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Penicillin allergy is a significant burden on patient, prescribing and hospital outcomes. There has been increasing interest in the incorporation of penicillin allergy testing (i.e. delabelling) into antimicrobial stewardship (AMS) programmes to reduce the burden of penicillin allergy labels and improve prescribing. In particular, there has been a focus on point‐of‐care penicillin allergy assessment and direct oral challenge for low‐risk phenotypes. The National Antibiotic Allergy Network has provided a guide to assist AMS clinicians with the incorporation of penicillin allergy programmes, in particular direct oral challenge, into Australian hospitals. [ABSTRACT FROM AUTHOR]

In this study delafloxacin resistance mechanisms in Escherichia coli strains were analyzed. Delafloxacin is a new fluoroquinolone, that is approved for clinical application however, resistance against this agent is scarcely reported. In our study 37 E. coli strains were included and antimicrobial susceptibility testing was performed for ciprofloxacin, delafloxacin, levofloxacin, moxifloxacin, ceftazidime, cefotaxime, imipenem. Six delafloxacin resistant E. coli strains were selected for whole-genome sequencing and all of them exhibited resistance to other fluoroquinonlones and showed an extended-spectrum beta-lactamase phenotype. The six delafloxacin resistant E. coli strains belonged to different sequence types (STs) namely, ST131 (2 strains), ST57 (2 strains), ST162 and ST15840. Each delafloxacin resistant strain possessed multiple mutations in quinolone resistance-determining regions (QRDRs). Notably, three mutations in gyrA Ser83Leu, Asp87Asn and parC Ser80Ile were in strains of ST162, ST57 and ST15840. However, the two strains of ST131 carried five combined mutations namely, gyrA Ser83Leu, Asp87Asn, parC Ser80Ile, Glu84Val, parE Ile549Leu. Association of delafloxacin resistance and production of CTX-M-15 in ST131, CMY-2 in ST162 and ST15840 was detected. In this study a new ST, ST15840 of clonal complex 69 was identified. Our results demonstrate, that at least three mutations in QRDRs are required for delafloxacin resistance in E. coli. [ABSTRACT FROM AUTHOR]

E. coli and total coliforms are the most widely used indicator organisms for microbial monitoring of drinking water and recreational freshwater. In many remote and low-resource settings, however, conventional laboratory methods for quantifying these indicators are challenging or infeasible to perform due to limited access to laboratory facilities. The availability of rapid, low-cost methods for quantifying indicator organisms in freshwater samples without the need for laboratory facilities is crucial to facilitate the rapid and robust monitoring of microbial water quality in these types of settings. The global misuse and abuse of antimicrobials have contributed to the rise of antimicrobial resistance. Thus, simple culture methods are needed to detect indicators of such bacteria in freshwaters. In 2021, the World Health Organization released the Tricycle protocol to address this issue by providing guidance for culture-based detection of extended-spectrum beta-lactamase (ESBL)-producing E. coli in environmental samples. Our research goal was to compare the 100-ml sample volume ESBL E. coli quantal and enumerative commercial tests against the more complex Tricycle protocol to detect and quantify ESBL E. coli in surface waters. Both commercial tests gave results comparable with the results obtained using the Tricycle protocol, and the quantal and enumerative commercial tests were easier and faster to perform than the Tricycle protocol. [ABSTRACT FROM AUTHOR]

The overuse of β-lactam drugs as the primary approach to antibiotic treatment for Enterobacteria-related infections has led to the selection of β-lactam-resistant isolates, so resistance to β-lactams has become a serious concern worldwide today. This study aimed to examine the patterns of antibacterial resistance and the prevalence of extended-spectrum β-lactamases (ESBLs) genes. A total of 100 Escherichia coli isolates were collected from stool samples of children with diarrhea between December 2020 and August 2021 from three different hospitals in Mashhad, Iran. Antibacterial resistance patterns and frequency of ESBL genes including blaTEM, blaSHV, blaCTX-M and blaOXA were investigated using the Polymerase chain reaction (PCR) technique and phenotypic method. Overall, the highest resistance was towards erythromycin (100%), followed by amoxicillin-clavulanic acid (69%), trimethoprim-sulfamethoxazole (63%), and cefixime (63%). On the other hand, the highest susceptibility was detected to amikacin (98%), gentamicin (98%), nitrofurantoin (97%), and ciprofloxacin (74%), respectively. Moreover, 75% of all isolates were multi-drug resistant (MDR), and the majority of ESBL-positive isolates showed considerably higher resistance rates, especially to cephalosporins, compared to ESBL-negative isolates. PCR screening revealed that the most prevalent ESBL gene was blaTEM at 93%, followed by blaCTX-M at 55%, while blaOXA and blaSHV were the least common, at 10% and 6%, respectively. The results emphasized the increased number of ESBL resistance gene carriers and their global dissemination. In addition, the high rate of MDR bacteria highlights the importance of continuously assessing antimicrobials to achieve effective antibiotic treatments. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infection (UTI) is one of the most common medical complaints in the emergency department (ED). The aim of this study was to assess the real indication of an initial broad-spectrum treatment administered in the ED for hospitalized patients with a diagnosis of community-acquired UTI (CAUTI). Materials and methods: This is a monocentric observational retrospective study conducted in the ED of one of the largest tertiary care centers in Lebanon, on a two-year period, including adult patients admitted to the hospital for a CAUTI. The primary outcome was to evaluate the need of downgrading empirical antibiotherapy started in the ED. Secondary outcomes included a description of CAUTIs characteristics: prevalence and risk factors for (extended spectrum beta lactamases) ESBL-related infection, complicated and uncomplicated UTIs, empirical and targeted treatment, and finally the rate of adherence to local guidelines. Results: The most isolated strains on urine cultures were gram negative bacilli (GNB) with 29.1% producing ESBL; 69.4% of patients received an ESBL-targeting empirical treatment in the ED, in agreement with local guidelines, 46% of which needed a downgrade. Amikacin adjunction was only indicated in 42.8% of the cases. Patients who received antibiotics in the last 6 months had a 2.36 times higher risk of developing an ESBL-related infection. Conclusion: This study showed a high adherence rate to local recommendations suggesting the use of empirical ESBL-targeting antibiotherapy even in uncomplicated UTIs. However, the frequent need of de-escalation highlights the importance of establishing an efficient multi-drug resistant (MDR) bacteria surveillance system in the community in order to elaborate a stewardship program with more solid local guidelines. [ABSTRACT FROM AUTHOR]

Background: Production of extended-spectrum β-lactamases (ESBLs) is a common resistance mechanism in Enterobacteriaceae, leading to serious hospital-acquired infections. This study aimed to assess phenotypic, phylogenetic, and antibiotic resistance patterns among ESBL-producing Escherichia coli isolates recovered from two rural tertiary hospitals in Thailand. Results: Among 467 Enterobacteriaceae isolates, E. coli was the most prevalent 356 (76.2%) followed by K. pneumoniae 88 (18.8%), K. aerogenes 8 (1.7%), K. variicola 3 (0.6%), K. quasipneumoniae 1 (0.2%%), K. oxytoca 1 (0.2%), and unidentified 9 (1.9%). Of the 202 cephalosporin-resistant E. coli isolates, 195 (96.5%) were ESBL-producing and 7 (3.5%) were non-ESBL-producing. Clermont typing revealed that phylogroup B2 was predominant (43.3%), followed by phylogroups F (11.3%), D (10.3%), C (9.7%), and A (8.7%). Among the beta-lactamase-encoding genes, blaCTX−M (83.6%) and blaTEM (81.0%) were widely found among the isolates, and blaCTX−M−1 (60.7%) was the most common among the five blaCTX−M subgroups detected. The predominant ESBL was blaCTX−M−15 (58.3%). All isolates were resistant to cefotaxime (100%) and ampicillin (100%), followed by ciprofloxacin (91.3 %), ceftazidime (72.8 %), and tetracycline (64.1%). Conclusion: Our findings show that phylogroup B2 was the most prevalent phylogroup among ESBL-producing E. coli isolates in northeastern Thailand. Notably, the isolates mostly carried the blaCTX−M gene(s). [ABSTRACT FROM AUTHOR]

