Background/Objectives: The burden of hospital-acquired infections (HAIs) is particularly sub-stantial in low- and middle-income countries (LMICs). However, a comprehensive understanding of their prevalence in these regions is lacking. This systematic review aimed to evaluate the prevalence of HAIs in LMICs. Methods: Major databases, including Scopus, PubMed, and Web of Science, were thoroughly searched for published studies between January 1, 2000, and July 15, 2024. The PRISMA guidelines were followed for a comprehensive and systematic approach. The pooled prevalence of HAIs was estimated using a random-effects model and a 95% confidence interval (CI). Results: The literature search identified 87 studies reporting HAI prevalence in LMICs. The overall prevalence of HAIs across LMICs was 22% (95% CI: 17-28), with notable regional variations. The South-East Asian Region (SEAR) presented the highest prevalence at 37% (95% CI: 13-62), followed by the African Region at 25% (95% CI: 16-33). The European Region (EUR) had the lowest preva-lence, at 14% (95% CI: 5-23). In terms of income level, low-income countries had the highest prevalence at 37% (95% CI: 23-52), followed by lower-middle income at 22% (15-30) and up-per-middle income at 13% (95% CI: 6-20). Surgical site infections (SSIs) had the highest prevalence among infection types at 27% (95% CI: 23-31), followed by pneumonia at 23% (95% CI: 18-28) and urinary tract infections (UTIs) at 22% (95% CI: 19-26). Gastrointestinal infections (GIs) were less prevalent at 6% (95% CI: 3-9). Conclusions: This systematic review underscores the high prevalence of HAIs in most LMICs, with variations based on region and income level, emphasizing the need to facilitate the development of targeted prevention and control strategies to mitigate the impact of this critical public health issue, especially in resource-limited settings.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

Ionic liquid MIE-NH2 displays a new role of development of modification of glycoproteins of lactoferrin through a reductive amination mechanism to synthesize versatile pharmaceuticals. This work introduces a new strategy of modification of Lactoferrin by using methylimidazolium N-ethylamine, this ionic liquid MIE-NH2 linked to N-glycans in Lactoferrin derivatives. Using UPLC/ESI-QTOF and MALDI-TOF mass spectrometry to perform and detect the modifying of ionic liquid-linked glycoproteins. Relevantly, modifying the lactoferrin by MIE-H2 as a small molecule of ion liquid lactoferrin (IL-Lf), which could be a potential antiviral drug and it is achieved by inhibiting various targets. The probability of the lactoferrin modified as a small IL-Lf-molecule to inhibit any of these targets was investigated to find out its potency as a SARS-CoV-2 inhibitor. Molecular docking disclosed the activity of modifying glycoproteins - small IL-Lf-molecules containing amino groups and interaction with targeted Mpro, RdRp, TMPRSS2, and PLpro. Clinically, this study shows the a volubility to provide small IL-Lf-molecules as significantly important drugs that target main protease (Mpro), RNA dependent RNA polymerase (RdRp), transmembrane protease serine 2 (TMPRSS2), and Papain-like protease (PLpro).

(1) Background: Urinary tract infections (UTIs) are an important cause of perinatal and maternal morbidity and mortality. The aim of this study was to describe and compare the main pregnancy outcomes among pregnant patients with complicated and uncomplicated UTIs; (2) Methods: This retrospective study included 183 pregnant patients who were evaluated for uncomplicated UTIs and urosepsis in the Urology Department of ‘C.I. Parhon’ University Hospital, and who were followed up at a tertiary maternity hospital- ‘Cuza-voda’ from Romania between January 2014 and October 2023. The control group (183 patients) was randomly selected from the patient’s cohort who gave birth in the same time frame at the maternity hospital without urinary pathology. Clinical and paraclinical data was examined. Descriptive statistics and a conditional logistic regression model were used to analyze our data. (3) Results: Our results indicated that patients with urosepsis had increased risk of premature rupture of membranes (aOR: 5.59, 95%CI: 2.02- 15.40, p< 0.001) and preterm birth (aOR: 2.47, 95%CI: 1.15- 5.33, p= 0.02). We could not demonstrate a statistically significant association between intrauterine growth restriction and preeclampsia with the studied urological pathologies. (4) Conclusions: Careful UTIs screening during pregnancy is needed for preventing maternal-fetal complications.

Abstract. Marek's disease virus is an oncogenic avian herpesvirus and the problem of oncogenicity of this virus for humans remains unexplored. This pathology appeared in broiler chickens of 30 days and older, that is from now on the contact with poultry meat carries the risk of infecting people. This article analyzes the risks of the emergence of the epidemic potential of the Marek's disease virus in the Russian Federation taking into account the characteristics of modern pig and poultry farming. It was found that COVID 19 can serve as an additional factor in reducing the resistance of the population to herpesvirus infections. The COVID 19 epidemic is accompanied by folic acid deficiency which also increases the risk of contamination of diseases associated with DNA viruses, including an extended risk of animal viruse infection. Since, according to our estimates, Marek's disease occurred in at least 25% of broiler poultry farms in the Russian Federation, a possible expand in mortality from neoplasms of the reproductive system for the Russian Federation as a whole can contribute to the dynamics of oncological diseases of reproductive organs and breast cancer. Since 2011 a contagious form of intestinal pathology, vesicular enteritis, has widely spread at poultry farms in the Russian Federation. During periods of extending incidence of vesicular enteritis, we recorded cases of inflammation of the facial nerves and subfebrile temperature in contact persons, bursts of oncological diseases in veterinary personnel (ovarian cancer, breast cancer), abnormal and synchronous increases in the incidence of infectious larengotracheitis and Marek's disease in chickens under the age of 40 days which requires additional monitoring studies.

Viruses are the most common congenital infections and an important cause of fetal malformations, morbidity, and mortality. The effects of these infections, which are transmitted in-utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (where the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, parvovirus B-19, rubella, varicella and zika. There are currently very few efficacious antiviral agents licensed for use in pregnancy and therefore for most of these infections, prevention by means of immunisation (where there is a vaccine), administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss the current understanding of some of the congenital infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.

The reproductive health of women is governed by an optimal balance between the host-microbiota interaction. Depletion in the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With careful choice of polymers (natural, synthetic or semi-synthetic) hydrogels with specific properties such as stimuli-responsiveness, antimicrobial, and muco-adhesiveness can be tailored for higher therapeutic efficacy. In this review, the advnances in hydrogel strategies for the treatment of vaginal infections is presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

Nosocomial infections can be transmitted by contaminated hospital surfaces with resistant pathogens. conventional sanitations are not efficiently contributing to removing resistant pathogens. Bacteriophages suggest as decontaminating agents, safe, their selective ability to kill specific bacteria. This work aimed to assess the efficiency of a phage in removing Pseudomonas aeruginosa from different hard surfaces. The decontamination ability of phages w was tested in vitro against Pseudomonas aeruginosa strain. Cystoviridae Phages with titer (2 × 1012 PFU/mL) can efficiently reduce viable bacterial cells on contaminated surfaces. The treated surfaces with alcohol 70% and phage showed an evident drop of bacterial cell number from 1 h to 24 h. These results suggest that bacteriophages are biocontrol agents removing nosocomial infection pathogens transmitted by contaminated surfaces in the hospital environment.

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19.There is good reason to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID-19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background.

Blood stream infections (BSI) due to carbapenem-resistant gram-negative bacilli (CR-GNB), especially Klebsiella pneumoniae carbapenemase (KPC) and New-Delhi metallo-β-lactamase (NDM) producers, are a major concern of public health, as they are associated with high morbidity and mortality. We conducted a single-center, retrospective, observational study at a tertiary-care, teaching Greek hospital, to determine the incidence, 30-day and overall, in-hospital, crude mortality, risk factors and efficacy of best available treatment options in patients with BSIs from KPC- or NDM-producing GR-GNB. During the one-year study period, from 1st January to 31st December 2023, we recorded 133 episodes of BSIs in 118 unique patients; 79 episodes were due to KPC-producing and 54 to NDM-producing CR-GNB. Our study showed relatively high incidence of BSIs by both KPC- and NDM-producing CR-GNB (0.49 and 0.31 episodes per 1000 patient-days respectively). We found high 30-day crude mortality rates for patients with BSIs due to KPC- producing CR-GNB (26.4 %), and NDM-producing CR-GNB (37%), while BSIs due to NDM-producing P. aeruginosa had the highest 30-day (47.1%) and overall (70.6%) in-hospital, crude mortality. Beta-lactam/beta-lactamase inhibitors as monotherapy or in combination with other active agents used to treat KPC-producing CR-GNB were associated with improved survival rates (p=0.009).

Diabetic foot ulcers (DFUs) are a multifactorial pathophysiologic condition that occurs in patients with diabetes mellitus (DM). Approximately 9.1 to 26.1 million people are affected by DFUs annually. This condition can lead to progressive foot infections and, ultimately, foot amputation. Various microbes contribute to DFUs, including methicillin-resistant Staphylococcus. aureus, Pseudomonas aeruginosa, and Escherichia coli can form biofilms composed of complex matrices that create a protective shield around the microorganisms, enhancing their survival and resistance to treatment. Biofilm formation is a critical virulence factor directly associated with the onset and persistence of DFUs. It not only complicates the clinical management of these ulcers but also facilitates antibiotic resistance, necessitating a comprehensive approach to treatment. Effective management strategies must therefore target biofilm formation and the virulence factors associated with these pathogens. By addressing these elements, conventional antibiotics can be rendered more effective in treating diabetic foot ulcers. This approach aims not only to promote wound healing but also to address underlying causes and prevent further complications. This article seeks to highlight the significance of biofilm formation in DFUs, explore methodologies for studying this condition, as well as discuss demographic considerations and treatment options.

Multidrug resistant organisms (MDROs) outbreaks have been steadilyincreasing in Intensive care units (ICUs). Still, healthcare institutions and workers (HCW) reached no unanimity on how and when implementing infection prevention and control (IPC) strategies. We aimed to provide a pragmatic, physician practice-oriented, resume of strategies towards different MRDOs outbreaks in ICU. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios, education, isolation, decolonization, screening and hygiene practices, outbreak reporting, cost-effectiveness, reproduction-number(R0), and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician losing the big picture. IPC strategies proved their cost-effectiveness regardless typology, country, or pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, a rapid outbreak recognition tool elaboration (i.e., an easy-to-use mathematical model) would improve early diagnosis and spreading prevention. Further studies are needed to express in favor or against MDROs decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategies application has made, and still makes ICUs a major MDROs reservoir into the community. In a not-too-distant future genetic engineering and phage therapies could represent a plot-twist in MDROs IPC strategies.

The emergence and re-emergence of pathogens with pandemic potential has been a persistent issue throughout history. Recent decades have seen significant outbreaks of zoonotic viruses from members of the Coronaviridae, Filoviridae, Paramyxoviridae, Flaviviridae, and Togaviridae families, resulting in widespread infections. The continual emergence of zoonotic viral pathogens and associated infections highlights the need for prevention strategies and effective treatments. Central to this effort is the availability of suitable animal models, which are essential for understanding pathogenesis and assessment of transmission dynamics. These animals are also critical for evaluating the safety and efficacy of novel vaccines or therapeutics and are essential in facilitating regulatory approval of new products. Rapid development of animal models is an integral aspect of pandemic response and preparedness; however, their establishment is fraught by several rate-limiting steps, including selection of a suitable species, the logistical challenges associated with sharing and disseminating transgenic animals (e.g., the time-intensive nature of breeding and maintaining colonies), availability of technical expertise, as well as ethical and regulatory approvals. A method for rapid development of relevant animal models that has recently gained traction is the use of gene therapy vectors to express human viral receptors in readily accessible laboratory animals to enable virus infection and development of clinical disease. These models can be developed rapidly on any genetic background making mechanistic studies and accelerated evaluation of novel countermeasures possible. In this review, we will discuss important considerations for the effective development of animal models using viral vector approaches and review the current vector-based animal models for studying viral pathogenesis and evaluating prophylactic and therapeutic strategies.

