Search

Objective Early onset sepsis (EOS) is a significant cause of morbidity and mortality in the newborn period. This has led to overinvestigation and antibiotic overuse, which remains a concern in EOS management. Sepsis risk calculator (SRC), a tool validated in American and European populations, aids physicians in sepsis risk stratification and has been shown to decrease antibiotics overuse for EOS. The aim of the study was to evaluate the efficacy and safety of the SRC in a tertiary referral center in Lebanon. Methods This was a single-center retrospective cohort study, conducted at a tertiary medical center in Beirut, Lebanon, that included infants born at more than 34 weeks' gestational age between January 1, 2017 and January 1, 2019. Data was collected on risk factors for neonatal sepsis and the clinical management performed on each newborn. The SRC was used to calculate a sepsis risk score for each patient. Comparison between actual management performed and SRC recommendation was measured. Results We reviewed 3,085 charts, out of which 257 charts were excluded. Patients were stratified into two groups: high sepsis risk and low sepsis risk. Out of the 2,828 patients included, 81 infants (2.9%) had high risk of sepsis, out of which 2 patients had positive blood cultures. There were no patients with a low SRC score who had positive blood cultures. There were no patients who were supposed to receive antibiotics per the SRC recommendation who did not undergo workup for sepsis. Implementing SRC would have prevented antibiotics administration in 42 (1.5%) patients. Conclusion SRC was adequately capable of detecting neonates with sepsis without missing actual cases of EOS, providing initial support for its safety in the population studied. Implementing the SRC would result in reduced usage of antibiotics, laboratory tests, and admissions to the neonatal intensive care unit. [ABSTRACT FROM AUTHOR]

Bacteria affect food quality in developing countries by spreading through contaminated soils and water. Antibiotics are used indiscriminately to eliminate Gram-positive and Gram-negative bacteria, with varying degrees of success. The use of nanomaterials with bactericidal properties can minimize the overuse of antibiotics. In this study, a two-dimensional p-type ZnO powder was successfully synthesized and its bactericidal properties were demonstrated. The XRD and Raman spectroscopy results indicated the presence of wurtzite-phase ZnO with Oi as the predominant native defect, resulting in p-type conductivity. SEM analysis confirmed the two-dimensional morphology, and optoelectronic characterization revealed a bandgap of 3.17 eV. Despite this high bandgap value, a plasmonic effect was generated on the surface of two-dimensional ZnO, which enhanced its bactericidal properties when the powders were in contact with bacteria. From an initial colony level of 5.5 × 105 CFU/mL, a significant decrease in the number of Gram-positive bacteria to 1.15 × 105 CFU/mL was observed, whereas the number of Gram-negative bacteria slightly increased to 1.45 × 106 CFU/mL. The observed inhibition rates were higher than those achieved with the broad-spectrum antibiotic, as validated in this study. The use of two-dimensional ZnO may provide a sustainable solution for the eradication of waterborne pathogens using visible light alone. [ABSTRACT FROM AUTHOR]

Implementation of dedicated pediatric antimicrobial stewardship programs (ASPs) at 2 combined adult-pediatric hospitals with existing ASPs was associated with sustained decreases in pediatric antibiotic use out of proportion to declines seen in adult inpatient units. ASPs in combined hospitals may not detect excessive pediatric antibiotic use without incorporating pediatric expertise. [ABSTRACT FROM AUTHOR]

Background Pharmacies are popular first points of contact for mild infections in the community. Pharmacy services in many countries have expanded to include vaccines and point-of-care tests. In low- and middle-income countries such as Vietnam, poor enforcement of regulations results in substantial volumes of over-the-counter antibiotic sales. Point-of-care tests could provide an economically viable way to reduce antibiotic sales, while still satisfying customer demand for convenient healthcare. C-reactive protein point-of-care testing (CRP-POCT) can reduce antibiotic prescribing for respiratory illness in primary care. Here, we explore the acceptability and feasibility of implementing CRP-POCT in pharmacies in Vietnam. Methods We conducted a mixed-methods study between April and June 2021. A customer exit survey with 520 participants seeking acute respiratory infection treatment at 25 pharmacies evaluated acceptability and willingness-to-pay (WTP) for CRP-POCT and post-service satisfaction. Factors driving customers" acceptance and WTP were explored through mixed-effects multivariable regression. Three focus group discussions with customers (20 participants) and 12 in-depth interviews with pharmacists and other stakeholders were conducted and analyzed thematically. Results Antibiotics were sold to 81.4% of patients with CRP levels <10 mg/L (antibiotics not recommended). A total of 96.5% of customers who experienced CRP-POCT supported its future introduction at pharmacies. Patients with antibiotic transactions (adjusted odds ratio [aOR], 2.25; 95% confidence interval [CI], 1.13–4.48) and those suffering acute respiratory infection symptoms for more than 3 days (aOR, 2.10; 95% CI, 1.08–4.08) were more likely to accept CRP-POCT, whereas customers visiting for children (aOR, 0.20; 95% CI,.10–.54) and those with preference for antibiotic treatment (aOR, 0.45; 95% CI, 0.23–0.89) were less likely to accept CRP-POCT. A total of 78.3% (95% CI, 74.8–81.7) of customers were willing to pay for CRP-POCT, with a mean cost of US$2.4 (±1.1). Customer's income and cost of total drug treatment were associated with increased WTP. Enablers for implementing CRP-POCT included customers' and pharmacists' perceived benefits of CRP-POCT, and the impact of COVID-19 on perceptions of POCT. Perceived challenges for implementation included the additional burden of service provision, lack of an enabling policy environment, and potential risks for customers. Conclusions Implementing CRP-POCT at pharmacies is a feasible and well-accepted strategy to tackle the overuse of antibiotics in the community, with appeal for both supply and demand sides. Creating an enabling policy environment for its implementation, and transparent discussion of values and risks would be key for its successful implementation. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to elicit clinicians' perspectives to help reduce antibiotic prescribing for asymptomatic bacteriuria and improve a patient-centered educational brochure for older adults with urinary tract infections or asymptomatic bacteriuria. Methods Between October 2023 and April 2024, we conducted semi-structured qualitative interviews of clinicians who treat patients aged ≥65 years for urinary tract infections or bacteria in the urine, at infectious disease clinics, community senior living facilities, memory care clinics, and general practice. We developed an interview guide based on a behavior change framework and thematically analyzed written transcripts of audio-recorded interviews using inductive and deductive coding techniques. Results We identified several common themes surrounding management of asymptomatic bacteriuria from clinicians. These included an emphasis on ordering and interpreting urine tests, tension between guidelines and individual patient care for older adults, use of epidemiologic data to influence prescribing practices, pre-prepared communication talking points, and interest in educational materials for patients and clinical teams. Conclusions Education about the need for symptoms to supplement urine testing, data about the impact of overuse of antibiotics, and oral and written communication strategies should be addressed to reduce antibiotic prescribing for asymptomatic bacteriuria. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a major problem and a major global health concern. In total, there are 16 million deaths yearly from infectious diseases, and at least 65% of infectious diseases are caused by microbial communities that proliferate through the formation of biofilms. Antibiotic overuse has resulted in the evolution of multidrug-resistant (MDR) microbial strains. As a result, there is now much more interest in non-antibiotic therapies for bacterial infections. Among these revolutionary, non-traditional medications is quorum sensing inhibitors (QSIs). Bacterial cell-to-cell communication is known as quorum sensing (QS), and it is mediated by tiny diffusible signaling molecules known as autoinducers (AIs). QS is dependent on the density of the bacterial population. QS is used by Gram-negative and Gram-positive bacteria to control a wide range of processes; in both scenarios, QS entails the synthesis, identification, and reaction to signaling chemicals, also known as auto-inducers. Since the usual processes regulated by QS are the expression of virulence factors and the creation of biofilms, QS is being investigated as an alternative solution to antibiotic resistance. Consequently, the use of QS-inhibiting agents, such as QSIs and quorum quenching (QQ) enzymes, to interfere with QS seems like a good strategy to prevent bacterial infections. This review sheds light on QS inhibition strategy and mechanisms and discusses how using this approach can aid in winning the battle against resistant bacteria. [ABSTRACT FROM AUTHOR]

