ESBL-producing Enterobacterales Research Articles

Efficacy of carbapenem vs non carbapenem β-lactam therapy as empiric antimicrobial therapy in patients with extended-spectrum β-lactamase-producing Enterobacterales urinary septic shock: a propensity-weighted multicenter cohort study

BackgroundThe rise in antimicrobial resistance is a global threat responsible for about 33,000 deaths in 2015 with a particular concern for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and has led to a major increase in the use of carbapenems, last-resort antibiotics.MethodsIn this retrospective propensity-weighted multicenter observational study conducted in 11 ICUs, the purpose was to assess the efficacy of non carbapenem regimen (piperacillin–tazobactam (PTZ) + aminoglycosides or 3rd-generation cephalosporin (3GC) + aminoglycosides) as empiric therapy in comparison with carbapenem in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) urinary septic shock. The primary outcome was Day-30 mortality.ResultsAmong 156 patients included in this study, 69 received a carbapenem and 87 received non carbapenem antibiotics as empiric treatment. Baseline clinical characteristics were similar between the two groups. Patients who received carbapenem had similar Day-30 mortality (10/69 (15%) vs 6/87 (7%), OR = 1.99 [0.55; 5.34] p = 0.16), illness severity, resolution of septic shock, and ESBL-E infection recurrence rates than patients who received an empiric non carbapenem therapy. The rates of secondary infection with C. difficile were comparable.ConclusionsIn ESBL-E urinary septic shock, empiric treatment with a non carbapenem regimen, including systematically aminoglycosides, was not associated with higher mortality, compared to a carbapenem regimen.

Clinical efficacy of ertapenem vs. other carbapenems for the treatment of extended-spectrum-β-lactamase-producing Enterobacterales infection: A systematic review and meta-analysis

Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection. PubMed, Web of Science, and Cochrane Library were searched from their inception to November 29, 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included. A total of 6 studies meeting the selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-day mortality when compared with other carbapenems (10.7% [46/431] vs 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40-0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenems groups (mean differences, -6.02 days; 95% CI, -9.39 to -2.64). No significant differences were noted between the ertapenem and other carbapenems groups in terms of the rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97-1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97-1.06). Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections.

Quantification of time delay between screening and subsequent initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales: A post hoc subgroup analysis of the R-GNOSIS WP5 Trial.

The aim of this study was to quantify the time delay between screening and initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E). This study was a secondary analysis of contact isolation periods in a cluster-randomized controlled trial that compared 2 strategies to control ESBL-E (trial no. ISRCTN57648070). Patients admitted to 20 non-ICU wards in Germany, the Netherlands, Spain, and Switzerland were screened for ESBL-E carriage on admission, weekly thereafter, and on discharge. Data collection included the day of sampling, the day the wards were notified of the result, and subsequent ESBL-E isolation days. Between January 2014 and August 2016, 19,122 patients, with a length of stay ≥2 days were included. At least 1 culture was collected for 16,091 patients (84%), with a median duration between the admission day and the day of first sample collection of 2 days (interquartile range [IQR], 1-3). Moreover, 854 (41%) of all 2,078 ESBL-E carriers remained without isolation during their hospital stay. In total, 6,040 ESBL-E days (32% of all ESBL-E days) accrued for patients who were not isolated. Of 2,078 ESBL-E-carriers, 1,478 ESBL-E carriers (71%) had no previous history of ESBL-E carriage. Also, 697 (34%) were placed in contact isolation with a delay of 4 days (IQR, 2-5), accounting for 2,723 nonisolation days (15% of ESBL-E days). Even with extensive surveillance screening, almost one-third of all ESBL-E days were nonisolation days. Limitations in routine culture-based ESBL-E detection impeded timely and exhaustive implementation of targeted contact isolation.

