Pseudomonas species isolates were 30/100 to be identified by the API 20NE system as P. aeruginosa 12/30 (40%), P. fluorescens 8/30 (27%), P. putida 6/30 (20%) and P. alkylphenolia 4/30 (13%). The outcomes of this study have great significance for the strategic designation of QS quenching.
REVIEW | doi:10.20944/preprints201910.0255.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antimicrobial resistance; biofilm; efflux pump inhibitors; antibiotic potentiation; eskapee pathogens; gram-negative bacteria
Online: 22 October 2019 (10:22:56 CEST)
Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens, in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens.
ARTICLE | doi:10.20944/preprints202307.0036.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Antibiotic resistance; mcr-1; plasmid mediated colistin resistance; O25b-ST131; CTX-M
Online: 3 July 2023 (09:54:03 CEST)
The main aim of this study was to determine the prevalence of plasmid-mediated colistin resistance mcr-1 to mcr-5 genes among colistin and multi-drug resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter sp strains isolated from patients in a tertiary hospital in the city of Toluca, Mexico. 241 strains were included in the study. The presence of mcr genes among these strains was assessed by PCR and sequencing. In the case of mcr-carrying E. coli, further PCR tests were performed to determine the presence of blaCTX-M and whether the strains belonged to the O25b-ST131 clone. Conjugation experiments were carried to assess plasmid-mediated colistin resistance horizontal transmission. 12 strains (5.0%), of which four were E. coli; four, P. aeruginosa; three, K. pneumoniae and one, E. cloacae, were found to be resistant to colistin. Of these strains, two E. coli isolates were found to carry mcr-1. Both mcr-1-carrying E. coli strains were found to co-express blaCTX-M, belong to the O25b-ST131 clone and horizontally transmit their colistin resistance. The results of this study confirm the presence of plasmid-mediated colistin resistance in hospitalized patients in Mexico and demonstrated that the multidrug-resistant O25b-ST131 E. coli clone can acquire mcr genes and transmit such resistance trait to other bacteria.
ARTICLE | doi:10.20944/preprints202201.0225.v2
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Misdiagnosis; Random Amplification of Polymorphic DNA; 16S rRNA Sequencing; Loop-Mediated Isothermal Amplification; Antibiotic Resistance
Online: 19 January 2022 (11:39:41 CET)
Abstract Successful treatment against infectious agents depends on rapid and accurate detection of the causative organisms. Misdiagnosis can hamper such success while leading to improper advising of antibiotics. In Bangladesh, the majority of the diagnostic centers detect and identify pathogens through culture and biochemical test-based methods and suggest antibiotics based solely on the results of disk-diffusion methods. This pilot study tried to validate the identity of the isolates characterized by diagnostic facilities near Dhaka. One hundred and twenty pre-characterized clinical isolates were analyzed biochemically and genotypically. Random Amplification of Polymorphic DNA-PCR, rcsA, and phoA genes-based PCR, and Loop-Mediated Isothermal Amplification (LAMP)-based identification of Klebsiella pneumoniae and Escherichia coli, respectively, followed by 16S rRNA sequencing confirmed misidentification of some clinical pathogens of other genera as Klebsiella spp. and E. coli. According to the antibiotic susceptibility testing guidelines, antibiotic choice, sensitivity pattern, and breakpoint measurement are different for each group of organisms. The lack of adherence to proper standards results in misdiagnosis and may facilitate the development of antibiotic resistance. The pilot study observers misidentification of clinical pathogens identified by the diagnostic centers. Well-characterized rapid molecular techniques like LAMP are suggested in clinical diagnosis to avoid misdiagnosis and subsequently circumvent antibiotic resistance development.
ARTICLE | doi:10.20944/preprints201808.0272.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Staphylococcus aureus, meat, raw milk, antibiotics; antibiotic resistance genes
Online: 15 August 2018 (13:58:11 CEST)
Background: Staphylococcus aureus (S. aureus) occasionally threatens the life of the host as a persistent pathogen even though it is normal flora of humans and animals. We characterized drug resistance in S. aureus isolated from animal carcasses and milk samples from the abattoirs and dairy farms in the Eastern Cape Province. Methods: A 1000 meat swab samples and 200 raw milk samples were collected from selected abattoirs and dairy farms in the Eastern Cape Province, South Africa. S. aureus was isolated and positively identified using biochemical tests and confirmed by molecular methods. Antibiotic susceptibility test against 14 different antibiotics was performed against all isolates. Antibiotic resistance genes were also detected. Results: Of the 1200 samples collected, 134 (11.2%) samples were positive for S. aureus. Resistance ranged from 71.6% for penicillin G to 39.2% for tetracycline. Resistance gene (blaZ) was detected in 13 (14.9%), while msrA was found in 31 (52.5%) of S. aureus isolates. Conclusions: The present result shows the potential dissemination of multidrug-resistant S. aureus strains in the dairy farms and abattoirs in the Eastern Cape. Therefore, this implies that the organism may rapidly spread through food and pose serious public health risk
ARTICLE | doi:10.20944/preprints202303.0234.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: aluminum chlorohydrate; antibiotic resistance; minimum inhibitory concentration; quantitative reverse transcriptase-PCR; Staphylococcus epidermidis
Online: 13 March 2023 (14:04:54 CET)
This study investigates the effects of the antiperspirant aluminum chlorohydrate on the development of antibiotic resistance in commensal Staphylococcus epidermidis isolates. The isolates were exposed to aluminum chlorohydrate for 30 days, respectively. The bacteria that developed resistance to oxacillin, and ciprofloxacin were isolated, and the expression levels of some antibiotic resistance genes were determined by quantitative reverse transcriptase-PCR. Before and after the exposure, the minimum inhibitory concentration (MIC) values of the bacteria were determined by the microdilution method. A time-dependent increase was observed in the number of bacteria that developed resistance and increased the MIC value. Consistent with the ciprofloxacin resistance observed after exposure, an increase in the norA, norB/C, gyrA, gyrB, parC, and parE gene expressions was observed. In addition to aluminum chlorohydrate exposure, oxacillin resistance was observed in all test bacteria in the group subcultured only in the medium, suggesting that phenotypic resistance cannot be correlated with chemical exposure in the light of these data. The increase in mecA gene expressions of selected test bacteria that acquired resistance to oxacillin after exposure compared with control groups suggests that the observed resistance may be related to aluminum chlorohydrate exposure. To our knowledge, this is the first time in the literature that the effects of aluminum chlorohydrate as an antiperspirant on the development of antibiotic resistance in Staphylococcus epidermidis have been reported.
ARTICLE | doi:10.20944/preprints202212.0547.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: mecA; blaTEM-1; blaOXA-181; blaCTX-M-1; environmental-DNA; antibiotic-resistance
Online: 29 December 2022 (02:05:52 CET)
Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs
REVIEW | doi:10.20944/preprints202306.1921.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Antibiotic resistance; Drug designing; Bacterial mutation; Bacterial evolution; Horizontal gene transfer; Public and agricultural health
Online: 27 June 2023 (13:55:21 CEST)
Antibiotic resistance has emerged as one of the major concerns to public human health due to issues in treatment and control of major infectious diseases. From discovery of penicillin in 1940, the antibiotic resistance originated and now developed the microorganisms as resistive strains to the major available antibiotics. Furthermore, studies on this captivating activity of the microbes provide insight into the complexities of microbial physiology and may offer some guidance in preventing the onset and consequent development of antibiotic resistance. Despite of initiatives taken in last few decades to overcome the issues, the trends of antibiotic resistance gained much peak. Antibiotic resistance appears to have emerged as a result of various factors including antibiotics being misused and overused in both the medical field and the agricultural sector. Important factors in the development of antibiotic resistance also include bacterial mutation, unplanned evolution, and horizontal gene transfers. In addition, antibiotics resistance imposed the financial consequences to public health and drug development research. Future advancements related to innovative antibiotics and molecular drug designing become challenge for researchers due to intensive multiple antibiotics resistance among human population. Many researches have been conducted on origin, evolutionary aspect of antibiotic resistance and mechanisms of antibiotics resistance, but its effect on future drug development is little understood. Therefore, the recent review will highlight the role of antibiotic resistance in drug designing and impacts of antibiotic resistance on drug development in future.
ARTICLE | doi:10.20944/preprints202201.0131.v1
Subject: Medicine And Pharmacology, Other Keywords: methicillin-resistant Staphylococcus aureus; Matrix-Assisted Laser Desorption/Ionization Time-of-Flight; antibiotic susceptibility test; artificial intelligence
Online: 10 January 2022 (19:01:57 CET)
Combining Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) spectra data and artificial intelligence (AI) has been introduced for rapid prediction on antibiotic susceptibility test (AST) of S. aureus. Based on the AI predictive probability, the cases with probabilities between low and high cut-offs are defined as “grey zone”. We aimed to investigate the underlying reasons of unconfident (grey zone) or wrong predictive AST. A total 479 S. aureus isolates were collected, analyzed by MALDI-TOF, and AST prediction, standard AST were obtained in a tertiary medical center. The predictions were categorized into the correct prediction group, wrong prediction group, and grey zone group. We analyzed the association between the predictive results and the demographic data, spectral data, and strain types. For MRSA, larger cefoxitin zone size was found in the wrong prediction group. MLST of the MRSA isolates in the grey zone group revealed that uncommon strain types composed 80%. Amid MSSA isolates in the grey zone group, the majority (60%) was composed of over 10 different strain types. In predicting AST based on MALDI-TOF AI, uncommon strains and high diversity would contribute to suboptimal predictive performance.
ARTICLE | doi:10.20944/preprints201801.0136.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: polymer-drug association; inclusion nano-complex; an amphiphilic polymer; polysoaps; antibiotic resistance; ampicillin trihydrate
Online: 16 January 2018 (07:56:15 CET)
Biocompatible polymeric materials with potential to form functional structures in association with different therapeutic molecules have a high potential for biological, medical and pharmaceutical applications. Therefore, the protective capability of the inclusion nano-Complex formed between the sodium salt of poly(maleic acid-alt-octadecene) and a β-lactam drug (ampicillin trihydrate) on the chemical, enzymatic and biological degradation was evaluated. PAM-18Na was produced and characterized as reported previously. The formation of polymeric hydrophobic aggregates in aqueous solution was determined, using pyrene as a fluorescent probe. Furthermore, the formation of polymer-drug nano-complexes was characterized by Differential Scanning Calorimetry-DSC, viscometric, ultrafiltration/centrifugation assays, zeta potential and size measurements by dynamic light scattering-DLS. The PAM-18Na capacity to avoid the chemical degradation was studied through stress stability tests. The enzymatic degradation was evaluated from a pure β-lactamase, while the biological degradation was determined by different β-lactamase producing Staphylococcus aureus strains. When ampicillin was associated with PAM-18Na, the half-life time in acidic conditions increased, whereas both the enzymatic degradation and the minimum inhibitory concentration decreased to a 90 and 75%, respectively. These results suggest a promissory capability of this polymer to protect the β-lactam drugs against chemical, enzymatic and biological degradation.
