ARTICLE | doi:10.20944/preprints201911.0077.v1
Subject: Life Sciences, Microbiology Keywords: antibiotics; antibiotics resistance; antimicrobial resistance; dispensing; pharmacist; prescription; Tanzania
Online: 7 November 2019 (15:03:56 CET)
Background: Inappropriate use of antibiotics has been reported to contribute to the emergence and increase of antimicrobial resistance (AMR) in the world. Antibiotics are prescription-only medicines to be dispensed to a person with a legal prescription inscribed by a qualified medical practitioner. Enforcing the dispensing of antibiotics with prescription is a way to promote the rational use of antibiotics and preventing the development and spread of AMR. It is, therefore, the responsibility of a pharmacist to dispense or supervise the dispensing of antibiotics in pharmacies and ensure its rational use. This study aimed to assess pharmacists’ knowledge, attitude and practice regarding the dispensing of antibiotics without prescription in Tanzania. Methods: An online semi-structured questionnaire was designed, tested and shared with licensed pharmacists in Tanzania through an invitation link sent in their official WhatsApp groups. A list of names, contacts and emails of licensed pharmacists obtained from the Pharmacy Council was used to directly contact and request pharmacist to fill the questionnaire, in case the pharmacist contact was not on WhatsApp, a text SMS invitation was sent. Study data were collected and managed using REDCap electronic data capture tools hosted at Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. Data were then downloaded and exported into Statistical Package for Social Sciences (SPSS) version 20 for data analysis; Chi-square test was used to test association for categorical data, where a p-value of less than 0.05 was considered statistically significant. Results: More than 75% of pharmacists had excellent knowledge about the legal requirements for dispensing antibiotics and of the AMR challenge. Of the interviewed pharmacists, seventy-four percent admitted to dispensing antibiotics without prescription in their daily practice. The main reasons for administering antibiotics without prescription were the profitability nature of pharmacy business, a failure of the patient to get a prescription and lack of stringent regulatory authorities. Penicillins, macrolides and floroquinolones were the classes of antibiotics mostly dispensed without a prescription. Conclusion: The study shows that the dispensing of antibiotics without prescription is a common practice in Tanzania. The regulatory authorities should make regular inspections in pharmacies to detect this malpractice. The community should be trained on the importance of taking laboratory tests before getting medications for their sickness by a qualified medical practitioner.
REVIEW | doi:10.20944/preprints202009.0067.v1
Online: 3 September 2020 (09:29:32 CEST)
Background: The reported associations between time to first antibiotic dose after hospital arrival and short-term mortality have varied in prior studies of CAP. It is unclear the benefit of early antibiotics in all patients given the risks of antibiotic overuse and misdiagnosis; Methods: A PubMed and Google Scholar search was performed to identify articles detailing the epidemiology, prognosis, diagnosis, and preliminary management of CAP; Results: In sepsis, antibiotics should not be delayed, and should be administered as soon as possible after recognition. For moderate or severe CAP patients without sepsis, antibiotics should be administered as soon as the diagnosis of CAP is highly likely. For stable, non–critically ill patients with CAP, the timing of antibiotics is not as clear and available evidence does not recommend strict requirements. Antibiotic timing – both rapid and delayed could be used as indicators of quality care in differing clinical scenarios; Results: The dogma of starting antibiotics quickly, within a rigid timeframe of expectations and guidelines has not improved outcomes in pneumonia patients, and has led to an increase in antibiotic treatment in uninfected patients. Severity of illness is the key factor associated with poor outcomes and should more significantly guide the timing of antibiotic initiation.
ARTICLE | doi:10.20944/preprints202003.0244.v1
Subject: Chemistry, Organic Chemistry Keywords: antibiotics; β cells; streptozotocin; regioselective oxidation
Online: 15 March 2020 (13:12:33 CET)
With the increasing resistance of bacteria to current antibiotics, novel compounds are urgently needed to treat bacterial infections. Streptozotocin (STZ) is a natural product that has broad-spectrum antibiotic activity, albeit with limited use because of its toxicity to pancreatic β cells. In an attempt to derivatize STZ through structural modification at the C3 position, we performed the synthesis of three novel STZ analogues by making use of our recently developed regioselective oxidation protocol. Keto-STZ (2) shows the highest inhibition of bacterial growth (MIC and viability assays), but is also the most cytotoxic compound. Pre-sensitizing the bacteria with GlcNAc increased the antimicrobial effect, but did not result in complete killing. Interestingly, allo-STZ (3) revealed moderate concentration-dependent antimicrobial activity and no cytotoxicity towards β cells, and deoxy-STZ (4) showed no activity at all.
ARTICLE | doi:10.20944/preprints201812.0328.v1
Online: 28 December 2018 (04:20:40 CET)
The harmful nature of high concentrations of antibiotics to humans and animals requires urgent development of novel materials and techniques for their absorption. In this work, CTAB (Cetyltrimethyl Ammonium Bromide)-assisted synthesis of ZIF-8 (zeolitic imidazolate framework) derived hollow carbon (ZHC) was designed, prepared and used as a high-performance adsorbent, further evaluated by Langmuir and Freundlich isothermal adsorption experiments, dynamic analysis as well as theoretical calculation. The maximum capacities of ZHC on adsorbing tetracycline (TC), norfloxacin (NFO) and levofloxacin (OFO) are 267.3, 125.6 and 227.8 mg g-1, respectively, which delivers superior adsorptive performance when compared to widely studied inorganic adsorbates. The design concept of ZIFs-derived hollow carbon material provides guidance and insights for the efficient adsorbent of environmental antibiotics.