Use of the quantitative antibiogram method for assessing nosocomial transmission of ESBL-producing Enterobacterales in a French hospital

Extended-spectrum beta-lactamase-producing Enterobacterales (eESBL) have high prevalence in hospitals, but real-time monitoring of nosocomial acquisition through conventional typing methods is challenging. Moreover, patient-to-patient transmission varies between the main species, namely Escherichia coli and Klebsiella pneumoniae, which draws into question the relevance of applying identical preventive measures. To detect eESBL cross-transmission events (CTEs) using the quantitative antibiogram (QA) method in combination with epidemiological data (combined QA method), and to determine the effectiveness of standard or contact precautions for eESBL species. First, a validation set was used to compare the relevance of the combined QA method with a combination of pulsed-field gel electrophoresis and epidemiological data (combined PFGE method). Next, a 4-year retrospective analysis was conducted to detect eESBL CTEs in hospitalized patients. Two species were screened - ESBL E.coli (ESBL-Ec) and ESBL K.pneumoniae (ESBL-Kp). During the study, standard precautions alone were applied to patients with ESBL-Ec, whereas contact precautions were applied for patients with ESBL-Kp. As a proof of concept, use of the combined QA method and the combined PFGE method for the detection of CTEs gave identical results for E.coli, and similar results for at least 75% of K.pneumoniae. Overall, 722 patients with ESBL-Ec isolates and 280 patients with ESBL-Kp isolates were included in the retrospective analysis. Nine and 23 CTEs were identified for E.coli and K.pneumoniae, respectively, involving 20 (2.7%) and 36 (12.8%) patients, respectively. The combined QA method constitutes a rapid tool for epidemiological surveillance to detect CTEs. In the study hospital, standard precautions are sufficient to prevent acquisition of ESBL-Ec, whereas contact precautions must be implemented to prevent acquisition of ESBL-Kp.

Efficacy of ceftazidime/avibactam in various combinations for the treatment of experimental osteomyelitis in rabbits caused by OXA-48-/ESBL-producing Escherichia coli.

While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ceftazidime/avibactam in different combinations in an experimental model of OXA-48-/ESBL-producing Escherichia coli osteomyelitis. E. coli pACYC184 is a clinical strain harbouring blaOXA-48 and blaCTX-M-15 inserts, with 'increased exposure susceptibility' to imipenem (MIC, 2 mg/L), gentamicin (MIC, 0.5 mg/L), colistin (MIC, 0.25 mg/L), ceftazidime/avibactam (MIC, 0.094 mg/L) and fosfomycin (MIC, 1 mg/L), and resistance to ceftazidime (MIC, 16 mg/L). Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu of OXA-48/ESBL E. coli. Treatment started 14 days later for 7 days in six groups: (1) control, (2) colistin 150.000 IU/kg subcutaneously (SC) q8h, (3) ceftazidime/avibactam 100/25 mg/kg SC q8h, (4) ceftazidime/avibactam + colistin, (5) ceftazidime/avibactam + fosfomycin 150 mg/kg SC q12h, (6) ceftazidime/avibactam + gentamicin 15 mg/kg intramuscularly (IM) q24h. Treatment was evaluated at Day 24 according to bone cultures. In vitro, time-kill curves of ceftazidime/avibactam in combination showed a synergistic effect. In vivo, compared with controls, rabbits treated with colistin alone had similar bone bacterial density (P = 0.50), whereas ceftazidime/avibactam alone or in combinations significantly decreased bone bacterial densities (P = 0.004 and P < 0.0002, respectively). Bone sterilization was achieved using ceftazidime/avibactam in combination with colistin (91%) or fosfomycin (100%) or gentamicin (100%) (P < 0.0001), whereas single therapies were not different from controls. No ceftazidime/avibactam-resistant strains emerged in rabbits treated, regardless of the combination. In our model of E. coli OXA-48/ESBL osteomyelitis, ceftazidime/avibactam in combination was more effective than any single therapy, whatever the companion drug used (gentamicin or colistin or fosfomycin).