Background Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. Objectives To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. Methods We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. Results A total of 3296 BSI episodes with 454 419 days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [−70.03 DOT/1000 patient-days (PD), P  = 0.036] and a decreasing trend (−11.65 DOT/1000 PD per quarter, P  < 0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: −0.06 BSI/1000 PD per quarter, P  = 0.002). The decreasing trend was more significant for Enterobacterales : ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of −0.06 BSI/1000 PD and −0.08 BSI/1000 PD per quarter, respectively (all P  < 0.05). However, Pseudomonas aeruginosa BSI increased. Conclusions Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is a leading diagnosis for patients requiring critical care. Prediction of the causal organisms has proved challenging, and antibiotic overuse is a burning issue. Objective: This study aimed to compare the results of the BioFire FilmArray Pneumonia Panel (PN Panel) to standard diagnostic methods and evaluate its potential impact in an intensive care unit (ICU). Methods: This is a retrospective study including adult patients admitted to the ICUs with a diagnosis of pneumonia. The agreement between the PN panel results and the standard diagnostic method was analyzed. Actual and potential adjustments of antimicrobials after the PN panel results were reviewed and compared. Results: Two hundred ninety three patients with pneumonia were included. The PN panel identified at least one pathogen in 159 specimens (54.2%), while the standard diagnostic method identified at least one pathogen in 132 specimens (45.0%). Positive percentage agreement between the PN panel and standard‐of‐care culture reached 94%, and negative percentage agreement reached 97%. Among 293 patients, the availability of PN results led to escalation of antimicrobials in 38 (19%) patients and de‐escalation or discontinuation of antimicrobials in 95 (32.4%) patients. Conclusion: This pilot study showed the PN panel could provide accurate results on the causative pathogens and detect resistant bacteria. It could reduce the use of broad‐spectrum antibiotics and overall antibiotic use. If the PN panel could be checked at the emergency department, targeted antibiotics could be administered when the patient arrived at the ICU. [ABSTRACT FROM AUTHOR]

The overprescription of antibiotics due to diagnostic uncertainty and inappropriate patient expectations influence antimicrobial resistance. This research assesses (i) whether communicating diagnostic uncertainty reduces expectations of receiving antibiotics and (ii) which communication strategies minimise unintended consequences of such communication. In two experimental online studies conducted in January and April 2023, participants read a vignette describing a doctor consultation for an ear infection and expressed their expectations of receiving antibiotics, trust in their doctor, rated the doctor's reputation and provided their intention to get a second doctor's opinion. Study 1 (N = 2213) investigated whether communicating diagnostic uncertainty and social externalities of antibiotic use (the negative social impacts of developing antibiotic resistance) decreases expectations for antibiotics and explores potential unintended consequences on the doctor–patient relationship. In Study 2 (N = 527), we aimed to replicate and extend the findings by adding specific treatment recommendations. Disclosing diagnostic uncertainty (vs. certainty) and communicating (vs. not communicating) the social externalities of antibiotic overuse reduced patients' expectations of receiving antibiotics. Yet, communicating uncertainty impaired trust in the doctor and the doctor's reputation. Combining the communication of uncertainty with specific treatment recommendations—particularly delayed antibiotic prescriptions—showed important to prevent these unintended consequences. [ABSTRACT FROM AUTHOR]

Bacterial pneumonia is a common disease with significant health risks. However, the overuse antibiotics in clinics face challenges such as inadequate targeting and limited drug utilization, leading to drug resistance and gut dysbiosis. Herein, a dual-responsive lung inflammatory tissue targeted nanoparticle (LITTN), designed for targeting lung tissue and bacteria, is screened from a series of prepared nanoparticles consisting of permanent cationic lipids, acid-responsive lipids, and reactive oxygen species-responsive and phenylboronic acid-modified lipids with different surface properties. Such nanoparticle is further verified to enhance the adsorption of vitronectin in serum. Additionally, the optimized nanoparticle exhibits more positive charge and coordination of boric acid with cis -diol in the infected microenvironment, facilitating electrostatic interactions with bacteria and biofilm penetration. Importantly, the antibacterial efficiency of dual-responsive rifampicin-loaded LITTN (Rif@LITTN) against methicillin-resistant staphylococcus aureus is 10 times higher than that of free rifampicin. In a mouse model of bacterial pneumonia, the intravenous administration of Rif@LITTN could precisely target the lungs, localize in the lung infection microenvironment, and trigger the responsive release of rifampicin, thereby effectively alleviating lung inflammation and reducing damage. Notably, the targeted delivery of rifampicin helps protect against antibiotic-induced changes in the gut microbiota. This study establishes a new strategy for precise delivery to the lung-infected microenvironment, promoting treatment efficacy while minimizing the impact on gut microbiota. Intravenous antibiotics play a critical role in clinical care, particularly for severe bacterial pneumonia. However, the inability of antibiotics to reach target tissues causes serious side effects, including liver and kidney damage and intestinal dysbiosis. Therefore, achieving precise delivery of antibiotics is of great significance. In this study, we developed a novel lung inflammatory tissue-targeted nanoparticle that could target lung tissue after intravenous administration and then target the inflammatory microenvironment to trigger dual-responsive antibiotics release to synergistically treat pneumonia while maintaining the balance of gut microbiota and reducing the adverse effects of antibiotics. This study provides new ideas for targeted drug delivery and reference for clinical treatment of pneumonia. [Display omitted] [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a public health problem exacerbated by the overuse and misuse of antibiotics and the inadequate capacity of laboratories to conduct AMR surveillance. This study assessed the capacity of laboratories in seven faith-based hospitals to conduct AMR testing and surveillance in Zambia. This multi-facility, cross-sectional exploratory study was conducted from February 2024 to April 2024. We collected and analysed data using the self-scoring Laboratory Assessment of Antibiotic Resistance Testing Capacity (LAARC) tool. This study found an average score of 39%, indicating a low capacity of laboratories to conduct AMR surveillance. The highest capacity score was 47%, while the lowest was 25%. Only one hospital had a full capacity (100%) to utilise a laboratory information system (LIS). Three hospitals had a satisfactory capacity to perform data management with scores of 83%, 85%, and 95%. Only one hospital had a full capacity (100%) to process specimens, and only one hospital had good safety requirements for a microbiology laboratory, with a score of 89%. This study demonstrates that all the assessed hospitals had a low capacity to conduct AMR surveillance, which could affect diagnostic stewardship. Therefore, there is an urgent need to strengthen the microbiology capacity of laboratories to enhance AMR surveillance in Zambia. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a prevalent chronic inflammatory skin disease, most common in adolescence and often persisting into adulthood, leading to severe physical and psychological impacts. The primary etiological factor is Cutibacterium acnes infection. The overuse of antibiotics for acne treatment over recent decades has led to the emergence of antibiotic-resistant Cutibacterium acnes strains. In this study, we isolated and characterized a novel bacteriophage, vB_CacS-HV1, from saliva samples. The average nucleotide identity analysis indicated that vB_CacS-HV1 is a new species within the Pahexavirus genus, enhancing our understanding of this underexplored group. vB_CacS-HV1 demonstrates favorable stability, lacks potentially harmful genetic elements (virulence factors, antibiotic resistance genes, transposons, and integrases), and exhibits potent lytic and anti-biofilm activities against Cutibacterium acnes at low concentrations. These advantages highlight vB_CacS-HV1's potential as a promising antibacterial agent that could possibly be complementary to antibiotics or other treatments for acne therapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Tonsillitis is common in children and is predominantly caused by viruses and, less frequently, by bacteria such as group A beta-hemolytic streptococcus. The treatment primarily involves supportive care; however, the overuse of antibiotics remains a concern due to rising antibiotic resistance. Probiotics, particularly Lactobacillus strains, have been shown to modulate immune responses, offering a potential alternative treatment. Materials and Methods: Our prospective single-arm, open-label study included 98 pediatric patients aged 5–15 years with recurrent throat and tonsil infections, from October 2022 to January 2023. Patients received lozenges containing heat-killed Lactobacillus helveticus MIMLh5. Monthly follow-ups involved a comprehensive ear, nose, and throat examination, throat cultures, and recording the frequency of infections and antibiotic use. Data were analyzed using SPSS 29.0, with statistical significance set at p < 0.05. Results: After three months, significant reductions were observed in the occurrences of nose and throat infections (p < 0.001), enlarged submandibular glands (p < 0.001), and positive throat cultures (p < 0.001). Antibiotic and corticosteroid prescriptions also significantly decreased (p < 0.001). Among children aged 5–10 years, significant improvements were noted in throat and tonsil infections (p < 0.001) and positive throat cultures (p = 0.012). Overall, there was a substantial reduction in school days missed (p < 0.001). Conclusions: The use of paraprobiotic Lactobacillus helveticus MIMLh5 lozenges significantly reduced the incidence of recurrent throat and tonsil infections in children, decreased the need for antibiotics and corticosteroids, and improved overall clinical outcomes without adverse effects. These findings support the use of paraprobiotic supplements as a safe and effective preventive measure for pediatric throat and tonsil infections. [ABSTRACT FROM AUTHOR]