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.

The developments of confirmed daily Sars-CoV-2 infections can be modeled a posteriori in a comparatively simple and satisfactory way by means of a special exponential function: its exponential coefficient varies exponentially with time itself. This property enables the function to directly simulate the „daily case“ curve fragments observed for the first waves of the current epidemics in a number of counties and countries. Linear combinations of two or more of the functions allow for the modeling of the complete curves observed in the vast majority of all regions for which case number developments have been tabulated.

Background: Vertical transmission of HIV infection can occur during pregnancy, during childbirth or through breastfeeding. The recommendations issued by the various international guidelines (WHO 2010, EACS 2017, DHHS 2017) on the safety of breastfeeding of HIV-infected women in effective antiretroviral treatment do not provide univocal indications referring to individual countries the choice to advise or advise against such procedure. Methods: A retrospective study was conducted in a small cohort of HIV-infected pregnant women who, despite the information received, decided to breastfeed their children. The observation was carried out in the period between March 2017 and June 2021. In all newborns, prophylaxis therapy was initiated at birth, according to the treatment guidelines, the scheme adopted involved the administration of zidovudine (AZT) orally for 4 weeks, started immediately after the childbirth. Breastfeeding time was, on average, 5 months. Results: No contagion was diagnosed. All infants were tested for HIV-RNA at birth, 1, 3, and 6 months after birth, and 1, 3 and 3 months after stopping breastfeeding. Conclusions: The data obtained represent, in our opinion, a solicitation to discuss and re-evaluate scientific evidence that starting from "Undetectable Equals Untransmittable" (U = U) can open a scientific and cultural review of breastfeeding.

In May 2022, WHO reported an outbreak of Mpox in several European countries which were previously Mpox free. Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in Central and West Africa. The sudden emergence of Mpox outside Africa and its subsequent rapid spread lead the WHO to declare the outbreak as Public Health Emergency of International Concern. As of May 15, 2023, a total of 87,704 confirmed cases and 140 deaths had been reported from 111 countries and territories worldwide. Looking back on this outbreak one year later, several important questions have arisen. Here, we address these questions using the classic five Ws: What, When, Where, Who and Why? We discuss these questions and outline what needs to be done to prevent, or at least minimize, outbreaks from emerging and re-emerging viral infection.

The emergence of antimicrobial resistance (AMR) Candida auris presents a formidable global health challenge, causing severe healthcare-associated infections with high mortality rates. Its ability to colonize surfaces and resist standard disinfectants undermines traditional hygiene practices, prompting an urgent need for novel strategies. Ultraviolet C (UVC) light offers a promising approach due to its rapid and broad-spectrum germicidal efficacy. This review comprehensively examines the current knowledge of UVC LED technology in combating C. auris, highlighting its effectiveness, limitations, and potential applications in healthcare hygiene. UVC light has potent activity against C. auris, including multidrug-resistant (MDR) strains. UVC can reduce C. auris on contaminated surfaces, aiding in transmission prevention. This review explores implementation strategies, including mobile UVC systems for targeted disinfection of high-risk areas and equipment, integration into air handling units (AHUs) to continuously disinfect recirculating air, and incorporation into water treatment systems. Current limitations in our understanding of UVC safety and effectiveness necessitate further research to optimize application protocols and ensure treatment safety while maintaining efficacy against C. auris. Integrating UVC disinfection technology into infection control programs holds promise for strengthening hygiene practices that will curb the global spread of C. auris and improve patient outcomes.

The SARS-CoV-2 have caused a devastating pandemic of all times in the recent human history. However, there is a serious paucity in high quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccinations. Out of 389 isolates used in different aspects, 298 was examined before and during the pandemic (n=149 before, n=149 during), death rates were 32% during compared to only 7.4% before pandemic with significant association (P value = 0.000000075). Death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128) indicating a highly significant value (P value = 0.00000000000088). However, analysis of patients without other respiratory problems (n=28) indicated that among the remaining 270 patients, death was 30% in co-infected patients (n=150) and only 0.8% in non-coinfected (n=120) with high significant P value= 0.00000000076. The trending patterns of co-infections before, during, and after vaccinations showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram-negatives in totals of (n= 149 before/n= 149 during): Klebsiella pneumonia (n = 11/49 before/during; E. coli n=10/24, A. baumannii n=8/25, and Ps. Aeruginosa n= 5/16, and S. aureus 13/1. Nevertheless, in post vaccination phase, (n= 91) gender-specific co-infections were examined for potential differences in susceptibility. Methicillin resistant S. aureus (MRSA) dominated both genders followed by E. coli in males and females with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place mostly in male patients. The drastic decline in K. pneumoniae and Gram-negatives post-vaccination strongly imply a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.

The SARS-CoV-2 infection is a cause of hypoxemic acute respiratory failure, leading to frequent intensive care unit (ICU) admission. Due to invasive organ support and immunosuppressive therapies, these patients are prone to nosocomial infections. Our aim was to assess the value of daily measurements of C-reactive protein (CRP) and Procalcitonin (PCT) in the early identification of ICU-acquired infections in COVID-19 patients Methods: We undertook a prospective observational cohort study (12 months). All adult me-chanically-ventilated patients admitted for ≥ 72 hours to the ICU with COVID-19 pneumonia were divided into an infected group (n=35) and a non-infected group (n=83). Day 0 was considered as the day of the diagnosis of infection (infected group) and day 10 of ICU stay (non-infected group). The kinetics of CRP and PCT were assessed from day -10 to day 10 and evaluated using a general linear model, univariate, repeated-measures analysis. Results: 118 patients (mean age 63 years, 74% males) were eligible for the analysis. The groups did not differ in patients' age, gender, CRP, and PCT serum levels at ICU admission. However, the infected group encompassed patients with a higher severity (SOFA score at ICU admission, p=0.009) and a higher 28-day mortality (p<0.001). Before D0, CRP kinetics showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (p<0.001), while PCT kinetics did not appear to retain diagnostic value to predict superinfection in COVID-19 patients (p=0.593). Conclusion: COVID-19 patients who develop ICU-acquired infections exhibited different biomarker kinetics before the diagnosis of those infections. Daily CRP monitoring and the recognition of the CRP kinetics could be useful in the prediction of ICU-acquired infections.

Introduction: Urinary tract infections (UTIs) are a significant global health issue, especially among women, with growing concerns related to antibiotic resistance and adverse effects. The Uromune® vaccine, a sublingual bacterial lysate, represents a promising therapeutic alternative by enhancing immune responses against uropathogens. Methods: This retrospective study, conducted at Hospital Universitari de Sant Joan de Reus from January 2017 to August 2022, evaluated the effectiveness of Uromune® in treating recurrent UTIs (rUTIs). Patients received personalized autovaccines administered as two sublingual puffs daily for three months. Clinical, microbiological, and demographic data were analyzed to assess treatment outcomes and identify recurrence-associated factors. Results: Forty-nine patients (mean age, 61 years, and 59.2% women) were included in the study. Uromune® treatment decreased UTI episodes, from 3.73 ± 0.97 the year before to 0.98 ± 1.36 (P &lt; 0.001) the year after its administration. The number of patients who suffered three or more episodes per year dropped from 43 (87.7%) before the intervention to 7 (14.3%) afterward. The maximum effectiveness of the autovaccine was observed three months post-administration, with 44 patients not experiencing any UTI episodes. Regression analysis identified having had a urostomy, chronic kidney disease, and being immunosuppressed as predictors of recurrence. Conclusion: The Uromune® autovaccine effectively reduced the frequency of rUTIs and associated hospitalizations, offering substantial relief to patients. These findings support the integration of Uromune® into routine clinical practice as a viable alternative to conventional antibiotic treatments.

The genus Aeromonas is widely distributed in aquatic environments. It is frequent as a fish pathogen, but has also been described associated to human infections. Most human cases are caused by A. caviae, A. veronii biovar sobria, and A. hydrophila, though A. dhakensis is becoming increasingly important. Transmission happens primarily by ingestion or contact with aquatic collections, or by consumption of contaminated food, especially of aquatic origin. Increasing resistance has been described in Aeromonas to penicillins, including their combinations with classical b-lactamase inhibitors, cephalosporins and carbapenems. Among the b-lactam antibiotics, only the 4th generation cephalosporins remain almost uniformly active. In addition, the simultaneous presence of resistance genes to 3rd generation cephalosporins and carbapenems in the same isolates is increasing. Recently, the presence of mobile genes linked to colistin resistance has also been described, in some cases with resistance percentages higher than 30%. Most likely, this evolution of colistin resistance is linked to its use in aquaculture, and, together with the evolution of b-lactam resistance, may be turning this genus into a reservoir of resistance genes that may affect other species much more frequently linked to human infections, such as Enterobacterales.

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.

A combination of Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) hydrosols is proposed as an in situ thermo-gelling vehicle for the nasal drug delivery of chlorhexidine-silver nanoparticles conjugates (SN-CX). Varying ratios of P407 and HPMC were applied in the presence and absence of SN-CX in order to optimize the gelation temperature (Tg) to values close to the physiological nasal such (30–34°C). Mechanisms for the observed gelation phenomena were suggested based on viscosimetry, texture analysis, and dynamic light scattering. Tests were carried out for sprayability, washout time, in vitro drug release, ex vivo permeation, and antimicrobial activity. When applied separately, HPMC was found to lower the P407 gelation temperature, whereas SN-CX increased it. However, in the presence of HPMC, SN-CX interfered with the P407 micellar organization in a principally contrasting way, while leading to an even further decrease in Tg. SN-CX-loaded nasal formulation composed of P407 16% and HPMC 0.1% demonstrated a desired gelation at 31.9 °C, good sprayability (52.95% coverage of the anterior nasal cavity), mucoadhesion for 70 min under simulated nasal clearance, expedient release and permeation, and preserved anti-infective activity against seasonal Influenza virus and beta-coronavirus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and other pathogens. Our findings suggest that the current development could be considered a potential formulation of a protective nasal spray against respiratory infections.

Healthcare-Associated infections (HAIs) affect more than 100 million patients each year worldwide. These infections are mainly caused by multi-resistant bacterial strains (MDR) such as Acinetobacter Baumanii which is responsible of high mortality rate in immunocompromised individuals. However, the treatment is further aggravated by the abuse of antibiotics, the lack of vaccine and the emergence of resistance posing a huge challenge for the discovery of new therapeutic drugs to overcome this nosocomial infection. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acitenobacter baumanii. The cytotoxicity of these DS was investigated on the HEp-2 cell line by the MTT cell viability assay. Thereafter, we studied morphological alterations caused by the action of one of the active peptides on the bacterial membrane using Atomic Force Microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibit antibacterial activity with MICs ranging from 3.125 to 12.5 μg/mL and MBCs ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that DS might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter infections.

probiotics. However, these bacteria caused rare infections mostly in diabetic and immunocompromised subjects in presence of risk factors such as prosthetic hearth valves and dental procedures or caries. The scope of this survey was re-assessing the pathogenic potential of lactobacilli based on the infection case reports published in the last three years. In 2019, 2020 and 2021 17, 15 and 16 cases, respective-ly,.including endocarditis, bacteremia and other infections, were reported. These annual numbers are higher than observed previously. Lacticaseibacillus rhamnosus (13 cases), comprising strain GG (ATCC 53103) with established applications in healthcare, L. paracasei (7 cases), Lactobacillus acidophilus (5 cas-es), L. jensenii (5 cases), Lactiplantibacillus plantarum (3 cases), L. paraplantarum, L. delbrueckii subsp. del-brueckii, L. gasseri, L. paragasseri, Limosilactobacillus fermentum and L. reuteri (1 case each) were involved. Virulence characterization of two strains that caused infections, a derivative of L. rhamnosus GG and L.paracasei LP10266, indicated that increased biofilm forming capacity favors pathogenicity and it is determined by variable genetic traits. This survey highlighted that strains of lactobacilli able to cause infections were little characterized genet-ically. Instead, to avoid that these bacteria become a hazard, genetic stability should be periodically re-evaluated by whole genome sequencing (WGS) to ensure that only non-pathogenic variants are ad-ministered to vulnerable individuals.