Genomic evidences of gulls as reservoirs of critical priority CTX-M-producing Escherichia coli in Corcovado Gulf, Patagonia

Extended spectrum β-lactamase (ESBL)-producing Enterobacterales has spread rapidly around the world, reaching remote areas. In this regard, wild birds that acquire ESBL producers from anthropogenically impacted areas can become reservoirs, contributing to further dissemination of antimicrobial-resistant bacteria categorized as critical priority pathogens to remote environments, during migration seasons. We have conducted a microbiological and genomic investigation on the occurrence and features of ESBL-producing Enterobacterales in wild birds from the remote Acuy Island, in the Gulf of Corcovado, at Chilean Patagonia. Strikingly, five ESBL-producing Escherichia coli were isolated from migratory and resident gulls. Whole-genome sequencing (WGS) analysis revealed the presence of two E. coli clones belonging to international sequence types (STs) ST295 and ST388, producing CTX-M-55 and CTX-M-1 ESBLs, respectively. Moreover, E. coli carried a wide resistome and virulome associated with human and animal infections. Phylogenomic analysis of global and publicly genomes of E. coli ST388 (n = 51) and ST295 (n = 85) clustered gulls isolates along to E. coli strains isolated from the environment, companion animal and livestock in the United States of America, within or close to the migratory route of Franklin's gull, suggesting a possible trans hemispheric movement of international clones of WHO critical priority ESBL producing pathogens.

Re-evaluation of cefepime or piperacillin/tazobactam to decrease use of carbapenems in ESBL-producing Enterobacterales urinary tract infections (REDUCE-UTI).

To re-examine the use of non-carbapenems (NCBPs), specifically piperacillin/tazobactam and cefepime, for ESBL-producing Enterobacterales (ESBL-E) urinary tract infections (UTIs). Retrospective cohort study of adults hospitalized between January 2016 and June 2020 with pyuria on urinalysis, a urine culture positive for ESBL-E treated with a study antibiotic (meropenem, ertapenem, cefepime or piperacillin/tazobactam) and did not meet criteria for study exclusion. To compare carbapenems (CBPs) with cefepime or piperacillin/tazobactam for the treatment of ESBL-E UTI. The primary outcome was clinical cure, defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days and resistance emergence within 30 days. One-hundred and thirty-three patients were included, based on definitive therapy received; 69 (51.9%) received CBP and 64 (48.1%) received NCBP therapy. Of the total patient population, 17 (12.8%) were admitted to the ICU, 84 (63.1%) had a complicated UTI and 64 (48.1%) had pyelonephritis. There was no difference in clinical cure between the CBP and NCBP groups (95.7% versus 96.9%, P = 0.999). Additionally, no differences in secondary outcomes were observed. When compared with CBPs, cefepime and piperacillin/tazobactam resulted in similar clinical cure, in-hospital mortality, recurrence and resistance emergence in the treatment of ESBL-E UTI.

Multidrug-resistant Enterobacterales responsible for septicaemia in a neonatal intensive care unit in Morocco

Neonatal sepsis with multidrug resistant (MDR) bacteria is an important cause of morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of MDR in bacteria responsible of sepsis in neonates was determined. From July to December 2019, documented bacteraemia from 524 neonates hospitalized in a neonatal intensive care unit (NICU) in Morocco were collected. WGS was used to determine the resistome, MLST and phylogeny. Among the 199 documented bacteraemia, 40 (20%) and 20 (10%) were due to MDR K. pneumoniae (Kp) and E. hormaechei (Eh), respectively. Of these, 23 (38.5%) were early neonatal infections (≤ 3 days of life). Twelve different STs were observed among Kp isolates with ST1805 (n=10), and ST307 (n=8), being the most prevalent. Twenty-one Kp (53%) possessed blaCTX-M-15 gene, of which 6 co-produced an OXA-48, 2 an NDM-7, and 2 OXA-48 and NDM-7. BlaOXA-48 gene was present in 11 (27.5%), blaNDM-1 in 13 (32.5%), and blaNDM-7 in 4 isolates of Kp (10.0%). Eighteen Eh (90.0%) produced an ESBL. Three SHV-12 that co-produced CMY-4 and NDM-1, and 15 CTXM-15 of which 6 co-produced OXA-48. Twelve different STs belonging to 3 different Eh subspecies were observed with one to 4 isolates. Kp and Eh isolates belonging to the same ST had less than 20 SNP differences, and were found throughout the study period, highlighting their endemic presence in the NICU. Thirty percent of neonatal sepsis (23 early- and 37 late-neonatal sepsis) were due to highly-drug resistant carbapenemase- and/or ESBL producing-Enterobacterales.