ARTICLE | doi:10.20944/preprints201906.0119.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: audit; utilization; surgery; antibiotics; perception; infections; hospitals
Online: 13 June 2019 (09:52:04 CEST)
Background and objectives: The appropriate use of antibiotics is the main strategy of Antimicrobial stewardship program. This study was planned to evaluate the quality of antibiotic prescriptions, its adherence with standard guidelines and surgeons’ perception regarding antibiotic use in surgeries. Methods: A prospective cross-sectional observational and survey-based study comprised of two sections: Phase 1; to investigate the antibiotic utilization in three most common abdominal surgical procedures during 9 months (January 2017 to September 2017). The appropriateness of antibiotics was compared with evidence-based guidelines. Phase 2; the surgeon’s perspectives were evaluated through a self-administered questionnaire (13 items) during the next three months (October 2017 to December 2017). Descriptive statistics, chi-square and Fisher’s exact tests analysis were used through SPSS Statistical Package 21.0. Results: A total of 866 eligible surgical cases out of 1015 were investigated. An acute appendectomy (n= 418; 48.2%) was most common surgical intervention followed by laparoscopic cholecystectomy (n= 278; 32.1%) and inguinal hernia (n= 170; 19.7%). About 97.5% of patients received antibiotics. Among these, 9.5% adhered according to guidelines with respect to correct choice, 40% for timing, 100% for dose and route (optimal value 100%). The ceftriaxone (J01XD04; n= 503; 59.5%) was most frequently prescribed antibiotic. A 200 participants (response rate 70.6%) filled out a validated questionnaire (internal consistency; α ≥ 0.7). One hundred and thirty-eight (69%) reported the overuse of antibiotics and most of them (97%) preferred broad-spectrum antibiotics instead of narrow-spectrum. The participants reported that non-availability hospital-based guidelines (n=193; 96.5%), prescribing of antibiotics without guidelines (n=186; 93%), underestimation of infection (n=177; 88.5%), lack of consensus (n=135; 67.5%) and poor awareness about guidelines (n=122; 61%) were the main determinants in their health care settings. Conclusions: The compliance of Surgical antibiotic was far below the recommendations of guidelines. The urgent needs of awareness among surgeons and implementation of antimicrobial stewardship program were important recommended interventions for appropriate use antibiotics.
ARTICLE | doi:10.20944/preprints202208.0289.v1
Subject: Chemistry, Applied Chemistry Keywords: layered double hydroxides; magnetic nanoparticles; phthalocyanines; antibiotics removal
Online: 16 August 2022 (11:12:42 CEST)
Considerable efforts have been made in recent years to identify an optimal treatment method for the removal of antibiotics from wastewaters. A series of supramolecular organic-inorganic magnetic composites containing Zn-modified MgAl LDHs and Cu-phthalocyanine as photosensitizer have been prepared with the scope to β-lactam antibiotics removal from aqueous solutions. The characterization of these materials confirmed the anchorage of Cu-phthalocyanine onto the edges of the LDH lamellae, with a negligible part inserted in the interlayer space. The removal of β-lactam antibiotics occurred via a concerted adsorption and photocatalytic degradation. The efficiency of the composites was depending on i) the LDH: magnetic nanoparticle (MP) ratio, that is strongly correlated to the textural properties of the catalysts, and ii) the phthalocyanine loading in the final composite. A maximum of the efficiency was achieved with a removal of ~93% of antibiotics after 2h of reaction.
REVIEW | doi:10.20944/preprints202208.0236.v1
Subject: Life Sciences, Microbiology Keywords: Archaea; transcription inhibition; RNA polymerase; viruses; evolution; antibiotics
Online: 12 August 2022 (11:25:05 CEST)
Multisubunit RNA polymerases (RNAP) carry out transcription in all domains of life; during vi-rus infection, RNAPs are targeted by transcription factors encoded by either the cell or the virus, resulting in the global repression of transcription with distinct outcomes for different host-virus combinations. These repressors serve as versatile molecular probes to study RNAP mechanisms, as well as they aid the exploration of druggable sites for the development of new antibiotics. Here, we review the mechanisms and structural basis of RNAP inhibition by the viral repressor RIP and the crenarchaeal negative regulator TFS4, which follow distinct strategies. RIP operates by occluding the DNA-binding channel and mimicking the initiation factor TFB/TFIIB. RIP binds tightly to the clamp and locks it into one fixed position, thereby preventing conformational oscil-lations that are critical for RNAP function as it progresses through the transcription cycle. TFS4 engages with RNAP in a similar manner to transcript cleavage factors such as TFS/TFIIS through the NTP-entry channel; TFS4 interferes with the trigger loop and bridge helix within the active site by occlusion and allosteric mechanisms, respectively. The conformational changes of RNAP described above are universally conserved and are also seen in inactive dimers of eukaryotic RNAPI and several inhibited RNAP complexes of both bacterial and eukaryotic RNA polymer-ases, including inactive states that precede transcription termination. A comparison of target sites and inhibitory mechanisms reveals that proteinaceous repressors and RNAP-specific antibiotics use surprisingly common ways to inhibit RNAP function.
ARTICLE | doi:10.20944/preprints202101.0040.v1
Subject: Medicine & Pharmacology, Allergology 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/preprints202008.0134.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Proportionate prevalence; spatial distribution; antibiotics; supportive therapy; Jhenaidah
Online: 5 August 2020 (15:37:06 CEST)
A descriptive epidemiological study has been conducted using hospital database of Teaching Veterinary Hospital (TVH) at Jhenaidah Government Veterinary College (JGVC) from July 2018 to June 2019. The study aimed to estimate the proportionate prevalence of different livestock and poultry diseases along with their spatiotemporal distribution and drug prescribing pattern. A total of 960 clinical cases were recorded during the study period. Ectoparasitic cases were proportionately higher in cattle (25.2%), whereas Peste des Petits Ruminants (PPR) cases were more frequent in goat (53.4%). The proportionate prevalence of other cases in cattle was Fascioliasis (14.3%), Myiasis (11.2%) and Foot and Mouth Disease (FMD) (7.2%). The proportionate prevalence of other cases in goats were vitamin and mineral deficiency (12.3%), bloat (5.2%), abscess (4.7%), and dog bite (1.2%). Again, the proportionate prevalence of poultry diseases was Infectious Bursal Disease (41.2%), salmonellosis (33.4%), fowl cholera (13.7%) and pox (7.8%). Most of the cattle cases were highly prevalent during the summer season except fascioliasis. In goat, PPR was predominated in the rainy season whereas myiasis was in the winter. Around 92% of disease cases were spatially located within the 2.5 km radius of the TVH of JGVC where only 0.9% of disease cases came from >10km away from TVH of JGVC. Simple linear regression identified a significant relation (p=0.01) with the distance and number of diseased animals came to the hospital. Antimicrobials belonging to b-Lactam group were most frequently prescribed for both poultry (48.6%), cattle (32.5%) followed by goat (9.2%), however sulfar drugs (34.8%) were commonly prescribed for goat cases. This type of study is very novel in Jhenaidah region of Bangladesh that might contribute to the researchers for further investigation.
ARTICLE | doi:10.20944/preprints201804.0163.v1
Subject: Physical Sciences, Optics Keywords: Raman microspectroscopy; optical tweezers; optofluidics; E. coli; antibiotics
Online: 12 April 2018 (08:37:01 CEST)
Analyzing the cells in various body fluids can greatly deepen the understanding of the mechanisms governing the cellular physiology. Because of the variability of physiological and metabolic states, it is important to be able to perform such studies on individual cells. Therefore, we developed an optofluidic system in which we precisely manipulated and monitored individual cells of Escherichia coli. We used laser tweezers Raman spectroscopy (LTRS) in a microchamber chip to manipulate and analyze individual E. coli cells. We subjected the cells to antibiotic cefotaxime, and we observed the changes by the time-lapse microscopy and Raman spectroscopy. We found observable changes in the cellular morphology (cell elongation) and in Raman spectra, which were consistent with other recently published observations. We tested the capabilities of the optofluidic system and found it to be a reliable and versatile solution for this class of microbiological experiments.