In diabetic foot infections (DFI), the clinically virulence of skin commensals are generally pre-sumed to be of low virulence. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria); and, pyogenicpathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1,018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pyogenicpathogenic patho-gens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxy-gen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs 24 %, p=0.23) or microbiological recurrence (11% vs 17 %, p=0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confi-dence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may equally base on oral non-beta-lactam antibiotic agents susceptible to the corresponding skin pathogens.

High rates of resistance to antibiotics are associated with healthcare-related infections, thus appealing for the urgent need for effective antimicrobials against these maladies. The present study aims to determine the chemical composition of essential oil (EO) from Clausena anisata leaves, and evaluate their antibacterial activity against selected nosocomial bacteria. Fresh leaves of Clausena anisata were subjected to a steam distillation using a Clevenger apparatus to afford the essential oil. The phytochemical composition of this oil was analyzed using gas chromatography-mass spectrometry (GC-MS). The essential oil was further tested against selected nosocomial bacteria, including Staphylococcus and Klebsiella species, among others, using a microdilution method. As a result, 0.77% of essential oil was extracted from fresh leaves of Clausena anisata. The GC-MS analysis revealed that the as-prepared essential oil contain E-anethole (70.77%), methyl isoeugenol (13.85%), estragole (4.10%), γ-terpinene (3.33%), myrcene (2.82%) and sabinene (0.77%), with E-anethole being the major constituent. Meanwhile, twenty two compounds were identified in the EO of Clausena anisata leaves through gas chromatography. Upon antibacterial test against selected nosocomial pathogens, the E-anethole-rich essential oil exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 3.91 to 125 µg/mL and 7.81 to 125 µg/mL, respectively, indicative of a bactericidal orientation of the plant’s essential oil (MIC/MBC ratio: 4). This novel contribution highlights the scientific validation of the use of Clausena anisata leaves in the traditional treatment of various infectious diseases. However, toxicity and pharmacokinetic studies, mechanistic basis of the antibacterial action, and in vivo antibacterial experiments of the E-anethole-rich essential oil of Clausena anisata should be investigated to successfully use this plant in the treatment of infectious diseases.

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.

This lack of information is due to the primary role of HSTs in fungal pathogenesis, which often masks the functions of NSTs and CWDEs. So, the toxic effects of A. alternata metabolites due to NSTs and CWDEs have received minor attention than those reported for HSTs mycotoxins [11]. A wider study of the activity of isolated fungal metabolites can allow the identification of compounds directly related to the pathogenic activity of the fungus, making it possible to create chemo libraries that facilitate the linking of the structure of the compounds with the species that produce it and its effect on host and non-host crops, as well as with biosynthetic features [12]. In this context, our work reports a study focused on NSTs and CWDEs used by an A. alternata strain isolated from infected pears in Italy. To this aim, the characterization of hydrolytic enzyme activities of A. alternata and the identification of the metabolites produced in vitro were performed. Furthermore, the phytotoxic activity of the isolated compounds was evaluated on pear (host and non-host varieties) and lemon fruits [13]. Finally, the competition of A. alternata with other pathogens was evaluated to investigate the role of NSTs on co-infections.

Since the early 2000s, high-risk E. coli clones that presented a highly virulent and multidrug resistance profile have been identified, and their genome is completely sequenced. Molecular techniques make it possible to follow the evolution and spread of those clones in different parts of the world. The results of several studies monitoring the emergence of new high-risk E. coli clones showed an increase in the number of clones and the virulence strategies and in the emergence of clones with the ability to cause intestinal and urinary infections combined with a multidrug resistance profile. We certainly can't stop the emergence of new high-risk clones. The remaining questions are: How can we use the knowledge about E. coli high-risk clones to our advantage in the war against multidrug antibiotic resistance? How can we stop the spread of those clones and improve diagnostic and treatment stewardship? This is a challenge that requires collaboration and shared knowledge.

Malaria is a long-standing disease and one of the top life-threatening diseases, yet its treatment has not changed, while the world has already embraced the Fourth Industrial Revolution (4IR). A wave of research on digitizing monitoring mechanisms of such a deadly disease has surfaced. Automated malaria screening is one of the detection processes which are gaining popularity in the research domain. However, the process needs to be coupled with other processes aiming a nationally or regionally contextualised malaria monitoring system. This paper proposes a digital malaria monitoring system in the context of an African country or region. One advantage of such a digital system is that is enables a novel disease spread forecasting model based on the dynamics of different malaria types. The architecture of the diagnosis system is described, and the disease spread model is mathematically modelled in terms of a SPITR (Susceptible- Protected- Infected-Treated- Recovered) epidemic model which is further analysed. The forecasting model is expressed and analysed whereas experiments are conducted using a Monte Carlo simulation method. The design of the monitoring system has inspired how predictions can be made in the complex cases such as mixed infections. Results show that reinforcing the model parameter makes a significant improvement on the disease prediction.

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuates their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.

The Infectious and Tropical Diseases Department of University of Brescia organized free rapid screening tests for HIV and HCV as part of the Fast Track City commitment. A cross-sectional study was conducted, consisting of an anonymous, multiple-choice questionnaire that was administered to individuals who underwent the screening or consultation. The study aimed to compare knowledge and attitudes towards HIV and HCV between age groups (18-40 vs. >40) and sexual orientations (heterosexual vs. LGBTQ+). Overall, 333 questionnaires were completed. Individuals over the age of 40 and those who identified as heterosexual had the lowest level of knowledge about HIV transmission (7.9% and 30% respectively), undetectable=untransmittable (19.7% and 39.4% respectively) and PrEP (9.2% and 18.2% respectively). They were also less willing to cohabit with people with HIV (PLHIV). Only 9.6% of the population demonstrated high levels of knowledge for both HIV and HCV. People over the age of 40 had the largest gaps in knowledge and would benefit the most from educational and prevention interventions.

Recently Candida auris has emerged as a multi-resistant fungal pathogen, with a significant clinical impact, and has become a critical issue in WHO fungal priority list, due to its unique ability to persist for long time on human skin and hospital environments. It is therefore fundamental to reinforce hospital surveillance protocols to limit nosocomial outbreaks. The study purpose was the Fourier-Transform Infrared Spectroscopy (FT-IR) application to investigate the phylogenetic relationships between isolated strains within the C. auris outbreak at the university Intensive Care Unit of a Tertiary University hospital in Turin (Italy). In order to calculate a clustering cut-off, intra- and inter-isolates distance values were analysed. Data showed the presence of a major cluster Alfa and a minor cluster Beta with a defined C. auris clustering cut-off. The results were validated by an external C. auris strain and Principal Component and Linear Discriminant Analysis. The application of FT-IR technology had allowed to obtain important information about the phylogenetic relationships between the analysed strains, defining for the first time a “not WGS-based” clustering cut-off with a statistical-mathematical approach. FT-IR could represent a valid alternative to molecular methods for rapid and cost saving typing of C. auris strains with important clinical implications.

Community pharmacists are involved in antimicrobial stewardship through self-care advice and delivering medications for uncomplicated infections. Objectives This mixed methods study aimed to identify opportunities to enhance the role of community pharmacists in the management of patients with suspected or confirmed urinary tract infection (UTI). Methods Data collection was through a service user survey (n=51) and pharmacist surveys and semi-structured interviews before (16 interviews, 22 questionnaires) and after (15 interviews, 16 questionnaires) trialling UTI leaflets designed to be shared with patients. Data were analysed inductively using thematic analysis and descriptive tabulation of quantitative data. Results Twenty-five percent (n=13/51) of service users with urinary symptoms sought help from a pharmacist first and 65% (n=33/51) were comfortable discussing their urinary symptoms with a pharmacist in a private space. Community pharmacists were confident as the first professional contact for service users with uncomplicated UTI (n=13/16, 81%), but indicated the lack of a specific patient referral pathway (n=16/16, 100%), the need for additional funding and staff (n=10/16, 62%), and the importance of developing prescription options for pharmacists (5/16, 31%). All community pharmacists reported playing a daily role in controlling antimicrobial resistance by educating service users about viral and bacterial infections and promoting a healthy lifestyle. Enhancing their role will need greater integrated working with general practices and more prescribers based in community pharmacy. Conclusion This study suggests that community pharmacists could play a greater role in the management of uncomplicated UTI. The current reconfiguration of primary care in England with primary care networks and integrated care systems could provide a real opportunity for this collaborative working with potential learning for international initiatives.

This study investigates Autism Spectrum Disorders (ASD) in Greece, focusing on estimating prevalence and identifying regional disparities in children aged 4 to 7 years. Utilizing a quantitative, descriptive, and exploratory methodology, the research employed a structured questionnaire to gather extensive maternal and child health data. The sample consisted of 517 mothers of children diagnosed with ASD from all over Greece contributing to a nuanced understanding of ASD predictors. The study aims to elucidate the role of prenatal factors in the likelihood of an ASD diagnosis and their impact on the subsequent functionality of children with ASD. The study identified significant predictors of lower functionality in children with ASD, including higher maternal age, delayed ASD diagnosis, lower family income, and higher birth order. Prenatal health issues, such as vaginal bleeding and infections, also influenced functional outcomes. Notably, a family history of neurological or psychiatric conditions appeared protective. The regression model demonstrated robust predictive power, underscoring the complexity of genetic, environmental, and socioeconomic factors in ASD development. The findings advocate for early diagnosis and intervention, systematic screening, and addressing socioeconomic disparities to improve functional outcomes. The results support evidence-based service development and policy adjustments to enhance early identification, intervention, and rehabilitation for children with ASD. Establishing standardized case-recording procedures and an ASD register at national and regional levels is recommended for systematic monitoring and resource evaluation.

In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for the introduction and establishment of these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed by these emergent infections.

Urinary tract infections (UTIs) caused by Klebsiella pneumoniae can lead to severe clinical complications and even death. An alternative treatment option for infected patients is using bacteriophages (phages). In the present study, we isolated phage KP-1 from sewage water using K. pneumoniae as a host. Whole genome analysis indicated that the genome was a double-stranded linear 176,096-bp long DNA molecule with 41.8% GC content and did not contain virulence or antibiotic resistance genes. The inactivation potential of phage KP-1 was assessed in broth at an MOI of 1 and 10, and a maximum inactivation of 4.9 and 5.4 log CFU/mL was observed after 9 h, respectively. The MOI of 10 efficacy was also assessed in urine to evaluate the phage’s performance in an acidic environment. A maximum inactivation of 3.8 log CFU/mL was observed after 9 h. The results indicate that phage KP-1 could be used to control UTIs caused by K. pneumoniae; however, further studies using phage cocktails to broader the phage’s spectrum of activity and phages in micro- or nanocarriers to avoid the negative effect of the low pH of the urine on phage viability, are necessary.