Carbapenem-Resistant and ESBL-Producing Enterobacterales Emerging in Central Texas.

Carbapenem-resistant Enterobacterales (CRE) are subject to intense global monitoring in an attempt to maintain awareness of prevalent and emerging resistance mechanisms and to inform treatment and infection prevention strategies. CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are not usually examined collectively in regards to their shared pool of resistance determinants. Here, we genetically and phenotypically assess clinical isolates of CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales in the growing region of Central Texas, where CRE are emergent and occurrence of non-carbapenemase-producing-CRE (non-CP-CRE) infections is increasing. CRE (n=16) and ESBL-producing Enterobacterales (n=116) isolates were acquired from a regional hospital in Central Texas between December 2018 and January 2020. Isolates were assessed genetically and phenotypically using antibiotic susceptibility testing, targeted PCR, and whole genome sequencing. CRE infections are increasing in incidence in Central Texas, and Klebsiella pneumoniae is causing the majority of these infections. Moreover, K. pneumoniae sequence type (ST) 307 is commonly found among both non-CP-CRE and EBSL-producing strains. Isolates carry similar plasmids harboring the gene for the ESBL CTX-M-15 and belong to the global lineage, rather than the Texas lineage, of ST307. Antibiotic resistance profiles, sequence data, and clinical records suggest that porin mutations may promote the transition of ST307 isolates from ESBL-producing to non-CP-CRE. In addition to antibiotic resistance mechanisms, several CRE isolates harbor active colicinogenic plasmids, which might influence the competitiveness of these bacteria during patient colonization. K. pneumoniae of the global ST307 lineage is circulating in Central Texas and is responsible for both non-CP CRE and ESBL-producing Enterobacterales infections. Enhanced surveillance is needed to understand the possible routes for the emergence of non-CP-CRE from EBSL-producing strains.

Characteristics of Extended-Spectrum β-Lactamase Producing Enterobacterales Isolated from Dogs and Cats, 2011-2021.

The rising prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales is a significant threat to animal and human health. This study aims to describe the clinical features, antimicrobial susceptibility patterns, and genotypic features of infections associated with ESBL-producing Enterobacterales in dogs and cats seen at a tertiary referral veterinary teaching hospital. Enterobacterales isolated from dogs and cats that underwent ESBL testing during the study period were identified using a search of the hospital antimicrobial susceptibility test software database. Medical records of confirmed ESBL isolates were reviewed, and the source of infection, clinical findings, and antimicrobial susceptibility were recorded. Genomic DNA from bacterial isolates was evaluated for antimicrobial resistance genes with whole genome sequencing. Thirty ESBL-producing isolates were identified based on phenotypic testing (twenty-nine from dogs, one from a cat); twenty-six were Escherichia coli and the remainder were Klebsiella spp. Bacterial cystitis was the most commonly identified (8/30, 27%) clinical problem associated with infection. Resistance to three or more antimicrobial classes was identified in 90% (27/30) of isolates, and all isolates were susceptible to imipenem. Over 70% of isolates were susceptible to piperacillin-tazobactam, amikacin, and cefoxitin. BlaCTX-M-15 was the most common ESBL gene identified, present in 13/22 (59%) isolate genomes. A wide range of clinical infections were identified. Piperacillin-tazobactam and amikacin may be alternatives to carbapenem therapy. Further, larger-scale studies are needed.