ARTICLE | doi:10.20944/preprints202311.0657.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: de novo antibiotic resistance; fitness cost; (p)ppGpp; reactive oxygen species; compensatory evolution
Online: 9 November 2023 (14:53:45 CET)
Resistance evolution during exposure to non-lethal levels of antibiotics is influenced by various stress responses of bacteria which are known to affect growth rate. Here, we aim to disentangle how the interplay between resistance development and associated fitness costs is affected by stress responses. We performed de novo resistance evolution of wild-type strains and single-gene knockout strains in stress response pathways using four different antibiotics. Throughout resistance development, the increase in minimum inhibitory concentration (MIC) is accompanied by a gradual decrease in growth rate, most pronounced with amoxicillin or kanamycin. By measuring biomass yield on glucose and whole-genome sequences at intermediate and final timepoints, we identified two patterns of how the stress responses affect the correlation between MIC and growth rate. First, single-gene knockout E. coli strains associated with reactive oxygen species (ROS) acquire resistance faster and mutations related to antibiotic permeability and pumping out occur earlier. This increases the metabolic burden of resistant bacteria. Second, the ΔrelA knockout strain which has reduced (p)ppGpp synthesis, is restricted in its stringent response, leading to diminished growth rates. The ROS-related mutagenesis and the stringent response are vulnerabilities within the fitness of resistant strains that can possibly be targeted to prevent development of resistance.
ARTICLE | doi:10.20944/preprints202111.0176.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: whole genome sequencing; antibiotic resistance; Salmonella Enteritidis; Salmonella Typhimurium; Salmonella Bovismorbificans; colistin resistance; mcr-1; mcr-9
Online: 9 November 2021 (13:46:05 CET)
Polymyxin resistance, determined by mcr genes located on plasmid DNA, currently pose a high epidemiological threat. Non-typhoid Salmonella (NTS) are one of the key pathogens causing diarrheal diseases. Here, we report the isolation and whole genome sequencing of multidrug colistin-resistant/susceptible isolates of non-typhoid Salmonella enterica serovars carries mcr genes. Non-typhoid strains of Salmonella enterica subsp. enterica were isolated during microbiological monitoring of the environment, food, and diarrheal disease patients between 2018 and 2020 in Russia (n=586). mcr-1 genes were detected using a previously developed qPCR assay and whole genome sequencing of mcr positive isolates was performed by both short-read (Illumina) and long-read (Oxford Nanopore) approaches. Three colistin-resistant isolates including two isolates of S. Enteritidis and one isolate of S. Bovismorbificans carried the mcr-1.1 gene located on IncX4 and IncI2 conjugative plasmids, respectively. The phenotypically colistin-susceptible isolate of S. Typhimurium carried a mcr-9 gene on plasmid IncHI2. In conclusion, we present the first three cases of mcr gene carrying NTS isolates detected in Russia with both outbreak and sporadic epidemiological background.
ARTICLE | doi:10.20944/preprints202304.1195.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19 pandemic; antimicrobial resistance; infectious diseases consultation; multi-drug resistant bacteria; infection prevention and control group; antibiotic stewardship
Online: 29 April 2023 (03:23:00 CEST)
Introduction: The reduced implementation of surveillance programs and limited bedside infectious diseases consultations due to the pressure of COVID-19 pandemic in healthcare systems led to increased rates of irrational use of antimicrobials and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). Material-Methods: This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram positive and negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the Intensive Care Unit (ICU). Additionally, bloodstream infections with requested infectious diseases consultation were reported (n=400), determining whether these were carried out via telephone contact or at the patient's bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization and clinical outcome were analysed. Results: A total of 4569 strains of Gram positive and negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018-2019, a total of 246 infectious diseases consultations were carried out, while during the period 2020-2022 154, with the percentage of telephone consultations 15% and 76% respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic and 28-day mortality was significantly reduced in cases with bedside consultations. Conclusion: Empowering of infectious diseases surveillance programs and committees, rational use of antimicrobials agents and bedside infectious diseases consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains.
ARTICLE | doi:10.20944/preprints202301.0033.v2
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Staphylococcus aureus; clinical mastitis; antibiotic resistance (AR) prevalence; AR phenotype; AR genotype; recent trend
Online: 22 January 2023 (06:50:19 CET)
This study was aimed to examine the recent trends of antibiotic resistance (AR) prevalence in Staphylococcus aureus isolated from milk of animals with clinical mastitis in areas of the Abruzzo and Molise regions in central Italy. Fifty-four S. aureus isolates could be obtained from routine testing for clinical mastitis agents carried out in the author institution in years 2021 and 2022. These were analyzed for phenotypic resistance to eight antibiotics recommended for testing by European norms and belonging to the antibiotic classes used for mastitis treatment in milk producing animals. Moreover, the presence of 14 transferable genetic determinants encoding resistance to the same antibiotics was analyzed by qPCR tests developed in this study. Phenotypic resistance to non-β-lactams was infrequent, with only one 2022 isolate resistant to clindamycin. However, low level resistance to the β-lactam cefoxitin was observed in 59.2% isolates in both years making these isolates classifiable as methicillin resistant. The AR genotypes detected were blaZ gene (50% 2021 isolates and 44.4% 2022 isolates), ermC/T- aphA3-blaZ (one 2021 isolate), ant6-ermC/T-aphA3-blaZ (one 2021 isolate), ermB-blaZ (one 2022 isolate) and mecA-mph (one 2022 isolate). An interview to the veterinarians who conferred the samples, regarding antimicrobials prescribed for mastitis treatment and criteria of usage, indicated a possible causal relation with the AR test results. The low prevalence of AR genotypes, not increasing in time, most probably reflecting the reported management of antibiotic therapies in farms. However, the frequently observed cefoxitin resistance needs to be explained genotypically, further monitored and limited by modifying antibiotic usage practices. The identification of a mecA positive isolate in 2022 suggests to investigate further if this genotype is emerging locally.
ARTICLE | doi:10.20944/preprints202303.0539.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Antibiotic resistance; metallo-β-lactamases; metal-dependent enzymes; broad-spectrum inhibitors; inhibition assays; enzyme kinetics
Online: 31 March 2023 (03:35:02 CEST)
Metallo-β-lactamases (MBLs) are a group of Zn(II)-dependent enzymes that pose a major threat to global health. They are linked to an increasing number of multi-drug resistant bacterial pathogens, but no clinically useful inhibitor is yet available. Since β-lactam antibiotics, which are inactivated by MBLs, constitute ~65% of all antibiotics used to treat infections, the search for clinically relevant MBL inhibitors is urgent. Here, derivatives of a 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile (1a) were synthesised and their inhibitory effects assessed against representatives of each of the three subgroups of MBLs (B1, B2, B3). Several compounds are potent inhibitors of each MBL tested, making them excellent candidates for the development of broad-spectrum drug leads. In particular, compound 5f is highly potent across the MBL subfamilies, with Ki values in the low µM range. Furthermore, this compound also dis-plays synergy in combination with antibiotics such as penicillin G, cefuroxime or meropenem. This molecule thus represents one of the most promising compounds developed yet to combat MBLs.
ARTICLE | doi:10.20944/preprints202108.0361.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Neisseria gonorrhoeae; E. coli; K. pneumoniae; Acinetobacter; P. aeruginosa; fluoroquinolones; antimicrobial resistance; stewardship; antibiotic consumption; bystander selection
Online: 17 August 2021 (10:32:27 CEST)
It is unclear how important it is to reduce fluoroquinolone consumption in the general population to prevent the spread of fluoroquinolone resistance in Neisseria gonorrhoeae (bystander selection). Methods We assessed bystander selection by using Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in N. gonorrhoeae was correlated with the prevalence of fluoroquinolone resistance in four other gram-negative species - Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results Fluoroquinolone resistance in N. gonorrhoeae was positively associated with homologous resistance in all 4 species - A. baumanii. (ρ=0.61, P=0.0003, E. coli (ρ=0.67, P<0.0001), K. pneumoniae (ρ=0.52, P=0.0004) and P. aeruginosa (ρ=0.40, P=0.0206). Positive associations were also found between the national prevalence of fluoroquinolone resistance and fluoroquinolone consumption in the general population in the preceding year for 4 of the 5 species. Conclusions Gonococcal fluoroquinolone resistance can be productively viewed as being part of a syndemic of fluoroquinolone resistance. Strengthening antimicrobial stewardship programs may help retard the spread of fluoroquinolone resistance in N. gonorrhoeae.
REVIEW | doi:10.20944/preprints202307.0741.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Fermented foods; Antibiotic-resistant bacteria; Antibiotic-resistant genes
Online: 12 July 2023 (09:30:13 CEST)
Fermented food products are widely consumed for their nutritional and health-promoting properties earning them a central place in diets around the globe. However, these foods can present a paradox, as they have the potential to harbor not only beneficial probiotics but also antibiotic-resistant (AR) microbes and genes. The impact of AR in fermented foods has far-reached implications, such as its potential effects on human health, repercussions in the food industry, and environmental consequences. An in-depth analysis of AR in fermented foods, including dairy products, fermented fruits and vegetables, meat products, and beverages, would provide insights into the extent and ramifications of the issue with these foods. Therefore, this review systematically presents the status of AR in fermented foods, with a particular focus on AR bacteria and genes within this category of food products. The review also highlights the complexities of AR in fermented foods, emphasizing the role of bacterial adaptation during the fermentation process and the dynamics of bacterial gene transfer. Various contributing factors to AR are brought into focus, including intrinsic resistance among bacteria in fermented foods and the potential risk of contamination with pathogenic bacteria. Moreover, this review presents a range of mitigation strategies, from the development of novel antimicrobials to advances in fermentation technology and regulatory control. This comprehensive perspective on the intricate interplay between AR and fermented food will potentially pave the way for more targeted research and mitigation strategies in this critical area.
ARTICLE | doi:10.20944/preprints202305.1186.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: E. coli; environment; antibiotic resistance; antibiotic resistance genes
Online: 17 May 2023 (04:43:22 CEST)
We survey the diversity of antimicrobial resistance profiles of Escherichia coli (E. coli) isolates and molecular genotypes by means of phylogenetic groups circulating in complex aquatic habitats, such as sewage and receiving waters bodies as well as in clinical environment in Boeotia regional district of Greece. The predominant resistant profile among all environmental and clinical isolates was to penicillins - ampicillin (AMP) and piperacillin (PIP). ESBLs resistance related profiles were observed both in environmental and clinical isolates. Phylogenetic group B2 was the predominant in clinical isolates, whilst group A was dominant in environmental isolates. We report that reclaimed river water and wastewater are reservoirs of R and MDR E. coli to commonly used antibiotics in clinical practice posing putative threats for human and animal health.
ARTICLE | doi:10.20944/preprints202104.0257.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: information media; video; patient’ knowledge; antibiotic use; antibiotic resistance
Online: 9 April 2021 (10:23:20 CEST)
Irrational use or misuse of antibiotics, particularly by outpatients, increases antibiotic resistance. A lack of public knowledge about ‘Responsible use of antibiotics’ and ‘How to obtain antibiotics’ is a major cause of this. This study aimed to assess the effectiveness of an educational video about antibiotics and antibiotics use to increase outpatient's knowledge in two public hospitals in East Java, Indonesia. A quasi-experimental research setting was used with a one-group pretest-posttest design, carried out from November 2018 to January 2019. The study population consisted of outpatients, to whom antibiotics were prescribed, in two public hospitals in East Java, Indonesia. Participants were selected using a purposive sampling technique; 98 outpatients at MZ General Hospital in S regency and 96 at SG General Hospital in L regency were included. A questionnaire was used to measure the respondents’ knowledge and consisted of five domains, i.e. definition of infections and antibiotics, obtaining the antibiotics, directions of use, storage instructions, antibiotic resistance. The knowledge test score was the total score of the Guttman scale (a dichotomy of ‘yes’ or ‘no’ answers). To determine the significance of the difference in knowledge before and after providing the educational video and in the knowledge score between hospitals, the (paired) Student’s t-test was applied. The educational videos significantly improved outpatients' knowledge, which increased with 41% in MZ General Hospital and 42% in SG General Hospital. An educational video is a useful method to improve the knowledge of the outpatients regarding antibiotics.