Aims: The lack of information about the inter variability of the test results obtained by CLSI and EUCAST requires further clarifications to interpret antimicrobial susceptibility patterns better. This study aimed to compare the CLSI and EUCAST interpretations of the antimicrobial susceptibility test results of the ESBL–producing uropathogenic Escherichia coli and Klebsiella pneumonia strains. Methods: After obtaining 157 ESBL-producing E. coli and 95, ESBL-producing K. pneumonia isolates from the urine specimens of the patients, Kirby-Bauer’s disc diffusion method was used for conducting antimicrobial susceptibility test. The test procedures and the interpretation of the results were carried out according to the year 2017 versions of both of the two guidelines. For the statistical comparison of concordance between the two guidelines, the Kappa coefficients and the concordance rates were calculated. Results: The results were graded in the range from perfect to poor agreement. For E. coli, interpretations of the AST results revealed a moderate to perfect agreement between both methods. Weighted Kappa agreement scores in the range from 0.42 to 1. The agreement for AMC, TPZ30/6, ceftazidime 10, meropenem, and aztreonam was poor without any inconsistencies. For Klebsiella, the kappa agreement score was in the range from 0.25 to 1. It was incompatible with AMC, TPZ 30/6, ceftazidime 10, aztreonam; there was poor agreement for cefepime, amikacin and ertapenem. Conclusions: Our results showed agreement between the two guidelines for uropathogenic extended-spectrum ß-lactamase producing Escherichia coli and Klebsiella pneumoniae but also showed inconsistencies between two guidelines. Therefore, the results of our study contribute to the comparison of these guidelines for interpreting antibiotic susceptibilities.

Antimicrobial resistance (AMR), a serious global public health challenge, may have accelerated development during the COVID-19 pandemic because antibiotics were prescribed for COVID-19. This study aimed to assess antibiotics use before and during the pandemic and correlate the results with the rate of resistant microorganisms detected in hospitalized patients during the study period. This single centre study looked retrospectively at four years of data (2018–2021) from Royal Hospital, Muscat, Oman. The consumption rate was presented as the antibiotic consumption index, the ratio of defined daily dose (DDD) per 100 bed-days. Analyses were performed using the nonparametric test for trend across the study period. Correlation between antibiotic consumption indexes and the isolated microorganisms in the four-year study period was performed using Spearman’s rank correlation coefficient. We compared data from the pre-COVID-19 to the COVID-19 period. Though more patients were admitted pre-COVID-19 (132,828 versus 119,191 during COVID-19) more antibiotics were consumed during the pandemic; vancomycin and ceftriaxone had higher consumption during than before the pandemic (p-values 0.001 and 0.036, respectively). Vancomycin-resistant Enterococcus (VRE) and Candida. auris were detected more during the COVID-19 period with p-values of 0.026 and 0.004, respectively. Carbapenem-resistant Enterobacterales (CRE), vancomycin resistant Enterococcus spp., and C. auris were detected more often during the pandemic with p-values of 0.011, 0.002, and 0.03, respectively. Significant positive correlations between antibiotic consumption and drug resistant isolates were noted. This study confirms that the overuse of antibiotics triggers the development of bacterial resistance; our results emphasize the importance of antibiotic control.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are known for efficacy in managing blood sugar levels in type 2 diabetes and also improving cardiovascular and renal outcomes. However, increased risk of urogenital infections (UGIs) remains a significant concern in their safety profile. This study aimed to investigate the association between SGLT2i therapy and UGIs in a real-world clinical set up of a tertiary care centre in India. The key hypothesis was SGLT2i use is associated with incidence of UGIs while the secondary hypothesis included the relationship of the incidence of risk with the dose. Methods: This was a six-month prospective observational study, that enrolled 309 adults ≥18 years of age, who were newly prescribed SGLT2 inhibitors, particularly Dapagliflozin 5 mg and 10 mg from October 2023. The incidence of UGIs was assessed through patient interviews and medical records during the follow up from 2 weeks of initiation. UGIs were defined as clinical manifestations that resolved on SGLT2i discontinuation or appropriate treatment. Results: Of 309 initiators, 300 patients were followed up. 9 patients didn’t follow up in OPD. From these, 58 (19.3%)patients developed UGIs, comprising of 47 (15.6%) bacterial infections and 11 (3.6%) UGIs of fungal origin. The association was performed on basis of logistic regression analysis which revealed a statistically significant association of UGIs with the prescription of SGLT2i. Higher doses of SGLT2 inhibitors was observed to be associated with significantly increasing the risk of UGIs (p < 0.05). No significant risk factors such as body mass index (BMI), age, sex, HbA1c, or educational status were identified to have significant associations with UGI occurrence. Conclusion: This study highlights a clinically relevant association between SGLT2i use and urogenital infections.

Whereas there is an increasing number of scientific publications investigating the optimal anti-biotic treatment for diabetic foot infections, we are lacking corresponding data in the adult non-diabetic (postsurgical) foot infection population. We therefore established one of the largest single-center databases on this topic and retrospectively investigate failures of a combined sur-gical and antibiotic therapy for surgical site foot infections. Overall, 17.4% of the episodes expe-rienced any therapeutic failures; especially among the infected ankle prostheses. In contrast, neither the age, the biological sex, pathogens, the duration of post-debridement antibiotic treatment, the number of surgical debridement, or the use of negative-pressure wound care could alter the failure risk. In multivariate logistic regression analyses, the duration of postsur-gical antibiotic use was completely indifferent (as a continuous variable with odds ratio 1.0, 95% confidence interval 0.96-1.03), or when stratified into inter-tertiary groups. Our results poten-tially enable shorter applications of systemic antibiotics in favor of a better stewardship in the non-diabetic adult population. Consecutive prospective-randomized trials are under way to identify eligible patient populations for a potentially shorter durations in surgical site infections after elective foot and ankle surgery.

Positively charged polyelectrolytes hold significant potential as materials for creating antibacterial coatings. Water-soluble macromolecules can be easily deposited onto a treated surface through various techniques, forming a film that provides antimicrobial properties to the surface through electrostatic interactions with bacterial membranes. The structural and molecular weight characteristics of the polymers play a crucial role in the physical and mechanical properties of the coatings. In this study, we investigated the properties of branched polyethyleneimine (PEI) and linear polydiallyldimethylammonium chloride (PDADMAC) coatings with different molecular weights of polymer samples to determine their suitability as stable coatings with antibacterial properties against foodborne bacteria. Using thermogravimetric analysis, dynamometry, and dynamic light scattering, we examined the physicochemical and mechanical properties of the macromolecules in water solutions and in coatings. Microbiological study was conducted to analyze the biocidal activity of the polycations in solutions and on the surface of coatings. Our findings showed that the moisture saturation of the polycationic coatings did not significantly depend on the chemical nature of charged groups or the molecular weight or architecture of macromolecules. Moreover, biocidal activity was not found to depend on the molecular weights of PEI and PDADMAC. However, the lowering of the molecular weight of polymers resulted in the loss of cohesive forces in the coatings and to dramatically loss of the stability towards wash-off with water. The diffusion coefficient (D0) of macromolecules was identified as a key parameter for the wash-off mechanism. Films formed by molecules with D0 below 1×10-7 cm2/s demonstrated high resistance to wash-off procedures. We demonstrated that PEI and PDADMAC samples with high molecular weights showed high antimicrobial activity towards L. monocytogenes. Our results highlight the importance of macromolecule characteristics in the development of new biocidal coatings based on polycations.

A study was conducted to investigate the occurrence of Trypanosoma vivax infection in 72 Murrah buffaloes from Soure, a municipality located on Marajó Island. The aim of the research was to identify the presence of T. vivax in the buffalo population. Blood samples were collected, followed by DNA extraction and polymerase chain reaction (PCR) analysis using the primers TviCatL1 and DTO 155. T. vivax DNA was detected in one 36-month-old female with a body condition score of 2 (on a scale of 1 to 5), although the animal exhibited no clinical signs of infection. These findings suggest that T. vivax is not frequently circulating among the tested buffaloes, or that the animals may be in the chronic phase of infection, which is often characterized by low parasitemia levels. The identification of T. vivax in a clinically asymptomatic animal underscores the importance of using molecular diagnostics for early detection and monitoring of the parasite in buffalo herds, especially in regions where the presence of T. vivax may be underestimated. This study contributes to understanding the epidemiological status of T. vivax in buffaloes on Marajó Island, highlighting the need for ongoing surveillance in endemic areas.

Sanitisation has become a major component of everyday life, with emphasis on the hands and surfaces. The face remains unsanitised due to the lack of an acceptable sanitiser. The use of masks has been mandated to reduce the spread of the pathogens by covering the face, however, there remain issues with the use of personal protective equipment. The face remains a harbour for upper respiratory tract infections, with constant deposition of microbes. By reducing microbial load, the risk of both infection and severity are reduced. HOCl has proven antimicrobial and anti-inflammatory activity, including efficacy against SARS-CoV-2. A facial sanitiser, alongside hand sanitisers and masks, improves protection against SARS-CoV-2. The advantages of regular sanitising of the face and mask include reduced level of microbial contamination, risk of biofilm formation, and respiratory tract and skin infections. HOCl was reviewed as a face and mask sanitiser, concluding that it was an ideal product.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing some antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrating remarkable efficacy against planktonic cells and biofilms of MRSA, outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, was showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wound in mice. Together the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

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.

Background: Fungi are ubiquitous microorganisms that are easily dispersed through the air. In healthcare environments, indoor air can favor the spread of healthcare-associated fungal infections, compromising mainly immunocompromised hospitalized individuals. Thus, this study aimed to evaluate the indoor air contamination in healthcare environments, investigating mainly the presence of potentially pathogenic yeasts. Methods: Indoor air samples were collected from twelve healthcare environments (hospital and medical clinics). After the growth, isolation, and purification of the yeast colonies, the isolates were identified by polymerase chain reaction using species-specific primers for yeasts of the genus Candida and sequencing of D1/D2 domains of the large ribosomal subunit (LSU rRNA). Results: Fourteen yeast species were identified, including emerging pathogens. Species of clinical importance such as Candida parapsilosis, Candida orthopsilosis, Candida glabrata, Rhodotorula mucilaginosa, and Trichosporon mucoides were present. C. Parapsilosis was the most prevalent species, followed by Rodothorula mucilaginosa. Conclusions: The present study shows that potentially fungal pathogens were present in air samples from healthcare environments, proving the role of indoor air in spreading infections. Thus, monitoring air quality in healthcare environments is a fundamental approach in developing infection control measures, especially those related to invasive fungal infections.

Metchnikovellids (Microsporidia: Metchnikovellida) are poorly studied hyperparasitic micro-sporidia that live in gregarines inhabiting the intestines of marine invertebrates, mostly poly-chaetes. Our recent studies showed that the diversity of the metchnikovellids might be signifi-cantly higher than previously thought, even within a single host. Four species of metchnikovellids were found in the gregarines inhabiting the gut of the polychaete Pygospio elegans from littoral populations of the White and Barents Seas: the eugregarine Polyrhabdina pygospionis is the host for Metchnikovella incurvata and M. spiralis, while the archigregarine Selenidium pygospionis is the host for M. dogieli and M. dobrovolskiji. The most common species in the White Sea is M. in-curvata, while M. dobrovolskiji prevails in the Barents Sea. The gregarines within a single worm could be infected with different metchnikovellid species. However, co-infection of one and the same gregarine with several species of metchnikovellids has never been observed. The difference in prevalence and intensity of metchnikovellid invasion apparently depends on the features of the life cycle and on the development strategies of individual species.