Outcomes associated with empiric cefepime for bloodstream infections caused by ceftriaxone-resistant, cefepime-susceptible Escherichia coli and Klebsiella pneumoniae

BackgroundCefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L. MethodsThis single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours. ResultsFifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2–6) days and 7 (5–10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016). ConclusionMortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Genetic and phenotypic analyses of mcr-harboring extended-spectrum β-lactamase-producing Escherichia coli isolates from companion dogs and cats in Japan

The emergence of mcr plasmid-mediated colistin-resistant extended-spectrum β-lactamase (ESBL)-producing Enterobacterales among companion dogs and cats poses a risk of the animals acting as reservoirs for cross-species transmission. However, current knowledge of mcr-harboring ESBL-producing Enterobacterales in companion dogs and cats is still limited; thus, the genetic and phenotypic characteristics of the bacterial isolates and plasmids, in companion dogs and cats, remain to be elucidated. Here, we identified mcr gene-harboring ESBL-producing Escherichia coli isolates during whole-genome sequencing of ESBL-producing E. coli isolates from a dog and a cat in Osaka, Japan. Colistin-resistant MY732 isolate from a dog carried two plasmids: mcr-1.1-harboring IncI2 plasmid and blaCTX-M-14-harboring IncFIB plasmid. Conjugation assays revealed that both plasmids can be co-transferred even though the IncFIB plasmid lacked a conjugal transfer gene cassette. The other isolate MY504 from a cat harbored two bla genes and mcr-9 on the identical IncHI2 plasmid. This isolate was not resistant to colistin, which is likely to be due to deletion of the regulatory two-component QseBC system associated with the mcr-9 expression. To the best of our knowledge, this is the first report of a colistin-resistant ESBL-producing E. coli isolate harboring mcr-1 from a companion dog in Japan. Given that the mcr gene-harboring IncI2 and IncHI2 plasmids in this study shared high homology with plasmids from human or animal-derived Enterobacterales, companion dogs and cats may act as important reservoirs for cross-species transmission of the mcr gene in the community, in Japan.

Epidemiology of extended-spectrum β-lactamases in Enterobacterales in Taiwan for over two decades.

The emergence of antimicrobial resistance among microorganisms is a serious public health concern, and extended-spectrum β-lactamases (ESBL)-producing Enterobacterales is one of the major concerns among antibiotic-resistant bacteria. Although the prevalence of ESBL in Enterobacterales has been increasing with time, the prevalence of ESBL could differ according to the species, hospital allocation, sources of infections, nosocomial or community acquisitions, and geographic regions. Therefore, we conducted a comprehensive review of the epidemiology of ESBL-producing Enterobacterales in Taiwan. Overall, the rates of ESBL producers are higher in northern regions than in other parts of Taiwan. In addition, the genotypes of ESBL vary according to different Enterobacterales. SHV-type ESBLs (SHV-5 and SHV-12) were the major types of Enterobacter cloacae complex, but Serratia marcescens, Proteus mirabilis, Escherichia coli, and Klebsiella pneumoniae were more likely to possess CTX-M-type ESBLs (CTX-M-3 and CTX-M-14). Moreover, a clonal sequence type of O25b-ST131 has been emerging among urinary or bloodstream E. coli isolates in the community in Taiwan, and this clone was potentially associated with virulence, ESBL (CTX-M-15) production, ciprofloxacin resistance, and mortality. Finally, the evolution of the genetic traits of the ESBL-producing Enterobacterales isolates helps us confirm the interhospital and intrahospital clonal dissemination in several regions of Taiwan. In conclusion, continuous surveillance in the investigation of ESBL production among Enterobacterales is needed to establish its long-term epidemiology.