ARTICLE | doi:10.20944/preprints202311.0944.v1
Subject: Medicine And Pharmacology, Emergency Medicine Keywords: Pseudomonas; Acinetobacter; antibiotic
Online: 15 November 2023 (01:57:40 CET)
The Emergency Department (ED) represents an important setting for addressing inappropriate antimicrobial prescribing practices, due to the time constraints and duration of microbiolo-gical diagnosis. The purpose of this study was to evaluate the etiology and antimicrobial resistance (AMR) pattern of the community-acquired pathogens, as well as the epidemiological characteristics of patients admitted through ED, in order to guide appropriate antibiotic therapy. (2) Methods: A retrospective observational study was performed on 657 patients, from whom clinical samples for microbiological diagnosis were collected, in the first 3 days after presentation in the ED. The identification of pathogens and the antibiogram with minimum inhibitory concentration determination were carried out according to the laboratory protocols. (3) Results: From the 767 biological samples analyzed, 903 microbial isolates were identified. E. coli was isolated most frequently (24.25%), followed by Klebsiella spp, S. aureus (SA) and non-fermentative Gram-negative bacilli. E. coli strains maintained their natural susceptibility to most antibiotics tested. In the case of Pseudomonas spp. and Acinetobacter spp., increased rates of AMR were identified. Also, 32.3% of SA strains were community-acquired MRSA. (4) Conclusions: The introduction of rapid microbiological diagnostic methods in emergency medicine is imperative in order to timely identify AMR strains and improve therapeutic protocols.
REVIEW | doi:10.20944/preprints201807.0091.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: bacterial infection; antibiotic resistance; bacteriophage; antibiotic therapy; phage therapy; review
Online: 5 July 2018 (10:09:09 CEST)
Bacteriophages, viruses that are widespread throughout the world, are highly specific for bacteria, usually of a single species and often of a particular strain. After being discovered and isolated 100 years ago, their use, called phage therapy, was instituted in medicine two years later and quickly used around the world to treat various bacterial infections. In the West, phage therapy was overshadowed in the second half of the 20th century by antibiotic therapy, which was then thought to be the definitive solution. But because of the increase in bacterial resistance to antibiotics, the idea of using bacteriophages in medicine has been reawakened. The innumerable observations reported over the years in the literature constitute an invaluable experience. We and some of our colleagues have, in the last decade treated some patients compassionately. With the available documentation and our own experience we discuss the potential indications and limitations of phage therapy. The observation of the increasing number of therapeutic failures in the announced perspective of a post-antibiotic era, we believe, that the introduction of bacteriophages into the therapeutic arsenal seems conceivable today to two preconditions: that their production as biologic drug meets current regulatory standards and that the benefit-risk assessment was conducted in a modern setting. Phage therapy could be applied as a substitution or supplement to antibiotic therapy under multiple circumstances in different modes, precise indications and limits.
ARTICLE | doi:10.20944/preprints202109.0197.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: One-health; food-animals; E. coli; K. pneumoniae; Acinetobacter; P. aeruginosa; fluoroquinolones; antimicrobial resistance; antibiotic consumption
Online: 13 September 2021 (09:55:56 CEST)
BackgroundIt is unclear what underpins the large global variations in the prevalence of fluoroquinolone resistance in gram-negative bacteria. We tested the hypothesis that different intensities in the use of quinolones for food-animals plays a role. MethodsWe used Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in human infections with Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was correlated with the use of quinolones for food producing animals. Linear regression was used to assess the relative contributions of country-level quinolone consumption for food-animals and humans on fluoroquinolone resistance in these 4 species. ResultsThe prevalence of fluoroquinolone resistance in each species was positively associated with quinolone use for food-producing animals (E. coli [ρ=0.55; P<0.001], K. pneumoniae [ρ=0.58; P<0.001]; A. baumanii [ρ=0.54; P=0.004]; P. aeruginosa [ρ=0.48; P=0.008]). Linear regression revealed that both quinolone consumption in humans and food animals were independently associated with fluoroquinolone resistance in E. coli and A. baumanii. ConclusionsReducing quinolone use in food-producing animals may help retard the spread of fluoroquinolone resistance in various gram negative bacterial species.
ARTICLE | doi:10.20944/preprints202308.0869.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: donkey; Escherichia coli; antibiotic resistant
Online: 10 August 2023 (13:21:14 CEST)
Escherichia coli (E. coli) is a common pathogen in veterinary clinical infections, typically not causing disease. However, under certain conditions, it can cause severe diarrhea, septicemia, and respiratory infections in domestic animals. Here, we report a large-scale mortality event in young donkeys, caused by E. coli infection in a farm with a herd of 340 donkeys, of which over 100 were under 4 months old. The characteristics of the E. coli strain were determined through clinical observation, complete blood count, blood biochemical analysis, H&E staining, histopathological examination, 16S rRNA analysis, and antibiotic sensitivity testing. A mice experiment using the isolated bacteria was also conducted, resulting in the onset of clinical and pathological symptoms similar to those observed in the donkeys. Molecular Evolutionary Genetic Analysis (MEGA) showed that the isolated bacteria, named CEG-GZL20, shared 99.98% sequence identity with E. coli. CEG-GZL20 exhibited high antibiotic resistance and only showed sensitivity to two antibiotics, Tetracycline and Gentamicin. As E. coli is a key component of the gut microbiota, responsible for digestion, nutrient absorption, and immune health, diseases and mortality caused by E. coli have significant implications for animal husbandry and human health.
ARTICLE | doi:10.20944/preprints202307.0935.v1
Subject: Biology And Life Sciences, Aquatic Science Keywords: antibiotic-resistant; doxycycline; microorganisms; ecosystems
Online: 14 July 2023 (07:57:19 CEST)
Antibiotics are released into the environment either directly in an unchanged form or in a partially metabolized form. The discharge is usually through untreated waste or industrial treatment effluents. The potential concern is the uptake of these antibiotics by crops irrigated by treated wastewater. This study collected wastewater from eight points at the Pagla, Kadamtali, Dhaka treatment plant. Here we consider three crucial antibiotics, Doxycycline, Ciprofloxacin, and Tetracycline, used mainly during the last two years of the pandemic. A PDA detector was used in high-performance liquid chromatography (HPLC) analysis to determine the raw and processed effluent antibiotics. The most frequently seen antibiotics in natural wastewater were Doxycycline and Ciprofloxacin, with the highest concentration of 0.23µgL-1and 0.20 µgL-1(raw water), respectively. Tetracycline was not detected in natural water. Contrarily, Doxycycline was discovered in the Pagla plant's completed water and had the highest concentration (0.12 gL-1), whereas Ciprofloxacin and Tetracycline were not found in the dead water. The findings of this study showed that Doxycycline was still present in both the raw and processed effluent. Both natural and finished wastewater was subjected to a microbial-resistant test in the presence of all three antibiotics. The results revealed that the samples detected both heterotrophic bacteria and total coliform. The viable aerobic heterotrophic bacteria ranged between 5.421 and 4.754 log cfu/ml. Total bacteria load gradually decreased in the finished wastewater.
ARTICLE | doi:10.20944/preprints202304.1097.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: MRSA; enterotoxin; virulence; antibiotic resistance
Online: 28 April 2023 (03:36:42 CEST)
The presence of Staphylococcus aureus in six dry-cured meat-processing facilities was investigated. S. aureus was detected in 3.8% of surfaces from five facilities. Prevalence was clearly higher during processing (4.8%) than after cleaning and disinfection (1.4%). Thirty eight isolates were typified by PFGE and MLST. Eleven sequence types (STs) were defined by MLST. ST30 (32%) and ST12 (24%), were the most abundant. Enterotoxin genes were detected in 53% of isolates. The enterotoxin A gene (sea) was present in all ST30 isolates, seb in one ST1 isolate and sec in two ST45 isolates. Sixteen isolates harbored the enterotoxin gene cluster (egc) with four variations in the sequence. The toxic shock syndrome toxin gene (tst) was detected in 82% of isolates. Regarding the antimicrobial resistance, twelve strains were susceptible to all the antibiotics tested (31.6%). However, 15.8% were resistant to three or more antimicrobials, and therefore multidrug-resistant. Our results showed that, in general, efficient cleaning and disinfection procedures were applied. Nonetheless, the presence of S. aureus with virulence determinants and resistance to antimicrobials, and particularly multidrug resistant MRSA ST398 strains might represent a potential health hazard for consumers, even though the pathogen was not isolated from final products.
ARTICLE | doi:10.20944/preprints202103.0140.v1
Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: culturability; antibiotic resistance; wastewater treatment
Online: 4 March 2021 (08:20:47 CET)
Bacterial resistance to antibiotics is a growing global concern, threatening human and environ-mental health, particularly among urban populations. Wastewater treatment plants (WWTPs) are thought to be “hotspots” for antibiotic resistance dissemination. The conditions of WWTPs, in conjunction with the persistence of commonly used antibiotics, may favor the selection and trans-fer of resistance genes among bacterial populations. WWTPs provide an important ecological niche to examine the spread of antibiotic resistance. We used heterotrophic plate count methods to identify phenotypically resistant cultivable portions of these bacterial communities and charac-terized the composition of the culturable subset of these populations. Resistant taxa were more abundant in raw sewage and wastewater before the biological aeration treatment stage. While some antibiotic resistant bacteria (ARB) were detectable downstream of treated wastewater re-lease, these organisms are not enriched relative to effluent-free upstream water, indicating effi-cient removal during treatment. Combined culture-dependent and culture-independent analyses revealed a stark difference in community composition between culturable fractions and the envi-ronmental source material, irrespective of culturing conditions. Higher proportions of the envi-ronmental populations were recovered than predicted by the widely accepted 1% culturability paradigm. These results represent baseline abundance and compositional data for ARB commu-nities for reference in future studies addressing the dissemination of antibiotic resistance associ-ated with urban wastewater treatment ecosystems.
ARTICLE | doi:10.20944/preprints202311.0980.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: Analysis; antibiotic; Djibouti; HPLC; spectrophotometer; TLC
Online: 17 November 2023 (07:56:38 CET)
The analysis of drugs is a priority in public health, particularly antibiotics which develop resistance due, among other things, to bad dosages or poor quality of the active substance. In this study, we evaluated eight antibiotics available in health centers in Djibouti through qualitative and quantitative analysis. The tests were based on high-purity reference products. In qualitative analysis by HPLC, only amoxicillin presented two impurity peaks. This observation is found in the dosage of this active ingredient with a value of 83 ±0.6 mg instead of the 500 mg indicated on the label. It will be necessary to diversify the sample’s provenance to seek the origin of this degradation.