REVIEW | doi:10.20944/preprints202105.0337.v1
Subject: Medicine & Pharmacology, Allergology Keywords: antibacterial agents; antibiotics; COVID-19; drug misuse; odontogenic infection
Online: 14 May 2021 (14:03:42 CEST)
This review revisits clinical use of antibiotics for most common acute oro-dental conditions; we aim to provide evidence governing antibiotics use when access to oral healthcare is not available, as during the ongoing outbreak of the severe acute respiratory syndrome coronavirus 2. In this rapid review, articles were retrieved after conducting a search on PubMed and Google Scholar. Relevant publications were selected and analyzed. Most recent systematic reviews with/without meta-analyses and societal guidelines were selected. Data were extracted, grouped, and synthesized according to the respective subtopic analysis. There were evidence supporting the use of antibiotics in common oro-dental conditions as temporary measure when immediate care is not accessible, such as in case of localized oral swellings as well as to prevent post-extraction complications. No sufficient evidence could be found in support of antibiotic use for pain resulting from pulpal origin. Consequently, antibiotic use may be justified to defer treatment temporarily or reduce risk of complications in case of localized infection and tooth extraction, when no access to immediate dental care is possible.
REVIEW | doi:10.20944/preprints202103.0722.v1
Subject: Chemistry, Analytical Chemistry Keywords: food; safety; electrochemical biosensors; bacteria; toxins; pesticides; antibiotics; contaminants
Online: 30 March 2021 (10:02:34 CEST)
Safety and quality are key issues for the food industry. Consequently, there is a growing demand to preserve the food chain and products against substances toxic, harmful to human health such as contaminants, allergens, toxins, or pathogens. For this reason, it is mandatory to develop highly sensitive, reliable, rapid, and cost-effective sensing systems/devices such as electrochemical sensors/biosensors. Generally, conventional techniques are limited by long time of analyses, expensive and complex procedures, and they require skilled personnel. Therefore, the development of performant electrochemical biosensors can significantly support the screening of food chain and products. Here, we report some of the recent developments in this area and analyze the contributions produced by electrochemical biosensors in the food screening and the challenges to address.
ARTICLE | doi:10.20944/preprints202011.0221.v1
Subject: Medicine & Pharmacology, Allergology Keywords: appropriate antibiotics use; primary care; quality improvement; mixed-methods
Online: 5 November 2020 (18:11:28 CET)
The cluster randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance, 2017-2020) promoted the appropriate use of antibiotics for acute non-complicated infections in primary care networks (PCNs) in Germany. A process evaluation aimed to provide insights into determinants of practice and explored factors associated with antibiotic prescribing patterns. In a nested mixed-methods approach, a three-waves survey used study-specific questionnaires for participating physicians and medical assistants to assess potential impacts and uptake of the complex intervention program. Stakeholders received a one-time online questionnaire to reflect on network-related aspects. Semi-structured, open-ended interviews with a purposive sample of physicians, medical assistants and stakeholders explored aspects regarding the acceptance of the program components for daily practice and the perceived sustainability of intervention component effects. The intervention components were perceived to be smoothly integrable into practice routines. The highest uptake was reported for the educational components: feedback reports, background information, e-learning modules, and disease specific quality circles. Participation in PCNs was seen as motivational factor for guideline-oriented patient care and the adoption of new routines Future approaches to fostering appropriate use of antibiotics by targeting health literacy competencies and clinician’s therapy decisions should combine evidence-based information sources, audit and feedback reports and QCs.
ARTICLE | doi:10.20944/preprints201912.0416.v1
Subject: Chemistry, Analytical Chemistry Keywords: multiparametric assay; rapid tests; immunochromatography; antibiotics; non-equilibrium interactions
Online: 31 December 2019 (16:25:33 CET)
The presented study is focused on the impact of binding zones locations at immunochromatographic test strips into analytical parameters of multiplex lateral flow assay. Due to non-equilibrium conditions for such assays the duration of immune reactions influences significantly on analytical parameters, and the integration of several analytes into one multiplex strip may cause essential decrease of sensitivity. To choose the best location of binding zones, we have tested reactants for immunochromatographic assays of lincomycin, chloramphenicol, and tetracycline. The influence of the distance to the binding zones on the intensity of coloration and limit of detection (LOD) was rather different. Basing on the obtained data, the best order of binding zones was chosen. In comparison with non-optimal location the LODs were 5-10 fold improved. The final assay provides LODs 0.4, 0.4 and 1.0 ng/mL for lincomycin, chloramphenicol, and tetracycline, respectively. The proposed approach can be applied for multiassays of other analytes.
REVIEW | doi:10.20944/preprints201911.0163.v2
Subject: Medicine & Pharmacology, Other Keywords: individual therapy; metabolism of antibiotics; dosage choice; inflammation; biomarkers
Online: 16 December 2019 (11:25:16 CET)
In the modern world, the problem of antibiotic therapy is acute. Despite the diversity of existing antibiotic drugs, their efficacy decreases as new, resistant forms of pathogenic microorganisms emerge. It is extremely difficult to control such processes and even more difficult to treat severe bacterial infections. In such situations, an individual approach to each patient is required and physicians need parameters to estimate the efficacy of antibiotic therapy. This review discusses the significance of monitoring the content of antibiotics in the blood for this purpose, in combination with the content of inflammatory markers, such as C-reactive protein and procalcitonin. The basic principles of antibiotic therapy, and factors in the resistance of microorganisms to antibiotics, are examined. Approaches to assess the efficacy of antibiotic therapy, as well as methods to detect antibiotics and inflammatory markers in the blood of patients, and comparative assessment of their capabilities and limitations, are described.