Background Environmental disinfection is essential for reducing spread of healthcare-associated infections (HAIs). Previous studies report conflicting results regarding the effects of ultraviolet (UV) light in reducing infections. This trial evaluated the impact of adding pulsed-xenon UV (PX-UV) to standard terminal cleaning in reducing environmentally implicated HAIs (eiHAIs). Methods The Lowering the Acquisition of MDROs with Pulsed-xenon (LAMP) trial was conducted in 2 hospitals (15 inpatient wards) utilizing a cluster-randomized, controlled, double-blinded, interventional crossover trial comparing standard terminal cleaning followed by either PX-UV (intervention arm) or sham (control arm) disinfection. The primary outcome was incidence of eiHAIs from clinical microbiology tests on the fourth day of stay or later or within 3 days after discharge from the study unit. EiHAIs included clinical cultures positive for vancomycin-resistant enterococci, extended-spectrum beta-lactamase–producing Escherichia coli or Klebsiella pneumonia , methicillin-resistant Staphylococcus aureus , and Acinetobacter baumannii , and stool polymerase chain reaction (PCR) positive for Clostridiodes difficile. Results Between 18 May 2017 and 7 January 2020, 25 732 patients were included, with an incidence of 601 eiHAIs and 180 954 patient-days. There was no difference in the rate of eiHAIs in the intervention and sham arms (3.49 vs 3.17 infections/1000 patient-days, respectively; RR, 1.10; 95% CI,.94–1.29; P =.23). Study results were similar when stratified by eiHAI type, hospital, and unit type. Conclusions The LAMP study failed to demonstrate an effect of the addition of UV light disinfection following terminal cleaning on reductions in rates of eiHAIs. Further investigations targeting hospital environmental surfaces and the role of no-touch technology to reduce HAIs are needed. Clinical Trials Registration. ClinicalTrials.gov identifier: NCT03349268; R01HS024709. [ABSTRACT FROM AUTHOR]

We report identification of 5 patients with infections caused by NDM-5-producing Escherichia coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management. [ABSTRACT FROM AUTHOR]

This study describes ceftazidime-avibactam use in 17 young children from a resource-constrained country, where intra-abdominal infection was common. All-cause mortality was 53%. Earlier initiation, dose optimization, recording infusion times, and reviewing the need for additional antibiotics were identified as easy-to-implement-antimicrobial-stewardship interventions. [ABSTRACT FROM AUTHOR]

Background Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. Methods We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21–28), and late follow-up (LFU; Days 35–42). Results A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P  = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. Conclusions Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (particularly bacterial resistance to antibiotics) represents a major public health issue worldwide. There is growing concern that more and more bacteria are becoming resistant to antibiotics as a result of genetic mutations. In this article, we describe the main mechanisms through which bacteria can resist the action of antibiotics and the transfer of resistance between bacteria of the same species or different species. Some bacteria acquire resistance to multiple antibiotics from different classes, becoming multidrug- resistant bacteria, which are increasing globally and can cause severe infections, making them difficult to treat and contributing to the spread of this resistance (examples: methicillin- resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum β-lactamase-producing Enterobacteriaceae, etc.). The major causes of antibiotic resistance development are the excessive use of antibiotics and the transmission of resistant pathogens in human and animal populations, as well as between humans, animals and the environment. It is important to note the transmission of resistant bacteria within healthcare-associated institutions. Globally, antibiotic resistance is a serious threat due to its continuous increase and the diminishing effectiveness of common antibiotics, with the risk of returning to the pre-antibiotic era. Thus, international health organizations are raising the alarm, highlighting the urgent need to improve surveillance, prevention, and control of bacterial resistance to antibiotics, as well as the need for research development to identify rapid and accurate diagnostic tests for detecting infections caused by resistant bacteria and to develop new medications. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Enterobacterales bloodstream infections (E-BSI) cause a significant burden of disease in children and are associated with antimicrobial resistance. We assessed temporal changes in the population-based incidence of E-BSI in children in Queensland, Australia. METHODS: We conducted a cohort study of incidents of E-BSI occurring in children in Queensland between 2000 and 2019, with a total population of 19.7 million child years. Infections were linked to clinical outcomes in hospital admissions and vital statistics databases. We estimated age- and sex-standardized E-BSI incidence rates over time. Secondary outcomes included the proportion of extended-spectrum b-lactamase phenotypes per year, hospital length of stay, and mortality. RESULTS: We identified 1980 E-BSI in 1795 children. The overall age- and sex-standardized incidence rate was 9.9 cases per 100 000 child years, which increased from 7.3 to 12.9 over the period studied, an increase of 3.9% (95% confidence interval: 3.1-4.7) per year. There were 3.6 cases of E. coli bloodstream infection per 100 000 child years, increasing annually by 4.7% (3.5-5.9). The Salmonella sp. bloodstream infection incidence was 3.0 cases per 100 000 child years, which increased from 2013 by 13.7% (3.8-24.3) per year. The proportion of extendedspectrum β-lactamase E. coli increased over time. Mortality and length of stay were higher among children with comorbidities than those without (4.0% vs 0.3%, and 14 vs 4 days, respectively, P < .001). CONCLUSIONS: The age- and sex-standardized incidence of E-BSI almost doubled in Queensland children over 2 decades, driven by increases in Salmonella sp. and E. coli. Increasing resistance of E. coli should prompt the inclusion of children in antimicrobial clinical trials. [ABSTRACT FROM AUTHOR]

Background: Cefazolin is guideline recommended for perioperative prophylaxis in orthopedic surgery. Despite its unique R1 side chain, cefazolin is often avoided in patients with beta-lactam allergy with concern for cross reactivity. Objectives: The primary outcome was the percentage of patients who received cefazolin perioperatively. Secondary outcomes included the percentage of patients with a beta-lactam allergy clarified following the telephone interview and clinical outcomes including acute kidney injury, surgical site infection, Clostridioides difficile infection, and re-admission at 30 and 90 days. Methods: This single-center, quasi-experimental study evaluated a pilot program in which a pharmacist phoned patients > 18 years of age with a scheduled orthopedic surgery and a documented beta-lactam allergy to assess their allergy preoperatively. Recommendations to use cefazolin were based on an algorithm. Patients were divided into pre- and post-intervention cohorts. Results: A total of 832 patients were screened for inclusion with 135 and 66 patients included in the pre- and post-intervention cohorts. No significant difference was identified in the primary outcome. In the post-intervention cohort, 62% had a beta-lactam reaction updated in the electronic medical record. Those with a beta-lactam allergy delabeled or made less severe were numerically more likely to receive cefazolin than those with an unchanged reaction or a reaction made more severe (95.2% vs 68% vs 65%). There were no differences in clinical outcomes between groups. Conclusion: A pharmacist-conducted preoperative beta-lactam allergy interview in adult patients undergoing elective orthopedic surgery improved beta-lactam allergy documentation but, did not result in increased utilization of cefazolin. [ABSTRACT FROM AUTHOR]

Background: Acquired 16S rRNA methyltransferases (16S-RMTases) confer high-level resistance to aminoglycosides and are often associated with β-lactam and quinolone resistance determinants. Methods: Using PCR, whole-genome sequencing and conjugation experiments, we conducted a retrospective genomic surveillance study of 16S-RMTase-producing Enterobacterales, collected between 2006 and 2023, to explore transmission dynamics of methyltransferase and associated antibiotic resistance genes. Results: Among the 10,731 consecutive isolates, 150 (1.4%) from 13 species carried armA (92.7%), rmtB (4.7%), and rmtF + rmtB (2.7%) methyltransferase genes. The coexistence of extended-spectrum β-lactamase (blaCTX-M-3/15, blaSHV-12, blaSFO-1), carbapenemase (blaNDM-1/5, blaVIM-1/4/86, blaOXA-48), acquired AmpC (blaCMY-2/4/99, blaDHA-1, blaAAC-1), and plasmid-mediated quinolone resistance (qnrB, qnrS, aac(6′)-Ib-cr) genes within these isolates was also detected. Methyltransferase genes were carried by different plasmids (IncL/M, IncA/C, IncR, IncFIB, and IncFII), suggesting diverse origins and sources of acquisition. armA was co-transferred with blaCTX-M-3/15, blaNDM-1, blaVIM-4/86, blaOXA-48, blaCMY-4, aac(6′)-Ib-cr, qnrB, and qnrS, while rmtF1 was co-transferred with blaSFO-1, highlighting the multidrug-resistant nature of these plasmids. Long-read sequencing of ST6260 K. pneumoniae isolates revealed a novel resistance association, with rmtB1 and blaNDM-5 on the chromosome, blaOXA-232 on a conjugative ColKP3 plasmid, and rmtF1 with blaSFO-1 on self-transmissible IncFIB and IncFII plasmids. Conclusions: The genetic plasticity of plasmids carrying methyltransferase genes suggests their potential to acquire additional resistance genes, turning 16S-RMTase-producing Enterobacterales into a persistent public health threat. [ABSTRACT FROM AUTHOR]