The negative effect of COVID-19 pandemic has reach world economy due to absence from work for SARS-CoV-2 infection in workers, among other things. However, some economic areas are essential to society and people must continue working outside home, to support economic reactivation; their serological profile could be different from global population. Cross-sectional study. Workers from health, construction, public transportation, public force, bike delivery messengers, independent or informal commerce areas, and residents of Bucaramanga or its metropolitan area were invited to participate. All participants self-completed a virtual survey and a blood test was taken to assess IgG and IgM with ARC COV2 test. Seroprevalence was estimated considering a complex survey design, correcting for finite population effect and adjusting for test performance. 7.045 workers were enrolled; 59.9% were women, most were residents of Bucaramanga and working in health occupations. Global adjusted seroprevalence was 19.5% (IC95% 18.6 - 20.4), being higher for Girón [27.9% (CI95% 24.5 - 31.30]). Workers with multiple contact with people during working hours or using public transportation to go to work had higher frequency of seropositivity for SARS-CoV-2. Seroprevalence among workers living in these four municipalities from the Colombian northeast area is still low.

Background: Detection of small proportion of serious bacterial infections (SBI) with potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (i) infected patients with no suspicion of SBI (n = 75); (ii) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC) and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without - the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86%. (95% CI 77–93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.

Abstract: Background: Our goal was to evaluate whether wearing personal protective equipment (PPE) such as an N95, or a surgical mask during the (COVID-19) pandemic had really reduced the cases of influenza in the state of Wisconsin. Methods: Respiratory Virus Surveillance Reports from the Wisconsin Department of Health Services (DHS) and the Centers for Disease Control and Prevention (CDC) were used to compare the rates of Influenza during the seasons of 2018-2019 and 2020-2021. Results: The number of cases, hospitalizations, and mortality rates with Influenza had significantly decreased in the 2020-2021 season compared to the Influenza season of 2018-2019. Discussion: Reducing the burden of influenza illnesses, hospitalizations, and deaths on the health care system is imperative. Wearing masks should be addressed for the most vulnerable.

The severe respiratory distress syndrome (SRDS) has been a significant clinical issue in modern respiratory medicine. Its role in COVID-19 pandemic is not well defined. Outside-the-hospital SRDS is usually community-acquired septic pneumonia; however, in-hospitals incidences are complicated by co-infections. While SRDS is genetically selected in European and African origins, these are not clear in Middle East, particularly in COVID-19 backgrounds. There is a severe paucity in high quality data on correlations between COVID-19, ARDS, co-infectome, and patient demographics. We have conducted a comprehensive investigation on 298 patients for associations of SRDS, coinfections, and patient demographics on COVID-19 patients’ outcomes. Of these, 9.4% (n=28) had SRDS, and the rest (90.6%) had not. 54% of those with SRDS died while 84% survived; SRDS fatality was highly significant (Chi-square test P-value = 0.00000246). Irrespective of gender, the age of patients was significantly associated with SRDS (72.9 +/-8.9) compared to those without it (56.2 +/-15.1). However, there was no significant difference neither in the age of admitted patients before COVID-19 (58.5 +/-15.3) and during COVID-19 (57.2 +/-15.5) nor in the gender and COVID-19 fatality (Fisher Exact test 2-sided 1.000, 1-sided .546) ruling out that SRDS age-specificity were selected by virus susceptibility. A 100% of SRDS patients without bacterial co-infections survived while only 25% of those with co- infectome did not; this association was highly significant (P value= 0.00041). Co-infections alone without underlying SRDS was also associated with high fatality among patients (P value= 0.00000000076). Almost all COVID-19 patients without co-infectome (99.2%) survived while 28% of those with bacterial co-infection died. The major bacterial pathogens that potentially predisposed to SRDS, were Acinetobacter baumannii, and Escherichia coli either alone or in a mixed infection with Klebsiella pneumoniae were predominant species identified during SRDS attack. Thus, Gram-negative co-infectome potentially induced fatal SRDS aggravating COVID-19 outcome. These findings have significant clinical implications in specific differential diagnosis of SRDS syndromes for subsequent empiric therapy and patient management strategies. Future vertical investigation for similar mechanisms of cytokine-induced SRDS by Gram negative pathogens is imperative since hypervirulent strains are rapidly circulating in the region. The study is limited by a single center study confined to Ha’il hospitals; large scale investigation in major national hospitals would gain more insights.

Bovine respiratory disease is still a major concern in feedlots and has major economic impact. Another consequence of respiratory infections is the use of antimicrobial molecules to control bacterial pathogens. This can participate to the emergence and shedding of antimicrobial re-sistance that can threaten animal as well as human health. Appeasing pheromones with their capacity to reduce stress and thus their ability to preserve the functions of the immune system have been proposed to reduce the use of antimicrobial substances. In the current report we as-sessed the effect of appeasing pheromone administration on bovine health and performance during the fattening period. Zootechnical and health parameters as well as whole blood immune transcript expressions were measured over weeks in young bulls to determine the effect of the pheromone. We observed a reduction of clinical signs at day 30 in young bulls who received the pheromone and a higher expression of interleukin 8 transcripts in this group than in the control group. Our results are in line with previous reports in bovine and other mammals and ask for further studies to shed more light on the beneficial impact of appeasing pheromones and to de-cipher their exact mechanisms of action.

Approaches to identification of metabolites have progressed from early biochemical pathway evaluation to modern high dimensional metabolomics which is a powerful tool to identify and characterize biomarkers of health and disease. While traditionally considered relevant in the context of classic metabolic diseases, immunometabolism has emerged as an important area of study as leukocytes generate key metabolites important to innate and adaptive immunity. Herein we discuss the metabolomic signatures and pathways perturbed during infection as well as vaccination. For example, changes in lipid and amino acid pathways (e.g., tryptophan, serine, and threonine) have been noted during infection while carbohydrate and bile acid pathways have shift upon vaccination. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying host response to infection and vaccination, and its integration with other systems biology platforms will add further impact to our studies of health and disease.

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.

Background: Infections caused by S. aureus strains encoding Panton-Valentine leukocidin (PVL-SA) have become increasingly relevant in community settings and can cause severe conditions in pediatric populations. We present a pediatric case of invasive disease caused by PVL-SA and provide a literature review of severe manifestations caused by these strains in children. Methods: A PubMed search (February 2024) evidenced studies that included relevant clinical outcomes, diagnostics, and treatments, excluding cases of asymptomatic infection or adult populations. Logistical multivariate analysis was used to find predictors of the need for intensive care. Results: A 10-year-old boy came to the attention of our Pediatric Infectious Diseases Unit with fever, chest pain, and tachypnea. A rapid worsening of his clinical conditions was observed, with the development of necrotizing pneumonia, osteomyelitis, deep vein thrombosis (DVT), and multiple abscesses. Blood cultures confirmed the presence of PVL-producing methicillin-resistant S. aureus (MRSA). The initial treatment included linezolid and ceftaroline and was later adjusted to clindamycin, daptomycin, and fosfomycin, with clinical improvement. Discussion: Our review collected 36 articles, including 156 pediatric cases of severe PVL-SA infection. Bacteremia was present in 49% of cases, lung infection in 47%, and osteomyelitis in 37%. The presence of pulmonary localization was predictive of the need for intensive care, O.R. 25.35 (7.46 - 86.09; p&lt;0.001). Anti-toxin molecules were used in about half the cases where information on treatment was reported. Our report highlights the capacity of PVL-SA to cause life-threatening complications in children, while also discussing the full range of its clinical spectrum and the most effective therapeutic approaches.

Since association between myocardial infarction (MI) and respiratory infections has been described for influenza-viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. First data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss: pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; what emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) is the most common cause of urinary tract infections (UTIs). They are often multidrug-resistant (MDR), making them challenging to treat. Additionally, virulence mechanisms as biofilm formation are associated with persistent UTIs. Aims: To reveal a possible association between patients’ risk factors and UTIs caused by MDR or biofilm-forming ExPECs and characterize ExPECs causing asymptomatic bacteriuria, community- (CA), or hospital-acquired (HA) UTIs in hospitalized patients in Brazil. Methods: Bacterial DNA was extracted from the urine of 63 hospitalized patients and sequenced using short-read sequencing. Antibiotic susceptibility was evaluated using VITEK-2, and the biofilm-forming, adhesion, and invasion abilities were quantitatively assessed. Results: Antibiotic resistance rates were high, and the majority of UTIs were complicated CA-UTIs. Most MDR- and ESBL-producing E. coli isolates belonged to high-risk lineages and were associated with UTIs in patients with comorbidities and over 60 years of age. The mortality rate of patients infected with MDR-isolates was higher than of those infected with non-MDR isolates. Most isolates were biofilm-forming, but no association with patients’ risk factors was found. Conclusions: Complicated UTIs caused by MDR- and biofilm-forming bacteria are frequently found in hospitalized patients in Brazil suffering from a UTI and are associated with high-risk lineages.

Understanding microbial composition in upper respiratory infections (URIs) is critical for effective diagnosis and treatment. Precision Metagenomic next-generation sequencing p(mNGS) can provide a comprehensive yet clinically relevant profile of respiratory infection. The hybridization capture-based targeted sequencing generated a precision metagenomics profile of 29 patients with acute URIs. Nasopharyngeal samples were collected from the subjects suspected of respiratory infection, and p(mNGS) was performed using the Illumina®/IDbyDNA Respiratory Pathogen ID/AMR Panel (RPIP). The dataset obtained from the mNGS analysis contains a wealth of information on the composition of acute URI microbiota, including the relative abundance of known pathogens and potential clinical implications. The dataset represents a valuable resource for future research endeavors in respiratory medicine, infectious disease epidemiology, and therapeutic interventions. In addition, the dataset offers significant potential for reuse and integration with other omics datasets. The comprehensive nature of the mNGS data allows the exploration of associations between the respiratory microbiota and host factors such as clinical outcomes, immune responses, or genetic predisposition. Combining this dataset with other relevant datasets, such as transcriptomics or metabolomics, could provide a deeper understanding of the complex interactions between the microbiota and the host in acute URIs.

We conducted many model simulations to understand the causes of the damages of coronavirus to lung tissues and constructed a diagram showing viral development, immune response and damage accumulation curves. We found that main causes are (1) the phase lag between the viral reproduction process and a belayed immune response, (2) the direct viral damages and massive collateral damages which are mainly caused by belated immune responses, and (3) further tissue damages triggered by accumulated wastes in lungs. We deduced from those causes that the key strategies for preventing lung damages include avoiding direct lung infection, altering host-virus interactions, promoting immune responses, diluting virus concentrations in lung tissues by promoting viral migration to the rest of the body, maintaining waste removal balance, protecting heart function and renal function, avoiding other infections, reducing allergic reactions and other inflammation, etc. We finally discussed how to use dietary, medical, emotional, lifestyle, environmental, mechanical factors, etc. to alter disease outcomes. We show why true benefits of those factors cannot be determined by randomized controlled trials, and why the multiple-factor optimization approach can be highly effective by examining organ usable capacity in the cause of death. This treatment protocol using water, air, salt, sound, temperature, emotion, exercise, etc. can be the most powerful cures for viral and non-viral lung infections because they do not depend on molecular specificity and are freely available to anyone.