ARTICLE | doi:10.20944/preprints201908.0084.v1
Online: 7 August 2019 (03:37:10 CEST)
Multiple studies have shown that hospital settings are poorly cleaned during terminal cleaning. The adequacy of these cleaning methods has been undermined by presence of multi drug resistant bacteria on hospital surfaces. This case is even more serious in developing countries leading to health care- associated infections that pose a great threat to patients, visitors and health care providers in hospital settings.This study used various microbiological techniques to test for antibiotic susceptibility profiles of bacteria present at Thika Level 5 Hospital surfaces, Kenya. A simple random cross sectional study was performed, with a total of 85 samples being collected from five different sites. The sites included male and female wards, health care personnel offices, latrine, and kitchen surfaces. Samples were collected using sterile swabs, dipped in normal saline, and transported to the laboratory within 2Hours for processing.Of the 85 plates cultured, 47 plates showed bacterial growth (55%) on selective media with a significant P value of 0.0357. Seven different species of bacteria were identified biochemically from all sites, Escherichia coli was the most abundant species (28%), and the least was Salmonella typhii (5%). Multiple drug resistance was common in the different bacteria identified. All isolates were resistant to chloramphenical and susceptible to gentamycin. The most resistant microorganism was Staphylococcus aureus (50%), and the least resistant microorganism was Klebsiella pneumoniae (12.5%). The antimicrobial resistant bacterial species identified in this study have been documented to cause serious health care associated infections. These results present a significant public health concern because there is a possibility of patients, staff and visitors contacting nosocomial infections when they come into contact with surfaces at Thika Level 5 Hospital surfaces, Kenya.
ARTICLE | doi:10.20944/preprints201808.0272.v1
Subject: Life Sciences, 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/preprints201802.0090.v1
Subject: Life Sciences, Microbiology Keywords: antibiotics; geomicrobiology; Illumina sequencing; microbiome diversity; Streptomyces; Cave microbiology
Online: 12 February 2018 (16:30:42 CET)
Moonmilk are cave carbonate deposits that host a rich microbiome including antibiotic-producing Actinobacteria making these speleothems appealing for bioprospecting. Here we investigated the taxonomic profile of the actinobacterial community of three moonmilk deposits of the cave “Grotte des Collemboles” via high-throughput sequencing of 16S rRNA amplicons. Actinobacteria was the most common phylum after Proteobacteria, ranging from 9 to 23% of the total bacterial population. Next to actinobacterial OTUs attributed to uncultured organisms at the genus level (~44%), we identified 47 actinobacterial genera with Rhodoccocus (4 OTUs, 17%) and Pseudonocardia (9 OTUs, ~16%) as the most abundant in terms of absolute number of sequences. Streptomycetes presented the highest diversity (19 OTUs, 3%), with most of OTUs unlinked to the culturable Streptomyces strains previously isolated from the same deposits. 43% of OTUs were shared between the three studied collection points while 34% were exclusive to one deposit indicating that distinct speleothems host their own population despite their nearby localization. This important spatial diversity suggests that prospecting within different moonmilk deposits should result in the isolation of unique and novel Actinobacteria. These speleothems also host a wide range of non-streptomycetes antibiotic-producing genera, and should therefore be subjected to methodologies for isolating rare Actinobacteria.
ARTICLE | doi:10.20944/preprints201701.0100.v1
Subject: Earth Sciences, Environmental Sciences Keywords: toxin release; blue-green algae; tetracycline antibiotics; environmental toxicology
Online: 23 January 2017 (09:42:15 CET)
The global usage of veterinary antibiotics is significant. These antibiotics can be released into the aquatic environment and exert toxic effects on non-target organisms. To explore the physiological effects of tetracycline antibiotics on aquatic life, the growth characteristics of and toxin release from the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were studied. Results showed that the toxicity order of the three target antibiotics was TC (tetracycline) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline) in terms of inhibition occurrence time and the EC10 and EC25 values. Further, the target antibiotics regulated the production of MC-LR (microcystin-LR) to different degrees. CTC destroyed the M. aeruginosa cells and resulted in a decreased MC-LR release but stimulated the ability to synthesise MC-LR. OTC had a relatively weaker toxicity compared with CTC, while TC was the most toxic among the three antibiotics. Therefore, TC is friendly to the aquatic environment because it simultaneously reduced the intracellular and extracellular MC-LR content. These results aid our understanding of the effects of tetracycline antibiotics on Microcystis aeruginosa, which is important for environmental evaluation and protection. These results are also helpful for guiding the application of veterinary antibiotics in agricultural settings.
ARTICLE | doi:10.20944/preprints202106.0052.v1
Subject: Life Sciences, Biochemistry Keywords: antibiotics; conventional; microbiology; microfluidics; microscopy; mycobacterium smegmatis; population; single cell
Online: 2 June 2021 (08:32:03 CEST)
To reveal rare phenotypes in bacterial populations conventional microbiology tools should be advanced to generate rapid, quantitative, accurate and high-throughput data. The main drawbacks of widely used traditional methods for antibiotic studies include low sampling rate and averaging data for population measurements. To overcome these limitations microfluidic-microscopy systems have great promise to produce quantitative single-cell data with high sampling rates. Using Mycobacterium smegmatis cells we applied both conventional assays and a microfluidic-microscopy method to reveal antibiotic-tolerance mechanisms of wild type and the msm2570::Tnmutant cells. Our results revealed that the enhanced antibiotic tolerance mechanism of the msm2570::Tn mutant was due to the low number of lysed cells during the antibiotic exposure compared with wild-type cells. This is the first study that characterized the antibiotic-tolerance phenotype of the msm2570::Tn mutant that has a transposon insertion in the msm2570 gene encoding a putative xanthine/uracil permease, which enrolls in uptake of nitrogen compound during nitrogen limitation. The experimental results indicate that the msm2570::Tn mutant can be further interrogated to reveal antibiotic killing mechanisms, in particularly, antibiotics those targets cell wall integrity.
ARTICLE | doi:10.20944/preprints202102.0060.v1
Subject: Biology, Anatomy & Morphology Keywords: Escherichia coli; magnetite nanoparticles; metals; antibiotics; genomics; pleiotropy; cell morphology
Online: 1 February 2021 (15:58:10 CET)
Experimental evolution was utilized to produce 5 magnetite nanoparticle-resistant (FeNP1-5) populations of Escherichia coli. The control populations were not exposed to magnetite nanoparticles. The 24-hour growth of these replicates was evaluated in the presence of increasing concentrations magnetite NPs as well as other ionic metals (gallium III, iron II, iron III, silver I) and antibiotics (ampicillin, chloramphenicol, rifampicin, sulfanilamide, tetracycline). Scanning electron microscope was utilized to determine cell size and shape in response to magnetite nanoparticle selection. Whole genome sequencing was carried out to determine if any genomic changes that resulted from magnetite nanoparticle resistance. After 25 days of selection magnetite resistance was evident in the FeNP treatment. The FeNP populations also showed a highly significantly (p < 0.0001) greater 24-growth as measured by optical density in metals (Fe (II), Fe (III), Ga (III), Ag and Cu II); as well as antibiotics (ampicillin, chloramphenicol, rifampicin, sulfanilamide, and tetracycline). The FeNP resistant populations also showed a significantly greater cell length compared to controls (p < 0.001). Genomic analysis of FeNP identified both polymorphisms and hard selective sweeps in the RNA polymerase genes rpoA, rpoB, and rpoC. Collectively, our results show that E. coli can rapidly evolve resistance to magnetite nanoparticles and that this result is correlated resistances to other metals and antibiotics. There were also changes in cell morphology resulting from adaptation to magnetite NPs. Thus, the various applications of magnetite nanoparticles could result in unanticipated changes in resistance to both metal and antibiotics.
