BACKGROUND: The global burden associated with antimicrobial resistance is of increasing concern. The aim of this study was to evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated (HCA) bacteremic urinary tract infections (BUTI).
METHODS: This is a post-hoc analysis a prospective multicenter study of patients with HCA-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression.
RESULTS: 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (OR 3.13, 95% CI 2.11-4.69, p<0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa etiology (OR 7.84, 95% CI 2.37-25.95; p=0.001). MDR was independently associated with prior use of fluoroquinolones (aOR 2.43; 95% CI 1.25-4.69), cephalosporins (aOR 2.14; 95% CI 1.35-3.41) and imipenem or meropenem (aOR 2.08; 95% CI 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but with longer hospital stay.
CONCLUSIONS: MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although was independently associated with longer duration of hospital stay.

Escherichia coli, a member of the commensal intestinal microbiota, is a significant aetiology of urinary tract infections (UTIs) and has a propensity for acquiring multidrug resistance characteristics, such as extended-spectrum beta-lactamases (ESBLs). Despite the increase in the incidence of ESBL-producing E. coli infections in sub-Saharan Africa, routine ESBL detection in Ghana is often absent, and molecular data on ESBL genotypes is scarce. Eleven ESBL-producing E. coli recovered from mid-stream urine samples were subjected to antimicrobial susceptibility testing and whole-genome sequence analyses. All isolates exhibited multidrug resistance, demonstrating phenotypic resistance to third-generation cephalosporins, such as cefotaxime, ceftazidime, and cefpodoxime. Three isolates demonstrated resistance to norfloxacin (a fluoroquinolone), and one isolate demonstrated intermediate resistance to ertapenem (a carbapenem). Analysis of the draft genomes identified multiple antimicrobial resistance genes including ESBL genotypes blaTEM-1B/TEM-190 (6/11 and 1/11, respectively), blaCTX-M-15/CTX-M-3 (7/11 and 1/11) and blaOXA-1/OXA-181 (3/11 and 1/11). The strains belong to 10 different serotypes and 10 different multilocus sequence types. This study provides information on phenotypic resistance in 11 ESBL E. coli from Ghana and AMR genotypes within their genomes.

UNASSIGNED: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae including Escherichia coli (E. coli), are recognized as a global public health threat due to their multidrug-resistant (MDR) phenotypes and their rapid dissemination in aquatic environments. Nevertheless, studies investigating the prevalence and antimicrobial resistance (AMR) profile of ESBL-producing E. coli in Lebanese surface water are limited.
UNASSIGNED: This study aimed to assess the physicochemical properties and microbial contamination load and to determine the distribution of AMR patterns of ESBL-producing E. coli in surface water samples from different sites in the North Governorate of Lebanon.
UNASSIGNED: Water samples were collected from 25 major sites in North Lebanon. These samples were analyzed for the presence of total coliforms, E. coli, and fecal enterococci. Phenotypic and genetic characterizations were then performed for E. coli isolates to determine their resistance patterns and phylogenetic groups.
UNASSIGNED: Fifty-six samples out of 100 samples were positive for ESBL-producing E. coli, mostly harboring blaCTX-M (40/56, 71%) including blaCTX-M-15 (33/40, 82%), blaTEM gene (36/56, 64%), blaSHV (20/56, 36%), and blaOXA (16/56, 29%) including blaOXA-48 gene (11/16, 69%). Most ESBL-producing E. coli isolates belonged to the extra-intestinal pathogenic phylogroup B2 (40/56, 71.4%) while 10/56 (17.9%) belonged to the commensal phylogroup A.
UNASSIGNED: Our results highlight the need to implement effective water monitoring strategies to control transmission of ESBL-producing E. coli in surface water and thus reduce the burden on human and animal health.