Longitudinal Study of Dynamic Epidemiology of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Pigs and Humans Living and/or Working on Pig Farms.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales have been increasingly isolated from pigs, highlighting their potential for transmission to humans living and/or working within pig farms. As longitudinal data on the prevalence and the molecular characteristics of such isolates from the high-risk farming population remain scarce, we performed a long-term study on 39 Dutch pig farms. Fecal samples from pigs, farmers, family members, and employees were collected during four sampling occasions with a 6-month period. The presence of ESBL-producing Enterobacterales and their molecular characteristics (ESBL gene, plasmid, and sequence types) were determined by standard methods. Data on personal and farm characteristics were collected using questionnaires. ESBL-producing Escherichia coli was present in pigs at least once for 18 of 39 farms and in 17 of 146 farmers, family members, and/or employees. Among these 417 E. coli isolates, blaCTX-M-1 was the most frequently observed ESBL gene in pigs (n = 261) and humans (n = 25). Despite the great variety in plasmid (sub)types and E. coli sequence types (STs), we observed genetic similarity between human- and pig-derived isolates in (i) ESBL gene, plasmid (sub)type, and ST, suggesting potential clonal transmission in seven farms, and (ii) only ESBL gene and plasmid (sub)type, highlighting the possibility of horizontal transfer in four farms. Five pig farmers carried ESBL producers repeatedly, of whom two carried an identical combination of gene, plasmid (sub)type, and ST over time. Human ESBL carriage was associated with both presence of ESBL producers in pigs and average number of hours working on the pig farm per week, while prolonged human carriage was observed only incidentally. IMPORTANCE Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli represents a public health hazard due to reduced therapeutic options for the treatment of infections. Although direct contact with pigs is considered a risk factor for human ESBL-producing E. coli carriage through occupational exposure, nationwide data regarding the occurrence of such isolates among pigs and humans living and/or working on farms remain scarce. Therefore, we determined (i) the longitudinal dynamics in prevalence and molecular characteristics of ESBL-producing E. coli in Dutch pig farmers and their pigs over time and (ii) the potential transmission events between these reservoirs based on genetic relatedness and epidemiological associations in longitudinal data. Our data suggesting the possibility of clonal and horizontal dissemination of ESBL-producing Escherichia coli between pigs and pig farmers can be used to inform targeted intervention strategies to decrease the within-farm human exposure to ESBL-producing E. coli.

Trends in the Rates of Extended-Spectrum-β-Lactamase-Producing Enterobacterales Isolated from Urine Cultures during the COVID-19 Pandemic in Ontario, Canada.

Worldwide, extended-spectrum β-lactamase (ESBL) rates are increasing at an alarming level with increasing rates of health care exposures, international travel, and antibiotic usage. In this study, we investigated whether enhanced social isolation, travel restrictions, and the reduced use of antibiotics in Ontario, Canada during coronavirus disease 2019 (COVID-19) pandemic had an impact on ESBL rates in urine cultures collected from the community and long-term-care (LTC) facilities across the province. Data from a total of 8.6 million urine cultures performed at LifeLabs Ontario from 2016 to 2021 were utilized for analysis. ESBL-producing Escherichia coli (ESBL Escherichia coli) and ESBL Klebsiella pneumoniae were identified using standard operating procedures. Data trends were estimated by interrupted time series (ITS) regression analysis. Among 2.3 million positive urine cultures, 48.9% and 7.2% grew E. coli and K. pneumoniae, of which 5.8% and 3.3% produced ESBLs, respectively. While the overall rate of ESBL isolation was higher in the pandemic period than in the prepandemic period, by ITS regression analysis of the monthly rates of ESBL isolation, decreasing trends were noted for ESBL E. coli in both the community and LTC facilities and for ESBL K. pneumoniae in the community. The ESBL K. pneumoniae rates in LTC facilities continued to increase throughout the COVID-19 period. By subgroup analysis for different genders, age groups, and local health integration network (LHIN) units, similar trends were seen in most cases (P < 0.05), except for a few densely populated LHINs where rate changes were not statistically significant. IMPORTANCE Community-onset urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales, particularly E. coli and K. pneumoniae, are a major public health concern. In this study, we assessed the impact of COVID-19 on ESBL rates in urine cultures in Ontario, Canada. Our results show the recent epidemiology of ESBL-producing Enterobacterales in urine cultures from both the community and LTC facilities in Ontario, Canada, and the impact of COVID-19 restrictions on ESBL trends for the entire province as well as different subgroups of the population based on demographic and geographic characteristics. Our results may have important public health implications in the context of the gradual easing of COVID-19 restrictions.

Cumulative Antibiogram: A Rapid Method to Hinder Transmission of Resistant Bacteria to Oral Cavity of Newborn Babies.