REVIEW | doi:10.20944/preprints202004.0416.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: citation classics; top-cited articles; antibiotics; bibliometric analysis; antibacterial; antimicrobials
Online: 23 April 2020 (15:20:39 CEST)
Citation frequencies represent the most significant contributions in any respective field. This bibliometric analysis aimed to identify and analyze the 100 most-cited publications in the field of antibiotics and to highlight the trends of research in this field. “All databases” of Clarivate Analytics' Web of Science was used to identify and analyze the 100 publications. The articles were then cross-matched with Scopus and Google Scholar. The frequency of citation ranged from 940 to 11051 for the Web of Science, 1053 to 10740 for Scopus, and 1162 to 20041 for Google Scholar. Five hundred thirteen authors made contributions to the ranked list, and Robert E.W. Hancock contributed in six articles, which made it to the ranked list. Sixty-six scientific contributions originated from the United States of America. In contrast, five publications were linked to the University of Manitoba, Canada, that was identified as the educational organization, which made the most contributions (n=5). According to the methodological design, 26 of the most cited works were review-type closely followed by 23 expert opinions/perspectives. Eight articles were published in Nature journal, making it the journal with the most scientific contribution in this field. Correlation analysis between the publication age and citation frequency was found statistically significant (P = .012).
ARTICLE | doi:10.20944/preprints201809.0378.v1
Subject: Biology, Other Keywords: enterobacteriaceae; antibiotics; beta-lactamases; beta-lactam resistome; whole genome sequencing
Online: 19 September 2018 (09:47:42 CEST)
Beta-lactam resistant bacteria, commonly resident in tertiary hospitals, have emerged as a worldwide health problem because of ready-to-eat vegetable intake. We aimed to characterize the genes providing resistance to beta-lactam antibiotics in Enterobacteriaceae, isolated from five commercial salad brands for human consumption in Mexico City. 25 samples were collected, grow in blood agar plates, the bacteria were biochemistry identified and antimicrobial susceptibility testing was done, the carried family genes were identified by endpoint PCR and the specific genes were confirmed with WGS by NGS. 12 positive cultures were identified and their microbiological distribution was as follows, 8.3% for Enterobacter aerogene (n=1), 8.3% for Serratia fonricola (n=1), 16.7% for Serratia marcesens (n=2), 16.7% for Klebsiella pneumoniae (n=2), and 50% (n=6) for Enterobacter cloacae. The endpoint PCR results showed 11 colonies positive for blaBIL (91.7%), 11 for blaSHV (91.7%), 11 for blaCTX (97.7%), 12 for blaDHA (100%),4 for blaVIM (33.3%), 2 for blaOXA (16.7%), 2 for blaIMP (16.7%), 1 for blaKPC (8.3%) and 1 for blaTEM (8.3%) gene, all samples were negative blaROB, blaCMY, blaP, blaCFX and blaLAP gene. The sequencing analysis revels a specific genotypes for Enterobacter cloacae (blaSHV-12, blaCTX-M-15, blaDHA-1, blaKPC-2); Serratia marcescens (blaSHV-1, blaCTX-M-3, blaDHA-1, blaVIM-2); Klebsiella pneumoniae (blaSHV-12, blaCTX-M-15, blaDHA-1); Serratia fonticola (blaSHV-12, blaVIM-1, blaDHA-1) and Enterobacter aerogene (blaSHV-1, blaCTX-M-1, blaDHA-1, blaVIM-2, blaOXA-9). Our results indicate that beta-lactam resistant bacteria have acquired integrons with a different number of genes that providing panresistance to beta-lactam antibiotics, including penicillins, oxacillins, cefalosporins, monobactams, carbapenems and imipenems.
CONCEPT PAPER | doi:10.20944/preprints202202.0114.v1
Subject: Medicine & Pharmacology, Urology Keywords: urinary tract infection; cystitis; D-mannose; antibiotics; acute cystitis symptom score
Online: 8 February 2022 (13:25:24 CET)
Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.
ARTICLE | doi:10.20944/preprints202201.0234.v1
Subject: Life Sciences, Microbiology Keywords: AMR, Surveillance; One Health Approach; Alternative Antibiotics; Comparative Medicine; Phage Therapy
Online: 17 January 2022 (14:46:22 CET)
Antibiotics are in excessive use that has extensively increased antimicrobial resistance worldwide which has become the major public concern among the countries. To control this threat proper monitoring of the antimicrobial usage along with the increasing rate of antimicrobial resistance (AMR) is required. Further, surveillance of both the parameters is highly recommended for comparing the differences in distinct countries. Moreover, alternatives for antibiotics are also surveyed and are being researched for quick use in the near future. AMR is an issue that needs immense attention from various sectors. Thus, intervention of multisector is highly encouraged for better outcomes. One Health is one of the approaches that play a vital role in resolving this issue. In this research paper, six different European countries are discussed in terms of antimicrobial usage and AMR in the human and livestock sectors with the help of literature study and various reports published by different organizations. Data study has been conducted to collect the data for comparison study. Data sources of AMR and antimicrobial usage are analyzed and a thorough comparison of both antimicrobial use and AMR are conducted. Also, the application of One Health is studied for a balanced system. This article provides about various surveillance systems that are formed only to keep a track on the upcoming situation of AMR and the consumption of antimicrobials by the humans as well as animals. The article does not provide about all the details required to monitor the AMR issue but firmly allow the readers to get acknowledged with the broad information about the antimicrobial resistance across the six countries of Europe. The regular data collected by the different organizations play a vital role in monitoring the status of AMR and antimicrobial usage by humans and in live stocks. These annual reports have highly helped the government to decide for alternatives and have focused in many training activities to combat the AMR situation globally. AMR prevention is linked to the One Health concept. As antibiotic resistance genes persist on an interface between environment and animal and animal health, an approach is required in all three areas that stress the concept of 'One Approach to Health.'