ARTICLE | doi:10.20944/preprints202310.0291.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: ocular infections; bacteria contamination; antibiotic resistance
Online: 5 October 2023 (13:33:16 CEST)
Periodic assessment of bacterial contamination is necessary as it allows proper guidance in cases of eye infections through the use of appropriate antibiotics. Due to the extensive use of antibiotic treatment, most of the contamination flora is resistant to the usual ophthalmic antibiotics. The present study shows an updated picture of the susceptibility of Gram-positive and Gram-negative bacteria found on the ocular surface to the most commonly used antibiotic agents in patients undergoing cataract surgery. A total of 993 patients were included in the study with ages between 44 and 98 years old. Conjunctival culture was collected 7 days before cataract surgery. The response of Gram-positive and Gram-negative bacteria to various antibiotic classes like glycopeptides, cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, phenicols, tetracyclines, rifamycins, macrolides and penicillins was assessed. From the tested antibiotics, vancomycin had 97.8% efficacy on Gram-positive bacteria. In the cephalosporin category, we observed an increased resistance of the cefuroxime for both Gram-positive and negative bacteria. Antibiotics that have more than 90% efficacy on Gram-positive bacteria are: meropenem, imipenem, netilmicin, amikacin and rifampicin. On Gram-negative bacteria, we found 100% efficacy of all tested fluoroquinolones, aminoglycosides (except for tobramycin), doxycycline, azithromycin, clarithromycin and chloramphenicol. The current study illustrates patterns of increased resistance of certain bacteria present on ocular surface to some of the commonly used antibiotics in ophthalmological clinical practice. One such revealing example is cefuroxime, which has been highly used as an intracameral antibiotic for the prevention of bacterial endophthalmitis after cataract surgery.
ARTICLE | doi:10.20944/preprints202308.1387.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: bio-graphen; metal-free; doped; antibiotic
Online: 22 August 2023 (07:35:03 CEST)
Wastewater contaminated with antibiotics is a major environmental challenge. We developed here the green synthesis of bio-graphenes by using natural precursors (Xanthan, Chitosan, Boswellia, Tragacanth). The use of these precursors can act as templates to create 3D doped graphene structures with special morphology. Also, this method is a simple method for in-situ synthesis of doped graphenes. The elements present in the natural polymers (N) and other elements in the natural composition (P, S) are easily placed in the graphene structure and improve the catalytic activity due to the structural defects, surface charges, increased electron transfers, and the high absorption. In this mechanism, O2 dissolved in water absorbs onto the positive charged C in doped graphenes to create oxygenated radicals, which enables the degradation of antibiotic molecules. Light irradiation increases the amounts of radicals and rate of antibiotic removal. The results have shown that the hollow cubic Chitosan-derived graphene has shown the best performance due to the doping of N, S, and P. The Boswellia-derived grapheme shows the highest surface area, but lower catalytic performance, which indicates the more effective role of doping in the catalytic activity. The effect of oxygen and light were also studied to accelerate the degradation process.
REVIEW | doi:10.20944/preprints202304.1124.v2
Subject: Chemistry And Materials Science, Other Keywords: copper coordination; copper homeostasis; antibacterial; antibiotic
Online: 23 May 2023 (08:01:12 CEST)
Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.
ARTICLE | doi:10.20944/preprints202110.0033.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Antibiotic resistance; text mining; therapy; database
Online: 4 October 2021 (08:58:52 CEST)
Antimicrobial resistance (AMR) is one of the top 10 threats affecting global health. AMR defeats the effective prevention and treatment of infections caused by microbial pathogens including bacteria, parasites, viruses and fungi (WHO). Microbial pathogens have natural tendency to evolve and mutate over time resulting in AMR strains. The set of genes involved in antibiotic resistance also termed as “antibiotic resistance genes” (ARGs) spread through species by lateral gene transfer thereby causing global dissemination. While this biological mechanism is prevalent in the spread of AMR, human methods also augment through various mechanisms such as over prescription, incomplete treatment, environmental waste etc. A considerable portion of scientific community is engrossed in AMR related work trying to discover novel therapeutic solutions for tackling resistant pathogens. Comprehensive inspection of the literature shows that diverse therapeutic strategies have evolved over recent years. Collectively, these therapeutic strategies include novel small molecules, newly identified antimicrobial peptides, bacteriophages, phytochemicals, nanocomposites, novel phototherapy against bacteria, fungi and virus. In this work we have developed a comprehensive knowledgebase by collecting alternative antimicrobial therapeutic strategies from literature data. We have used subjective approach for datamining new strategies resulting in broad coverage of entities and subsequently add objective data like entity name, potency, safety information etc. The extracted data was organized KOMBAT (Knowledgebase Of Microbes’ Battling Agents for Therapeutics). A lot of these data are tested against AMR pathogens. We envision that this database will be noteworthy for developing future therapeutics against resistant pathogens. The database can be accessed through http://kombat.igib.res.in/.
ARTICLE | doi:10.20944/preprints202106.0116.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: PPTase; NRPS; indigoidine; PptT; antibiotic screening
Online: 3 June 2021 (13:22:33 CEST)
A recently-validated and underexplored drug target in Mycobacterium tuberculosis is PptT, an essential phosphopantetheinyl transferase (PPTase) that plays a critical role in activating enzymes for both primary and secondary metabolism. PptT possesses a deep binding pocket that does not readily accept labelled coenzyme A analogues that have previously been used to screen for PPTase inhibitors. Here we report on the development of a high throughput, colorimetric screen that monitors the PptT-mediated activation of the non-ribosomal peptide synthetase BpsA to a blue pigment (indigoidine) synthesising form in vitro. This screen uses unadulterated coenzyme A, avoiding analogues that may interfere with inhibitor binding, and requires only a single-endpoint measurement. We benchmark the screen using the well-characterised Library of Pharmaceutically Active Compounds (LOPAC1280) collection, and show that it is both sensitive and able to distinguish weak from strong inhibitors. We further show that the BpsA assay can be applied to quantify the level of inhibition and generate consistent EC50 data.
REVIEW | doi:10.20944/preprints202007.0589.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: β-lactamase; convergent evolution; antibiotic resistance
Online: 24 July 2020 (13:59:24 CEST)
The probability of the evolution of a character depends on two factors: the probability of moving from one character state to another character state and the probability of the new character state fixation. More the evolution of a character is probable more convergent evolution will be witnessed, consequently, convergent evolution could mean that the convergent character evolution result as a combination of these two factors. We investigate this phenomenon by studying the convergent evolution of biochemical functions. We use for the investigation the case of β-lactamases. β-lactamases hydrolyzes β-lactams which are antimicrobials able to block the DD-peptidases involved in bacterial cell wall synthesis. β-lactamase activity is present in two different superfamilies: the metallo-β-lactamase and the serine β-lactamase superfamily. The mechanism used to hydrolyze the β-lactam is different for the two superfamilies. We named this kind of evolution an allo-convergent evolution. We further show that the β-lactamase activity evolved several times within each superfamily, a convergent evolution type that we named iso-convergent evolution. Both types of convergent evolution can be explained by the two evolutionary mechanisms discussed above. The probability of moving from one state to another is explaining the promiscuous β-lactamase activity present in the ancestral sequences of each superfamily, while the probability of fixation is explained in part, by positive selection as the organisms having β-lactamase activity allows them to resist to organism secreting β-lactams. Indeed a mutation increasing the β-lactamases activity will be selected as the organisms having this activity will have an advantage over the others.
REVIEW | doi:10.20944/preprints201805.0315.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: Neisseria gonorrhoeae; antibiotic resistance; gonorrhea; treatment
Online: 23 May 2018 (07:46:34 CEST)
Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.
ARTICLE | doi:10.20944/preprints202303.0032.v1
Subject: Public Health And Healthcare, Primary Health Care Keywords: Antibiotic stewardship; antibiotic prescribing; COVID-19; primary care; electronic health records; Antmicrobial Stewardship; AMS; General Practice
Online: 2 March 2023 (04:25:37 CET)
COVID-19 pandemic-related pressures on primary care may have driven inappropriate continuation of antibiotic prescriptions. Yet prescribing modality (repeat/non-repeat) has not previously been investigated in a pandemic context. Using the OpenSAFELY-TPP analytics platform, we analysed repeat/non-repeat prescribing frequency in monthly patient cohorts between Jan 2020–2022. In-depth analysis was conducted on Jan 2020 (“pre-pandemic”) and Jan 2021 (“pandemic”) cohorts. Per-patient prescribing and clinical conditions were determined by searching primary care record data using clinical code lists. Repeat prescribing was defined as >=3 prescriptions in a 6 month lookback period. Associations between demographics (e.g. age, sex, geography) and repeat/non-repeat prescribing were explored using unadjusted risk ratios. Antibiotic prescribing declined from May 2020; non-repeat prescribing declined more strongly than repeat prescribing (maximum declines -26% vs -11%, respectively). In the pandemic cohort, older patients were at higher risk of prescribing (especially repeat prescribing). The most common clinical conditions for repeat prescribing were COPD comorbidity and urinary tract infection. Comorbidities were more common among repeat vs non-repeat prescribed patients. In the pandemic cohort, vs pre-pandemic, repeat and non-repeat prescribing for comorbidities generally declined less compared with shorter-term conditions (infections, including COPD exacerbation/lower respiratory tract infection). Our findings inform ongoing development of stewardship interventions in England..
ARTICLE | doi:10.20944/preprints202311.0361.v1
Subject: Public Health And Healthcare, Other Keywords: Listeria monocytogenes; serogroup; MLST; MVLST; antibiotic susceptibility
Online: 6 November 2023 (15:07:54 CET)
Objectives Listeria monocytogenes (LM), the etiological agent of Listeriosis, can cause foodborne zoonosis. In this study, we characterized 23 strains that caused human listeriosis in Palermo (Sicily, Italy) during the period 2018-2020. In addition, we assessed the phenotypic susceptibility of clinical isolates to antibiotics in accordance with EUCAST guidelines. Methods The serogroup was determined by PCR. While MLST and MVLST were identified through the sequencing of housekeeping genes. Finally, susceptibility to antibiotics was assessed by means of the Phoenix automatic system. Results Patients hospitalized with listeriosis were predominantly males (56% vs. 44% of females). The cases were not associated with pregnancy included patients >65 years of age (60%), two of whom were affected by cancer, while cases associated with pregnancy included two pregnant women and three preterm infants. Data collected found that the main pathologies shown by patients were meningitis (60,9%) and bacteremia (39,1%). The LM strains were isolated from blood (52%), cerebrospinal fluid (26%), cerebrospinal fluid + blood (13%), blood + nasal swab (4%), and ascitic fluid (4%). The predominant serogroup was IVb (96%), whereas only one strain belonged to serogroup IIa (4%). Among the strains with serotype 4b, 4d, 4e, ST 2/VT 21 (92%) and ST6/VT19 (4%) were determined, while only isolates with serotype 1/2a, 3a show ST155/VT45 (CC155). Conclusion This study revealed the widespread circulation of a single clinical strain (ST2/VT21) associated with suspected food contamination, demonstrating the importance of carrying out molecular epidemiological surveillance. Our clinical isolates were susceptible to the assayed beta-lactams, in agreement with the literature data.
REVIEW | doi:10.20944/preprints202212.0348.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibiotic; biofilm; infections; Staphylococcus aureus; therapeutic antibiofilm
Online: 20 December 2022 (03:24:37 CET)
Staphylococcus aureus is a microorganism frequently associated with implant-related infections, owing to its ability to produce biofilms. These infections are difficult to treat because antimicrobials must cross the biofilm to effectively inhibit bacterial growth. Although some antibiotics can penetrate the biofilm and reduce the bacterial load, it is important to understand that the results of routine sensitivity tests are not always valid for interpreting the activity of different drugs. In this review, a broad discussion on the genes involved in biofilm formation, quorum sensing, and antimicrobial activity in monotherapy and combination therapy is presented that should benefit researchers engaged in optimizing the treatment of infections associated with S. aureus biofilms.