Purpose Methods Findings Conclusions Understanding drivers of antibiotic use is key to limiting the development of antimicrobial resistance. Outpatient antibiotic prescribing rates vary substantially across and within states. Kentucky is one of the highest prescribing states, and the southeastern region has rates that are drastically higher than the national average and urban areas of the state. We sought to examine provider perceptions of antibiotic use in this rural area to more effectively guide future interventions and policy.This study utilized Medicaid prescription claims to identify providers who frequently prescribe antibiotics to children in southeastern Kentucky. Semistructured qualitative interviews were conducted to elicit provider perspectives on antibiotic overuse.Individual, in‐person interviews were conducted with 25 providers from a variety of practices and training backgrounds (private, nonprofit, retail, physician, advanced practice registered nurses, etc.). The following themes emerged as issues that prescribers consider to contribute to antibiotic overuse: (1) caregiver pressure, especially from grandparents or families who desire a ‘quick fix’; (2) business concerns and competition and (3) cultural factors related to poverty and rural locations. Interviewed providers were supportive of public education and had mixed views on the effectiveness of delayed fill or provider feedback initiatives.This study highlights unique challenges associated with antibiotic prescribing in rural areas. Findings will guide future interventions through adaptation of existing strategies to better serve this vulnerable population. [ABSTRACT FROM AUTHOR]

The overuse of antibiotics currently results in the presence of various antibiotics being detected in water bodies, which poses potential risks to human health and the environment. Therefore, it is highly significant to remove antibiotics from water. In this study, we developed novel rod-like NiCo-phyllosilicate hybrid catalysts on calcined natural zeolite (NiCo@C-zeolite) via a facile one-pot process. The presence of the zeolite served as both a silicon source and a support, maintaining a high specific surface area of the NiCo@C-zeolite. Remarkably, NiCo@C-zeolite exhibited outstanding catalytic performance in antibiotic degradation under PMS activation. Within just 5 min, the degradation rate of metronidazole (MNZ) reached 96.14%, ultimately achieving a final degradation rate of 99.28%. Furthermore, we investigated the influence of catalyst dosage, PMS dosage, MNZ concentration, initial pH value, and various inorganic anions on the degradation efficiency of MNZ. The results demonstrated that NiCo@C-zeolite displayed outstanding efficacy in degrading MNZ under diverse conditions and maintained a degradation rate of 94.86% at 60 min after three consecutive cycles of degradation. Free radical quenching experiments revealed that SO•−4 played a significant role in the presence of NiCo@C-zeolite-PMS system. These findings indicate that the novel rod-like NiCo-phyllosilicate hybrid catalysts had excellent performance in antibiotic degradation. [ABSTRACT FROM AUTHOR]

Background: Inappropriate or overuse of antibiotic prescribing in primary care highlights an opportunity for antimicrobial stewardship (AMS) programs aimed at reducing unnecessary use of antimicrobials through education, policies and practice audits that optimize antibiotic prescribing. Evidence from the early part of the pandemic indicates a high rate of prescribing of antibiotics for patients with COVID-19. It is crucial to surveil antibiotic prescribing by primary care providers from the start of the pandemic and into its endemic stage to understand the effects of the pandemic and better target effective AMS programs. Methods: This was a matched pair population-based cohort study that used electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Participants included all patients that visited their primary care provider and met the inclusion criteria for COVID-19, respiratory tract infection (RTI), or non-respiratory or influenza-like-illness (negative). Four outcomes were evaluated (a) receipt of an antibiotic prescription; (b) receipt of a non-antibiotic prescription; (c) a subsequent primary care visit (for any reason); and (d) a subsequent primary care visit with a bacterial infection diagnosis. Conditional logistic regression was used to evaluate the association between COVID-19 and each of the four outcomes. Each model was adjusted for location (rural or urban), material and social deprivation, smoking status, alcohol use, obesity, pregnancy, HIV, cancer and number of chronic conditions. Results: The odds of a COVID-19 patient receiving an antibiotic within 30 days of their visit is much lower than for patients visiting for RTI or for a non-respiratory or influenza-like-illnesses (AOR = 0.08, 95% CI[0.07, 0.09] compared to RTI, and AOR = 0.43, 95% CI[0.38, 0.48] compared to negatives). It was found that a patient visit for COVID-19 was much less likely to have a subsequent visit for a bacterial infection at all time points. Conclusions: Encouragingly, COVID-19 patients were much less likely to receive an antibiotic prescription than patients with an RTI. However, this highlights an opportunity to leverage the education and attitude change brought about by the public health messaging during the COVID-19 pandemic (that antibiotics cannot treat a viral infection), to reduce the prescribing of antibiotics for other viral RTIs and improve antibiotic stewardship. [ABSTRACT FROM AUTHOR]

Background and Aim: Pseudomonas aeruginosa is an infectious agent of great importance for animals and humans. It causes serious infections that show high resistance to antibiotics. This study investigated the molecular detection of blaOXA-23 gene in antibiotic-resistant P. aeruginosa strains isolated from cows and humans. Materials and Methods: In total, 120 samples, comprised 60 from cows (30 milk and 30 nasal discharge) and 60 from their owners (30 urine and 30 sputum), were individually collected, cultured, and tested for P. aeruginosa through molecular analysis targeting the blaOXA-23 gene. P. aeruginosa antibiotic-resistant isolates were identified by performing antibiotic susceptibility testing and detecting biofilm formation. Results: In total, 74.17% positive P. aeruginosa isolates, including 66.67% and 81.67% for cows and humans, respectively. Subsequently, positive cow isolates were detected in 60% of milk samples and 73.33% of nasal discharge samples; while positive human isolates were detected in 76.67% of urine samples and 86.66% of sputum samples. Targeting blaOXA-23 gene, 58.43% of cultured isolates were positive for P. aeruginosa by polymerase chain reaction. Respectively, positive isolates were detected in 66.67% and 45.46% of cow milk and nasal discharges as well as in 60.87% and 61.54% of human urine and sputum. The antibiotic susceptibility test revealed that all isolates were resistant to all applied antibiotics, particularly imipenem. Results of biofilm formation revealed 67.31% total positives, including 51.43% strong, 34.285% moderate, and 14.285% weak reactions. In addition, although values of the total positive cows and humans differed insignificantly, total positives showed insignificant variation between values of milk and nasal discharges of cows as well as between urine and sputum of humans; however, significant differences were identified in the distribution of strong, moderate, and weak positivity of these samples. Conclusion: Antibiotic overuse contributes extensively to increasing the prevalence of resistant P. aeruginosa isolates carrying the blaOXA-23 gene in both cows and humans. Furthermore, studies in other Iraqi areas are necessary to support our findings. The main limitations include that the number of tested samples is relatively low, and there is a need to use a large number of samples from different sources. Also, the current methods for detection of resistant isolates are still culture-based approaches. [ABSTRACT FROM AUTHOR]