The aim of this study was to evaluate the proportion of resistance to a temocillin, tigecycline, ciprofloxacin, and chloramphenicol phenotype called t2c2 that resulted from mutations within the ramAR locus among extended-spectrum β-lactamases-Enterobacterales (ESBL-E) isolated in three intensive care units for 3 years in a French university hospital. Two parallel approaches were performed on all 443 ESBL-E included: (i) the minimal inhibitory concentrations of temocillin, tigecycline, ciprofloxacin, and chloramphenicol were determined and (ii) the genomes obtained from the Illumina sequencing platform were analyzed to determine multilocus sequence types, resistomes, and diversity of several tetR-associated genes including ramAR operon. Among the 443 ESBL-E strains included, isolates of Escherichia coli (n = 194), Klebsiella pneumoniae (n = 122), and Enterobacter cloacae complex (Ecc) (n = 127) were found. Thirty-one ESBL-E strains (7%), 16 K. pneumoniae (13.1%), and 15 Ecc (11.8%) presented the t2c2 phenotype in addition to their ESBL profile, whereas no E. coli presented these resistances. The t2c2 phenotype was invariably reversible by the addition of Phe-Arg-β-naphthylamide, indicating a role of resistance-nodulation-division pumps in these observations. Mutations associated with the t2c2 phenotype were restricted to RamR, the ramAR intergenic region (IR), and AcrR. Mutations in RamR consisted of C- or N-terminal deletions and amino acid substitutions inside its DNA-binding domain or within key sites of protein-substrate interactions. The ramAR IR showed nucleotide substitutions involved in the RamR DNA-binding domain. This diversity of sequences suggested that RamR and the ramAR IR represent major genetic events for bacterial antimicrobial resistance.IMPORTANCEMorbimortality caused by infectious diseases is very high among patients hospitalized in intensive care units (ICUs). A part of these outcomes can be explained by antibiotic resistance, which delays the appropriate therapy. The transferable antibiotic resistance gene is a well-known mechanism to explain the high rate of multidrug resistance (MDR) bacteria in ICUs. This study describes the prevalence of chromosomal mutations, which led to additional antibiotic resistance among MDR bacteria. More than 12% of Klebsiella pneumoniae and Enterobacter cloacae complex strains presented mutations within the ramAR locus associated with a dysregulation of an efflux pump called AcrAB-TolC and a porin: OmpF. These dysregulations led to an increase in antibiotic output notably tigecycline, ciprofloxacin, and chloramphenicol associated with a decrease of input for beta-lactam, especially temocillin. Mutations within transcriptional regulators such as ramAR locus played a major role in antibiotic resistance dissemination and need to be further explored.

UNASSIGNED: Urinary tract infections (UTIs) due to extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae are among the leading causes of morbidity and mortality in older adults. Identifying associated factors for ESBL production may contribute to more appropriate empirical treatment.
UNASSIGNED: This was a prospective observational study. Hospitalized patients of age > 65 with community-onset or hospital-acquired upper UTI due to E. coli or Klebsiella pneumoniae were included. A multivariate analysis was performed.
UNASSIGNED: A total of 97 patients were included. ESBL prevalence among UTIs with E. coli or Klebsiella pneumoniae was 69.1% (n = 67). CRP values at the time of UTI diagnosis were found to be significantly higher in the ESBL-producing group (p = 0.004). The multivariate analysis revealed that male gender (OR: 2.72, CI: 1.02-7.25), prior recurrent UTI (OR: 3.14, CI: 1.21-8.14), and the development of secondary bacteremia (OR: 4.95, CI: 1.03-23.89) were major associated factors for UTI in older adults due to ESBL-producing E. coli and Klebsiella pneumoniae.
UNASSIGNED: Severe UTI in older men with a history of recurrent UTI may be a warning to the clinician for ESBL production in the setting of high ESBL prevalence. Carbapenems may be prioritized in the empirical treatment of patients with known risk factors for ESBL.

We developed a prediction model for cefotaxime resistance in patients with K. pneumoniae bacteremia. Adult patients with K. pneumoniae bacteremia were grouped into derivation (from March 2018 to December 2019) and validation (from January 2020 to August 2020) cohorts. The prediction scoring system was based on factors associated with cefotaxime resistance identified by the logistic regression model. A total of 358 patients were enrolled (256 for derivation, 102 for validation). In the multivariable analysis, age ≥65 years, hospital-acquired infection, prior antimicrobial use, and an updated Charlson comorbidity index ≥3 points were associated with cefotaxime resistance in the derivation cohort. When each variable was counted as 1 point, the values of the area under the curve were 0.761 in the derivation and 0.781 in the validation cohorts. The best cutoff value using the Youden index was ≥2 with 73.6% sensitivity and 67.5% specificity. Our simple scoring system favorably predicted cefotaxime resistance.

BACKGROUND: Specific data concerning the efficacy of alternative antibiotics for carbapenems against complicated urinary tract infections (cUTIs) attributed to antimicrobial-resistant (AMR) uropathogens are lacking.
OBJECTIVE: This study aimed to assess the efficacy of carbapenems and non-carbapenem antibiotics in the clinical outcomes of cUTIs caused by AMR uropathogens.
METHODS: In this systematic review and meta-analysis, databases, including MEDLINE/PubMed, the Cochrane Library, Embase and ClinicalTrials.gov, were searched. The study eligibility criteria were research articles conducted as randomised controlled trials that evaluated the composite outcomes of cUTIs. Participants were adult patients with cUTIs caused by gram-negative uropathogens resistant to third-generation cephalosporins. The intervention involved a non-carbapenem class of antimicrobial agents with in vitro activities against gram-negative uropathogens resistant to third-generation cephalosporins. Two independent researchers assessed the risk-of-bias using the second version of the Cochrane risk-of-bias tool for randomised trials. The treatment effects on each outcome were estimated as a risk ratio (RR) with a 95 % confidence interval (CI) using the random-effects model. Heterogeneity was assessed using the Cochrane Q-test and I2 statistics.
RESULTS: Through database searches, 955 articles were retrieved. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. No significant differences in efficacy were observed between alternative antibiotics and carbapenems (composite outcome, RR, 0.96; 95 % CI, 0.63-1.49; I2 = 21 %; low certainty of evidence).
CONCLUSIONS: Alternative antibiotics had clinical efficacy similar to that of carbapenems for treating patients with cUTI caused by gram-negative uropathogens resistant to third-generation cephalosporins.