ARTICLE | doi:10.20944/preprints202108.0031.v1
Subject: Medicine & Pharmacology, Allergology Keywords: antibiotics; antimicrobial resistance; antimicrobial stewardship; AWaRe; Pharmacovigilance; Lareb; adverse drug reactions
Online: 2 August 2021 (12:27:02 CEST)
(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and Pharmacovigilance (PV) has the potential to strengthen current antimicrobial stewardship (AMS) strategies. This study aimed to characterise AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre (Lareb); (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs).; (3) Results: Between 1998 and Jan 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n=89; 35%), colistin (n=30; 11,9%), ciprofloxacin (n=16; 6,35%), doxycycline (n=14; 5,5%) and aztreonam (n=12; 4,76%). The most frequently used PTs were drug ineffective (n=71; 28%), pathogen resistance (n=14; 5%) and drug resistance (n=13; 13%). A total of 119 reports (74%) suggested use-related issues. Watch antibiotics were in 54% of the reports and Reserve antibiotics were in 19%. In the Watch group, “Off label use” and “Product use in unapproved indication” were the most frequent PTs and majority of reports on Reserve antibiotics were coded as “Off label”. (4) Conclusions: Addressing AMR using the PV methods will provide an opportunity for PV expansion and could encourage further investment in both in AMS programs and PV systems.
ARTICLE | doi:10.20944/preprints202105.0308.v1
Subject: Biology, Anatomy & Morphology Keywords: Indonesia; biodiversity; novel antibiotics; drug screening; bioactivity; gene cluster networking; GNPS
Online: 13 May 2021 (14:05:00 CEST)
Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two-thirds of all clinically used antibiotics. Thus, exploiting Indonesia’s microbial diversity for actinomycetes may lead to the discovery of novel antibiotics. A total of 422 actinomycete strains were isolated from three different unique areas in Indonesia and tested for their antimicrobial activity. Nine potent bioactive strains were prioritized for further drug screening approaches. The nine strains were cultivated in different solid and liquid media and a combination of genome mining analysis and mass spectrometry (MS)-based molecular networking was employed to identify potential novel compounds. By correlating secondary metabolite gene cluster data with MS-based molecular networking results, we identified several gene cluster-encoded biosynthetic products from the nine strains, including naphthyridinomycin, amicetin, echinomycin, tirandamycin, antimycin, and desferrioxamine B. Besides, eight putative ion clusters and numerous gene clusters were detected that could not be associated with any known compound, indicating that the strains can produce novel secondary metabolites. Our results demonstrate that sampling of actinomycetes from unique and biodiversity-rich habitats, such as Indonesia, along with a combination of gene cluster networking and molecular networking approaches, accelerates natural product identification.
ARTICLE | doi:10.20944/preprints201904.0070.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: mycoplasma pneumoniae pneumonia; macrolide antibiotics; antibiotic resistance; corticosteroids; prednisolone; methylprednisolone; children
Online: 7 April 2019 (12:35:26 CEST)
Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015-2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24-36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP) (1-2 mg/kg) was administered for mild pneumonia patients, and IVMP (5 -10 mg/kg/day) for severe pneumonia patients. If patients showed persistent fever for 36-48 hours or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Eighty-five patients received only a broad-spectrum antibiotic without macrolide. The mean age and the male:female ratio were 5.6 ± 3.1 years, respectively. Seventy-four percent of patients (190/257) showed immediate defervescence within 24 h, and 95.7% (246/257) of patients showed defervescence within 72 h with improvements in clinical symptoms. Eight patients who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.
HYPOTHESIS | doi:10.20944/preprints202004.0269.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; SARS-CoV-2; pandemic; antibiotics; immune response; mitochondria; epidemiology; health policy
Online: 16 April 2020 (12:14:30 CEST)
Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients’ immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.
ARTICLE | doi:10.20944/preprints201809.0077.v1
Subject: Life Sciences, Microbiology Keywords: Garlic, Antibiotics, Lomé, Uropathogenic bacteria, Urinary Tract Infection, Multidrug resistance and alternative therapy.
Online: 5 September 2018 (01:35:46 CEST)
The urinary tract infection (UTI) is the most common bacterial infection, especially in women. The increased incidence of UTIs, at the last decades have paralleled with the growing emergence of antibiotic resistance. The aim is to evaluate aqueous garlic extract (AGE) susceptibility against multidrug-resistant (MDR) bacteria isolated in urine of women. The investigation of antibacterial propriety and time kill effect of AGE was performed by the well method, microdilution method and spectrophotometer assay. Antibiotics susceptibility assay revealed that the nine MDR bacteria had high resistance against Amoxicillin/ clavulanic acid (100%) and Erythromycin (100%), Cefotaxime (83.33%) and Ceftazidime (83.33%). AGE exhibited potent antibacterial activity against the nine MDR bacteria tested. In Gram-negative bacteria, the inhibition diameters ranged from 20 ± 3 to 32 ± 4 mm, with Minimum Inhibitory Concentrations (MICs) ranging from 10% to 12.5% (w/v) and Minimum Bactericidal Concentration (MBCs) was 12.5 % (w/v). Gram-positive bacteria exhibited diameters ranging from 38 ± 2 to 45 ± 1 mm; MIC and MBC values ranged from 05 to 10 % (w/v) and were found more susceptible than Gram-negative bacteria. To conclude, this investigation shown that AGE have high potential antibacterial to use as an alternative to treat women UTIs.
REVIEW | doi:10.20944/preprints202104.0031.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Community-Acquired Pneumonia; Hospital-Acquired Pneumonia; COVID-19; Antibiotics; Mes-enchymal Stem Cells; Corticosteroids
Online: 1 April 2021 (16:18:25 CEST)
Pneumonia remains a major cause of morbidity and mortality worldwide, especially during COVID-19 pandemic. With the significant global health burden that pneumonia poses, it is es-sential to improve therapeutic and management strategies. The increasing emergence of antibiotic resistant bacterial strains limits options for effective antibiotic use. New antibiotics for treatment of pneumonia may address deficits in current antimicrobial drugs, with an ability to cover both typical, atypical, and resistance pathogen. Several of these newer drugs also have structural characteristics that allow for a decreased propensity in development of bacterial resistance. Po-tential use of stem cell therapies in place of corticosteroid treatments may also offer an im-provement in patient outcomes. Human mesenchymal stem cell treatments have shown efficacy and safety in treating COVID-19 induced pneumonia. Combined treatment with both stem cells and antibiotics in pneumonia in a rabbit model has also shown significantly increased efficacy in comparison to antibiotic treatment alone, presenting yet another possible route for a novel strategy in treating pneumonia, though additional future studies are necessary before clinical implementation. While pneumonia remains a major disease of concern, having newer approved antibiotics as well as novel therapies such as stem cell treatments in the pipeline offers clinicians more options in effectively treating pneumonia.