A rapid bacterial diagnostic is needed more and more in the treatment of patients, because of the emergence of antibiotic resistance. The cumulative antibiogram, an annual report that monitors antimicrobial resistance trends in health care facilities, may provide a profile of empirical therapy useful in diverse emergency situations, such as transmission of resistant bacteria to oral cavity of newborn babies. We aimed to draw a profile of antibiotic resistance encountered. We assessed the antibiotic resistance (ABR) profile in childbearing women and newborn babies in Ploiesti Obstetrics and Gynecology Hospital by the disk diffusion method characterizing the multidrug-resistant organisms after isolation and identification by phenotypic tests. Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E), Carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant Enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Group B Streptococcus (VR-GBS) were detected. The prevalence of antibiotic resistance was 11.32% (53/468), while the prevalence of the ESBL-E, MRSA, VRE and VR-GBS strains was 8.34% (39/468). Within the bacteria isolated from fifty-three childbearing women, the prevalence of ESBL-E, MRSA, VRE and VR-GBS was 22.64% (12/53), 32.08% (17/53), 11.32% (6/53) and 7.55% (4/53). In the whole studied group, the prevalence was 2.56% (12/468), 3.63% (17/468), 1.28% (6/468) and 0.86% (4/468). Resistant bacteria were detected at birth in the oral cavity of the newborn babies in all cases. Maternal and neonatal isolates shared similar characteristics. Cumulative antibiogram is useful in case of empiric treatment needed in diverse emergencies, such as transmission of resistant bacteria to oral cavity of newborn babies.

Epidemiology and molecular typing of multidrug-resistant bacteria in day care centres in Flanders, Belgium.

The global prevalence and spread of multidrug-resistant organisms (MDROs) represent an emerging public health threat. Day care centre (DCC) attendance is a risk factor for MDRO carriage in children and their environment. This study aimed to map the epidemiology of carriage and potential transmission of these organisms within 18 Flemish DDCs (Belgium). An MDRO prevalence survey was organised between November 2018 and February 2019 among children attending the centres. Selective chromogenic culture media were used for the detection of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), carbapenemase-producing Enterobacterales (CPE), and vancomycin-resistant Enterococci (VRE) in faecal swabs obtained from diapers or jars (n=448). All isolated MDROs were subjected to resistance gene sequencing. A total of 71 of 448 samples (15.8%) yielded isolates of ESBL-E with a predominance of Escherichia coli (92.2% of ESBL-E) and ESBL resistance gene blaCTX-M-15 (50.7% of ESBL coding genes in E. coli). ESBL-E prevalence varied between DCCs, ranging from 0 to 50%. Transmission, based on the clonal relatedness of ESBL-E strains, was observed. CPE was identified in only one child carrying an E. coli with an OXA-244 gene. VRE was absent from all samples. The observed prevalence of ESBL-E in Flemish DCCs is high compared with previous studies, and our findings re-emphasise the need for rigorous hygiene measures within such centres to control the further spread of MDROs in the community.

Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil.

The spread of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of β-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The β-lactamase-encoding genes were investigated using polymerase chain reaction. High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-β-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. C/A and C/T were active against microorganisms with β-lactam-resistant phenotypes, except when resistance was mediated by metallo-β-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more β-lactamase-encoding genes (62.5% and 77.4%, respectively).

Low potential of persistence and dissemination of antimicrobial-resistant Enterobacterales by wild nutria (Myocastor coypus) in a local river of Gifu Prefecture.

Environmental pollution caused by antimicrobial resistance is a global public health concern. To investigate the contribution of nutrias (Myocastor coypus) to the presence of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales in the Ijira River, prevalence of ESBL-producing Enterobacterales in their feces was examined using deoxycholate-hydrogen sulfide-lactose agar containing cefotaxime. Additionally, the composition of the fecal microbiota of nutria was examined using DNA metabarcoding analysis of the 16S ribosomal RNA gene and compared with that of Amami rabbit, deer, fox, and raccoon dog. The absence of ESBL-producing Enterobacterales and substantially lower abundance of Enterobacterales was observed in the feces of nutrias than in those of other wild mammals. Our results suggest the low potential of antimicrobial-resistant Enterobacterales persistence and dissemination by nutria.

Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.

Temocillin is a β-lactam that is not hydrolysed by ESBLs. To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ± 15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6). The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.