ARTICLE | doi:10.20944/preprints202208.0378.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Antibiotic resistance; Colonization; Prevalence; GBS; Resistance phenotype
Online: 22 August 2022 (08:04:16 CEST)
Group B Streptococcus (GBS), a commensal in the body, causes a wide range of infectious diseases. The colonisation levels of GBS and its resistance profile to antibiotics provide important information useful for orienting prevention strategies. There is little data available on the subject with determination of resistance phenotypes in Cameroon. We therefore aimed to determine the prevalence of colonization, antibiotic resistance, including patterns of inducible resistance to clindamycin of GBS in Yaounde. To achieve this goal, a prospective cross-sectional study with an analytical component was carried out from the 28th June to the 29th August 2020 at the BIOSANTE laboratory and the Yaounde Gynaeco-Obstetrics and Paediatrics hospital. Vaginal swabs and urine were collected on 163 women. This samples were analysed using 5% defibrinated sheep blood agar and chocolate plus polyvitex agar. The isolates were identified using the morphology of the colony, Gram staining, haemolysis, catalase test and latex grouping test. Antibiotic susceptibility testing was done by disk diffusion method following the recommendations of the ACFSM 2019. The double disk diffusion method was used to identify isolates with clindamycin inducible resistance. Our data was analysed by the software SPSS version 2.1. The results obtained showed that the global prevalence of colonization by GBS was 37% (57/163), 40.35% in non-pregnant women and 59.65% in pregnant women. Pregnancy (P-value = 0.019) and gestational age (P-value = 0.025) constituted the risk factors of maternal colonization by GBS. In addition, the strains of GBS were resistant to all antibiotics tested. A D test showcased that 64.7% of GBS were resistant in a constitutive manner to clindamycin. We also note the presence of M phenotypes. As a whole, our results demonstrate that the rate of GBS colonization in this study was similar or higher than those in the previous report in Cameroon. All this indicates that attention should be paid to this bacterium in the monitoring of antimicrobial resistance and in the care of pregnant women and newborns.
REVIEW | doi:10.20944/preprints202206.0193.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: aminosugar; antibiotic; biosynthesis; glycosylation; lemonomycin; total synthesis
Online: 14 June 2022 (04:55:21 CEST)
Lemonomycin (1) was first isolated from the fermentation broth of Streptomyces candidus in 1964. The complete chemical structure was not elucidated until 2000 with extensive spectroscopic analysis. Lemonomycin is currently known as the only glycosylated tetrahydroisoquinoline antibiotic. Its potent antibacterial activity against Staphylococcus aureus and Bacillus subtilis and complex architecture make it an ideal target for total synthesis. In this short review, we summarize the research status of lemonomycin for biological activity, biosynthesis and chemical synthesis. The unique deoxy aminosugar-lemonose was proposed to play a crucial role in biological activity, as shown in other antibiotics, such as arimetamycin A, nocathiacin I, glycothiohexide α, and thiazamycins. Given the self-resistance of the original bacterial host, the integration of biosynthesis and chemical synthesis to pursue efficient synthesis and further derivatization is in high demand for the development of novel antibiotics to combat antibiotic-resistant infections.
CASE REPORT | doi:10.20944/preprints202202.0291.v1
Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: granulomatous cheilitis; latent tuberculosis; IGRA; antibiotic treatment
Online: 23 February 2022 (12:08:19 CET)
The granulomatous cheilitis (GC) presents a heterogeneous group of disorders characterised by a granulomatous inflammation/reaction of the lips to various stimuli. Numerous etiologies have been proposed, including genetic, immunologic, allergic and infectious. Among the secondary causes of GC, a distant infection by Mycobacterium tuberculosis should be considered. The GC could be the clinical presentation of a tuberculide resulting from a hypersensitivity reaction to an underlying focus of active or latent tuberculosis infection (LTBI). This communication describes a woman diagnosed with GC related to LTBI, who responded well to antituberculosis treatment.
REVIEW | doi:10.20944/preprints202111.0397.v1
Subject: Medicine And Pharmacology, Complementary And Alternative Medicine Keywords: Bacteriophage therapy; MRSA; antibiotic resistance; virulence factors
Online: 22 November 2021 (13:54:16 CET)
The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.
ARTICLE | doi:10.20944/preprints202111.0248.v1
Subject: Biology And Life Sciences, Virology Keywords: Bacteriophage therapy; antimicrobial resistance; Salmonella; antibiotic synergy
Online: 15 November 2021 (10:44:07 CET)
The prevalence of multidrug resistant bacterial diseases is a major global health risk. Multidrug resistant bacterial diseases are prevalent, and the need for novel methods of treatment is essential to the preservation of public health. Annually foodborne pathogens cause 1.35 million infections and 26,500 hospitalizations in the United States alone. Foodborne pathogens such as Salmonella spp. are a major threat to public health. Bacteriophages offer a unique method for the treatment of these multidrug resistant bacteria. We studied the infection dynamics of a potential mono-phage therapy of Salmonella typhimurium under various pathophysiological conditions. Furthermore, we determined the resistance dynamics of Salmonella typhimurium against P22 phage treatment. We also determined synergy with antibiotics such as ampicillin and kanamycin. This research helps to further define and show the versatility of bacteriophages as potential novel treatment methods.
BRIEF REPORT | doi:10.20944/preprints202104.0187.v2
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Antibiotic use, Neonatal Units, EpicLatino, Latin America.
Online: 9 April 2021 (13:24:43 CEST)
Background: Recent years have seen chaos in the neonatology use of antibiotics with diverse opinions and recommendations in international guidelines and societies. This has created great uncertainty in which cases to use, for how long, and which tests apply to make these decisions. We conducted a retrospective cohort study about the use of antibiotics in the EpicLatino neonatal units and a Latin American network database, after noting these variations in the 2019 report. Methods: For the year 2019 using the EpicLatino database, we included cases (only first admission) ≤32 weeks gestational age at birth, excluding one unit that did not accept to participate. The number of cases and days receiving antibiotics were recorded as well as the progression for each unit. Inappropriate use of antibiotics was defined as greater than 3 days in patients with negative cultures (blood/CSF cultures) excluding: major malformations, urinary tract infections, necrotizing enterocolitis (NEC) and cases with suspected chorioamnionitis in the mother (the latter two only during the course of diagnosis of NEC or chorioamnionitis). This study was approved by the EpicLatino board of directors and by the participating units. Results: A total of 6,543 days of antibiotics were observed, 49.5% of cases had at least one positive blood/CSF culture. A total of595 days of antibiotics without justification were found in 72 courses in 61 cases; 14/72(19.4%) had no diagnosis of infection in the database, 7/72(9.7%) did not document any culture throughout their stay, and 37/72(51,4%) obtained only one blood/CSF culture during their entire stay. Most diagnosis were clinical sepsis and in 24/58(41%) curses, a diagnosis of pneumonia with a poor positive culture correlation was found. Furthermore, 74% of the units didn´t use pneumonia as a justification to use antibiotics. Other diagnosis found: Conjunctivitis, NEC 1A and rotavirus NEC. Conclusions: Although the method of reviewing the use of antibiotics in a database has a number of limitations, especially the cause that motivated the use of antibiotics and other tools used for diagnosis of infections, the notable differences between units is striking. Although it is difficult to make recommendations to all units, it is important to control infections in some units and in others to reduce the excessive use of antibiotics, especially with diagnosis of pneumonia in neonates and negative blood/CSF cultures.
ARTICLE | doi:10.20944/preprints202010.0116.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: antibiotic conjugates; ciprofloxacin; multidrug resistance bacteria; triphenylphosphonium
Online: 6 October 2020 (10:16:11 CEST)
Multidrug resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach; we have modified the antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-ester-PPh3), to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3 and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (MRSA) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with an MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivates induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria, through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.
ARTICLE | doi:10.20944/preprints201712.0029.v2
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: blood stream health care associated infections; neonates; risk factors, antibiotic use, antibiotic resistance; neonatal intensive care unit; India
Online: 30 January 2018 (08:03:04 CET)
Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.
ARTICLE | doi:10.20944/preprints202311.0608.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Klebsiella pneumoniae; Dairy products; foodborne; Antibiotic sensitivity; Libya.
Online: 9 November 2023 (07:23:51 CET)
Klebsiella pneumoniae is one of the most common causes of clinical and asymptomatic mastitis in dairy cattle, also in milk and dairy products affecting its quality. Mastitis caused by K. pneumoniae is even more serious due to its poor response to antibiotic therapy. This study was conducted to detect and identify the presence of K. pneumoniae in milk and dairy products. A total of 234 samples were randomly collected from various locations in Libya. Samples were examined for the presence of K. pneumoniae by conventional cultural techniques that included cultivation in violet red bile agar plus 4-methylumbelliferyl-ß-D-glucuronide (VRBA + MUG) broth, and CHROM agar followed by identification by PCR and partial sequencing of 16S rRNA. Out of the 234 samples of milk and dairy products collected, 16 (6.8%) of the isolates revealed mucoid colonies on agar media phenotypically suggested to be K. pneumoniae. The isolates identification was confirmed by molecular techniques (16S rRNA). Among examined samples, K. pneumoniae was recovered from she camel’s milk, raw cow’s milk, raw fermented milk, Maasora cheese, Ricotta cheese, soft cheese, full cream milk powder, milk powder infant formula, cereal baby food and growing up formula. From the 16 K. pneumoniae isolates; antibiotic susceptibility testing was performed on 12 isolates, the results showed that K. pneumoniae isolates were resistant to more than 8 antibiotics, interestingly, two isolates revealed MBL production. This study emphasized the relationship between K. pneumoniae and raw milk, cheese, milk powder and infant milk retailed in Libya, which is considered as a risk for human health as many of these products did not comply with microbiological criteria of international and/or Libyan standards. The necessary precautions have to be taken to carry out effective sanitary practices during the production in dairy plants, handling and distribution in the markets particularly at local small manufacture scale.
REVIEW | doi:10.20944/preprints202304.0591.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibiotics; antibiotic resistance; multidrug resistance genes; molecular mechanisms
Online: 19 April 2023 (10:54:50 CEST)
Antibiotic resistance among bacterial pathogens is recognized as a major threat to human health worldwide. The emergence of multidrug-resistant bacteria can also be found in the community settings, apart from hospital environment, which indicates that reservoirs of antibiotic resistance genes do exist outside the hospital. The growth of antibiotic resistance is a consequence of bacterial adaptations in response to selective pressures. To survive in this hostile environment, bacteria develop defence mechanisms such as chemical modification of antibiotics, enzyme-catalysed antibiotic degradation, altered permeability, antibiotic efflux, mutation of target sites and biofilm formation, resulting in resistance to nearly all currently available antibiotics used in the clinical practice. The present review summarizes insights into the molecular mechanisms underlying the antibiotic resistance which is useful for planning strategies to combat antibiotic resistance and devise innovative therapeutic tools to fight against multidrug-resistant bacterial species.
REVIEW | doi:10.20944/preprints202210.0218.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Bactericidal; Bacteriostatic; Antibiotic(s); Antimicrobial Therapy; Narrative review
Online: 17 October 2022 (02:05:28 CEST)
Sepsis is a serious and life-threatening medical emergency associated with dysregulated host immune responses to infection. Like cerebral vascular or acute cardiovascular incidents, sepsis is considered a time-dependent condition having severe and long-term consequences on human health. Apart from organ support, prompt administration of appropriate antimicrobial therapy is crucial to limit the burden of complications related to sepsis in ICU patients. The management of septic patients requires comprehensive and multi-disciplinary strategies for an adequate diagnosis. Most of the ICU population receives empirical antibiotic therapy without having a confirmed diagnosis. The misuse of antibiotics in intensive care units may increase the possibility of developing multidrug resistance along with considerable ecological side effects. The first doses of empirical anti-microbial therapy are slightly higher, regardless of the presence or absence of organ dysfunction, which may upregulate the production of circulating pro-and-anti-inflammatory mediators, having negative effects on the general well-being of the patients. This notion supports the introduction of individualized antimicrobial approaches based on local patterns of resistance to ensure the appropriate dosage of empirical therapy, as well as to limit the emergence of multidrug resistance in advanced-care patients. The adequacy and treatment duration must be viewed at regular intervals for effective de-escalation, and novel diagnostic approaches must be introduced to improve the quality of care in the ICU population.