ARTICLE | doi:10.20944/preprints201809.0034.v2
Subject: Social Sciences, Sociology Keywords: Antimicrobial resistance; antibiotics; health behaviour; health education; survey; development studies; rural; LMICs; Lao PDR
Online: 9 October 2018 (15:47:58 CEST)
Education and awareness raising are the primary tools of global health policy to change public behaviour. Considering the limitations of awareness agenda and the lack of social research to inform alternative approaches, our objective was to generate new empirical evidence on the consequences of antibiotic-related awareness raising in a low-income country context. We implemented an educational activity in two Lao villages to share general antibiotic-related messages, but also to learn about people’s conceptions and health behaviours. Two rounds of census survey data enabled us to assess the activity’s outputs, its knowledge outcomes, and its immediate behavioural impacts in a difference-in-difference design. Our panel data covered 1,130 adults over two rounds, including 58 activity participants and 208 villagers exposed indirectly via conversations in the village. We found that activity-related communication circulated among more privileged groups, which limited its indirect effects. Among participants, the activity influenced the awareness and understanding of “drug resistance,” while effects on attitudes were minor. Evidence on behavioural impacts was sparse and mixed, but the range of possible consequences included a disproportionate uptake of antibiotics from formal healthcare providers. Our study casts doubt on the continued dominance of awareness raising as a behavioural tool to address antibiotic resistance.
ARTICLE | doi:10.20944/preprints202112.0053.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: diabetes type-1; T1D; diabetes type-2; T2D; antibiotics; antibiotic classes; microbiome; dysbiosis; prevalence; concordance
Online: 3 December 2021 (12:45:23 CET)
Abstract: Several publications have raised the issue that the development of diabetes is preceded by alteration of the microbiome (dysbiosis) and hence, the role of environmental factors, triggering dysbiosis, should be considered. Antibiotics are powerful agents inducing dysbiosis and the authors wanted to explore the possible relationship between the consumption of different major classes of antibiotics and the prevalence of diabetes (type-1, /T1D/, type-2 /T2D/) in thirty European countries. According to our hypothesis, if such association exists, the dominant use of certain major antibiotic classes might be reflected in the prevalence of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes (T1D and T2D) estimated for 2019 and featured in the Diabetes Atlas with the average yearly consumption of major antibiotic classes of the previous 10 years (2010-19) extracted from the ECDC yearly reports on antibiotic consumption in Europe. Pearson correlation and variance analysis were used to estimate the possible relationship. Strong, positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A /p: 0.001/) and the narrow spectrum penicillin (J01CE /p: 0,006/, CF /p: 0.018/). Strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase resistant penicillin (J01CR /p: 0.003/), macrolide (J01F /p: 0.008/) and quinolone (J01M /p: 0.001/). T2D showed significant positive associations with cephalosporin (J01D /p: 0.048/) and quinolone (J01M /p: 0.025/), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA /p: 0.67/). Countries with the highest prevalence of diabetes (first 10 positions) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (first 10 positions) as indicated by variance analysis. Countries with high prevalence of T1D showed high consumption of tetracycline (p: 0.015), and narrow spectrum, beta-lactamase sensitive penicillin (p: 0.008), and low consumption of “inhibitor” antibiotics (broad-spectrum, beta-lactamase resistant, combination penicillin (p: 0.005), cephalosporin (p: 0.036), and quinolone (p: 0.003). Countries with a high prevalence of T2D consumed more cephalosporin (p: 0.084), quinolone (p: 0.54), and less broad-spectrum, beta-lactamase sensitive penicillin (p: 0.012) than other countries. Conclusion/Interpretation: The development of diabetes-related dysbiosis might be attached to higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics shoving negative (inhibitory) associations. Those groups of antibiotics are different in T1D and T2D
REVIEW | doi:10.20944/preprints202109.0491.v1
Subject: Life Sciences, Microbiology Keywords: Tuberculosis; Mycobacterium; Diagnostics; Drug Discovery; Antibiotics; Antimicrobial Re-sistance; Microfluidics; Single-Cell Analysis; Bioengineered Models
Online: 29 September 2021 (11:34:04 CEST)
Tuberculosis (TB) remains a global healthcare crisis with an estimated 10 million new cases and 1.4 million deaths per year TB is caused by infection with the major human pathogen Mycobacte-rium tuberculosis, which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models which capably mimic all physiological condi-tions of the infection, and high-throughput drug screening platforms. Microfluidic-based tech-niques provide single-cell analysis which reduces experimental time, the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review out-lines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculo-sis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB.
ARTICLE | doi:10.20944/preprints202108.0225.v1
Subject: Biology, Physiology Keywords: microglia; gut-brain axis; antibiotics; glutamatergic synapses; hippocampus; patch clamp; hippocampal slices.; microbiota; neurons; glutamatergic trasmission
Online: 10 August 2021 (10:04:00 CEST)
‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.
ARTICLE | doi:10.20944/preprints202108.0369.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; gut-brain axis; motilin; serotonin; gamma-aminobutyric acid; gonadal hormones; hypothalamic-pituitary-thyroid axis; antidepressants; macrolide antibiotics
Online: 18 August 2021 (07:39:37 CEST)
Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.
ARTICLE | doi:10.20944/preprints202106.0061.v1
Subject: Medicine & Pharmacology, Allergology Keywords: antimicrobial resistance; AMR; Infections; antibiotics; inappropriate prescribing; healthcare pro-fessionals; education; training; antimicrobial stewardship programs; continuous professional development
Online: 2 June 2021 (09:58:36 CEST)
(1) Background: Factors reported in literature associated with inappropriate prescribing of antimicrobials, such as physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians' decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing `antimicrobials would minimize the risk of resistance and, consequently, improve patients' clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. (2) Methods: Cross-sectional study conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed validated and piloted survey specific with closed-ended questions. A value of P <0.05 was considered for statistical significance. All data analysis was performed using Statistical Package for Social Sciences (IBM SPSS version 23.0). (3) Results: 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All the respondents acknowledged effectiveness and previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) were key factors influencing physicians’ choice during antimicrobial prescribing. (4) Conclusion: The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials, were reported to be common practices. Further, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials and using antimicrobials without physician prescription (self-medication) were the key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines.