Background: The adverse effects of antimicrobial resistance (AMR) are manifesting worldwide. A major contributing factor to AMR is the inappropriate use of antimicrobials in humans and animals. It is imperative to raise awareness among medical students of the current public health challenges of AMR and make them antibiotic guardians because they are the future medical doctors. This survey was designed to assess the knowledge of AMR and habits of antimicrobial use (AMU) among medical students as a means to guide them in their future practice. Methodology: This descriptive cross-sectional survey was conducted among medical students of the College of Medicine, University of Nigeria (UNN), Enugu State, Nigeria, from July to September 2021. The sample size of 602 was calculated using an online Raosoft sample size calculator. Pretested structured questionnaires, designed to collect information on students’ knowledge of antimicrobials and factors responsible for emergence of AMR as well as the students’ habits of antimicrobial use, were self-administered to consenting students. The data were analyzed using descriptive and inferential statistics. Results: Of the 602 questionnaires administered to the students, 550 were filled out, giving a response rate of 91.4%. Out of the 550 respondents, 60.4% were females, majority (51.1%) of the respondents were between the ages of 21 and 25 years. Regarding knowledge, 97.2%, 62.5%, and 54.2% have heard of the terms ‘antibiotic resistance’, ‘multi-drug drug resistance’ and ‘antimicrobial stewardship’ respectively. About 97.3% knew that AMR was a global problem, however only 64.7% felt that it was a problem for medical students. Surprisingly, 20.4% indicated that viruses were sensitive to antibiotics. Regarding the students’ habit of antimicrobial use, only 22.2% always consult a doctor before starting an antibiotic, 13.1% go for laboratory tests, and 90.5% always take antibiotics anytime they have a fever. Above half of the participants (56.5%) do not complete the dosage of the antibiotics while 63.5% keep leftover antibiotics for future use. In assessing the factors responsible for AMR emergence, 88.8% responded not adhering to a doctor's prescription and 92.0% responded poor quality of drugs, while only 42.8% responded that overuse of antibiotics in livestock is a factor. Conclusion: Our study gave an insight into the knowledge gap and the need to increase awareness and education on AMR and AMS among the medical students, especially in the early phase of their academic and professional training. [ABSTRACT FROM AUTHOR]

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3 nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel's morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global public health threat caused by the misuse and overuse of antibiotics. It leads to infections becoming difficult to treat, causing serious illness, disability, and death. Current antibiotic development is slow, with only 25% of current antibiotics exhibiting novel mechanisms against critical pathogens. Traditional medicinal plants' secondary metabolites offer potential for developing novel antibacterial compounds. These compounds, often with strong antimicrobial activity, can be used to develop safe and effective antibacterial chemotherapies. This study investigated the antibacterial activity of Phyllanthus niruri Linn. extracts against a panel of bacterial pathogens using disc diffusion and microdilution assays and quantified by calculation of minimum inhibition concentration (MIC). Additionally, the effects of combinations of the extracts and selected conventional antibiotics were examined by sum of fractional inhibition concentration (ƩFIC) calculation and isobologram analysis. Liquid chromatography–mass spectrometry (LC-MS) phytochemistry analysis was used to identify noteworthy compounds in the active extracts and the Artemia nauplii bioassay was used to evaluate toxicity. The aqueous and methanolic extracts exhibited notable antibacterial activity in the broth microdilution assay against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) (MIC = 669 µg/mL and 738 µg/mL, respectively). The methanolic extract also showed noteworthy antibacterial action in the broth assay against Klebsiella pneumoniae (MIC = 738 µg/mL). The aqueous extract had noteworthy growth inhibitory activity against Bacillus cereus (MIC = 669 µg/mL), whilst the methanolic extract demonstrated good antibacterial activity against that bacterium (MIC = 184 µg/mL). The aqueous and methanol extracts showed minimal antibacterial action against Shigella flexneri and Shigella sonnei. The extracts were subjected to LC-MS analysis, which revealed several interesting phytochemicals, including a variety of flavonoids and tannins. The antibacterial activity and lack of toxicity of the P. niruri extracts indicates that they may be worthwhile targets for antibiotic development and further mechanistic and phytochemistry studies are required. [ABSTRACT FROM AUTHOR]

The overuse of traditional antibiotics has resulted in bacterial resistance and seriously compromised the therapeutic efficacy of traditional antibiotics, making the exploration of new antimicrobials particularly important. Several studies have shown that bioactive peptides have become an important source of new antimicrobial drugs due to their broad-spectrum antibacterial action and lack of susceptibility to resistance. In this study, a novel bioactive peptide Nigrosin-6VL was characterised from the skin secretion of the golden cross band frog, Odorrana andersonii, by using the 'shotgun' cloning strategy. Modifications on the Rana Box of Nigrosin-6VL revealed its critical role in antimicrobial functions. The peptide analogue, 2170-2R, designed to preserve the Rana Box structure while enhancing cationicity, exhibited improved therapeutic efficacy, particularly against Gram-negative bacteria, with a therapeutic value of 45.27. Synergistic studies demonstrated that 2170-2R inherits the synergistic antimicrobial activities of the parent peptides and effectively enhances the antimicrobial capacity of cefepime and gentamicin against both planktonic cells and biofilms. Specifically, 2170-2R can synergise effectively with cefepime and gentamicin against different strains of P. aeruginosa biofilms. Consequently, 2170-2R holds promise as a potent antimicrobial agent developed to combat infections induced by Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

Over the past few decades, the overuse of antibiotics has raised concerns about drinking water and potential health risks, especially the hydrochloride tetracycline (TC‐HCl). Therefore, it is crucial to develop a simple, low‐cost and high‐efficiency photocatalyst for the degradation of the pollutant. A novel photocatalyst with an S‐scheme heterojunction structure of AgIn5S8 and Bi2MoO6 was synthesized by using a solvothermal method. The heterojunction photocatalyst obtained demonstrates superior photocatalytic degradation activity for hydrochloride tetracycline (TC‐HCl) under visible light irradiation. It exhibits higher photocatalytic degradation performance than pure AgIn5S8 and Bi2MoO6 under the same conditions. The heterojunction with 3 % AgIn5S8 exhibited the highest degradation efficiency of 63.65 % within 40 minutes. Furthermore, the degradation rate is 6.21 times higher than that of AgIn5S8 and 2.18 times higher than that of Bi2MoO6. The improved photocatalytic activity is primarily attributed to the enhanced light absorption and the high rate of carrier separation resulting from S‐scheme heterojunctions. [ABSTRACT FROM AUTHOR]

Due to the overuse of antibiotics, the number of multidrug-resistant pathogen bacteria is rising in recent years posing a serious threat to human health. One promising alternative for treatment is the application of phage therapy using highly selective bacteriophages. Because of their selectivity, individual screens called phagograms for each patient are required to select phages from a phage library. Phagograms are mostly performed via bacterial cultivation on double layer agar plates and phage addition causing bacterial lysis. However, these assays are work-intensive and have a low ability for parallelization and automation. Hence, highly parallelizable and automatable microbioreactors in the lowest microliter scale could offer an economic solution increasing the throughput of phagograms. This paper demonstrates the applicability of a novel capillary-wave microbioreactor (cwMBR) to perform phagograms. Due to its small volume of only 7 µL and the open-droplet design, it can be easily automated and parallelized in future. Furthermore, the ability of online biomass measurement makes the cwMBR a perfect phagogram platform in the future. Herein, phagograms with E. coli and different concentrations of the phages MM02 and EASG3 were performed as proof of concept for phagograms in the cwMBR. Thereby, the cwMBR was able to measure differences in lysis kinetics of different phages. Furthermore, the phagograms were compared to those in conventional microtiter plate readers revealing the cwMBR as ideal alternative for phagograms as it combines favorable mixing conditions and a phage repellent hydrophilic glass surface with online biomass measurement in an open-droplet design for future parallelization and automation. [Display omitted] • Phage sensitivity tests called phagograms are mandatory for phage therapy. • State of the art phagograms are not highly parallelizable and automatable. • Novel capillary-wave microbioreactor (cwMBR) can perform parallelized phagograms. • cwMBR combines parallelizability and automatability with online biomass measurement. • cwMBR is able to measure lysis kinetics of phages. [ABSTRACT FROM AUTHOR]