Background/Objectives: The global emergence of antibiotic-resistant zooanthroponotic Escherichia coli strains, producing extended-spectrum beta-lactamases (ESBL-E) and persisting in the intestines of farm animals, has now led to the development of a pandemic of extra-intestinal infectious diseases in humans. The search for innovative probiotic microorganisms that eliminate ESBL-E from the intestines of humans and animals is relevant. Previously, we received three isolates of bifidobacteria: from milk of a calved cow (BLLT1), feces of a newborn calf (BLLT2) and feces of a three-year-old child who received fresh milk from this calved cow (BLLT3). Our goal was to evaluate the genetic identity of BLLT1, BLLT2, BLLT3 isolates using genomic DNA fingerprinting (GDF), to study the tolerance, adhesion, homeostatic and antibacterial activity of BLLT1 against ESBL-E. Methods: We used a complex of microbiological, molecular biological, and immunological methods, including next generation sequencing (NGS). Results: GDF showed that DNA fragments of BLLT2 and BLLT3 isolates were identical in number and size to DNA fragments of BLLT1. These data show for the first time the possibility of natural horizontal transmission of BLLT1 through with the milk of a calved cow into the intestines of a calf and the intestines of a child. BLLT1 was resistant to gastric and intestinal stresses and exhibited high adhesive activity to calf, pig, chicken, and human enterocytes. This indicates the unique ability of BLLT1 to inhabit the intestines of animals and humans. We are the first to show that BLLT1 has antibacterial activity against ESBL-E strains that persist in humans and animals. BLLT1 produced 145 ± 8 mM of acetic acid, which reduced the pH of the nutrient medium from 6.8 to 5.2. This had an antibacterial effect on ESBL-E. The genome of BLLT1 contains ABC-type carbohydrate transporter gene clusters responsible for the synthesis of acetic acid with its antibacterial activity against ESBL-E. BLLT1 inhibited TLR4 mRNA expression induced by ESBL-E in HT-29 enterocytes, and protected the enterocyte monolayers used in this study as a bio-model of the intestinal barrier. BLLT1 increased intestinal alkaline phosphatase (IAP) as one of the main molecular factors providing intestinal homeostasis. Conclusions: BLLT1 shows promise for the creation of innovative functional nutritional products for humans and feed additives for farm animals that will reduce the spread of ESBL-E strains in the food chain. [ABSTRACT FROM AUTHOR]

The global emergence of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae presents a significant public health threat and complicates antibiotic treatment for infections. This study aimed to determine the prevalence of ESBL-producing K. pneumoniae in a clinical setting, analyze their antimicrobial susceptibility profiles, and characterize both phenotypic and genetic determinants. A total of 507 non-duplicate clinical isolates of Enterobacterales were collected between 2019 and 2020, and third-generation cephalosporin resistance was screened by disk diffusion. Identification of K. pneumoniae was confirmed using biochemical tests and PCR with species-specific primers. Antimicrobial susceptibility testing was conducted using disk diffusion, and phenotypic ESBL production was confirmed using the combined disk method. Multiplex PCR detected ESBL genes (blaTEM, blaSHV, and blaCTX-M) and identified blaCTX-M groups. The genetic relatedness of ESBL-producing strains was assessed using the ERIC-PCR approach. Fitty-four isolates were confirmed as ESBL producers, all classified as multidrug-resistant (MDR). All ESBL-producing K. pneumoniae isolates exhibited resistance to ampicillin and cefotaxime, with high resistance rates for ciprofloxacin (98.2%), azithromycin (94.4%), piperacillin–tazobactam (88.9%), and trimethoprim (83.3%). Genotypic analysis revealed blaCTX-M was present in 94.4% of isolates, blaSHV in 87%, and blaTEM in 55.5%. The blaCTX-M-1 group was the most prevalent, accounting for 96.1% of isolates. Co-harboring of blaCTX-M, blaSHV, and blaTEM occurred in 42.6% of isolates, with co-carrying of blaCTX-M, and blaSHV was observed in 23/54 isolates. The ERIC-PCR analysis revealed 15 distinct types, indicating high genetic diversity. These findings highlight the urgent need for ongoing monitoring to control the spread of ESBL among K. pneumoniae and emphasize the importance of early detection and appropriate antibiotic selection for effectively treating infection caused by these pathogens. [ABSTRACT FROM AUTHOR]

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Background: This meta-analysis was conducted to compare the efficacy of ceftazidime-avibactam combination therapy with that of monotherapy in the treatment of carbapenem-resistant Gram-negative bacterial (CR-GNB). Methods: A literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was conducted until September 1, 2023. Only studies that compared CZA combination therapy with monotherapy for CR-GNB infections were included. Results: A total of 25 studies (23 retrospective observational studies and 2 prospective studies) involving 2676 patients were included. There was no significant difference in 30-day mortality between the study group receiving combination therapy and the control group receiving monotherapy (risk ratio [RR] 0.91; 95% confidence interval [CI] 0.71–1.18). In addition, no significant differences were observed between the study and the control group in terms of in-hospital mortality (RR 1.00; 95% CI 0.79–1.27), 14-day mortality (RR 1.54; 95% CI 0.24–9.91), 90-day mortality (RR 1.18; 95% CI 0.62–2.22), and clinical cure rate (RR 0.95; 95% CI 0.84–1.08). However, the combination group had a borderline higher microbiological eradication rate than the control group (RR 1.15; 95% CI 1.00–1.32). Conclusions: Compared to monotherapy, CZA combination therapy did not yield additional clinical benefits. However, combination therapy may be associated with favorable microbiological outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. Methods: This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0–18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. Findings: Among 224 surgeries (median age 38.5 months (IQR 22–85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0–1), PICU stay 3 days (IQR 2–4) and hospital stay 6.5 days (IQR 5–10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. Conclusion: Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The present work primarily focuses on the monitoring of antimicrobial resistance from fecal Escherichia coli from wildlife, an important environmental task due to the spread of resistant bacteria. In total, 128 E. coli isolates recovered from 66 wild animals were analyzed. Their resistance was tested against 17 antibiotics. An approximate percentage of 22.1% of the animals was found to carry multidrug-resistant E. coli, and 0.93% carried strains producing extended-spectrum β-lactamase (ESBL). The highest resistance was observed against ampicillin; all of the isolates were susceptible to amikacin and carbapenems. Therefore, such findings bring concerns about the dissemination of resistant bacteria among wildlife and any further impacts on public health. Antimicrobial resistance (AMR) surveillance in fecal Escherichia coli isolates from wildlife is crucial for monitoring the spread of this microorganism in the environment and for developing effective AMR control strategies. Wildlife can act as carriers of AMR bacteria and spread them to other wildlife, domestic animals, and humans; thus, they have public health implications. A total of 128 Escherichia coli isolates were obtained from 66 of 217 fecal samples obtained from different wild animals using media without antibiotic supplementation. Antibiograms were performed for 17 antibiotics to determine the phenotypic resistance profile in these isolates. Extended-spectrum β-lactamase (ESBL) production was tested using the double-disc synergy test, and 29 E. coli strains were selected for whole genome sequencing. In total, 22.1% of the wild animals tested carried multidrug-resistant E. coli isolates, and 0.93% (2/217) of these wild animals carried E. coli isolates with ESBL-encoding genes (blaCTX-M-65, blaCTX-M-55, and blaEC-1982). The E. coli isolates showed the highest resistance rates to ampicillin and were fully susceptible to amikacin, meropenem, ertapenem, and imipenem. Multiple resistance and virulence genes were detected, as well as different plasmids. The relatively high frequency of multidrug-resistant E. coli isolates in wildlife, with some of them being ESBL producers, raises some concern regarding the potential transmission of antibiotic-resistant bacteria among these animals. Gaining insights into antibiotic resistance patterns in wildlife can be vital in shaping conservation initiatives and developing effective strategies for responsible antibiotic use. [ABSTRACT FROM AUTHOR]