ARTICLE | doi:10.20944/preprints202207.0046.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: infectious keratitis; corneal infection; antibiotic susceptibility; antimicrobial resistance
Online: 4 July 2022 (09:41:43 CEST)
Infectious keratitis (IK) represents a major cause of corneal blindness. This study aims to investigate the demographics, risk factors, microbiological characteristics and antibiotic susceptibility patterns of IK in Taiwan over the past 15 years. A retrospective population-based study was conducted using the Chang Gung Research Database. Patients with IK were identified by diagnostic codes for corneal ulcer from 2004 to 2019. Of 7807 included subjects, 45.2% of patients had positive corneal cultures. The proportion of contact lens-related IK declined, while that of IK related to systemic diseases grew. The percentage of isolated gram-positive bacteria surpassed that of gram-negative bacteria in the 15-year period. The prevalence of Pseudomonas aeruginosa showed a decreasing trend (p = 0.004), whereas coagulase-negative Staphylococcus (CNS) and Propionibacterium species were increasingly detected (p < 0.001). Overall, the trend of antibiotic susceptibility of both gram-positive and gram-negative bacteria did not change throughout the study period. The susceptibility to the test antibiotics maintained over 90% in gram-negative isolates during 15 years. Vancomycin preserved 100% susceptibility to all gram-positive isolates. Since most tested antibiotics exhibited stable susceptibility over decades, this study reinforced that fluoroquinolones and fortified vancomycin continue to be good empiric therapies for treating bacterial keratitis in Taiwan.
REVIEW | doi:10.20944/preprints202205.0056.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: tetracyclines; doxycycline; limecycline; minocycline; pleiotrophy; non-antibiotic properties
Online: 6 May 2022 (03:34:44 CEST)
Tetracyclines are a group of antibiotics whose first representative was discovered over 70 years ago. Since then, they have been of great interest in dermatology. In addition to their antibacterial activity, they are able to inhibit metalloproteinases and exhibit anti-inflammatory, anti-apoptotic and antioxidant effects. The side effects have been thoroughly studied over the years. The most characteristic and important in daily dermatolgical practice are: phototoxicity, hyperpigmentation, onycholysis, photoonycholysis, induced lupus erythematosus, idiopathic intracranial hypertension. In this article, we summarize the use of tetracyclines in infectious diseases and inflammatory dermatoses, and further discuss indications where the efficacy and safety of tetracyclines have been highlighted over the past few years.
REVIEW | doi:10.20944/preprints202204.0004.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Neisseria gonorrhea; Zoliflodacin; Covid-19; Antibiotic-resistance; Treatment
Online: 1 April 2022 (07:26:28 CEST)
Background: Neisseria gonorrhea is a gram negative diplococci leads to sexually transmitted infection. N.gonorrhoeae is an obligate human pathogen that causes infection to the mucus-secreting epithelial cells both in male and female. In 2017 the centre of disease control and World Health Organization published the list of global priority pathogens-12 with denting therapeutic options, including antibiotic-resistant N. gonorrhoeae. Aim: During the covid-19 pandemic, excessive use of antibiotics is occurring which has lead to its resistance. The infection is widespread and intractable. If this happens, more people will be left with an incurable infection which may cause serious health problems. The possibility of untreatable gonorrhea is emerging larger, and hence, it is the need of an hour to develop new drug for treating it Methods and material: We characterized thoroughly zoliflodacin antibiotic, its clinical trials and effect on human health by using different keywords like “zoliflodacin”, “covid-19”, “clinical trials” from different data sources like Pub-Med, Google-Scholar, and Science-Direct. Result: Zoliflodacin targets antibiotic-resistant gonorrhea. Zoliflodacin shows therapeutic approach against N. gonorrhea. It acts by inhibiting bacterial type 2 topoisomerase with binding site in bacterial gyrase. It shows promising results against N. gonorrhea. Zoliflodacin is effective in treating gonococcal urogenital and rectal infection. Discussion: Antibiotic is the only option to treat N. gonorrhea. There is no vaccine available to treat gonorrhea. The new drug, zoliflodacin, specifically targets antibiotic-resistant gonorrhea. This is giving a hope to researchers. In this study, we elaborate the discovery of zoliflodacin, its mechanism of action, the current clinical trials, and the effectiveness of zoliflodacin.
ARTICLE | doi:10.20944/preprints202104.0194.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: antibiotic resistance, virulence factors, Klebsiella pneumoniae, Photodynamic therapy
Online: 7 April 2021 (11:28:18 CEST)
Background: The extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae is one of the leading causes of health-associated infections (HAI), whose antibiotic treatments have been severely reduced. Besides, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these strains. Thus, new therapies such as antimicrobial photodynamic inactivation (aPDI) are needed. Method: A collection of 118 clinical isolates of K. pneumoniae were characterized susceptibility and virulence through the determination of the minimum inhibitory concentration (MIC) of Amk, Cfx, Cfz, Imp, Mer, and Pip-taz, and by PCR, the frequency of the virulence genes, K2, magA, rmpA, entB, ybtS, and allS. Susceptibility to innate immunity, such as human serum, macrophages, and polymorphonuclear cells, was tested. All the strains were tested for sensitivity to the photosensitizer PSIR-3 (4µg/mL) in a 17µW/cm2 for 30 min aPDI. Results: A significantly higher frequency of virulence genes in ESBL than non-ESBL bacteria were observed. The isolates of the genotype K2+, ybtS+, and allS+ display enhanced virulence since they showed higher resistance to human serum as well as to phagocytosis. All strains are susceptible to the aPDI with PSIR-3 decreasing viability in 3log10. The combined treatment with Cfx improved the aPDI to 6log10 for the ESBL strains. The combined treatment is synergistic as it showed an FIC index value of 0.15. Conclusions: The aPDT effectively inhibits clinical isolates of K. pneumoniae, including the more risky strains of ESBL-producing bacteria and the K2+, ybtS+, and allS+ genotype. The aPDI with PSIR-3 is synergistic with Cfx.
REVIEW | doi:10.20944/preprints202101.0178.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: metalloproteins; zinc transporters; metal chelators; antibiotic resistance; antimicrobials
Online: 11 January 2021 (10:20:01 CET)
Zinc is a redox-inert trace element that is second only to iron in abundance in biological systems. In cells, zinc is typically buffered and bound to metalloproteins, but may also exist as a labile or chelatable (free ion) form. Zinc plays a critical role in prokaryotes and eukaryotes ranging from structural to catalytic to replication to demise. This review discusses the influential properties of zinc on various mechanisms of bacterial proliferation and synergistic action as anti-microbial element. We also touch upon the significance of zinc among eukaryotic cells and how it may modulate their survival and death through its inhibitory or modulatory effect on certain receptors, enzymes, and signaling proteins. A brief discussion on zinc chelators is also presented and chelating agents may be used with or against zinc to affect therapeutics against human diseases. Overall, the multidimensional effects of zinc in cells attest to the growing numbers of scientific research that reveal the consequential prominence of this remarkable transition metal in human health and disease.
ARTICLE | doi:10.20944/preprints202003.0425.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cancer; immune checkpoint inhibitors; survival; antibiotic; meta-analysis
Online: 29 March 2020 (06:43:23 CEST)
Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumors treated with ICIs. PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR > 1 associated with a worse outcome in ABs users compared to no-ABs users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51–2.84; P<.01). Similarly, PFS was inferior in ABs users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22–1.93; p<.01). In cancer patients treated with ICIs, AB use significantly reduces OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.
REVIEW | doi:10.20944/preprints202310.0950.v2
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: probiotics in poultry; Salmonella infections; antibiotic resistance; poultry health
Online: 9 November 2023 (02:28:48 CET)
Salmonella infection is one of major challenges to the poultry industry because of its pressing effects on health of poultry, food safety and human well-being that later may devastate economic losses to the poultry sector. The paper reviews public health implications and the use of antibiotics together with the risk of drug resistance. In recent years, the usage of probiotics in poultry industry has been growing to mitigate an increasing pressure to adopt sustainable farming practices. The mechanisms which probiotics may control Salmonella and important criteria for selecting effective probiotics in poultry are reported. Various studies highlighting the additional benefits of probiotics in poultry production in addition to Salmonella controls are also included. While probiotics offer promise in enhancing poultry health, challenges and limitations in their utilization must also be carefully considered.
ARTICLE | doi:10.20944/preprints202307.1085.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: chitosan nanoparticle; Schiff base; complexation; antimicrobial agent; antibiotic sensitivity
Online: 17 July 2023 (09:50:30 CEST)
The present study produced and characterised chitosan, chitosan nanoparticle, chitosan n – benzaldehyde Schiff base, chitosan nanoparticle n – benzaldehyde Schiff base, Fe(III) chitosan n – benzaldehyde Schiff base and Fe(III) chitosan nanoparticle n – benzaldehyde Schiff base for biomedical application as antimicrobial agents. The materials were characterized with Fourier Transform Infrared spectroscopy, X-ray Diffractogram and biologically evaluated using disc diffusion method with three gram-positive bacteria. The FTIR absorption peaks were shifted to a lower wave number than the micro materials from which it was modified. These clearly indicate the linkage between phosphate, ammonium ion, Schiff base and Fe(III) metal. The diffracted peaks of Fe(III) chitosan nanoparticle n – benzaldehyde Schiff base were new peaks at 2θ = 24o and 42o when compare to the peak of Fe(III) chitosan n – benzaldehyde Schiff base of 2θ = 22.5o and 34o. The difference in peak shift were attributed to the ionic bonding of the complexation of Fe(III) with the blending of benzaldehyde to chitosan – Tpp backbone structure. Fe(III) chitosan nanoparticle Schiff base has more antimicrobial activity against same bacteria and fungi tested than Fe(III) chitosan n – benzaldehyde Schiff base, chitosan n – benzaldehyde Schiff base and chitosan. The antimicrobial activities of the synthesised six materials shown that the materials have high activities than the above – mentioned standard drugs.