As a sooner or later risk, antimicrobial resistance due to the overuse of antibiotics is considered a nightmare facing humankind. The visible-light mineralization of antibiotic waste over nanoceramic photocatalysts is an innovative expectant method. Concerning this, nanostructured yttrium orthovanadate (YVO 4) is grown via an adapted sol-gel process tracked by loading of 1.0–4.0 wt% of silver oxide (Ag 2 O) to form heterojunction nanocomposite of Ag 2 O/YVO 4. The as-prepared heterostructures were applied for visible-light photoelimination of ciprofloxacin (CF) in water. The presence of Ag 2 O has enhanced both light absorbance and photogenerated carrier separation of YVO 4. The 3.0 to 4.0 wt% loading of Ag 2 O designated the thinnest bandgap of 2.4 eV regardless of the minor decrease in their specific surface areas from 220 in bare YVO 4 to 168 m2 g−1 for 3.0 % Ag 2 O/YVO 4. The complete mineralization of CF over 3.0 % Ag 2 O/YVO 4 was achieved after 60 min of light illumination at an optimized dose of 1.6 mg mL−1 and a reaction rate constant of 5.41 × 10−2 min−1. This improved photocatalyst has also a recyclable ability of ∼95 % of its initial photoactivity after the fifth experimental run. Therefore, the augmented light harvesting, surface texture, as well as superb carrier separation represent a key role in the performance of Ag 2 O/YVO 4. [ABSTRACT FROM AUTHOR]

Macrolide antibiotics, pivotal in clinical therapeutics, are confronting resistance challenges mediated by enzymes like macrolide esterases, which are classified into Ere-type and the less studied Est-type. In this study, we provide the biochemical confirmation of EstX, an Est-type macrolide esterase that initially identified as unknown protein in the 1980s. EstX is capable of hydrolyzing four 16-membered ring macrolides, encompassing both veterinary (tylosin, tidipirosin, and tilmicosin) and human-use (leucomycin A5) antibiotics. It uses typical catalytic triad (Asp233-His261-Ser102) from alpha/beta hydrolase superfamily for ester bond hydrolysis. Further genomic context analysis suggests that the dissemination of estX is likely facilitated by mobile genetic elements such as integrons and transposons. The global distribution study indicates that bacteria harboring the estX gene, predominantly pathogenic species like Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae, are prevalent in 74 countries across 6 continents. Additionally, the emergence timeline of the estX gene suggests its proliferation may be linked to the overuse of macrolide antibiotics. The widespread prevalence and dissemination of Est-type macrolide esterase highlight an urgent need for enhanced monitoring and in-depth research, underlining its significance as an escalating public health issue. Macrolide esterase EstX can degrade both veterinary and human-use 16-membered ring macrolides. This enzyme is widely distributed among pathogenic species and across 74 countries on 6 continents,with its dissemination likely facilitated by integrons and transposons. [ABSTRACT FROM AUTHOR]

Key Points: Question: Can computerized provider order entry (CPOE) prompts that provide patient-specific risk estimates for multidrug-resistant organisms (MDROs) reduce empiric extended-spectrum antibiotic use in patients admitted with pneumonia? Findings: In a cluster-randomized trial of 59 hospitals (n = 44 780 adults in the intervention period), CPOE prompts promoting standard-spectrum antibiotics for patients at low risk of infection with MDROs significantly reduced empiric extended-spectrum antibiotic use in hospitalized patients with pneumonia by 28.4%, without increasing intensive care unit transfers or length of stay. Meaning: Real-time electronic health record–generated recommendations for standard-spectrum antibiotics using patient-specific risk for MDRO-associated infections can substantially and safely reduce empiric extended-spectrum antibiotic use in patients hospitalized for pneumonia. Importance: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non–critically ill patients admitted with pneumonia. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non–critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020. Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies. Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P <.001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups. Conclusions and Relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged. Trial Registration: ClinicalTrials.gov Identifier: NCT03697070 This clinical trial examines the effect of an antibiotic stewardship bundle (education, feedback, and real-time multidrug-resistant organism risk-based CPOE prompts) vs routine stewardship on antibiotic selection during the first 3 hospital days in adults with pneumonia. [ABSTRACT FROM AUTHOR]

Key Points: Question: Can computerized provider order entry prompts that present patient-specific multidrug-resistant organism (MDRO) risk estimates reduce empiric extended-spectrum antibiotics in patients admitted with urinary tract infection (UTI)? Findings: In a cluster-randomized trial of 59 hospitals (n = 55 412 adults in the intervention period), computerized provider order entry prompts promoting standard-spectrum antibiotics for patients at low risk of infection with MDROs significantly reduced empiric extended-spectrum antibiotic use in hospitalized patients with UTI by 17.4% without increasing intensive care unit transfers or length of stay. Meaning: Real-time electronic health record–generated recommendations for standard-spectrum antibiotics using patient-specific risk for MDRO-associated infections can safely reduce empiric extended-spectrum antibiotic use in patients hospitalized for UTI. Importance: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017–September 30, 2018) and 15-month intervention period (April 1, 2019–June 30, 2020). Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods. Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P <.001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively. Conclusions and Relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers. Trial Registration: ClinicalTrials.gov Identifier: NCT03697096 This clinical trial evaluates whether computerized provider order entry prompts providing patient- and pathogen-specific multidrug-resistant organism risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of urinary tract infections. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is an escalating global health crisis, driven by the overuse and misuse of antibiotics. Multidrug‐resistant Gram‐negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, are particularly concerning due to their high morbidity and mortality rates. In this context, endolysins, derived from bacteriophages, offer a promising alternative to traditional antibiotics. This study introduces LysJEP8, a novel endolysin derived from Escherichia phage JEP8, which exhibits remarkable antimicrobial activity against key Gram‐negative members of the ESKAPE group. Comparative assessments highlight LysJEP8's superior performance in reducing bacterial survival rates compared to previously described endolysins, with the most significant impact observed against P. aeruginosa, and notable effects on A. baumannii and K. pneumoniae. The study found that LysJEP8, as predicted by in silico analysis, worked best at lower pH values but lost its effectiveness at salt concentrations close to physiological levels. Importantly, LysJEP8 exhibited remarkable efficacy in the disruption of P. aeruginosa biofilms. This research underscores the potential of LysJEP8 as a valuable candidate for the development of innovative antibacterial agents, particularly against Gram‐negative pathogens, and highlights opportunities for further engineering and optimization to address AMR effectively. [ABSTRACT FROM AUTHOR]