UNASSIGNED: Klebsiella pneumoniae is an opportunistic pathogen responsible for causing nosocomial and community-acquired infections. Its pathogenicity is associated with a variety of virulence factors and antibiotic resistance. The aim of the present study was to compare virulence attributes between ESBL and non-ESBL producing isolates.
UNASSIGNED: A total of 113 K. pneumoniae including 56 ESBL and 57 non ESBL-producers were collected in Bushehr province, Iran, from November 2017 to February 2019. Enzymatic profile, hypermucoviscosity and biofilm formation were investigated phenotypically. In addition, the presence of rmpA, aerobactin, kfu, allS, mrkD, ybtS, entB, iutA, fimH, wabG, wcaG, K1 and K2 genes were detected by PCR and sequencing.
UNASSIGNED: There was no statistically significant difference in enzymatic profile between ESBL and non-ESBL producers. The prevalence of the hypermocoviscosity was lower among ESBL compared to non-ESBL producers but the intensity of biofilm was higher in the ESBL producers. Among the virulence genes, K1, rmpA, iutA, and aero were observed only in non-ESBLs. Moreover, the carriage of allS, K, K2, rmpA, iutA and aero genes was higher in hypermucoviscous in comparison with non hypermucoviscous isolates.
UNASSIGNED: The identification of potentially pathogenic isolates plays an important role in preventing their spread as well as the success of their treatment.

BACKGROUND: Antimicrobial stewardship focuses on identifying patients who require extended-spectrum beta-lactamase (ESBL)-targeted therapy. \'Rule-in\' tools have been researched extensively in areas of low endemicity; however, such tools are inadequate for areas with high prevalence of ESBL-producing pathogens, as almost all patients will be selected.
OBJECTIVE: To develop a machine-learning-based \'rule-out\' tool suitable for areas with high levels of resistance.
METHODS: Gradient-boosted decision trees were used to train and validate a risk prediction model on data from 17,913 (45% ESBL) patients with Escherichia coli and Klebsiella pneumoniae in urine cultures. The predictive power of different sets of variables was evaluated using Shapley values to evaluate the contributions of variables.
RESULTS: The model successfully identified patients with low risk of ESBL resistance in ESBL-endemic areas (area under receiver operating characteristic curve 0.72). When used to select the 30% of patients with the lowest predicted risk, the model yielded a negative predictive value ≥0.74. A simplified model with seven input features was found to perform nearly as well as the full model. This simplified model is freely accessible as a web application.
CONCLUSIONS: This study found that a risk calculator for antibiotic resistance can be a viable \'rule-out\' strategy to reduce the use of ESBL-targeted therapy in ESBL-endemic areas. The robust performance of a version of the model with limited features makes the clinical use of such a tool feasible. This tool provides an important alternative in an era with growing rates of ESBL-producing pathogens, where some experts have called for empirical use of carbapenems as first-line therapy for all patients in areas with high prevalence of ESBL-producing pathogens.

Earlier studies have validated the isolation of extended-spectrum beta-lactamase-producing Salmonella (ESBL-Sal) strains from food. While poultry is recognized as a reservoir for Salmonella contamination, pertinent data regarding ESBL-Sal remains limited. Consequently, the Ministry of Food and Drug Safety has isolated Salmonella spp. from retail meat and evaluated their antibiotic susceptibility and genetic characteristics via whole-genome sequencing. To further elucidate these aspects, this study investigates the prevalence, antibiotic resistance profiles, genomic characteristics, and homology of ESBL-Sal spp. obtained from livestock-derived products in South Korean retail outlets. A total of 653 Salmonella spp. were isolated from 1,876 meat samples, including 509 beef, 503 pork, 555 chicken, and 309 duck samples. The prevalence rates of Salmonella were 0.0%, 1.4%, 17.5%, and 28.2% in the beef, pork, chicken, and duck samples, respectively. ESBL-Sal was exclusively identified in poultry meat, with a prevalence of 1.4% in the chicken samples (8/555) and 0.3% in the duck samples (1/309). All ESBL-Sal strains carried the blaCTX-M-1 gene and exhibited resistance to ampicillin, ceftiofur, ceftazidime, nalidixic acid, and tetracycline. Eight ESBL-Sal isolates were identified as S. Enteritidis with sequence type (ST) 11. The major plasmid replicons of the Enteritidis-ST11 strains were IncFIB(S) and IncFII(S), carrying antimicrobial resistance genes (β-lactam, tetracycline, and aminoglycoside) and 166 virulence factor genes. The results of this study provide valuable insights for the surveillance and monitoring of ESBL-Sal in South Korean food chain.