Extended-spectrum Β-lactamase Producing Enterobacteriaceae Research Articles

Which trial do we need? Piperacillin-tazobactam compared with a carbapenem for treatment of graft pyelonephritis caused by extended spectrum β-lactamase–producing Enterobacteriaceae

Which trial do we need? Piperacillin-tazobactam compared with a carbapenem for treatment of graft pyelonephritis caused by extended spectrum β-lactamase–producing Enterobacteriaceae

Area-Based Socioeconomic Status Measures and Incidence of Community-Associated ESBL-Producing Enterobacteriaceae, 2017

Background: Extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-Ent) have emerged as a significant antimicrobial-resistance threat in the community in recent years. To better characterize ESBL-Ent in the community, we examined associations between community-associated ESBL-Ent incidence rates and area-based socioeconomic status (SES) characteristics. Methods: Cases were identified through active, laboratory- and population-based surveillance for ESBL-Ent in 3 Emerging Infections Program (EIP) sites (New Mexico, New York, and Tennessee) from October through December 2017. We defined a case as first isolation of Escherichia coli, Klebsiella pneumoniae, or K. oxytoca from a normally sterile body specimen or urine in a surveillance-site resident, with resistance to ≥1 extended-spectrum cephalosporin and nonresistance to all carbapenems tested. Epidemiologic data were abstracted from medical records. Cases were considered community associated if no significant prior healthcare exposures (ie, inpatient healthcare facility stay, surgery, chronic dialysis, indwelling devices, or external catheters) were documented. Case residential addresses were geocoded and linked to US Census Bureau data to obtain census-tract level SES measures. Census tracts were dichotomized by the percentage living in rural areas (0–49% or ≥50%); census tracts were stratified into quartiles for all other characteristics. Incidence rate ratios (IRR) for each measure, controlling for EIP site, were calculated using Poisson regression. Results: Among 742 ESBL-Ent cases with medical records available, 355 (47.1%) were community associated; of these, 327 case addresses (92.1%) were successfully geocoded. The combined annualized 2017 incidence rate for community-associated ESBL-Ent was 83.2 cases per 100,000 persons. The highest incidence of community-associated ESBL-Ent was seen in census tracts with the lowest median income (IRR, 1.4; 95% CI, 1.0–2.0) and with the highest percentages of persons without health insurance (IRR, 1.3; 95% CI, 1.0–1.7), with <12th-grade education (IRR, 1.5; 95% CI, 1.1–2.1), living in urban areas (IRR, 1.5; 95% CI, 1.0–2.2), foreign-born (IRR, 1.4; 95% CI, 1.0–2.0), or speaking limited English (IRR, 1.5; 95% CI, 1.1–2.0). There were no significant differences across quartiles for population density, income inequality, the percentage of the population living below poverty, or the percentage of households with crowding (>1 occupant or room). Conclusions: Social determinants of health, such as coverage for healthcare, appear to be important contributors to community-associated ESBL-Ent transmission. Higher rates in areas with more foreign-born persons and persons with limited English proficiency suggest a role for recent travel in importation and spread in specific communities. These findings provide additional information about the epidemiology of ESBL-Ent in the community and have potential implications for control efforts.Funding: NoneDisclosures: None

Clinical and Genetic Characteristics of Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae Among Canadian Children

Background: Infections with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) in nonoutbreak settings have not demonstrated the presence of dominant strains. Our objective was to determine the incidence, clinical characteristics, and genetic characteristics of ESBL-E infections among a group of Canadian children. Methods: From 2012 through 2017, patients aged ≤18 years with first-episode ESBL-E infections who presented at a pediatric center were reviewed. All clinical isolates were phenotypically identified in the laboratory as ESBL-producers. Demographic and clinical data were collected, including comorbid conditions, presence of devices, and previous antibacterial exposure. Community-associated infection was defined as a positive culture from a sterile site within the first 48 hours of hospital admission and no healthcare exposure during the preceding year. Isolates were sent to the Public Health Ontario Laboratory for whole-genome sequencing. Multilocus sequence typing was used to determine clonal relationship. Results: During the study period, 102 patients were identified with first-episode ESBL-E infection, and the proportion of ESBL-E isolates among all clinical isolates of E. coli and Klebsiella spp increased from 0.6% to 2.6% between 2012 and 2017, respectively (P = .001). The median age was 1 year (interquartile range, 0.8–5 years). Women comprised 66% of cases. No comorbid conditions were noted among 58 patients (57%), and 24% had previous antibiotic exposure, most frequently a cephalosporin (16%). ESBL-E was most frequently isolated in the urine (91%) and least frequently in the blood (2.2%) and was predominantly Escherichia coli (90%). Infection was most frequently diagnosed in the outpatient setting (61%); there were 11 healthcare-associated infections. Whole-genome sequencing of ESBL-E isolates revealed predominance of blaCTX-M-15 (63 isolates, 62%) and blaCTX-M-27 (16%) genes, and sequence type (ST) 131 (41%). Mutations conferring fluoroquinolone nonsusceptibility were noted among 62 isolates (61%), most frequently associated with ST131 (38 of 62 isolates, 61%) and among all 5 isolates with ST1193, an emerging multidrug-resistant E. coli clone. In addition, 15 patients had recurrence of ESBL-E infection at median of 113 days (IQR, 26–208); blaCTX-M-27 was found in 33% of recurrent infections compared to 12% of primary infections (P = 0.045). Conclusions: This study is the first in Canada to provide whole-genome sequencing data regarding ESBL-E in a pediatric population. The gene blaCTX-M-15 and ST131 clone were predominant. More than 60% of infections were community associated and demonstrated cross resistance to fluoroquinolones. With 76% of infections in antibiotic-naïve children, ESBL-E is a public health concern, and a One Health approach is critical to understanding the epidemiology and curbing the spread of multidrug-resistant Enterobacteriaceae.Funding: NoneDisclosures: None