Background and Objectives: During the coronavirus pandemic, the overuse of antibiotics to reduce coinfections and mortality may be contributing to the rise of antimicrobial resistance. In this study, we aim to investigate the antibiotic resistance changes of Acinetobacter baumannii post-COVID-19 pandemic in Northern Iran. Materials and Methods: The current study is a cross-sectional study. Between 2022 and 2023, 2190 clinical samples were collected from patients with healthcare-associated infections (HAIs) at four hospitals in Sari, which served as corona centers after the COVID-19 pandemic. Antimicrobial sensitivity was determined using standard broth macro-dilution, and resistance genes were detected using multiplex PCR. Results: Based on the results co-amoxiclav had a resistance rate of 100%, while piperacillin/tazobactam showed the least resistance rate of 29.82%. In terms of GM MIC values, colistin was the most potent against multi-drug resistant isolates. The frequency of bla OXA-51, ampC, aphA6, and bla NDM genes were 100%, 99.12%, 90.35%, and 69.30% respectively. Conclusion: Our study revealed high multi-drug resistance rates. Piperacillin/tazobactam recommended for treating multidrug resistant Acinetobacter baumannii infections in Northern Iran. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses a serious threat to human health worldwide and its incidence continues to increase owing to the overuse of antibiotics and other factors. Macrolide antibiotics such as erythromycin (EM) have immunomodulatory effects in addition to their antibacterial activity. Long-term, low-dose administration of macrolides has shown clinical benefits in treating non-infectious inflammatory respiratory diseases. However, this practice may also increase the emergence of drug-resistant bacteria. In this study, we synthesized a series of EM derivatives, and screened them for two criteria: (i) lack of antibacterial activity and (ii) ability to suppress tumor necrosis factor-α (TNF-α) production in THP-1 cells stimulated with lipopolysaccharide. Among the 37 synthesized derivatives, we identified a novel 12-membered ring macrolide EM982 that lacked antibacterial activity against Staphylococcus aureus and suppressed the production of TNF-α and other cytokines. The effects of EM982 on Toll-like receptor 4 (TLR4) signaling were analyzed using a reporter assay and Western blotting. The reporter assay showed that EM982 suppressed the activation of transcription factors, NF-kB and/or activator protein 1 (AP-1), in HEK293 cells expressing human TLR4. Western blotting showed that EM982 inhibited the phosphorylation of both IkB kinase (IKK) β and IkBα, which function upstream of NF-kB, whereas it did not affect the phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and c-Jun N-terminal kinase, which act upstream of AP-1. These results suggest that EM982 suppresses cytokine production by inhibiting phosphorylation of IKKβ and IkBα, resulting in the inactivation of NF-kB. [ABSTRACT FROM AUTHOR]

Vibrio parahaemolyticus can cause acute gastroenteritis, wound infections, and septicemia in humans. The overuse of antibiotics in aquaculture may lead to a high incidence of the multidrug-resistant (MDR) pathogen. Nevertheless, the genome evolution of V. parahaemolyticus in aquatic animals and the mechanism of its antibiotic tolerance remain to be further deciphered. Here, we investigated the molecular basis of the antibiotic tolerance of V. parahaemolyticus isolates (n = 3) originated from shellfish and crustaceans using comparative genomic and transcriptomic analyses. The genome sequences of the V. parahaemolyticus isolates were determined (5.0–5.3 Mb), and they contained 4709–5610 predicted protein-encoding genes, of which 823–1099 genes were of unknown functions. Comparative genomic analyses revealed a number of mobile genetic elements (MGEs, n = 69), antibiotic resistance-related genes (n = 7–9), and heavy metal tolerance-related genes (n = 2–4). The V. parahaemolyticus isolates were resistant to sub-lethal concentrations (sub-LCs) of ampicillin (AMP, 512 μg/mL), kanamycin (KAN, 64 μg/mL), and streptomycin (STR, 16 μg/mL) (p < 0.05). Comparative transcriptomic analyses revealed that there were significantly altered metabolic pathways elicited by the sub-LCs of the antibiotics (p < 0.05), suggesting the existence of multiple strategies for antibiotic tolerance in V. parahaemolyticus. The results of this study enriched the V. parahaemolyticus genome database and should be useful for controlling the MDR pathogen worldwide. [ABSTRACT FROM AUTHOR]

Objectives: While factors contributing to dental antibiotic overprescribing have previously been described, previous work has lacked any theoretical behavior change framework that could guide future intervention development. The purpose of this study was to use an evidence‐based conceptual model to identify barriers and facilitators of appropriate antibiotic prescribing by dentists as a guide for future interventions aimed at modifying antibiotic prescribing. Methods: Semi‐structured interviews were conducted with dentists from the National Dental Practice Based Research Network (PBRN) exploring patient and practice factors perceived to impact antibiotic prescribing. Audio‐recorded telephone interviews were transcribed and independently coded by three researchers. Themes were organized around the COM‐B model to inform prospective interventions. Results: 73 of 104 dentists (70.1%) were interviewed. Most were general dentists (86.3%), male (65.7%), and white (69.9%). Coding identified three broad targets to support appropriate dental antibiotic prescribing among dentists: (1) increasing visibility and accessibility of guidelines, (2) providing additional guidance on antibiotic prescribing in dental scenarios without clear guidelines, and (3) education and communication skills‐building focused on discussing appropriate antibiotic use with patients and physicians. Conclusions: The findings from our study are consistent with other studies focusing on antibiotic prescribing behavior in dentists. Understanding facilitators and barriers to dental antibiotic prescribing is necessary to inform targeted interventions to improve appropriate antibiotic prescribing. Future interventions should focus on implementing multimodal strategies to provide the necessary support for dentists to judiciously prescribe antibiotics. [ABSTRACT FROM AUTHOR]

Background: Antibiotic overuse in pediatric patients with upper respiratory tract infections (UR-TIs) raises concerns about antimicrobial resistance. This study examines the impact of antibiotics on hospital stay duration and fever resolution in pediatric patients diagnosed with viral infections via a multiplex polymerase chain reaction (PCR) respiratory panel. Methods: In the pediatric ward of Imam Abdulrahman Bin Faisal Hospital, a retrospective cohort analysis was conducted on pediatric patients with viral infections confirmed by nasopharyngeal aspirates from October 2016 to December 2021. Cohorts receiving antibiotics versus those not receiving them were balanced using the gradient boosting machine (GBM) technique for propensity score matching. Results: Among 238 patients, human rhinovirus/enterovirus (HRV/EV) was most common (44.5%), followed by respiratory syncytial virus (RSV) (18.1%). Co-infections occurred in 8.4% of cases. Antibiotic administration increased hospital length of stay (LOS) by an average of 2.19 days (p-value: 0.00). Diarrhea reduced LOS by 2.26 days, and higher albumin levels reduced LOS by 0.40 days. Fever and CRP levels had no significant effect on LOS. Time to recovery from fever showed no significant difference between antibiotic-free (Abx0) and antibiotic-received (Abx1) groups (p-value: 0.391), with a hazard ratio of 0.84 (CI: 0.57–1.2). Conclusions: Antibiotics did not expedite recovery but were associated with longer hospital stays in pediatric patients with acute viral respiratory infections. Clinicians should exercise caution in prescribing antibiotics to pediatric patients with confirmed viral infections, especially when non-critical. [ABSTRACT FROM AUTHOR]

Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed. Aspiration can manifest as either bacterial aspiration pneumonia (BAP) or aspiration pneumonitis (AP), which are challenging to distinguish potentially leading to overprescription of antibiotics and the emergence of multidrug-resistant bacteria. This study aims to assess the accuracy of the Infectious Diseases Society of America (IDSA) and British Thoracic Society (BTS) criteria in differentiating BAP from AP in comatose ventilated patients following drug poisoning. This cross-sectional study included 95 patients admitted for drug poisoning at the Lille University Hospital intensive care department, between 2013 and 2017, requiring mechanical ventilation and receiving antibiotics for aspiration. Patients were categorized as having bacterial complications if tracheal sampling yielded positive culture results, and if they were otherwise considered to have chemical complications. The sensitivity, specificity, positive predictive value, and negative predictive value of IDSA and BTS criteria in identifying patients with bacterial complications were evaluated. Among the patients, 34 (36%) experienced BAP. The IDSA criteria demonstrated a sensitivity of 62% and specificity of 33%, while the BTS criteria showed a sensitivity of 50% and specificity of 38%. Both the IDSA and BTS criteria exhibited poor sensitivity and specificity in identifying microbiologically confirmed pneumonia in comatose ventilated patients following drug poisoning. [ABSTRACT FROM AUTHOR]