Antibiotic-loaded bone cement (ALBC) plays a pivotal role in infection prevention and treatment related to musculoskeletal surgery. The release efficacy of antibiotics from ALBC is closely tied to its surface area, yet little is known about the effective release depth. To investigate the relationship between surface area, volume, and antibiotic elution, spheric ALBC specimens with consistent outer diameters but different internal metal sphere diameters were prepared. Two vancomycin doses were utilized in ALBC specimens with an outer diameter of 35 mm: high (4 g) and low (1 g). Each dosage group included five specimens containing embedded metal spheres with diameters of 15, 25, 29, 32, or 33 mm. The resulting shell-like ALBC specimens had thicknesses of 10 mm, 5 mm, 3 mm, 1.5 mm, or 1 mm, respectively. The specimens were immersed in sterile phosphate buffer solution, and antibiotic elution was measured at designated sampling times (1, 3, 6, 10, 24, 48, 72, and 168 hours). Methylene blue was employed to visualize penetration depth. Vancomycin elution did not display statistically significant differences between high- and low-dose groups. In both groups, specimens with 1 mm thickness exhibited a higher vancomycin release efficiency (high-dose group: 18560±5474 μg, 6.7%; low-dose group: 2017±419 μg, 2.6%), decreasing sharply in thicker ALBC specimens. Methylene blue penetration depth showed no apparent difference between high-dose and low-dose groups. ALBC thickness does not significantly impact antibiotic elution, while surface area and antibiotic dose exert notable effects. These in vitro findings offer potential applications in clinical treatments for musculoskeletal infections.

Current routine diagnosis of a life-threatening central nervous system (CNS) infections is based on commercial multiplex real-time PCR (RT-PCR) and in-vitro culture investigations, targeting a limited number of pathogens, which requires implementation of a universal diagnosis at the point-of-care laboratory. This study aimed to document a case of non-routinely diagnosed meningoencephalitis in a twelve-year-old patient in Niger Republic. Metagenomic-based on real-time sequencing was applied directly on DNA/RNA extracted from 50 µL leftover CSF sample using Oxford Nanopore MinION, to detect all residual microorganisms non-routinely targeted by RT-PCR panel. In parallel, 1 ng DNA/RNA was used for paired-end Illumina library preparation to confirm the MinION results. Real-time analysis of MinION data detected 132 WU Polyomavirus specific reads after one-hour run. Blast nucleotide of the fasta sequences after assembly of both Illumina and Nanopore reads against NCBI GenBank database identified WU polyomavirus strain W33 (GenBank accession no: GU296367.1). Haemophilus influenzae specific reads (667 reads) were detected which explains the possible co-infection bacteria-DNA virus in this case. Blastn after total reads assembly identified H. influenzae strain PittGG (GenBank accession n° CP000672), belonging to the non-typable H. influenzae genotype by muti-locus-sequence-typing analysis. Furthermore, Achromobacter xylosoxidans (599 reads) were detected in this patient. Based on these findings, we classified this case as polymicrobial meningoencephalitis. Using RT-mNGS, the pathogen genome could be detected directly from a clinical sample, with no specific target. This technique seems to be an adapted method to diagnose non-routinely detectable pathogens, as well as their genotype and antimicrobial susceptibility in reduced time.

Urinary tract infections in kidney transplant patients are a real challenge. We conducted a retrospective observational study, enrolling all kidney transplant patients hospitalized for urinary tract infection (UTI), with the objective to evaluate the epidemiology, clinical sta-tus, therapeutic management, and clinical outcome of kidney transplant patients hospi-talized for urinary tract infection in a university hospital. From our real-life experience, infection with multidrug-resistant germs was confirmed as a risk factor for the severe evolution of the infection and at the same time the re-evaluation of immunosuppressive therapy could be an important therapeutic strategy in the course of infection. Prompt ini-tiation of empiric antibiotic therapy upon initiation of microbiological investigations could potentially reduce the risk of severe infection progression.

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.

Background: Chikungunya virus (CHIKV) diagnosis have become a challenge for primary care physicians in areas where zika virus and/or dengue virus are present. Case definitions for the three arboviral infections are overlapping. Methods: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. Results: 295 patients with confirmed CHIKV infection were included. A screening tool was made using symmetric arthritis (4 points), fatigue (3 points), rash (2 points) and ankle joint pain (1 point). The ROC curve identified a cut-off value and a score ≥ 5.5 was considered positive to identify CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. Conclusion: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune mediated rheumatic disesases (IMRD) patients are scarce. This study describes breakthrough COVID-19 among IMRD patients participating of SAFER-study, a Brazilian multicentric cohort evaluating safety, effectiveness and immunogenicity of SARS-Cov-2 vaccines in autoimmune diseases. Descriptive analysis and a binary logistic regression model, to evaluate predictors of COVID-19-related hospitalization, were performed. P-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with mean (SD) age 40.23 (13.19) years. Patients received 2 (19%), 3 (70%) or 4 (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n=150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n=112) was with BNT162b2 (40%) or ChAdOx1 (26%). COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84, CI: 1.9-18.5, p=0.002) and treatment with corticosteroids (OR: 2.94, CI: 1.02-8.49, p=0.0043) associated with higher odds of hospitalization, while the increasing number of vaccine doses was protective (OR: 0.37, CI: 0.15-0.9, p=0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favour of booster vaccination in IMRD patients.

Skin wounds and their infections by antibiotic resistant bacteria (ARB)are very common in small animals, posing the risk of acquiring ARB by pet owners or antibiotic resistance gene (ARG) transfer to the owners’ microbiota. The aim of this study was to identify the most common pathogens infecting wounds of companion animals, assess their antibiotic resistance and determine the ARGs using culture-based, molecular and proteomic methods. A total of 136 bacterial strains were isolated from wound swabs. Their species was identified using chromogenic media, followed by MALDI-TOF spectrometry. Disk diffusion was used to test the antibiotic resistance and twelve ARGs were detected using PCRs. The dominant species included Staphylococcus pseudintermedius (9.56%), E. coli and E. faecalis (both n=11, 8.09%). Enterobacterales were mostly resistant to amoxicillin/clavulanic acid (68.3% strains), all Pseudomonas were resistant to ceftazidime, piperacillin/tazobactam, imipenem and tylosin, Acinetobacter was mostly resistant to tylosin (55.5%), all Enterococcus were resistant to imipenem, 39.2% of Staphylococci were resistant to clindamycin. Among ARGs, strA (streptomycin resistance), sul3 (sulfonamide resistance) and blaTEM, an ESBL determinant, were the most frequent. The risk of ARB and ARD transfer between animals and humans causes the need to search for new antimicrobial therapies in the future veterinary medicine.

Protozoa and helminths are responsible for several intestinal parasite infections (IPIs). Generally helminth infections are very unsafe but scarcely reported in high-income countries, while protozoa and helminth co-infections are usually reported in children living in inadequate hygienic-sanitary conditions and in rural areas. However, the impact of growing globalization, intense travelling, international adoptions and high levels of immigrants and refugees has significantly incremented the incidence of oro-faecal parasitosis in non endemic areas. Although most IPs clear without treatment when population, even children, emigrate from endemic to different geographical areas, some IPIs such as strongyloidiasis may persist for decades as subclinical infections or as low-grade disease with nonspecific clinical manifestations, unless to reappear under impairment conditions. Herein we report an unusual case of Giardia lamblia and Trichuris spp. chronic asymptomatic co-infection in a healthy adopted Romanian child, living in a Central Italy rural area, and an hidden case of Strongyloides stercoralis in an adopted Burundian child, resident in South Italy, long misdiagnosed as a recurrent undefined dermatitis. Our report suggests the need to review primary care practitioner guidelines and children's hospital procedures for appropriate IPIs screening and follow-up, hence providing new screening and prevention strategies, in agreement with international guidelines.

Introduction: Tuberculosis (TB) is one of the most prevalent respiratory diseases in the world. In 2020 there were at least 9.9 million new infections, with 1.5 million deaths. Approximately 10% of people infected with Mycobacterium tuberculosis (LTBI) develop the disease during the first 2 to 5 years after infection. Currently in South America, the diagnosis of LTBI continues to be per-formed through the Mantoux tuberculin skin test (TST). Objective: The objective of our study was to compare the sensitivity of a new immunofluorescence IGRA test against a widely available IGRA kit on the market. Material and method: Close contact to infectious patients with TB, or HIV patients or immunocompromised for another cause were recruited. Two interferon gamma release assay (IGRA) diagnostic kits were used and compared with TST. Results: 76 patients were recruited. 93.42% were Chilean nationality, 98.68% of the patients did not have immunosuppres-sion. The sensitivity of the new technique was 88.89% and specificity 92.50% in the study popula-tion compared to the IGRA previously used. In the subgroup older than 36 years, the sensitivity was 95.65% and the specificity 89.47%. Conclusion: IGRA techniques are a new resource in clini-cal laboratories to be able to make an accurate diagnosis in LTBI in the region of the Americas. In our population, the greatest benefit of this new IGRA would be observed in people over 36 years of age, where the sensitivity of the technique was like that of the currently available test.

Respiratory tract infections (RTIs) are one of the main causes of hospitalization and mortality causing substantial economic burden to healthcare systems globally. As opposed to the previous belief that respiratory infections are caused by a single pathogen, studies have shown that most RTIs are a result of a combination of bacterial and/or viral pathogens infecting the host. The clinical manifestation of RTIs is very similar (i.e., syndrome), often showing Influenza-like illness (ILI) symptoms. While COVID-19 has dominated ILI over the past few years, there are many other pathogens that are responsible for ILI. In addition, it is not uncommon to have coinfections with multiple pathogens in patients presenting with ILI and that such coinfections can even exacerbate the disease severity of RTIs. Therefore, an insight into coinfections can help with accurate disease prognosis, patient care management and outcomes. The goal of this study was to identify the different organisms in symptomatic patients presenting with ILI.

Sexually transmitted infections encompass considerable effects on human sexual and reproductive health. Its presence is ubiquitous despite decades of prevention and management. The present study has been conducted to provide an insightful bibliometric analysis of syphilis based on the Scopus repository. Therefore, given the dearth of a consolidated bibliometric analysis on Syphilis, this investigation aimed to compile the literature of the last century (1921-2021) to gain insight into the publications pertinent to the burden, diagnosis, treatment, and management of Syphilis. In this study, we have provided the year-wise, and subject-wise publications, type of articles, country, funding organizations, institutions, citations, and H-index. The data obtained from the Scopus database was exported to CSV file format and then converted to Microsoft Excel version for analysis to curtail the chances of error in the information. It has been evidenced that the USA possesses the highest track of proven publications. Therefore, this study considerably contributes to the future leaders, researchers & specialists/ clinicians of the domain

In the context of the COVID-19 pandemic, thousands of healthcare workers (HCWs) infected with COVID-19 have lost their lives worldwide. At the early stage of the epidemic, when COVID-19 was still not considered as a pandemic, a large number of Chinese HCWs were infected. Officials reported that more than 3,000 HCWs in Hubei contracted the virus at the early stage of the outbreak due to limited knowledge of the virus. Following reports of overloaded local hospitals, more than 42,000 medical staff, including those from the military, were dispatched to Hubei from across the country. At the peak of the fight, one in 10 intensive care medics in China were working in Wuhan. During fighting against COVID-19 in China, although a large number of HCWs were infected by SARS-CoV-2 in the early stages of the epidemic, the timely adoption of measures indicated that, a faster rate of diagnosis could be achieved, patients were isolated in-time, HCWs’ safety was prioritized, training on basic protective knowledge and unified management of HCWs was strengthened, and effective protective measures were implemented. This resulted in the accomplishment of zero SARS-CoV-2 infection among the 42,632 members of the national medical teams sent to Hubei, and the number of COVID-19 cases among HCWs in local hospitals also significantly decreased, thereby indicating that hospital-acquired infections of SARS-CoV-2 among HCWs are fully preventable.