ARTICLE | doi:10.20944/preprints202305.2212.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: GBS; Antibiotic susceptibility pattern; pregnant women; Wolaita Sodo; Ethiopian
Online: 2 June 2023 (04:53:16 CEST)
Background: Streptococcus agalactiae or Group B Streptococcal colonization of the gastrointestinal and genital tracts of pregnant women usually remains asymptomatic; even if it is the critical determinant of infection in neonates and young infants. It causes early and late onset of invasive Group B Streptococcus (GBS) disease manifesting as septicemia, meningitis and pneumonia. Now it is recognized as an important cause of maternal and neonatal morbidity and mortality in many parts of the world including Ethiopia where the magnitude of the problem has been little studied. The aim of this study was to assess the prevalence of GBS colonization, to identify associated risk factors and antimicrobial susceptibility pattern among pregnant women at selected health facilities of Wolaita Sodo Town, Southern Ethiopia. Methodology: A health facility based cross-sectional study design was conducted at WSUCSH & Wolaita Sodo Health Center from June to August, 2022. A total of 279 pregnant women who were in ANC follow up with at 35-37 weeks of gestation were included. For GBS isolation, recto-vaginal swabs were inoculated in 1ml Todd-Hewitt broth medium supplemented with 10μg/ml colistin and 15μg/ml nalidixic acid and followed by identification of isolates based on colonial morphology, gram stains, catalase reaction and CAMP tests. Antimicrobial susceptibility testing was performed using modified Kirby–Bauer disk diffusion method. All collected data were organized in Epi info 22.214.171.124, then transfer tabulated using SPSS version 20. Logistic regression analysis was used to see the association between variables. Finally, the p-value < 0.05 were considered statistically significant. Results: In present study, 279 pregnant mothers included and their age was between 15 to 38 years with a mean of 26.5 ± 4.5 years. Of all participants, the highest 120 (43.01%) were housewives. The overall carriage rate of GBS was 67(24.0%). GBS colonization showed a statistically significant association with college and above levels of maternal education [AOR= 6.610, 95% CI (1.724 - 25.349), P=0.01]. High susceptibility of GBS isolate was seen to Penicillin G & Chloramphenicol (92.5%) for each, Ampicillin, and Ceftriaxone (89.6%) each, following Vancomycin (74.62%), and Erythromycin (77%). Relatively, GBS showed high resistance to Tetracycline (88 %). Conclusion: In this study, the overall prevalence of GBS colonization was 24.0%. College and above educational level was statistically significant with GBS colonization. This study used to give attention to the management of pregnant women by making GBS culture one of the routine diagnoses during ANC follow-up and to prevent infection by early detection.
REVIEW | doi:10.20944/preprints202304.0916.v1
Subject: Medicine And Pharmacology, Emergency Medicine Keywords: pneumonia; bacteremia; sepsis; procalcitonin; diagnosis; biomarker; outcome; antibiotic stewardship
Online: 25 April 2023 (10:00:11 CEST)
Community-acquired pneumonia (CAP) is among the most common causes of death and one of the leading healthcare concerns worldwide. It can evolve into sepsis and septic shock, which have a high mortality rate, especially in critical patients and comorbidities. The definitions of sepsis were revised in the last decade as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. Procalcitonin (PCT), C-reactive protein (CRP), and complete blood count including white blood cells are among the most commonly analyzed sepsis-specific biomarkers also used in pneumonia in a broad range of studies. It appears to be a reliable diagnostic tool to expedite care of these patients with severe infections in the acute setting. PCT was found superior to most other acute phase reactants and indicators, including CRP as a predictor of pneumonia, bacteremia, sepsis and poor outcome. In addition, PCT use is beneficial to judge timing for cessation of antibiotic treatment in most severe infectious states. The clinicians should be aware of strengts and weaknesses of known and potential biomarkers in expedient recognition and management of severe infections. This manuscript is intended to present an overview of the definitions, complications and outcomes of CAP and sepsis, with special regard to PCT and other important markers.
REVIEW | doi:10.20944/preprints202207.0254.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: Antibiotic Resistance; CwPAMS; National Action Plans; Pharmacy; One Health
Online: 18 July 2022 (09:03:53 CEST)
Antimicrobial resistance (AMR) is a global health problem threatening safe, effective healthcare delivery in all countries and settings. The ability of microorganisms to become resistant to the effects of antimicrobials is an inevitable evolutionary process. The misuse and overuse of antimicrobial agents has increased the importance of a global focus on antimicrobial stewardship (AMS). This review provides insight into the current AMS landscape and identifies contemporary actors and initiatives related to AMS projects in eight African countries (Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia), which form a network of countries participating in the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme. We focus on common themes across the eight countries, including the current status of AMR, infection prevention and control, AMR implementation strategies, AMS, antimicrobial surveillance, antimicrobial use, antimicrobial consumption surveillance, a one health approach, digital health, pre-service and in-service AMR & AMS training, access to and supply of medicines, and the impact of COVID-19. Recommendations suitable for adaptation are presented, including the development of a national AMS strategy and incorporation of AMS in pharmacists’ and other healthcare professionals' curricula for pre-service and in-service training.
ARTICLE | doi:10.20944/preprints202109.0032.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Pseudomonas; Efflux Pumps; Virulence; Evolution; Antibiotic Resistance; Cystic Fibrosis
Online: 2 September 2021 (08:02:02 CEST)
Antibiotic resistant Pseudomonas aeruginosa infections are the primary cause of mortality in people with cystic fibrosis (CF). Yet it has only recently become appreciated that resistance mutations can also increase P. aeruginosa virulence, even in the absence of antibiotics. Moreover, the mechanisms by which resistance mutations increase virulence are poorly understood. In this study we tested the hypothesis that mutations affecting efflux pumps can directly increase P. aeruginosa virulence. Using genetics, physiological assays, and model infections, we show that efflux pump mutations can increase virulence. Mutations of the mexEF efflux pump system increased swarming, rhamnolipid production, and lethality in a mouse infection model, while mutations in mexR that increased expression of the mexAB-oprM efflux system increased virulence during an acute murine lung infection without affecting swarming or rhamnolipid gene expression. Finally, we show that an efflux pump inhibitor, which represents a proposed novel treatment approach for P. aeruginosa, increased rhamnolipid gene expression in a dose-dependent manner. This finding is important because rhamnolipids are key virulence factors involved in dissemination through epithelial barriers and cause neutrophil necrosis. Together, these data show how current and proposed future anti-Pseudomonal treatments may unintentionally make infections worse by increasing virulence. Therefore, treatments that target efflux should be pursued with caution.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Canephron, antibiotic, urinary tract infections, cohort study, herbal treatment
Online: 13 April 2021 (13:11:11 CEST)
Objective: The goal of the present study was to evaluate the treatment with Canephron® after the diagnosis of acute cystitis or urinary tract infection (UTI) with regards to the risk of a sporadic recurrent UTI, frequent recurrent UTIs, UTI associated sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis) compared to standard antibiotic treatment. Methods: This retrospective cohort study was based on data from the IMS® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron® or standard antibiotics between January 2016 and June 2019 in general practitioner (GP), gynecologist, or urologist practices from which data were obtained. Multivariable regression models were used to investigate the association between Canephron® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI associated sick leave, amount of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron® were adjusted for age, sex, insurance status, and Charlson Comorbidity Score (CCI). Results: 2,320 Canephron® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron® prescription was significantly associated with less sporadic recurrences of UTI infections 30-365 days after the index date (odds ratio [OR]: 0.66; 95% conﬁdence interval [CI]: 0.58–0.72), as well as with less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49–0.88), and with minor additional antibiotic prescription within 31-365 days (OR: 0.57; 95% CI: 0.52-0.63). No significant differences were observed between the Canephron® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86–1.14), new antibiotic prescription within 1-30 days (OR: 1.01; 95% CI: 0.87-1.16) and occurrences of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67-1.48). Conclusion: These real world data show that Canephron® is an effective and safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment in particular also to strengthen antimicrobial stewardship strategies.
REVIEW | doi:10.20944/preprints202009.0709.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Escherichia coli; Clostridium perfringens; broiler; antibiotic-free; production; chicken
Online: 29 September 2020 (12:46:00 CEST)
United States is the largest producer and the second largest exporter of broiler meat in the world. In the U.S, broiler production is largely converting to antibiotic-free programs which has caused an increase in morbidity and mortality within broiler farms. Escherichia coli and Clostridium perfringens are two important pathogenic bacteria readily found in the broiler environment and result in annual billion-dollar losses from colibacillosis, gangrenous dermatitis, and necrotic enteritis. Broiler industry is in search of non-antibiotic alternatives including novel vaccines, prebiotics, probiotics, and housing management strategies to mitigate production losses due to these diseases. This review provides an overview of the broiler industry and antibiotic free production, current challenges, and emerging research on antibiotic alternatives to reduce pathogenic microbial presence and improve bird health.
REVIEW | doi:10.20944/preprints202007.0393.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Enterococcus; antibiotic resistance; vancomycin resistance; public health; nosocomial opportunists
Online: 17 July 2020 (15:32:54 CEST)
Enterococci are gastrointestinal commensals whose hardiness allowed them to colonize very diverse environments, including soils, water, food and feed. This ability to overcome adverse conditions makes enterococci problematic once they colonize hospital niches. Together with the malleability of their genomes, the capacity to acquire and disseminate determinants of antibiotic resistance have contributed to convert what was once just another opportunistic pathogen into a first-class clinical problem. This review discusses the dimension of the emergence of enterococcal resistance to key antimicrobial agents, the dissemination of this resistance and its significance in terms of public health, with the aim of raising the awareness to the need to devise and implement monitoring programmes and effective antibiotic usage guidelines.
ARTICLE | doi:10.20944/preprints202006.0221.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: antibiotic residue; human health; milk; risk assessment; TLC; UHPLC
Online: 17 June 2020 (13:25:29 CEST)
Consumption of milk contaminated with antibiotic residues above the maximum residue limit (MRL) causes direct toxicity to humans and the development of superbugs that leads to the failure of antibiotic therapy and threatens human life. Besides, long-duration exposure might alter the nature of gut microflora results in the enhancement of many diseases. Therefore, we examined 300 raw and processed packet milk samples using thin layer chromatography (TLC) and ultra high performance liquid chromatography (UHPLC) method against five veterinary antibiotics and assessed the risk for consumers in Chattogram, Bangladesh. Risk analysis was calculated by using hazard quotient on the basis of 165 ml per capita milk consumption. We found a total of 7% prevalence of antibiotic residues in raw milk samples which were higher (8%) in individual samples than the pooled samples (4%). However, we did not find any processed packet milk samples as positive. The mean concentration of oxytetracycline residue was detected 61.29 µg/l and amoxicillin was 124 µg/l in individual milk samples. Risk analysis showed the hazard quotient values of 0.0056 for oxytetracycline and 0.0017 for amoxicillin residue which was confirmed that, no significant health risk associated with the consumption of milk produced and marketed in the study area. Our study might fill the gap of knowledge to measure the safety status of milk regarding public health issues.
ARTICLE | doi:10.20944/preprints201903.0146.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: antimicrobial stewardship; resistance; infections; antibiotic utilization; peer-reviewed literature
Online: 14 March 2019 (06:57:30 CET)
Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.
REVIEW | doi:10.20944/preprints201808.0090.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antimicrobial resistance; infection control practices; antibiotic resistance; pathogens; coevolution
Online: 5 August 2018 (10:18:40 CEST)
The antibiotic or antimicrobial resistance is rapidly spreading in microbes relevant to human health. Two visible major contributory factors have been the indiscriminate overuse of antimicrobials for preventing diseases in human and to enhance the productivity in agriculture sector. To mitigate the potential threat posed by post-antibiotic era, the global health stakeholders have been making extra efforts at a war footing to formulate and implement global and national plans of action. In the current article, an endeavour is made to provide a perspective to look beyond the current focus on just use of the antimicrobials. Attention has been drawn towards various obvious and not-so-obvious self-preservation infection-prevention practices in vogue from the pre-antibiotic era whose usage has been on decline in the antibiotic era for various reasons. Particularly, the practices with a clear potential to effectively decrease the spread of pathogens through contact, curtail the evolution and dissemination of the antimicrobial resistance in local environment and its introduction into the global community, should be Identified and strengthened to make them part of comprehensive hygiene and quarantine practices. Broadly, the suggestions pertaining to the personal and community hygiene including bereavement practices, isolation and quarantine of suspected pathogen carriers, and water and environment security have been made to invoke a constructive debate and discussion among various stakeholders for their evaluation and implementation to effectively delay the development of antimicrobial resistance wherever possible and disrupt its spread to pathogens.