ARTICLE | doi:10.20944/preprints202101.0050.v1
Subject: Biology, Anatomy & Morphology Keywords: antibiotics residue; antimicrobial resistance; ethno-veterinary practices; Herbal formulations; cattle health; dairy farmers; cost effective health care model
Online: 4 January 2021 (13:56:26 CET)
This study demonstrated that antibiotic residue in milk can be reduced when dairy farmers use Ethno-veterinary Practices (EVP) based on herbal alternatives to prevent and cure common clinical conditions in cattle instead of antibiotics. Of the 220 farmers selected for the study, 140 were trained and motivated to use validated herbal formulations, 80 were kept as control. Milk samples from the selected farmers (except Thirukanurpatti milk society) tested positive for antibiotic residue in the baseline survey. One year after interventions, the milk from 123 (87.86%) farmers out of 140, were without any detectable antibiotic residue, while samples from 11 farmers (7.85%) were low positive for either Beta-lactams or sulphonamides and 6 (4.29%) were positive for Beta lactams and/or sulphonamides. These 17 (11 + 6) farmers had used antibiotics along with herbal formulations. The milk samples from the control groups were positive for beta lactam and sulphonamide. There was suggestive significance of change in knowledge, attitude and practice of EVP among the farmers from Kerala and Tamil Nadu. A progressive reduction in the incidence of mastitis, enteritis, repeat breeding and cowpox were observed from 2016 to 2019 among the cows treated with EVP. Use of herbal alternative also resulted in a significant reduction in health care expenditure of cattle.
ARTICLE | doi:10.20944/preprints202209.0326.v1
Subject: Medicine & Pharmacology, Other Keywords: multidrug resistance organism; sepsis; adequate empirical antibiotics; source of infection; APACHE II; ICU length stay; predictors; risk factors; mortality
Online: 21 September 2022 (10:45:23 CEST)
Background: Multi-drug resistance organisms (MDRO) often cause increased morbidity, mortality, and length of stays (LOS). However, there is uncertainty whether the infection of MDRO increase the morbidity, mortality, and ICU-LOS. Objective: This study performed to determine the prevalence of MDRO in ICU, site of infection and the association of MDRO or site of infection with mortality. Secondary outcome was determined by ascertaining the association of MDRO or site of infection with (ICU-LOS). Methods: A retrospective cohort study was performed with adult sepsis patients in ICU. Univariate and multivariate (MVA) logistic regression with cox regression modeling were performed to compute the association of MDRO on ICU-mortality. MVA modelling was performed for ICU-LOS predictors. Results: Out of 228 patients, the isolated MDRO was 97 (42.5%) of which 78% were gram-negative bacteria. The mortality rate among those with MDRO was 85 (37.3%). The hospital acquired infection (HAI) was significantly predictor for ICU-LOS in univariate linear regression (R² = 0.034, P=0.005). In MVA linear regression, both Enterococcus faecalis infection and acinetobacter baumannii (AC) -MDRO were predictors for ICU-LOS with (R² = 0.478, P<0.05). In the univariate cox regression, only the infection with AC- MDRO was a risk factor for ICU-mortality with [ HR =1.802 (95% CI: 1.2 – 2.706; P = 0.005)]. Conclusions: Identifying risk factors for MDRO highlight the appropriate administration of empirical antibiotics and effectively control of source of infection which would reduce mortality and ICU-LOS. The usage of broad- spectrum antibiotics should be limited for those having substantial risk factors to acquire MDRO.
ARTICLE | doi:10.20944/preprints202011.0640.v1
Subject: Life Sciences, Biochemistry Keywords: Arthroplasty; prosthetic joint replacement; prosthetic joint infection; systemic antibiotic prophylaxis; Antibiotics; chlorhexidine gluconate; coagulase-negative staphylococci; tuf gene sequencing; staphylome; microbiome
Online: 25 November 2020 (12:56:25 CET)
The aim was to study alterations of bacterial communities in patients undergoing hip or knee arthroplasty to assess the impact of chlorhexidine gluconate soap decolonisation and systemic antibiotic prophylaxis. A Swedish multicentre, prospective collection of samples obtained from elective arthroplasty patients (n=83) by swabbing anterior nares, skin sites in the groin and the site of planned surgery, before and after arthroplasty surgery, was analysed by 16S rRNA (V3-V4) gene sequencing and a complementary targeted tuf gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial (p=0.04) and staphylococcal (p=0.03) groin communities after arthroplasty surgery with significant reductions in relative Corynebacterium (p=0.001) abundance and S. hominis (p=0.01) relative staphylococcal abundance. In nares, significant reductions occurred for S. hominis (p=0.02), S. haemolyticus (p=0.02), and S. pasteuri (p=0.003) relative to other staphylococci. S. aureus colonised 35% of anterior nares before and 26% after arthroplasty surgery. S. epidermidis was the most abundant staphylococcal species at all sampling sites. No bacterial genus or staphylococcal species increased significantly after arthroplasty surgery. Application of a targeted tuf gene sequencing approach provided auxiliary staphylococcal community profiles and allowed species-level characterisation directly from low biomass clinical samples.
Subject: Medicine & Pharmacology, Gastroenterology Keywords: ulcerative colitis; inflammatory bowel disease; pediatrics; FMT; probiotics; synbiotics; antibiotics; prebiotics; fecal microbiota transplant; colitis-associated cancer; colorectal cancer; CAC; CRC; dysbiosis
Online: 20 September 2021 (14:20:39 CEST)
Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we will discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.
REVIEW | doi:10.20944/preprints202005.0089.v1
Subject: Medicine & Pharmacology, Other Keywords: access to medicines; access to antibuotics; impact of access to medicines on public health; problems associated with access; use; abuse of antibiotics resistance; aware; Africa
Online: 5 May 2020 (17:03:07 CEST)
Access to medicines is one of the essential problems in Public Health of low- and middle-income countries (LMICs). The World Health Organization (WHO) defines access to medicines as the possibility of "having continuously accessible and affordable medicines in public or private health facilities that are within a kilometer of the place of residence." Access to medicines, as defined by the WHO, is not fully guaranteed in many LMICs and even in many regions of high-resource countries. The WHO identifies several factors as determinants of limitations in the access to medicines: rational selection, affordable prices, sustainable financing, and reliable health services. The action on these factors makes it possible to improve universal access to medicines with consequent improvement in Public Health. Adequate access to antibiotics and vaccination will avoid a large part of the deaths caused by infectious diseases in the LMICs. However, the emergence of resistance and the difficulties in vaccination campaigns due to socio-political or cultural problems make it challenging to fight many easily treatable infectious diseases. The use and abuse of antibiotics are inevitably associated with the appearance of resistances that make them ineffective. Thus, whereas limited access to antibiotics raises mortality rates from infectious diseases, generalized open access to them ends up eliminating their clinical value. Moreover, the contraction of research in this field for many years has reduced the success in discovering new drugs. Additionally, local market regulations, inadequate selection, inaccessible prices, especially for those of second and third-generation, inefficient health systems, and difficulties of administration and control of prescription compliance, especially in the case of combined therapies, are additional obstacles to universal access to antibiotics. In order to simultaneously improve access to antibiotics and keep resistances under control, it is necessary to develop training and education activities at different social levels (from patients to various Health Care Providers) to complement the national or supranational strategic plans.