In 2023, this study monitored nine types of antibiotics in the influent and effluent of wastewater treatment plants (WWTPs) in the urban and suburban areas of Tangshan. The total antibiotics concentration detected in influent WWTPs was highest in winter, followed by spring, summer, and autumn. The antibiotics concentration in influent and effluent urban WWTPs was higher than that in the suburban WWTPs in spring, summer, and winter, while the trend was reversed in autumn. Roxithromycin and oxytetracycline had a risk quotient (RQ) value of ≥0.1 in the effluent of WWTPs in winter, indicating that they are medium-risk antibiotics that pose a risk to the aquatic ecosystem after discharge. In the study area, the per capita pollution load of antibiotics was highest in spring, summer, and autumn for sulfamethoxazole, while it was highest in winter for ofloxacin. In the urban area, the use of roxithromycin, sulfamethoxazole, sulfamethoxazole, and ofloxacin was highest in spring, summer, autumn, and winter, respectively, while in suburban areas, the use of sulfamethoxazole, norfloxacin, sulfamethoxazole, and ofloxacin was highest during the same period. The use of antibiotics in the urban area was one order of magnitude higher than that in suburban areas, indicating a possible overuse of antibiotics in urban environments. [ABSTRACT FROM AUTHOR]

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals. [ABSTRACT FROM AUTHOR]

In the past few decades, the overuse of antibiotics has been a growing concern in the field of medicine. To address this issue, there has been increasing interest in the development of efficient treatment methods. Recently, research has shown that the modification of iron oxychloride with Mn, Co, or Ni can significantly enhance its performance in the degradation of tetracycline hydrochloride. This is attributed to the high similarity between Mn, Co, Ni and Fe, bimetallic systems can be constructed to improve the accelerated cycle of M(II)–M(III) and the activation of hydrogen peroxide, peroxymonosulfate and peroxydisulfate. Additionally, active substances such as SO4−·, ·OH, and 1O2 have been identified in the PS system, while ·OH and 1O2 are active in the H2O2 system. In this study, due to the presence of these active substances, the degradation rate of tetracycline hydrochloride within 10 min in three different systems such as hydrogen peroxide can reach 100%. These findings offer promising prospects for the development of more effective and sustainable treatment methods for antibiotic pollution. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are one of the most widely used drugs in hospitals, but they are often misused. The proper antibiotic use improves medication and patients' safety, lowers drug intake, costs and reduces the proliferation of resistant species. Aim and objectives: To determine the magnitude of inappropriate antibiotic prescription at Zagazig University Children's Hospital. Methods: This cross-sectional study was carried out in the pediatric department, faculty of medicine, Zagazig university on 1000 children. All patients were subjected to full medical history with stress on age, sex, diagnosis, past history and antibiotic regimen (begin, course, end). The investigations carried out to the patient were recorded. Clinical outcomes after the use of the antibiotics were carefully evaluated and registered. Results: 97.29% of the prescribed antibiotics were of the appropriate dose and 94.22% were of appropriate interval. 68.67% of the prescribed antibiotics fulfill the guidelines, while 31.32% not fulfill the guidelines. The most frequently prescribed antibiotics are Ampicillin/Sulbactam and 3rd generation cephalosporin while the least prescribed antibiotics are Amoxicillin/Clavulanic and cotrimoxazole. Conclusion: Antibiotics misuse and overuse are common, contributing to the rise of bacterial resistance. As a result, the main challenges in prescription of antibiotics are to achieve a rational choice and appropriate use of antibiotics and to recognize their potential problems. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is an intestinal infection that causes morbidity and mortality and places significant burden and cost on the healthcare system, especially in recurrent cases. Antibiotic overuse is well recognized as the leading cause of CDI in high-risk patients, and studies have demonstrated that even short-term antibiotic exposure can cause a large and persistent disturbance to human colonic microbiota. The recovery and sustainability of the gut microbiome after dysbiosis have been associated with fewer CDI recurrences. Fecal microbiota transplantation (FMT) refers to the procedure in which human donor stool is processed and transplanted to a patient with CDI. It has been historically used in patients with pseudomembranous colitis even before the discovery of Clostridioides difficile. More recent research supports the use of FMT as part of the standard therapy of recurrent CDI. This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status. [ABSTRACT FROM AUTHOR]

This document discusses the global increase in antibiotic use and the resulting concern over antimicrobial resistance. It highlights the significant impact of antibiotic consumption on public health and the potential for a post-antibiotic era if action is not taken. The document also emphasizes the importance of community awareness and education in combating antimicrobial resistance. It presents eight studies from various countries that investigate community antibiotic use and stewardship, revealing variations in knowledge, attitudes, and practices related to antibiotics. The findings underscore the need for targeted campaigns and interventions to improve knowledge and promote responsible antibiotic use in different communities. [Extracted from the article]

Antibiotics are commonly used to prevent and control aquaculture diseases. However, long-term overuse of antibiotics not only leaves residues but also leads to changes in the nitrogen cycle in water, which threatens the survival of aquaculture organisms. The current results showed that sulfamethoxazole had no significant effect on the nitrogen cycle process in the actual aquaculture concentration. The inhibitory effect of 1.05 mg/L norfloxacin on ammonia-oxidizing bacteria was significantly greater than that on ammonia-oxidizing archaea, and the gene abundance of AOB amoA on the 14th day increased by 2.48 times compared with the 7th day. Under the influence of 3.9 mg/L oxytetracycline, the gene abundance of AOB amoA decreased significantly, while the number of AOA amoA genes increased, suggesting that there may be functional redundancy between AOA and AOB. At the genus level in the norfloxacin group, the relative abundance of Sva0485 increased by 14.0% on the 7th day compared with the control group but decreased 12.77% in the addition group. The relative abundance of Firmicutes, another dominant species in the oxytetracycline group, was 25.9%. This study shows that the addition of antibiotics may have a negative effect on the nitrogen-cycling microorganisms in aquaculture water. [ABSTRACT FROM AUTHOR]

Objectives: Although metagenomic next-generation sequencing (mNGS) is commonly used for diagnosing infectious diseases, clinicians face limited options due to the high costs that are not covered by basic medical insurance. The goal of this research is to challenge this bias through a thorough examination and evaluation of the clinical importance of mNGS in precisely identifying pathogenic microorganisms in cases of sepsis acquired in the community or in hospitals. Methods: A retrospective observational study took place at a tertiary teaching hospital in China from January to December 2021. Data on 308 sepsis patients were collected, and the performance of etiological examination was compared between mNGS and traditional culture method. Results: Two hundred twenty-nine cases were observed in the community-acquired sepsis (CAS) group and 79 cases in the hospital-acquired sepsis (HAS) group. In comparison with conventional culture, mNGS showed a significantly higher rate of positivity in both the CAS group (88.21% vs. 25.76%, adj.P < 0.001) and the HAS group (87.34% vs. 44.30%, adj.P < 0.001), particularly across various infection sites and specimens, which were not influenced by factors like antibiotic exposure or the timing and frequency of mNGS technology. Sepsis pathogens detected by mNGS were broad, especially viruses, Mycobacterium tuberculosis, and atypical pathogens, with mixed pathogens being common, particularly bacterial-viral co-detection. Based on the optimization of antimicrobial therapy usingmNGS, 58 patients underwent antibiotic de-escalation, two patients were switched to antiviral therapy, and 14 patients initiated treatment for tuberculosis, resulting in a reduction in antibiotic overuse but without significant impact on sepsis prognosis. The HAS group exhibited a critical condition, poor prognosis, high medical expenses, and variations in etiology, yet the mNGS results did not result in increased medical costs for either group. Conclusions: mNGS demonstrates efficacy in identifying multiple pathogens responsible for sepsis, with mixed pathogens of bacteria and viruses being prevalent. Variability in microbiological profiles among different infection setting underscores the importance of clinical vigilance. Therefore, the adoption of mNGS for microbiological diagnosis of sepsis warrants acknowledgment and promotion. [ABSTRACT FROM AUTHOR]