The primary factor behind Enterobacteriaceae members' resistance to β-lactam antibiotics is extended spectrum β-lactamases. Infections of the urinary tract are most frequently caused by Escherichia coli, a member of the Enterobacteriaceae family (UTIs). About 80% of isolates that lead to urinary tract infections are E. coli. For the treatment of urinary tract infections (UTIs), beta-lactam antibiotics such as cephalosporins and penicillins are the most widely prescribed and safest antimicrobial medicines. Our goals were to look at the prevalence of E. coli that produces ESBL and identify drugs that work well against isolates of E. coli that produce ESBL from urine samples. To study the treatment option for urinary tract infections caused by extended spectrum β-lactamase producing E. coli. In all, 312 E. coli isolates were obtained from urine samples throughout the August 2022-December 2023 study period. Testing for antimicrobial susceptibility was done according to the CLSI guidelines. The double disk diffusion test revealed the presence of ESBL production. In the present study, out of the 312 E. coli isolates, 71(22.7%) were phenotypically identified as ESBL producers and 241(77.3%) were non-ESBL. Among 71 ESBL producing E. coli strains, 51 (71.8%) belong to In-patients and 20 (28.2%) belong to Out-patients gave statistically significant results. All ESBL (100%) were sensitive to Nitrofurantoin. In conclusion, our study is the first in-depth investigation of antibiotic resistance from a tertiary care hospital in Lucknow and it demonstrates a low incidence of ESBL among E. coli isolates. This may facilitate the implementation of control measures for hospital- and community-based illnesses caused by the emergence of antibiotic resistance. [ABSTRACT FROM AUTHOR]

This study explored the molecular epidemiology and resistance mechanisms of 271 non-duplicate Salmonella enterica (S. enterica) strains, isolated mainly from adults (209/271) in a tertiary hospital in Hangzhou between 2020 and 2021. Through whole-genome sequencing and bioinformatics, the bacterial strains were classified into 46 serotypes and 54 sequence types (ST), with S. Enteritidis, S. 1,4,[5],12:i:-, and S. Typhimurium being the most prevalent serotypes and ST11, ST34, and ST19 the most common STs. The strains isolated from adults were primarily S. Enteritidis (59/209), while from children were mainly S. 1,4,[5],12:i:- (20/62). Worryingly, 12.55% strains were multi-drug resistant (MDR), with resistance rates to cefepime (FEP), ceftazidime (CAZ), ceftriaxone (CRO) and cefotaxime (CTX) of 7.38%, 9.23%, 15.87% and 16.24%, respectively, and resistance rates to levofloxacin (LEV) and ciprofloxacin (CIP) of 8.49% and 19.19%, respectively. It is worth noting that the resistance rates of CRO and CTX in children reached 30.65%. A total of 34 strains carried extended-spectrum β-lactamase (ESBL) genes, dominated by blaCTX-M-65 (13/34) and blaCTX-M-55 (12/34); it is notable that one strain of S. Saintpaul carried both blaCTX-M-27 and blaCTX-M-55. The resistance mechanism to cephalosporins was mainly due to ESBL genes (20/43), and other genes included AmpC and β-lactamase genes. The strains resistant to quinolones mainly carried qnrS1 (27/53), and others included qnrB6, aac(6′)-Ib-cr, and mutations in gyrA and parC. One strain did not carry common quinolone resistance genes but had a parC (p.T57S) mutation to cause CIP resistance. This research provides vital insights into the molecular epidemiology and resistance mechanisms of clinical S. enterica, implicating possible infection control strategies. [ABSTRACT FROM AUTHOR]

Background Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes. Methods A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. Results There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6–8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were bla CTX-M-15 (34/94, 36%) and bla SHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6–6.4). Conclusions GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence, trends, and potential nosocomial transmission events of the hidden reservoir of rectal carriage of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). Methods: From 2013 to 2022, yearly point prevalence surveys were conducted in a large Dutch teaching hospital. On the day of the survey, all admitted patients were screened for ESBL-E rectal carriage using peri-anal swabs and a consistent and sensitive selective culturing method. All Enterobacterales phenotypically suspected of ESBL production were analysed using whole genome sequencing for ESBL gene detection and clonal relatedness analysis. Results: On average, the ESBL-E prevalence was 4.6% (188/4,119 patients), ranging from 2.1 to 6.6% per year. The ESBL-prevalence decreased on average 5.5% per year. After time trend correction, the prevalence in 2016 and 2020 was lower compared to the other year. Among the ESBL-E, Escherichia coli (80%) and CTX-M genes (85%) predominated. Potential nosocomial transmission events could be found in 5.9% (11/188) of the ESBL-E carriers. Conclusions: The ESBL-E rectal carriage prevalence among hospitalized patients was 4.6% with a downward trend from 2013 to 2022. The decrease in ESBL-E prevalence in 2020 could have been due to the COVID-19 pandemic and subsequent countrywide measures as no nosocomial transmission events were detected in 2020. However, the persistently low ESBL-E prevalences in 2021 and 2022 suggest that the decline in ESBL-E prevalence goes beyond the COVID-19 pandemic, indicating that overall ESBL-E carriage rates are declining over time. Continuous monitoring of ESBL-E prevalence and transmission rates can aid infection control policy to keep antibiotic resistance rates in hospitals low. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa has recently been labeled a major threat to public health due to its resistance to almost all commonly used antibiotics. Many factors have been suggested for P. aeruginosa's antibiotic resistance. The goal of this study is to find out what role SIM and NDM, which are related to carbapenem resistance, play in P. aeruginosa isolates from local clinical sources. In this study, out of 110 different clinical specimens, 50 were identified as P. aeruginosa from hospitalized patients. All of the isolates were characterized based on the biochemical test and confirmed using the VitekII compact system. P. aeruginosa isolates were tested for antibiotic susceptibility using 8 antibiotics, including: amikacin, tobramycin, ciprofloxacin, levofloxacin, imipenem, meropenem, piperacillin/tazobactam, ticarcillin, and clavulanate. Susceptibility testing results revealed that every isolate was highly resistant to Piperacillin/Tazobactam, with lower resistance to Ticarcillin/clavulanate (TCC). Using the broth dilution method, the minimum inhibitory concentration (MIC) of P. aeruginosa isolates resistant to meropenem ranged from 32µg/100µl to 128 µg/100µl. The EDTA combined disc test was used to detect the ability of P. aeruginosa isolates to produce carbapenemase, and the results showed that all isolates were carbapenemase producers. Additionally, conventional PCR confirmed the identification of P. aeruginosa using 16S. Realtime PCR was adopted to assess the expression of the NDM and SIM genes in 25 of the identified P. aeruginosa isolates. The mean of gene expression results for NDM showed increased expression compared to the control sample of 1.74, while the SIM gene showed expression of 0.95. These genes, SIM and NDM in class B (which are important for resistance in Pseudomonas aeruginosa), result from chromosomal changes that mutate the membrane permeability flow pump, causing excessive expression. [ABSTRACT FROM AUTHOR]

Aims The increasing prevalence of AmpC β-lactamase (AmpC)- and extended-spectrum β-lactamase (ESBL)- producing food pathogens is a serious public health concern. AmpC- and ESBL-producing Salmonella species pose a high risk of food contamination. This study aimed to investigate changes in the prevalence of Salmonella among food handlers in Japan from 2006 to 2021 using 100 randomly selected isolates from 2006, 2012, 2018, and 2021 with different serotypes and antimicrobial resistance patterns. Methods and results The average Salmonella isolation rate was 0.070% (19 602/27 848 713). Serotyping revealed that the most common serotypes were Enteritidis in 2006, Infantis in 2012, Agoueve/Cubana in 2018, and Schwarzengrund in 2021. Antimicrobial susceptibility testing showed that Salmonella isolates exhibited the highest resistance to streptomycin (<40%), followed by tetracycline (<20%–40%). Moreover, 6% of the Salmonella isolates produced cephalosporinases with the bla CMY-2, bla CTX-M-14, and bla TEM genes. The annual incidence of cephalosporin resistance has increased. Plasmid conjugation assays revealed that cephalosporin-resistant Salmonella spp. transmitted their resistance to Escherichia coli. Additionally, plasmid genome analysis showed that the insertion sequence IS 26 was encoded in the upstream and downstream regions of bla CTX-M-14 and qnrS1 in the IncHI1 plasmid, which could be transmitted to other bacteria. Conclusions The tested Salmonella isolates showed high resistance to specific antibiotics, with differences in resistance depending on the serotype. Further increase and spread of transmissible cephalosporin-resistant strains should be noted. [ABSTRACT FROM AUTHOR]