ARTICLE | doi:10.20944/preprints202310.0682.v1
Subject: Physical Sciences, Fluids And Plasmas Physics Keywords: photocatalytic activity; microwave plasma; zinc oxide; antibiotic; dinitrophenol; solar radiation
Online: 11 October 2023 (10:51:16 CEST)
The presented work studies the processes of synthesis of nitrogen-containing structures of ZnO using atmospheric pressure microwave nitrogen plasma and investigates their photocatalytic activity in the processes of degradation of 2,4-dinitrophenol and the antibiotic ciprofloxacin when irradiated with sunlight. The work proposes an effective method for formation of photosensitive ZnO powders. Due to the features of plasma treatment in the open atmosphere of zinc metal microparticles, ZnO structures are formed with sizes from hundreds of nanometers to several micrometers with various micromorphologies. High photoactivity was demonstrated (rate constants 0.036 min-1 and 0.051 min-1) of synthesized ZnO structures during photo-degradation of 2,4-dinitrophenol and ciprofloxacin, respectively, when exposed to solar radiation. Photo-active structures of ZnO synthesized using microwave nitrogen plasma can find application in processes of mineralization of toxic organic compounds.
REVIEW | doi:10.20944/preprints202306.2248.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Biofilm formation; Biomaterials; Antibiotic resistance mechanisms; Biofilm infection; Antibiofilm strategies
Online: 30 June 2023 (12:03:39 CEST)
Bacterial biofilms can cause widespread infection. In addition to causing urinary tract infections and pulmonary infections in patients with cystic fibrosis, biofilms can help microorganisms adhere to the surfaces of various medical devices, causing biofilm-associated infections on the surfaces of biomaterials such as venous ducts, joint prostheses, mechanical heart valves, and catheters. Biofilms provide a protective barrier for bacteria and provide resistance to antimicrobial agents, which increases the morbidity and mortality of patients. This review introduces the formation process and drug resistance mechanism of biofilms in detail, and further summarizes the main characteristics of clinical persistent infection caused by biofilms and the many methods of treating biomaterial-related biofilm. This provides ideas and directions for the development of new biofilm infection strategies related to therapeutic materials.
REVIEW | doi:10.20944/preprints202304.0461.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: antibiotic; prescribing pattern; prescription; antimicrobial resistance; WHO AWaRe classification
Online: 18 April 2023 (02:54:31 CEST)
Background: The AWaRe tool was set up by the World Health Organization (WHO) to promote the rational use of antimicrobials. Indeed, this tool classifies antibiotics into four groups, Access, Watch, Reserve and not-recommended antibiotics. In Republic Democratic of Congo, data on antibiotic dispensing (prescribing) by health professionals according to the AWaRe classification are scarce. In this research work, we aimed to explore antibiotic dispensing pattern from health professionals according to the WHO AWaRe classification to strengthen the national antimicrobial resistance plan. Methods: For this purpose, a survey was conducted from July to December 2022 in the district of Tshangu in Kinshasa. From randomly selected drugstores, drug-sellers were interviewed and randomly selected customers attending those drugstores were included in the study for medical prescriptions collection. The prescribed antibiotics were classified into the Access, Watch, Reserve and not recommended antibiotics group and by antibiotics number by prescription among pharmacies surveyed. Results: Of 400 medical prescriptions collected, 301 (75.25%) contained antibiotics. Of 301 prescriptions containing antibiotics, 164 (164/301; 54.5%) contained one antibiotic, 117 (117/301; 38.9%) two antibiotics, 15 (15/301; 5%) three antibiotics and 5 (5/301; 1.6%) 4 antibiotics. Out of the total of 463 antibiotics prescribed, 169 (169/463; 36.5%) were from the Access group, 200 (200/463; 43.2%) from the Watch group and 94 (94/463; 20.3%) from not recommended antibiotics group, respectively. Based on the anatomical, therapeutic and chemical (ATC) classification, it can be seen that third generation cephalosporins contained 34.33% of the prescribed antibiotics, followed by penicillins 17.17%, macrolides 7.63%, aminoglycosides 7. 36% and Imidazoles 7.36%, thus accounting approximately for 74% of the classes of antibiotics prescribed. Of the 463 antibiotics prescribed, the most frequently prescribed antibiotics were Ceftriaxone (21.38%), Amoxicillin (11.01%), Gentamycin (5.61%), Amoxicillin-clavulanic acid (5 .61%), Azithromycin (4.97%) and Metronidazole (4.75%), thus accounting for approximately 54% of all antibiotics prescribed. Conclusion: These results highlight the importance of strict implementation of the national plan to combat antimicrobial resistance and the need to train health workers in the correct application of the WHO AWaRe classification.
ARTICLE | doi:10.20944/preprints202302.0291.v1
Subject: Chemistry And Materials Science, Physical Chemistry Keywords: Garcinia mangostana L.; Rind Extract; Antibiotic-Resistant; Streptomycin; Bioconjugation; Hemocompatibility
Online: 17 February 2023 (02:27:53 CET)
Background: Combinatorial therapy- “nano antibiotics” is an emerging field in nanoscience. In this present investigation, we attempted to combine the green synthesized noble metal nanoparticle and the antibiotic Streptomycin to form bio-conjugated nanoparticles. The newly synthesized Nano antibiotics acted as the antibiotic carrier, functioned as cargo, and delivered the antibiotic. Methods: Comparative studies between the noble metal nanoparticles were attempted for the first time on the grounds of their antibacterial activity. The antibacterial activity of the three noble metal nanoparticles was assessed against Streptomycin-resistant Bacillus sp.; the results obtained proved that silver nanoparticles were a potent antibacterial agent. Still, no antibacterial activity was exerted by gold, and platinum nanoparticles were for the Streptomycin-resistant strain Bacillus sp. To our surprise, the gold and platinum fabricated/bio-conjugated nanoparticle with the antibiotic showed 100% antibacterial activity, whose antibacterial activity was zero when functioning as a nanoparticle alone. Results: The combinatorial therapy of two different clauses of drugs majorly increased antibacterial activity. It enhanced the antibiotic to overcome the resistance exhibited by the bacterial pathogen, and the possible mechanism is elucidated in the present study. Also, an attempt has been made to assess the nanotoxicity of the nano-bioconjugates on RBC and compare their hemocompatibility. The results obtained in the current investigation demonstrate the enhanced antibacterial activity of the green synthesized nanoparticles conjugated with the streptomycin; their efficacy for combinational therapy against resistance in pathogenic organisms highlights the novelty of the work and the comparative study of three different noble metals nanoparticles (Ag, Au, Pt) from single agro-waste for the first time.
REVIEW | doi:10.20944/preprints202209.0021.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: herbal drugs; gut microbiota; antibiotic stewardship, uncomplicated infection, NSAID, homeostasis.
Online: 1 September 2022 (10:35:01 CEST)
Epithelial surfaces in humans are home to symbiotic microbes (i.e., microbiota) that influence the defensive function against pathogens depending on the health of the microbiota. Healthy microbiota contribute to the well-being of their host in general (e.g., via the gut-brain-axis), and their respective anatomical site in particular (e.g., oral, urogenital, skin or respiratory microbiota). Despite efforts towards a more responsible use of antibiotics, they are often prescribed for uncomplicated, self-limiting infections and can have a substantial negative impact on the gut microbiota. Treatment alternatives such as non-steroidal anti-inflammatory drugs may also influence the microbiota and thus can have lasting adverse effects. Herbal drugs offer a generally safe treatment option for uncomplicated infections of the urinary or respiratory tract. Additionally, their microbiota preserving properties allow for a more appropriate therapy of uncomplicated infections without contributing to an increase in antibiotic resistance or disturbing the gut microbiota. Here, herbal treatments may be a more appropriate therapy with a generally favorable safety profile.
ARTICLE | doi:10.20944/preprints202208.0132.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: civil science; antibiotic producers screening; actinomycetes; reporter systems; chartreusin; pikromycin
Online: 8 August 2022 (05:27:03 CEST)
Since streptomycin discovery, actinomycetes were the main source for new antibiotics, but after the Golden age (1950-1960th) the discovery rate significantly decreased. The high probability to rediscover well-known antibiotics led to a reduction in interest in soil bacteria as a source for new antibiotics. At the same time, actinomycetes remain a very promising reservoir for searching for new active molecules. In this work, we present several reporters containing eye-visible fluorescent protein genes, which can be used to increase the efficiency of determining the mechanism of antibiotics at the very initial stage of screening. Presented reporters and the following pipeline were optimized given the involvement of citizen scientists without specialized skills and equipment in order to utilize the reservoir of soil bacteria in the search for new antibiotic producers. The combination of mechanism-based approaches and civil science has proved its effectiveness in practice revealing a significant increase in the screening rate. Two new strains Streptomyces sp. KB-1 and BV113 were found to produce antibiotics pikromycin and chartreusin, respectively, demonstrating the efficiency of the pipeline.
ARTICLE | doi:10.20944/preprints202207.0402.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: antimicrobial resistance; One Health; poultry; poultry farmers; antibiotic use; Pakistan
Online: 26 July 2022 (10:33:42 CEST)
Antimicrobial resistance (AMR) due to community carriage of antibiotic-resistant bacteria is highly prevalent in the WHO South-East Asia region. One of the major reasons is the misuse of antibiotics in animal farming practices and at community level, which threatens both human and animal health. However, this multifaceted One Health (OH) problem of antibiotic use (ABU) in poultry farms and respective farmers is not well studied in countries like Pakistan. Therefore, we conducted n OH cross-sectional study in rural Punjab to explore the current practices of ABU in poultry and poultry farmers, associated factors, their healthcare-seeking behaviour and biosecurity practices. We found all the participating farmers using antibiotics for poultry, 60% of which were Colistin sulphate and Amoxicillin trihydrate. The significant consumption of antibiotics in poultry farms (60%) and poultry farmers (50%) was without prescription. Most of the farms (85%) had no wastewater drainage system, causing direct shedding of poultry waste and antibiotic residue in the surrounding environment. Lack of farmers’ education, professional farm training and duration of farming experience were the significantly associated factors with ABU and knowledge of AMR. Our study implies the necessity of an integrated OH-AMR policy with the inclusion of farmers’ education, mass awareness, and strict antibiotic usage guidelines.
REVIEW | doi:10.20944/preprints202204.0151.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Isocyanide-based multicomponent reactions; Antimicrobial Discovery; Antibiotic Resistance; Public Health
Online: 18 April 2022 (03:38:08 CEST)
Multicomponent reactions (MCR) have been used to synthesis a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique property of MCR, allowing researchers to quickly assemble libraries of compounds of biological interest and uncover novel leads as possible therapeutic agents. Isocyanide-based multicomponent reactions have proven to be extremely effective at swiftly specifying members of compound libraries, particularly in discovery of drug . The understanding of structure-activity correlations that drive the development of new goods and technology, requires structural variety in these libraries. In current world, antibiotic resistance is a major ongoing problem which is developing a problematic scenario in public health. The implementation of isocyanide based multicomponent reactions uphold a significant potential in this regard. By utilizing such reactions, new antimicrobial compounds can be discovered and fight against such concerns. This study discusses recent developments in antimicrobial medication discovery using isocyanide-based multicomponent reactions (IMCRs). Furthermore, the article emphasizes the potential of IMCRs in the near future.