Cycle threshold (Ct) values of SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests are associated with infectivity and viral load, and they could be an aid to forecast the evolution of SARS-CoV-2 outbreaks. The objective was to know the Ct values related to the incidence and reinfection of SARS-CoV-2 in successive outbreaks, which took place in nursing homes in Castellon (Spain) during 2020-2022, and to test its usefulness as an instrument of epidemic surveillance in nursing homes. Poisson regression and multinomial logistic regression were used in the analysis. We studied four nursing home SARS-CoV-2 outbreaks, and the average infection rate, reinfection rate, and case fatality were 72.7%, 19.9%, and 5.5%, respectively; 98.9% of residents were vaccinated with three doses of a mRNA SARS-CoV-2 vaccine. Ct values for first infections and reinfections were 27.1±6.6 and 31.9±5.4 (p = 0.000). Considering Ct values ≥30 versus

Respiratory viral infections, including influenza, respiratory syncytial virus (RSV), and, more recently, the coronavirus disease 2019 (COVID-19) pandemic, continue to pose significant global health threats. Conventional treatments for these infections often face challenges such as limited efficacy, the emergence of drug-resistant strains, and the requirement for frequent administration. In recent years, nanobodies have emerged as a promising class of therapeutic agents due to their unique properties, including small size, high stability, and specific binding capabilities. This mini-review article focuses on the application of nanobodies as spray and aerosol particles for the treatment of respiratory viral infections. Furthermore, we highlight the remarkable efficacy of nanobodies in preclinical and clinical studies against respiratory viruses, including their ability to neutralize viral particles, inhibit viral replication, and modulate the host immune response. We discuss the potential advantages of using nanobodies as inhalable formulations, including their improved delivery to the respiratory tract, enhanced stability in aerosol form, and reduced systemic side effects. Additionally, we explore the various strategies employed to engineer nanobodies for optimal aerosol delivery, such as conjugation to carrier particles or formulation as dry powders. We also examine the potential challenges and limitations associated with the development of nanobody-based aerosol therapies, including production scalability, cost-effectiveness, and regulatory considerations.

In recent years, antimicrobial resistance in many human pathogens has become a serious health concern. Since infections with resistant pathogens cannot be treated with traditional antimicro-bial drugs, new strategies are necessary to fight bacterial infections. Hybrid nano-systems may provide a solution to this problem, by combining multiple mechanisms for killing bacteria to synergistically increase the effectiveness of the antimicrobial treatment. In this review, we high-light recent advances in the development of hybrid nano-systems for the treatment of bacterial infections. We discuss the use of hybrid nano-systems for combinational therapy, focusing on various triggering mechanisms for drug release and the development of biomimetic nanomateri-als. We also examine inherently antimicrobial nano-systems and their uses in preventing infec-tions due to wounds and medical implants. This review summarizes recent advances and pro-vides insight into the future development of antimicrobial treatments using hybrid nanomateri-als.

Infectious disease is the leading cause of mortality in children under five. This study has investigated environmental factors related to the morbidity of acute respiratory infections (ARIs), diarrhea, and growth using geographical information systems (GIS) technology. Anthropometric, address and disease prevalence data were collected through the SEEM study in Matiari, Pakistan. Publicly available map data was used to compile coordinates of healthcare facilities. A Pearson correlation coefficient (r) was used to calculate the correlation between distance from healthcare facilities and participant growth and morbidity. Other continuous variables influencing these outcomes were analyzed using a random forest regression model. In this study of 416 children, we found participants living closer to secondary hospitals had lower prevalence of ARI (r=0.154, p&lt;0.010) and diarrhea (r=0.228, p&lt;0.001) as well as participants living closer to Maternal Health Centers (MHCs): ARI (r=0.185, p&lt;0.002) and diarrhea (r=0.223, p&lt;0.001) compared to those living near primary facilities. Our random forest model showed distance to have high variable importance in the context of disease prevalence. Our results indicated that participants closer to more basic healthcare facilities reported a higher prevalence of both diarrhea and ARI than those near more urban facilities, highlighting potential public policy gaps in ameliorating rural health.

Microorganisms belonging to the Lactobacillus genus are naturally associated or deliberately added to fermented food products and are widely used in probiotic food additives and supplements. Moreover these bacteria normally colonize mouth, gastrointestinal (GI) tract and female genitourinary tract of humans. They exert multiple beneficial effects and are regarded as safe microorganisms. However, infections caused by lactobacilli, mainly endocarditis, bacteremia and pleuropneumonia occasionally occur. The relevance of Lactobacillus spp. as opportunistic pathogens in humans and related risk factors and predisposing conditions are illustrated in this review article with more emphasis on the species L. rhamnosus, that has been more often involved in infection cases. The methods used to identify this species in clinical samples, to distinguish strains and to evaluate traits that can be associated to pathogenicity, as well as future perspectives for improving the identification of potentially pathogenic strains are outlined.

Carbapenem antibiotics are the drug of choice for treating multidrug-resistant bacterial infections. Metallo-beta-lactamases (MBLs) are carbapenemase capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, a need to assess the frequency and phenotypic resistance phenomena of two MBL genes in diarrheal and urinary tract infections (UTIs). Samples were collected through a cross-sectional study, with MBLs genes detected via PCR. Two hundred twenty eight diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively.  Total 142 UTI pathogens were obtained from 150 urine samples, with Klebsiella spp. (39%) and Escherichia coli (24%) are the major pathogens. Phenotypic resistance to amoxycillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively.  Twenty four diarrheal isolates carried either blaNDM-1 or blaVIM genes; the overall MBL gene prevalence was 10.5%. Thirty six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes.  MBL genes exhibited a strong association with phenotypic carbapenem and other beta-lactam antibiotic resistance. Resistance to carbapenems requires active surveillance and stewardship.

The resurgence of mpox, particularly in regions where the virus was previously non-endemic, has reignited interest in the cross-protective potential of smallpox antibodies. Given the genetic similarity between the mpox virus and variola virus (the causative agent of smallpox), antibodies generated against smallpox may offer a degree of protection against mpox. This study investigates the presence of smallpox and mpox antibodies in human immunoglobulin preparations containing IgG against both mpox virus and vaccinia virus using ELISA techniques. The implications of these findings for post-exposure prophylaxis (PEP) are discussed in light of the recent mpox outbreaks in Africa, as reported by the World Health Organization (WHO). Current data suggest that smallpox vaccination, even decades after eradication, may confer substantial protection against mpox, thereby serving as a critical tool in managing emerging outbreaks. Further the presence of mpox antibodies in immunoglobulin preparations was also significant. These findings strongly suggest the potential use of intravenous immunoglobulins preparation as possible therapeutic strategy. Particularly it also underscores the need for further research into the development of targeted post-exposure prophylaxis strategies that leverage the cross-reactivity of orthopoxvirus antibodies.

Hospital-acquired infections (HAIs) contribute to increased length of hospital stay, high mortality and higher health-care costs. Prevention and control of HAIs is a critical public health concern. We conducted a cross-sectional survey of 213 hospital health-care workers in Qassim, Saudi Arabia. We assessed Knowledge, Attitude and Practice (KAP) of standard infection control precautions using a structured questionnaire. Predictors of KAP were investigated using multivaraible logistic regression analyses and independent sample t tests. Prevalence of good (≥80% correct response) knowledge, attitude and practice were 67.6%, 61.5% and 73.2%, respectively. Predictors of good knowledge included age over 34 years (adjusted odds ratio: 30.5, p<0.001), and receiving training (13.3, p<0.001). Predictor of positive attitude was having >6 years of experience (5.5, p<0.001). While, the predictors of good practice were having >6 years of experience (2.9, p<0.01), previous exposure to HAIs (2.5, p<0.05) and training (3.5, p<0.01). However, being female (0.22, p<0.001) and older (>34 years) (0.34, p<0.01) were negatively associated with knowledge. Results indicate that older academic programs might not have adequately covered infection crontrol. Arranging training for HCWs might be useful in improving their knowledge of standard infection control precautions and is also expected to facilitate positive attitude and practice.

We present here a case of complex uterine anomaly – Obstructed HemiVagina with Ipsilateral Renal Agenesis (OHVIRA), also known as Herlyn-Werner-Wunderlich syndrome in a 13-year-old girl with the history of recurrent urinary tract infections (rUTI). In emergency room, trans-abdominal sonography revealed ovarian cyst and renal agenesis, without any suspicion of vaginal obstruction. This led to delay in the diagnosis of this uncommon anomaly. Finally, MRI findings confirmed the presence of OHVIRA syndrome. As the congenital anomalies of kidney and urinary tract (CAKUT) are in almost one third of cases associated with genital malformations, urologist should carefully search for patients with rUTI. The patient underwent simultaneous laparoscopy and vaginoscopy, what was in our opinion the most appropriate therapeutic decision. In this article we are also going to discuss the role of laparoscopy in the management of OHVIRA syndrome as well as other surgical techniques described in the literature.

This study examined the efficiency of a combined diagnostic approach in which bioamplification of Arizona 861 S1 citron was integrated with RT‒PCR to detect Citrus tristeza virus (CTV) and Hop Stunt Viroid (HSVd) in Citrus plants. The capacity of the combined method to diagnose mixed infections of CTV and HSVd, along with early single infections of both pathogens, was assessed by evaluating the incubation periods and differential detection capabilities between the combined and direct methods. The bioamplification method exhibited high sensitivity (100%) and specificity (100%) for CTV, enabling early detection even in patients with low-titer infections compared to direct RT‒PCR. However, for HSVd, the combined method achieved 50% sensitivity in early infections, highlighting the need for additional replicates to enhance diagnostic reliability. The relative concentrations of pathogens in mixed and simple infections were evaluated; the analysis revealed no significant differences, suggesting minimal interference between CTV and HSVd. This approach allows early detection of CTV but requires further refinement for HSVd diagnosis. These findings underscore the complementary roles of the cost-effectiveness of direct RT‒PCR and the sensitivity of the combined method in implementing effective disease control strategies in citrus crops.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

Fever remains an integral part of the acute clinical diseases management, esp. viral, for which effective therapeutics remain desired. However, the presence of often confusing fever reduction recommendations for COVID-19 in the public domain during the pandemic, as late as 28 April 2021, seems to suggest the reduction of any ‘uncomfortable’ fever ranging from 37.8 - 39oC, as opposed to WHO fever reduction guidelines (≥39oC), urgently need attention. The confusion could percolate down into different agencies who look up to these agencies for guidance in framing their own, denying the benefits of fever to populations, and effectively undo whatever successive WHO’s guidelines have achieved in the last two decades. The existence of conflicting guidelines in public domains which are open to interpretations has consequences to public health and the healthcare infrastructure, on implementation. For controlling acute infectious diseases, esp. viral, the fever remains the most important enabler. Historically, our chief obstacles to harnessing the benefits of fever in acute clinical diseases with limited therapeutics had been: a) widespread myths about ‘fevers’ arising from a general misunderstanding of basic facts; b) presence of confusing guidelines by different agencies which are open to alternate interpretation. The article attempts to briefly indicate the benefits of fever in disease resolution, dispel myths, underline vagueness in illustrative national guidelines and the need to align them with evidence-based WHO guidelines, as it has the potential to perpetuate myths/confusion in masses leading to adverse impact on disease management – more morbidity and mortality from diseases including COVID-19.