In the present study, a total of 102 samples were collected from chickens of different flocks, died due to suspected colibacillosis. Bacteriological and PCR methods were applied to detect avian pathogenic Escherichia coli (APEC). Phenotypic antimicrobial resistance (AMR) was determined by disk diffusion method. Extended spectrum beta lactamases (ESBL) detection was carried out via PCR by targeting blaTEM, blaSHV, blaOXA, and blaCTX-M groups 1, 2, and 9. Genes of eight virulence factors and class I integrons were also detected by PCR using gene specific primers. Culture, microscopic, biochemical tests and PCR recognised 69/102 (67.64%) samples as E. coli. Phenotypic AST revealed higher resistance against fluoroquinolone antibiotics, i.e., enrofloxacin (72.46%), levofloxacin (69.56%) & ciprofloxacin (66.66%), followed by amoxyclav (63.77%) and tetracycline (59.42%). Six isolates were found as pan-drug-resistant E. coli. A total of 48 (69.56%) and 7 (10.14%) isolates were positive for the presence of blaTEM and blaCTX-M-G9 genes, respectively, whereas 2 (2.90%) isolates each were found positive for blaSHV, blaOXA, and blaCTX-M-G1 genes. Among APEC associated virulence genes, iss (79.71%) was the most predominant, followed by tsh (50.72%), ast (30.43%), cvaf (26.08%), pap (23.18%), vat (8.69%) and stx-1 (1.44%). Thirty-two isolates harboured class I integrons, either with or without ESBL genes. Conclusively, the isolates under study showed pan and multiple-drug resistance, specifically against fluoroquinolone drugs. ESBL production was mediated principally through blaTEM and blaCTX-M-G9. Multiple virulence factors, toxins, and carriage & spread factor render these as zoonotically potential pathogens for humans. [ABSTRACT FROM AUTHOR]

Targeting the class A Beta lactamases Omega loop is an ideal way to combat drug resistance because of its significant role in the catalytic activity and deacylation process inhibition. Therefore, the molecular docking approach with computerized peptide-based in silico screening has been applied for the identification of inhibitors of TEM-type bLs. Among the subjected 105 peptides, Chrombacin (-47.8 KJ/mol), Gassericin A (-35.7 KJ/mol), Duramycin (-34.1 KJ/mol), Brevinin-1DYa (-34.0 KJ/mol), Amoebapore A (-31.2 KJ/mol), Mundticin ATO6 (-29.0 KJ/mol), Lactocyclicin Q (-26.3 KJ/mol), Cinnamycin (-25.9 KJ/mol showed highest binding energy. Among the peptides that showed the highest docking score Elafin, Cinnamycin, Duramycin interacted with Lys 73 of the a domain of catalytic residues of TEM-1 Beta lactamases, whereas Taromycin A, Gassericin A interacted with Lys 234 of the b domain, depicting a strong inhibition and also exhibited desirable physicochemical properties. Hence further in vitro examination of these cyclic peptides against the resistant strains is warranted to help design further novel inhibitors based on their scaffolds and also for the development of an effective drug combination regime. [ABSTRACT FROM AUTHOR]

Objectives The measurement of VOCs release in the headspace of a bacterial culture represents a new approach to rapidly assess antimicrobial susceptibility. Herein, we evaluated the diagnostic performance of the VITEK® REVEAL™ system directly from a collection of Gram-negative positive blood cultures. Materials and methods One hundred and twenty-eight positive blood cultures were included in the analysis (Enterobacterales, n  = 95; Pseudomonas aeruginosa , n  = 21; Acinetobacter baumannii complex, n  = 12). Samples were processed using VITEK® REVEAL™ according to the manufacturer's recommendations, and MICs of 22 antimicrobials were compared with those obtained using reference methods. Categorical agreement (CA), essential agreement (EA) and categorical errors were calculated. Results Overall, 2220 strain/antibiotic pair combinations were analysed. Of these, most were classified as resistant by reference antimicrobial susceptibility testing (1091/2220; 48.7%). The overall CA and EA were 97.6% and 97.7%, respectively. CA ranged from 97.5% in Enterobacterales to 97.9% in both P. aeruginosa and A. baumannii complex. The overall number of categorical discrepancies were: 18 very major errors (1.6%), 13 major errors (1.2%) and 22 minor errors (2.4%). EA ranged from 95.2% in P. aeruginosa to 98.1% in Enterobacterales. Screening test for ESBL phenotype was positive, indeterminate and negative in 13.7%, 32.6% and 27.4% of Enterobacterales isolates tested by both VITEK® REVEAL™ and the reference method, showing 100% CA. Conclusions VITEK® REVEAL™ represents a reliable tool to obtain antimicrobial susceptibility results of the main Gram-negative species directly from positive blood cultures with time to results of less than 8 h. [ABSTRACT FROM AUTHOR]

This study aims to identify bacterial contamination of Klebsiella pneumoniae and Escherichia coli producing Extended Spectrum Beta Lactamase (ESBL) isolated from rectal swabs of local animals on a dairy farm in Deyeng Village, Kediri, East Java. Interviews and observations were conducted with farmers to obtain the required risk factor data (cleanliness of drinking and eating places, drinking water sources, and administration of antibiotics to livestock). The number of samples tested in this study was 34 samples, including 12 chicken samples, 8 goat samples, 5 duck samples, 4 rabbit samples, 3 cat samples and 2 goose samples. Samples were isolated on MCA media + cefotaxime 1 mg/l and isolated again on MCA media without the addition of antibiotics to multiply pure bacterial colonies. The tests carried out to determine the presence of ESBLproducing bacteria are biochemical tests, namely the IMViC test (Indole, Methyl red, Voges-Proskauer, Citrate Utilization), TSIA (Triple Sugar Iron Agar) test, gram staining, and the Double Disk Standard Method test using ß-lactam disc antibiotics, namely cefotaxime 30µg, ceftazidime 30µg, and amoxycillineclavulanate acid 30µg. The results of this research were that 6 samples or 17.6% of ESBL-producing bacteria were identified from poultry groups (chickens, ducks and geese) from dairy farms in Deyeng Village, Kediri Regency, East Java. [ABSTRACT FROM AUTHOR]

BACKGROUND: Firearm injuries (FI) remain a significant cause of morbidity and mortality globally. Antibiotic use, supported by guideline recommendations for preventing post-injury infections in FI cases, encounters uncertainties regarding the selection of antimicrobial agents and associated outcomes. This study aimed to investigate the relationship between Injury Severity Scores (ISS) for FI cases presented to the emergency department. METHODS: We empirically revised antimicrobial treatment protocols based on culture results and mortality rates. In the study, 164 firearm injury cases, admitted to the emergency department in 2022 and subsequently hospitalized in clinics and intensive care units (ICU), were evaluated. Cases included in the study were categorized into four groups based on ISS: mild, moderate, severe, and profound injury severity. The study compared the timing of hospital presentation following the injury, hospital length of stay, tissue or blood culture positivity, empirical treatment administered, antimicrobial revision based on culture results, need for ICU admission, mortality status, and ISS among the cases. Data were analyzed using IBM SPSS Statistics 22.0 (SPSS Inc., Chicago, IL). Variables in trauma patients were compared among various groups using Pearson Chi-Square tests. Binary logistic regression tests were performed to identify independent risk factors. A significance level of p<0.05 was considered statistically significant. RESULTS: The study included 164 patients, all of whom were male. The mean age was calculated as 28.9±4.51 years. The average hospital length of stay was 25.54±21.81 days. Eighty-three patients (50.6%) required intensive care. Tissue cultures were obtained from 79 patients (48%). Bacterial growth was observed in 45 of these 79 patients (57%). The appropriate empirical antibiotic treatment rate, assessed among patients who received empirical treatment followed by culture-based antibiotic sensitivity testing, was 48.9%. It was observed that empirical antibiotic regimens were appropriate in 80% of cases in the mild group and 16.7% in the profound severe group (p=0.005). Our study compared the relationship between hospitalization duration and ISS groups. It was observed that hospitalization duration was significantly shorter in the mild group compared to the other groups (p=0.003, p=0.000, p=0.000). It was also observed that the need for ICU admission was higher in groups with higher ISS, indicating a correlation between higher ISS and increased ICU requirements (p=0.000). CONCLUSION: In conclusion, for cases of firearm injuries, we believe empirical antimicrobial therapy should be initiated with narrow-spectrum agents such as beta-lactam + beta-lactamase inhibitor or third-generation cephalosporin + nitroimidazole in the mild group, considering the lack of Pseudomonal activity. [ABSTRACT FROM AUTHOR]