Background: Overuse of antibiotics is a key driver of antimicrobial resistance (AMR) world-wide. Malawi continues to report rising cases of AMR among both in-patients and out-patients. We investigated antibiotic use and resistance patterns among patients with suspected first line antibiotic treatment failure at Rumphi District Hospital, Malawi. Methods: We used a cross-sectional study design in which records of patients data on culture and antimicrobial sensitivity tests were extracted, alongside treatment history from 2019 to March, 2023, retrospectively. We also included findings for point prevalence survey (PPS) conducted within four hospital wards in June, 2022 by a well-trained multi-disciplinary team from within the hospital. The data was analyzed for antibiotic use, characterization of pathogens and their susceptibility patterns using Microsoft excel and STATA-14 software. Results: A total of 85 patients' data records were reviewed on antibiotics resistance pattern in which 54 (63.5%) were females. Patient antibiotic history captured indicated Metronidazole (23%), Gentamycin (20%) and Doxycycline (23%) as the most frequently used antibiotics among clients referred for microbiological investigations. Among locally available antibiotics with over 50% sensitivity were Chloramphenicol (61%), ciprofloxacin (55%), and ceftriaxone (54%). Penicillins were among antibiotics with highest resistance: ampicillin (100%), amoxyclav (90%), Piperacilin-tazobactam (63%). The majority of patients came from STI clinic and presented with genital discharges 44% (n = 39). Over 80% of the isolated N. gonorrhoeae exhibited a reduced susceptibility to gentamycin. Prevalence of Methicillin resistant staphylococcus Aureus (MRSA) was 46% and were mostly isolated from wound pus. Among 80 data records of the patients reviewed during PPS, Ceftriaxone (54.3%) and Metronidazole (23.3%) emerged as the most frequently used antibiotics in the wards which were prescribed empirically without a microbiological indication. Conclusion: In this study setting, we observed high use of watch antibiotics along with problem of multi-drug resistant infections in patients experiencing clinical failure in a variety of clinical syndromes. The findings underline the need to revamp diagnostic microbiology to increase the uptake of antimicrobial susceptibility testing to guide specific prescriptions of broad-spectrum antibiotics in the watch list. [ABSTRACT FROM AUTHOR]

Introduction: To effectively regulate and reduce antibiotic use, in the livestock sector, a thorough understanding of the flow of veterinary antibiotics will help to identify key nodes in the chain for targeted interventions. The aim of this study was to understand the flow of antibiotics from import to end-user, and identify relevant governance mechanisms. Methods: A mixed methods approach was used to collect data in three Kenyan counties (Nairobi, Kiambu, and Kajiado). Focus group discussions (n = 23), individual interviews (n = 148), and key informant interviews (n = 10) were conducted. Results: The key actors identified include primary wholesalers, secondary wholesalers, retailers, animal health service providers (AHSPs), and farmers. Kenya imports 100% of its veterinary antibiotics: primary wholesalers legally import antibiotics as finished pharmaceutical products (90%) or active pharmaceutical ingredients (10%) after approval by the Veterinary Medicines Directorate. Secondary wholesalers play a major role in the distribution of antibiotics (60% of antibiotics) from importers to farmers, AHSPs, and retailers. Some of the illegal sources of antibiotics include unlicenced/unauthorized middlemen and online platforms that sell directly to retailers, AHSPs, and farmers. Discussion: Despite the presence of various laws and regulations governing the antibiotic value chain, implementation has been a challenge due to financial and human resource constraints. This contributes to over-the-counter sale of antibiotics without prescription, unlicensed businesses selling antibiotics, illegal importation, and presence of poor-quality drugs. There is a need to review the applicability of existing policies and address policy gaps (e.g., product containing antibiotic combinations, and use of human critically important antibiotics) to ensure the prudent sale and use of antibiotics, pharmacovigilance, antimicrobial use surveillance, and developing a business model that aligns with antibiotic stewardship. Additional interventions include awareness raising and capacity building of the different stakeholders along the antibiotic distribution chain to reduce antibiotic mis- and overuse. [ABSTRACT FROM AUTHOR]

Background Antibiotic selection pressure in human medicine is a significant driver of antibiotic resistance in humans. The primary aspect of antibiotic consumption is associated with general practitioner (GP) prescriptions. We aimed to identify prescriber profiles for targeted antimicrobial stewardship programs using novel indicators. Methods A cross-sectional study was conducted in 2018 investigating GPs' antibiotic prescriptions in a French department, utilizing the reimbursement database of the national health service. Three antibiotic prescribing indicators were used. Specific targets were established for each indicator to identify the antibiotic prescribers most likely contributing to the emergence of resistance. Results Over 2018, we had 2,908,977 visits to 784 GPs, leading to 431,549 antibiotic prescriptions. Variations between GPs were shown by the 3 indicators. The median antibiotic prescription rate per visit was 13.6% (interquartile range [IQR], 9.8%–17.7%). Median ratios of the prescriptions of low-impact antibiotics to the prescriptions of high-impact antibiotics and of amoxicillin prescriptions to amoxicillin–clavulanic acid prescriptions were 2.5 (IQR, 1.7–3.7) and 2.94 (IQR, 1.7–5), respectively. We found 163 (21%) high prescribers of antibiotics with 3 distinct patterns: The first group overuses broad-spectrum antibiotics but without an overprescription rate per visit, the second group displays an overprescription rate but no excessive use of broad-spectrum antibiotics, and the third group shows both an overprescription rate and excessive use of broad-spectrum antibiotics. Conclusions Prescription-based indicators enable the identification of distinct profiles of antibiotic prescribers. This identification may allow for targeted implementation of stewardship programs focused on the specific prescribing patterns of each profile. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) stands out as the third-most common infection following gastrointestinal and respiratory tract infections. Over the past decade, the biomarker procalcitonin (PCT) has gained prominence to facilitate the detection of bacterial infections and reduce excessive antibiotic exposure. Objective: The objective of this study was to mitigate the overuse of antibiotics, by promoting the noninitiation or early discontinuation of empirical antibiotics, which would significantly help minimize the proliferation of multidrug-resistant bacteria. Methodology: A prospective observational study was carried out at the tertiary care center in the Department of General Medicine of Kalinga Institute of Medical Sciences, Bhubaneswar, involving 200 patients with symptoms of lower UTI such as increased frequency, urgency, burning micturition, retention, and suprapubic tenderness with or without positive urinalysis. Detailed demographic profiles along with symptoms at the time of admission were recorded in a pretested structured format. To determine a positive diagnosis of UTI, signs and symptoms of UTI with or without urinary cultures were tested. The PCT level was estimated using enhanced chemiluminescence technique. Other routine tests such as complete blood count, renal function test, liver function test, urine routine microscopy, culture, chest X-ray, and ultrasonography abdomen pelvis were done and recorded. All patients, who had an initial serum PCT level of < 0.5 ng/mL, were kept under observation with only conservative and symptomatic treatments. Patients were further reviewed for improvement in symptoms and repeat urine microscopy. All patients, who had an initial serum PCT level of > 0.5 ng/mL, were initiated with antibiotics as per the culture and sensitivity reports. Patients were followed up for improvement in symptoms with reports of repeated urinalysis. Results: Our study reported the fact that 9.5% of the patients with initial serum PCT = 0.5 ng/mL showed no improvement in symptoms despite starting antibiotics while significantly higher number of symptomatic patients (60%) with initial serum PCT < 0.5 ng/ml showed improvement in symptoms with conservative treatment without antibiotics. Conclusion: A lower PCT level rules out bacterial invasion and thus can be used as a novel marker in antibiotic stewardship. [ABSTRACT FROM AUTHOR]

Diagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. We developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022–2023) and 5-year pre-intervention MVP controls (2017–2022). VAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122–131], post-intervention rate 102 [95% CI: 92–112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177–1205], post-intervention rate 1149 [95% CI: 1116–1184], p 0.03). Implementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted. [ABSTRACT FROM AUTHOR]