Based upon 30-years of research by the author a new approach to hospital bed planning and international benchmarking is proposed. The number of hospital beds per 1000 population is commonly used to compare international bed numbers. This method is flawed because it does not consider population age structure or the effect of nearness-to-death on hospital utilization. Deaths are also serving as a proxy for wider bed demand arising from undetected outbreaks of 3000 species of human pathogens. To remedy this problem a new approach to bed modelling has been developed which plots beds per 1000 deaths against deaths per 1000 population. Lines of equivalence can be drawn on the plot to delineate countries with higher or lower bed supply. This method is extended to attempt to define the optimum region for bed supply in an effective health care system. England is used as an example of a health system descending into operational chaos due to too few beds and manpower. The former Soviet bloc countries represent a health system overly dependent on hospital beds. Several countries also show evidence for over-utilization of hospital beds. The new method is used to define a potential range for bed supply and manpower where the current most effective health systems currently reside. The method is applied to total curative beds, medical beds, psychiatric beds, critical care, geriatric care, etc., and can also be used to compare different types of healthcare staff, i.e., nurses, physicians, surgeons. Issues surrounding the optimum hospital size and the optimum average occupancy will also be discussed. The role of poor policy in the English NHS is used to show how the NHS has been led into a bed crisis. The method is also extended beyond international benchmarking to illustrate how it can be applied at a local or regional level in the process of long-term bed planning. Issues regarding the volatility in hospital admissions are also addressed to explain the need for surge capacity and why an adequate average bed occupancy margin is required for an optimally functioning hospital.

Background: Vaccination is one of the most effective life-saving medical interventions, and the introduction of SARS-CoV-2 vaccines was intended to prevent the serious implications of COVID-19. The objectives of the study were: i) to observe the humoral immune response to BNT162b2 vaccine and SARS-CoV-2 infection (mainly breakthrough infections), ii) to demonstrate the persistence of anti-SARS-CoV-2 antibodies over time in relation to the number of received vaccine doses and the course of infection, and iii) to determine adverse effects after primary vaccine doses. Methods: To assess the humoral response, IgG and IgA anti-S1 antibodies were quantified by ELISA assays. In total, the tests were carried out seven times in almost two years. Results: We demonstrated strong immunogenicity (compared to levels before primary vaccination, 150- and 20-fold increases in IgG and IgA, respectively) of the BNT162b2 vaccine. Over time, we observed a systematic decline in antibody levels, which may have contributed to breakthrough infections. Although they caused seroconversion similar to the booster, antibody levels in such patients fell more rapidly than after re-vaccination. On the other hand, in individuals who did not receive booster(s) and who did not present breakthrough infection, anti-SARS-CoV-2 antibodies returned to pre-vaccination levels after 20 months. The most commonly recognized adverse effects were injection site redness and swelling. Conclusion: Vaccination is highly effective in preventing the most severe outcomes of COVID-19 and should be performed regardless of prior infection. Booster doses significantly enhance anti-SARS-CoV-2 antibody levels and, in contrast to those obtained by breakthrough infection, they remain longer.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy was still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group-1 carcinogenic agents in humans by IARC. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was on average 8.7% of all cancer deaths registered yearly. Approximately 60% of deaths occurred in men and almost the whole burden was due to four infectious agents (Helicobacter pylori, HCV, HPV, and HBV). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Urinary tract infections are one of the main complications in kidney transplant patients, with a significant impact on graft function and survival. In fact, it is estimated that up to 74% of kidney transplant patients experience at least one episode of UTIs in the first year after transplantation, with an increased risk of graft loss and an increased risk of mortality. Several risk factors have been identified, such as female gender, old age, diabetes mellitus, immunosuppression, pre-transplant UTIs, urinary tract abnormalities and prolonged dialysis. The worsening burden of antimicrobial resistance is also in itself a risk factor and a major complication in evolution and management. The management of prophylaxis, asymptomatic bacteriuria, UTIs and UTIs are still an open challenge with some points to be clarified. Faced with such scenarios, our review aimed to evaluate the current epidemiology, to examine the risk factors and to consider all the possibilities and methods of management, giving a current view and evaluation of the topic.

Urinary tract infections (UTIs) caused by pathogens, particularly E. coli, have spontaneously become resistant to antimicrobial drugs in recent years. Therefore, regular monitoring and alternative strategies for the antimicrobial agent are crucial for combating antimicrobial resistance and bacterial biofilms. Here, we report a new cobalt iron oxide-conjugated tin oxide nanocomposite that can kill bacteria and treat multidrug-resistant E. coli posing UTIs. Following the isolation and identification of E. coli, we tested 57/134 samples against sixteen commonly used antibiotics phenotypically using the disk diffusion method to determine their sensitivity pattern. Of the 57 E. coli isolates, 66% (38/57) were multidrug-resistant. The E. coli isolates were resistant to cephradine (70.17%), ceftriaxone (59.64%), and azithromycin (59.64%), followed by cefixime (54.38%), cefuroxime sodium (52.63%), and co-trimoxazole (50.87%). X-ray diffraction results showed the crystallite sizes were about 5.68 and 8.84 nm in pure SnO2 nanoparticles and 95% SnO2-5% CoFe2O4 nanocomposite, respectively. Energy-dispersive X-ray spectroscopy and Fourier transform infrared determined the fundamental structure of the nanocomposite, encompassing Co, Fe, Sn, and O. Moreover, FTIR measurements implied that the distinct functional groups in both SnO2 and CoFe2O4 nanoparticles existed in a 95% SnO2-5% CoFe2O4 nanocomposite. Field emission scanning electron microscope analysis uncovered that the SnO2-CoFe2O4 nanocomposite had a size of roughly 24 nm and was spherical. In addition, the biosynthesized SnO2 nanoparticles and SnO2-CoFe2O4 nanocomposite were evaluated for their antibacterial activity. At a minimum 100 µg/mL concentration, SnO2 nanoparticles and SnO2-CoFe2O4 nanocomposite showed high antibacterial activity. The SnO2 nanoparticles and SnO2-CoFe2O4 nanocomposite demonstrated antibacterial activity on multidrug-resistant E. coli at 10 ± 0.7 and 16 ± 0.8 mm zone of inhibition, respectively. In conclusion, the new SnO2-CoFe2O4 nanocomposite might be a potential candidate for treating UTIs caused by drug-resistant E. coli in the foreseeable future.

Rationale: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency. Although most mutations are linked to the X chromosome, therefore affecting males, there are autosomal recessive forms that therefore affect both sexes. Clinically it is characterized by recurrent and severe bacterial and fungal infections, with formation of granulomas, due to the inability of phagocytes to generate reactive oxygen compounds, necessary for the intracellular death of phagocytosed microorganisms. Patient concerns: We reported a 12-year-old boy with pneumonia with pneumatocele of possible staphylococcal etiology at one year of age, bilateral orchitis secondary to Salmonella with hematogenous spread, osteomyelitis due to Salmonella, gastroenteritis due to Salmonella enteritidis, liver abscesses due to Staphycococcus aureus and lymphomatoid papulosis and pyodermititis. Diagnoses: In the biochemical diagnosis, the presence of yellow dye (NBT) and absence of dark bluish black dye (formazan) was evidenced. Regarding the genetic diagnosis, the presence of the mutation in exon 10 of CYBB (OMIM 306400) (Xp21.1) that encodes the gp91phox protein was demonstrated. Interventions and outcomes: Treatment was started with trimethoprim/sulfamethoxazole 400/80 mg every 24 hours via oral, and antifungal prophylaxis with itraconazole 200 mg every 24 hours orally is added, after which he does not present serious bacterial or fungal infections, not being able to administer immunomodulatory treatment with recombinant human Interferon gamma-1b. Lessons: The clinical finding of frequent severe infections associated with granulomas, CGD should be suspected. Treatment of this primary immunodeficiency is trimethoprim/sulfamethoxazole and itraconazole. Importantly, it indicated that the mutation in exon 10 of CYBB (Xp21.1) that encodes the gp91phox might influence the pathogenesis of CGD.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These pa-tients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmaco-logic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infec-tious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and modalities of vaccination in SOT adult candidates and recipients.

Necrotizing fasciitis is a life-threatening soft-tissue infection affecting the deep fascia and subcutaneous tissue. It is characterized by a fulminant course and high mortality rates. NF of the head and neck is very rare, most cases being odontogenic in origin. Streptococcus spp. and Staphylococcus spp. are the most common isolated organisms. If the infection progresses to descending mediastinitis the prognosis becomes very poor. Since the initial clinical features can be similar to those of a non-necrotizing deep cervical infection, a high degree of suspicion is critical for an early diagnosis. Computed tomography scan can be useful in the diagnosis and to define the extent of the infection. Early and aggressive surgical debridement of all compromised tissue and antibiotic therapy and fluid resuscitation are essential and should not wait for bacterial culture results. Despite prompt and adequate treatment, mortality of CNF can be as high as 35%.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotics carbenicillin on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of gram-positive and gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

Certain micronutrients exhibit immunomodulatory effects. However, no intervention has yet investigated the effect of an individualized supplementation on the severity of upper respiratory tract infections (URI). Therefore, we investigated whether a personalized supplementation moderates the incidence and severity of URI. Selenium, zinc, and vitamin D was measured from 59 healthy participants ) in dried blood spots. Accordingly, a personalized supplement was provided with or without the respective micronutrients. We used WURSS-21 questionnaires to assess the disease status. The blood values converged during the intervention and micronutrients no longer differed at the end of the intervention period between treated and untreated volunteers. The incidence and severity of the illness did not significantly differ between the groups. However, when analyzing the WURSS-21 score by the intention to treat, the initially randomized treatment arm revealed a significantly higher score than the placebo arm. Upon acute administration, individualized combination of selenium, zinc and vitamin D does not reduce the number or contribute to a milder course of URIs. Therefore, supplementation in acute infectious situations seems questionable. Further studies must address the habitual diet in more detail to better understand the impact of individual micronutrient status on the prevention of URI.

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.

The three-armed cluster-randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance) aimed to foster appropriate antibiotic use and reduce overprescribing in German ambulatory care to counter antibiotic resistance. Multi-faceted interventions targeted primary care physicians, teams and patients. This study examined effectiveness of the implementation program. ARena was conducted in 14 primary care networks with 196 practices. All arms received data-based feedback on antibiotics prescribing and quality circles. Arms II and III received different add-on components each. Primary outcome examined is the prescribing rate for systemic antibiotics for cases with non-complicated acute infections (upper respiratory tract, bronchitis, sinusitis, tonsillitis, otitis media). Secondary outcomes refer to prescribing of quinolones and guideline-recommended antibiotics. Based on pseudonymized quarterly claims data, mixed logistic regression models examined pre-post intervention antibiotic prescribing rate changes and compared to matched standard care. A significant rate reduction (arm I 11.7%; arm II 9.9%; arm III 12.7%) and significantly lower prescribing rates were observed for all arms (20.1%, 18.9% and 23.6%) compared to matched standard care (29.4%). Fluoroquinolone prescribing was reduced in all intervention arms and rates for recommended substances generally increased. No significant post-interventional difference between intervention arms was detected. Findings indicate implementation program impact compared to standard care. Trial registration: ISRCTN, ISRCTN58150046

We aimed to estimate the proportion of the population infected with SARS-CoV-2 in the first year of the pandemic. The study population consisted of outpatient adults with mild or no COVID-19 symptoms, and was divided into subpopulations with different levels of exposures. Of the subpopulation without known previous COVID-19 contacts 4143, of the subpopulation with known COVID-19 contacts 594 persons were investigated. IgG- and IgA-seroprevalence and RT-PCR positivity were determined in context with COVID-19 symptoms. We hope to have contributed to the understanding of the significance of the asymptomatic and mild infections in the long persistence of the pandemic.