Foodborne pathogens' transmission is essential in the spread of antibiotic resistance, and extended-spectrum beta-lactamase-producing Escherichia coli especially threatens public health. E. coli plays an essential role in the resistance to commonly used beta-lactam group antibiotics. Ready-to-eat (RTE) stuffed mussels are among many restaurants and street vendors, presenting potential health risks of food hygiene origin. 200 RTE stuffed mussels were collected from the Asian and European sides of Istanbul and analysed for the presence of E. coli. As a result of PCR analysis, E. coli was detected in 7 (3.5%) samples. An antibiotic susceptibility test was performed using the disc diffusion method to determine ESBL and carbapenem resistance. All isolates were resistant to ampicillin. The double-disk synergy test was performed as an ESBL phenotypic confirmation test, and no phenotypically ESBL-producing E. coli were detected. The bla TEM gene was detected in one isolate (14.2%) by mPCR, but bla CTX-M, bla SHV, and bla OXA genes were not observed. Meropenem and imipenem were used with the disk diffusion method for carbapenem resistance study, and no resistant isolate was found. Carbapenem resistance genes were investigated by monoplex PCR, and bla NDM-1, bla OXA-48, bla VIM, and bla IMP resistance genes were not detected. This is the first report on ESBL-producing E. coli in RTE stuffed mussels in Türkiye, which draws attention to a public health risk. [ABSTRACT FROM AUTHOR]

The global spread of antimicrobial resistance genes (ARGs) in Escherichia coli is a major public health concern. The aim of this study was to investigate the genomic characteristics of extended-spectrum β-lactamase (ESBL)-producing and third-generation cephalosporin-resistant E. coli from a previously obtained collection of 260 E. coli isolates from fecal samples of patients attending primary healthcare facilities in Addis Ababa and Hossana, Ethiopia. A total of 29 E. coli isolates (19 phenotypically confirmed ESBL-producing and 10 third-generation cephalosporin-resistant isolates) were used. Whole-genome sequencing (NextSeq 2000 system, Illumina) and bioinformatic analysis (using online available tools) were performed to identify ARGs, virulence-associated genes (VAGs), mobile genetic elements (MGEs), serotypes, sequence types (STs), phylogeny and conjugative elements harbored by these isolates. A total of 7 phylogenetic groups, 22 STs, including ST131, and 23 serotypes with different VAGs were identified. A total of 31 different acquired ARGs and 10 chromosomal mutations in quinolone resistance-determining regions (QRDRs) were detected. The isolates harbored diverse types of MGEs, with IncF plasmids being the most prevalent (66.7%). Genetic determinants associated with conjugative transfer were identified in 75.9% of the E. coli isolates studied. In conclusion, the isolates exhibited considerable genetic diversity and showed a high potential for transferability of ARGs and VAGs. Bioinformatic analyses also revealed that the isolates exhibited substantial genetic diversity in phylogenetic groups, sequence types (ST) and serogroups and were harboring a variety of virulence-associated genes (VAGs). Thus, the studied isolates have a high potential for transferability of ARGs and VAGs. [ABSTRACT FROM AUTHOR]

This retrospective study evaluates the incidence and risk factors of community-acquired urinary tract infections (CA-UTIs) linked to extended-spectrum beta-lactamase–producing Enterobacterales (ESBLPE). The study was conducted in a tertiary hospital in northern Israel and included children younger than 18 years with CA-UTIs due to Enterobacterales who were admitted to the emergency department, during the years 2017 to 2019. Among the 570 children, 9.8% had ESBLPE-associated CA-UTIs. This prevalence remained steady over the study period. ESBLPE exhibited substantial resistance to amoxicillin/clavulanic acid (62.5% vs 20.4%, P <.001, odds ratio [OR] = 6.5), trimethoprim/sulfamethoxazole (58.9% vs 18%, P <.001, OR = 6.6), ciprofloxacin (33.9% vs 3.1%, P <.001, OR = 15.9), piperacillin/tazobactam (26.8% vs 7%, P <.001, OR = 4.9), and gentamicin (21.4% vs 4.3%, P <.001, OR = 6.1), compared with non-ESBLPE. Risk factors for ESBLPE-associated UTIs included recent antibiotic treatment within the past 3 months (P =.003, OR = 3.5) and colonization with ESBLPE (P <.001, OR = 12.8). Given the variable incidence of ESBLPE, relying on local epidemiology for antibiotic selection pending culture results is crucial. The study finding of a low ESBLPE incidence, coupled with global concerns regarding carbapenem resistance, supports cautious use of broad-spectrum antibiotics in nonsevere cases. [ABSTRACT FROM AUTHOR]

Dumpsites generate leachates containing bacteria that may carry antibiotic resistance genes, such as extended spectrum β-lactamase (ESBL). However, the contribution of dumpsite leachates in the environmental spread of ESBL genes has not been investigated in greater detail. This study aimed to quantify the impact of Ajakanga dumpsite leachate on the spread of ESBL genes through surface water. The susceptibility of Escherichia coli isolated from dumpsite leachate and the accompanying surface water to selected antibiotics was assessed by the standardized disc diffusion method. The isolates were evaluated for phenotypic ESBL production using the double disc synergy test (DDST). The detection of ESBL genes in the isolates was carried out using a primer-specific polymerase chain reaction (PCR). Escherichia coli isolates from leachate (n = 26/32) and surface water (n = 9/12) expressed ESBL phenotype. The ESBL-producing isolates showed the highest level of resistance to the 3rd generation cephalosporin antibiotics: cefotaxime (100%), cefpodoxime (97%), ceftazidime (97%), with low resistance observed to imipenem (6%) and azithromycin (3%). All the isolates were multidrug-resistant, showing resistance to three or more classes of antibiotics. All the ESBL-producing E. coli obtained carried blaCTX−M, 21/35 (60%) carried blaTEM while none of the isolates bore blaSHV. This study found that ESBL-producing Escherichia coli from dumpsite leachate and nearby surface water had identical resistance signatures indicating the relatedness of the isolates, and that dumpsite leachate could contribute to the transfer of ESBL-producing bacteria and their genes to receiving surface water. This study has necessitated the need for a review of the guidelines and operational procedures of dumpsites to forestall a potential public health challenge. [ABSTRACT FROM AUTHOR]

Background: Several diagnostic environments in Uganda lack real-time, robust and high-throughput technologies for comprehensive typing of microbes, which is a setback to infectious disease surveillance. This study combined various wet laboratory diagnostics to understand the epidemiology of pathogenic staphylococci isolated from animals in Uganda and the implications for global health security priorities. Methods: A retrospective study was conducted employing records and pathogenic staphylococci (from animals) archived at the Central Diagnostic Laboratory (CDL), Makerere University, Uganda, between January 2012 and December 2019. The bacteria were speciated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and tested for virulence factors [beta lactamases, lecithinase, deoxyribonuclease (DNase), haemolysins] and resistance to ten antimicrobials of clinical and veterinary relevance. Tetracycline and methicillin resistance genes were also tested. Results: The prevalent diseases were mastitis in cattle and skin infections in dogs. Of the 111 staphylococci tested by MALDI-TOF MS, 79 (71.2%) were Staphylococcus aureus, 27 (24.3%) were Staphylococcus pseudintermedius and 5 (4.5%) were Staphylococcus schleiferi. All these strains expressed haemolysins. The prevalence of strains with lecithinase, penicillinase, cephalosporinase and DNase was 35.9% (14/39), 89.7% (35/39), 0.0% (0/39) and 87.2% (34/39), respectively. Staphylococci were primarily resistant to early penicillins (over 80%), tetracycline (57.7%), and chloramphenicol (46.2%). Minimal resistance was noted with cloxacillin (0.0%), ciprofloxacin (9.6%), and cefoxitin (3.8%). The prevalence of multidrug resistance (MDR) was 78.8% for general staphylococci, 82.2% for S. aureus, 73.1% for S. pseudintermedius, and 60.0% for S. schleiferi. Multidrug resistant staphylococci were significantly more prevalent in the cattle isolates than in the dog isolates (P < 0.05). The prevalence of methicillin-resistant staphylococci (MRS) tested by resistance to cefoxitin and mecA carriage was 3.8%. These four strains were all isolated from dog skin infections. The tetK gene was the most predominant (35.4%), followed by tetM (25.0%). Conclusion: In resource-constrained settings, the approach of integrated diagnostics promises sustainable disease surveillance and the addressing of current capacity gaps. The emergence of MRS (zoonotic bacteria) in companion animals creates a likelihood of reduced treatment options for related human infections, a threat to global health. [ABSTRACT FROM AUTHOR]

Summary: The study aimed to assess Campylobacter jejuni prevalence in chicken meat, biofilm formation, virulence factors, antibiotic resistance, and molecular typing. In the study, 200 chicken meat samples were collected from local outlets and 51 (25.5%) isolates were identified as C. jejuni. Resistance rates to ampicillin, tetracycline, sulfamethoxazole/trimethoprim, and ciprofloxacin were 59%, 60%, 64%, and 64% respectively. Many of the isolates (49%) exhibited multidrug resistance. Beta‐lactamase and tetracycline resistance genes were found in 82.3% and 86.2% of isolates, respectively. Virulence genes were detected in various proportions. Biofilm formation was weak to moderate. ERIC‐PCR showed varied band profiles. Whole genome sequencing confirmed findings. The study highlights C. jejuni presence with antibiotic resistance, virulence and biofilm features in chicken meat, posing public health risks. [ABSTRACT FROM AUTHOR]

Background: The optimal method for implementing rapid diagnostic testing (RDT) into clinical practice has not been determined for gram-negative rod (GNR) bacteremia. At our institution, RDT was implemented in conjunction with real-time notification of results to decentralized clinical pharmacists. Objective: To determine the impact of RDT result notification plus real-time clinical pharmacist review on the management of GNR bacteremia. Methods: This retrospective, matched cohort study included patients with a positive blood culture for a GNR on the BIOFIRE® Blood Culture Identification 2 panel from September 2020 to August 2021 (historical) and October 2021 to September 2022 (interventional). Exclusion criteria were polymicrobial bacteremia, discrepant RDT results from traditional culture, 24-hour mortality, and comfort care or not admitted at the time of RDT result. Patients were matched based on age, pathogen, and resistance. The primary endpoint was time from Gram stain to appropriate antibiotic therapy. Results: This study consisted of 240 patients (n = 120 historical, n = 120 interventional). Escherichia coli was isolated in 71% of patients with extended-spectrum beta-lactamase-producing organisms isolated in 8%. There was no difference in median time to appropriate therapy (0 vs 0 hours, P = 0.28). There was a statistically significant decrease in time to first organism-directed change in therapy (40 vs 11 hours; P < 0.01). Length of stay, days of anti-pseudomonal therapy, and inpatient mortality did not differ between groups. Conclusion: Implementation of RDT plus real-time clinical pharmacist review did not significantly decrease time to appropriate therapy in patients with GNR bacteremia but significantly reduced time to organism-directed antibiotic changes. [ABSTRACT FROM AUTHOR]

The emergence and spread of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) pose significant challenges to the treatment and control of urinary tract infections, particularly among vulnerable populations, such as the elderly living in nursing care homes. In this study, we investigated the occurrence of ESBL genes in commensal E. coli isolated from urine samples of 118 elderly individuals residing in Ghanaian nursing care homes. A total of 195 ESBL genes were detected among 41 E. coli isolated from the study participants. All the isolates harboured at least one ESBL gene, and the majority of them (70.1%) carried at least four ESBL genes. Among the ESBL genes detected, CTXM825 was the predominant (14.1%). In antimicrobial susceptibility testing, 65.9% of the isolates showed resistance to cefepime, a fourth-generation cephalosporin, while 56.1% showed resistance to cefotaxime, a third-generation cephalosporin. Additionally, 46.3% of the isolates were multidrug-resistant, indicating resistance to antibiotics from multiple classes. In summary, we observed relatively high rates of resistance to antibiotics as well as alarming rates of ESBL genes in the isolated pathogens. These findings emphasise the urgent need for antimicrobial stewardship and infection control programmes to mitigate the spread of multidrug-resistant pathogens in nursing care homes. [ABSTRACT FROM AUTHOR]

1. The extensive use of antimicrobials in poultry production may contribute to the emergence of resistant bacteria. This study was conducted to determine the prevalence and resistance of different E. coli strains isolated from raw chicken meat and to investigate the possibility to use Lebanese native oregano essential oils as alternatives. 2. In total, 250 chickens from Lebanese markets were examined for the presence of E. coli. Isolates were then screened for susceptibility using 19 antibiotics and two essential oils extracted from oregano plants. 3. Of the 250 chickens tested, 80% were contaminated with E. coli. Main resistance was seen against amoxycillin, ampicillin, penicillin, tetracycline, tylosin, streptomycin and erythromycin. The highest rate of sensitivity was found in 86.1% of strains to Amoxycillin/Clavulanic acid, 80.09% to Tilmicosin. Both essential oils from Origanum syriacum (98%) and O. ehrenbergii (97.3%) showed promising potential in inhibiting the growth of the tested bacteria. Oil from O. syriacum exhibited superior efficacy against 200 E. coli strains, inhibiting 46.1% at 200 mg/l and all at 400 mg/l, while O. ehrenbergii oil showed slightly lower inhibition, affecting 41.6% at 200 mg/l and all at 400 mg/l. [ABSTRACT FROM AUTHOR]

Aims: The emergence of antibiotics resistance in Acinetobacter baumannii and Klebsiella pneumoniae threatens the efficacy of the treatment regime. This study was carried out to evaluate the antibiotic resistance and phylogenetic relatedness in the metallo-β-lactamase (MBL) producers K. pneumoniae and A. baumannii. Methodology and results: In the current study, nine clinical samples from inpatients at Lady Reading Hospital (LRH) were taken from the City Medical Laboratory, Peshawar (Pakistan). Morphological, biochemical and molecular identification of the bacterial strains showed that 6 isolates were K. pneumoniae while 3 were A. baumannii. The phylogenetic tree was constructed using software Finch TV, Codon code aligner and Mega X. Antibiotic susceptibility profiles showed that 89% of isolates were multidrug-resistant (MDR). Sixty-seven (67%) of K. pneumoniae isolates were positive for the Modified Hodge test (MHT), Combined-disc test (CDT) and MBL test. The minimum inhibitory concentration (MIC) of metallo-β-lactamase positive strains were recorded up to 256 μg/mL. MIC values for K. pneumoniae were relatively higher as compared to A. baumannii. Conclusion, significance and impact of study: The presence of a high percentage of MBL producer multidrugresistant K. pneumoniae and A. baumannii isolates reported in this study may indicate a major problem for clinicians by complicating the treatment of infections in hospital settings and need immediate attention. [ABSTRACT FROM AUTHOR]

This study aims to detect Escherichia coli which encodes beta-lactamase Cefotaxime (blaCTX-M) gene from the reproductive tract of Bali cattle with repeat breeder cases. This research was conducted from June to August 2021 using 16 Bali cattle with repeat breeder cases. The reproductive fluids were taken using a plastic sheet gun which was inserted into a Brain Heart Infusion medium, isolated in eosin-methylene blue agar (EMB) and identified using biochemical tests. Antibiotic susceptibility testing of E. coli was carried out using the disc diffusion method. Double-disk approximation test was used to screen the presence of E. coli which produces Extended-spectrum beta-lactamase. The polymerase chain reaction (PCR) method was used to detect the blaCTX-M gene of E. coli and sequences of the blaCTX-M gene were phylogenetically analyzed. The research results obtained three E. coli isolates from 16 reproductive tract fluids of Bali cattle. Antibiotic sensitivity tests showed that 100% of E. coli was resistant to penicillin G and oxytetracycline. 66.66% of E. coli was resistant to cefotaxime (CTX) and gentamicin, and 33.33% of E. coli was resistant to tetracycline. Escherichia coli isolates that were resistant to penicillin and CTX showed positive results in the double-disk approximation test. The results of E. coli detection using PCR showed that three E. coli isolates encoded the blaCTX-M gene located at 370 bp on gel electrophoresis. The results of the phylogenetic analysis showed that E. coli from the reproductive tract of Bali cattle was related to E. coli that encoded blaCTX-M-14 isolated from humans. [ABSTRACT FROM AUTHOR]

Background: Wound infections have been a problem in the field of medicine for a long time due to the emergence and re-emergence of drug resistance. The assessment of Betalactamase production, plasmid profiling and corresponding resistance pattern in the local terrain become important for a proper understanding of wound infection burden and its epidemiology. The study aimed to assess beta-lactamase production among multidrugresistant wound isolates from patients attending University College Hospital (UCH), Ibadan. Methods: Sample size of 370 was determined using the Cochran formula. Exudates from wounds were collected with sterile swab sticks, isolation and identification were performed using standard procedures. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer disc diffusion method, Beta Lactamase Production was carried out using the starch iodide acidimetric method. Double disc synergy test and combination disk were used for extended–spectrum beta-lactamases (ESBL) and metallo-beta-lactamase (MBL) detection respectively. Plasmid curing of two beta-lactamase procedures was carried out using sodium dodecyl sulphate (SDS). After which, post-curing antibiotics susceptibility testing was performed. Results: Result shows 339 isolates of which 56.9% were multidrugresistant. Beta-lactamase producers were 60.7% from which 5% and 14% were positive for ESBL and MBL test. Same resistance pattern to the antibiotics was observed in plasmidcured isolates, meaning that their resistance was not plasmid-mediated. Conclusion: The establishment of beta-lactamase producing capacity in the wound isolates in this study will help clinicians in the appropriate treatment of wound infections. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze the distribution of pathogens and antimicrobial resistance in bone and joint infections (BJIs) among children under four years old. Methods: A retrospective analysis was conducted on the clinical data of children under four years old who received inpatient treatment for BJIs at the Children's Hospital of Soochow University between January 2016 and December 2022. Results of bacterial culture and antimicrobial resistance were analyzed. Results: Among the 131 patients, 52 (39.7%) showed positive bacterial culture results. There were Gram-positive (G+) bacteria detected in 38 strains (73.07%), Gram-negative (G-) bacteria in 12 strains (23.08%), and fungi in 2 strains (3.85%). Thirty-one strains of Staphylococcus aureus (S. aureus) were detected (59.62%), including 7 MRSA strains (22.58%). The resistance rate of G+ bacteria to penicillin was 72.97%, while resistance to erythromycin and clindamycin was approximately 50%. No resistance was found against linezolid, vancomycin, and teicoplanin. G- bacteria showed a sensitivity of 100% to carbapenems, including meropenem, ertapenem, and imipenem, a resistance rate of 91.67% to ampicillin-sulbactam, and relatively high resistance rates to compound sulfamethoxazole, ampicillin/sulbactam, and piperacillin. Conclusions: Regional variations existed in the distribution of pathogens and antimicrobial resistance in children under four years old with BJIs. In our hospital, the most common pathogen is S. aureus, with MRSA accounting for approximately one-fourth of all S. aureus patients. Additionally, extended-spectrum β-lactamase (ESBL)-producing G- bacteria have been identified, underscoring the importance of careful consideration during empirical antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene. Methods: This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. Results: Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01). Conclusion: mPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted. [ABSTRACT FROM AUTHOR]

In a retrospective multicenter study of 575 patients with bloodstream infections or pneumonia due to wild-type AmpC β-lactamase–producing Enterobacterales, species with low in vitro mutation rates for AmpC derepression were associated with fewer treatment failures due to AmpC overproduction (adjusted hazard ratio, 0.5 [95% CI,.2–.9]). However, compared to cefepime/carbapenems, using third-generation cephalosporins as definitive therapy remained associated with this adverse outcome (15% vs 1%). [ABSTRACT FROM AUTHOR]

Background Little is known about the risk of progression from carbapenemase-producing Enterobacterales (CPE) carriage to CPE bloodstream infection (BSI) outside of high-risk settings. We aimed to determine the incidence of CPE BSI among CPE carriers and to assess whether the incidence differs by carbapenemase, species, and setting. Methods We conducted a nationwide population-based retrospective cohort study using national databases. The cohort consisted of all patients in Israel with CPE detected by screening from 1 January 2020 to 10 October 2022. We calculated the cumulative incidence of CPE BSI within 1 year among CPE carriers. We used a competing-risks model with BSI as the outcome and death as the competing risk. Results The study included 6828 CPE carriers. The cumulative incidence of CPE BSI was 2.4% (95% confidence interval [CI], 2.1–2.8). Compared with Klebsiella pneumoniae carbapenemase (KPC), the subhazard of BSI was lower for New Delhi metallo-β-lactamase (NDM) (adjusted subhazard ratio [aSHR], 0.72; 95% CI,.49–1.05) and oxacillinase-48-like (OXA-48-like) (aSHR, 0.60; 95% CI,.32–1.12) but these differences did not reach statistical significance. Compared with K. pneumoniae , the subhazard of BSI was lower for carriers of carbapenemase-producing Escherichia coli (aSHR, 0.33; 95% CI,.21–.52). The subhazard of BSI was higher among patients with CPE carriage first detected in intensive care units (aSHR, 2.10; 95% CI, 1.27–3.49) or oncology/hematology wards (aSHR, 3.95; 95% CI, 2.51–6.22) compared with medical wards. Conclusions The risk of CPE BSI among CPE carriers is lower than previously reported in studies that focused on high-risk patients and settings. The risk of BSI differs significantly by bacterial species and setting, but not by carbapenemase. [ABSTRACT FROM AUTHOR]

Gram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of β-lactamases. The early β-lactamase inhibitors (BLIs) are characterized by spectra limited to class A β-lactamases and ineffective against carbapenemases and most extended spectrum β-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC). These BL/BLI combination drugs, avibactam/avibactam, meropenem/vaborbactam, and imipenem/relebactam, have proven to be indispensable tools in this effort. However, non-KPC mechanisms of resistance are rising in prevalence and increasingly challenging to treat. It is critical for clinicians to understand the unique spectra of these BL/BLIs with respect to non-KPC CRO. In Part 1of this 2-part series, we describe the non-KPC attributes of the newer BL/BLIs with a focus on utility against Enterobacterales and Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

Objective: Understanding microbiota colonizing ocular surfaces is key to expedite antibiotic prophylactic options for ocular surgeries, and therefore, prevent subsequent surgical site infections (SSIs). To fill this critical gap, we aimed at determining the prevalence and antibiotic susceptibility patterns of bacteria colonizing the external ocular surfaces of 224 patients undergoing ocular surgeries at Bugando Medical Centre (BMC) in Mwanza, Tanzania between May and August 2023. Results: The study participants had a median age of 62.5 (interquartile range: 39.5–75.0) years. A total of 78.1% (175/224) ocular swabs were culture positive yielding 196 bacterial isolates. Staphylococcus epidermidis [43.4% (n = 85)], Staphylococcus aureus [21.9% (n = 43)] and Pseudomonas aeruginosa [14.3% (n = 28)] were the most common bacteria. There were low proportions of resistance among predominant Gram-positive and Gram-negative bacteria to gentamicin (≤ 25.0%), and similarly, low resistance among Gram negative bacteria was observed against 3rd generation cephalosporins (≤ 25.0%) and piperacillin-tazobactam (0.0%). Variable resistance profiles were notable to the most commonly used antibiotics (ciprofloxacin and tetracycline: 0.0–66.7%). Our findings underscore an urgent need to revisit antibiotic prophylactic guidelines for ocular surgeries in this tertiary hospital, and calls for prospective evaluation of incident SSIs post-ocular surgeries to guide specific management. [ABSTRACT FROM AUTHOR]