Risk factors associated with prolonged intestinal colonization of ESBL-producing Enterobacteriaceae - a prospective cohort study.

BackgroundExtended spectrum β-lactamase-producing Enterobacteriaceae (EPE) are responsible for a major part of the widespread antimicrobial resistance (AMR). Increased understanding of risk factors associated with intestinal colonization of EPE is crucial to implement adequate actions against AMR. The aim of this study was to define potential risk factors for prolonged intestinal colonization with EPE. A secondary aim was to analyze if patients were adequately informed about being infected or colonized by antibiotic-resistant bacteria.MethodsPatients with a positive clinical EPE culture from urine, blood or feces were recruited in a region in the south of Sweden. Selective EPE fecal cultures were obtained at least three months after the initial positive culture. Prolonged intestinal colonization was defined as the prevalence of any EPE in the follow-up fecal sample. Risk factors for prolonged intestinal colonization were evaluated by using a questionnaire and by retrospective review of medical records. A univariate model and a multivariate regression analysis were performed to identify possible risk factors for intestinal EPE colonization.ResultsOut of 143 patients included in the study, 57% remained positive for EPE at the second sampling. In a multivariate regression model, urological intervention, history of EPE infection and travel to Africa and/or Asia within 2 years were found to be significantly associated with prolonged intestinal colonization of EPE. Before being approached by us, 50% of patients displayed inadequate knowledge of EPE infection or colonization.ConclusionIn this prospective cohort study, urological intervention within 6 months and a history of EPE infection are independently associated with prolonged intestinal colonization with EPE. In contrast, travel to Africa and/or Asia within 2 years is associated with a decreased risk of prolonged intestinal colonization with EPE. There is room for improvement when it comes to patient information regarding EPE to decrease of spread.

Comparative Study Between β-Lactam/β-Lactamase Inhibitors as Alternatives for Carbapenems in the Treatment of Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae

Background In the era of the increase in carbapenem resistance, searching for alternative drugs becomes mandatory. In this study, an in vitro activity of β-lactam/β-lactamase inhibitors against extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) isolated from bloodstream infections was investigated. Methods Blood samples were collected from patients with bloodstream infections in both pediatric and internal medicine intensive care units of Tanta University Hospitals, Egypt. BacT/ALERT was used, and positive blood cultures were subcultured on MacConkey, blood, chocolate agar and then incubated at 5% to 10% CO2, 37°C for 24 hours. Identification of the bacterial isolates was performed by VITEK 2TM Compact 15. Susceptibility testing was performed for isolated Escherichia coli and Klebsiella species using Kirby-Bauer disk diffusion and minimum inhibitory concentration. E test strips were used for cefoperazone/sulbactam, ceftazidime/avibactam, and ceftolozane/tazobactam. All isolates that were resistant to third-generation cephalosporins as per Clinical and Laboratory Standards Institute recommendations were confirmed for ESBL detection by modified double-disk synergy test, VITEK2 system, and multiplex polymerase chain reaction. Results One hundred twenty-five Enterobacteriaceae were isolated; 100 of them (80%) were ESBL positive. The best used β-lactam/β-lactamase inhibitors were ceftazidime/avibactam and ceftolozane/tazobactam with lower minimum inhibitory concentration at which 50% of isolates are inhibited (≤0.016, 0.094 μg/mL, respectively) than that of meropenem (0.125 μg/mL), so they can be used as carbapenem sparers in the treatment of ESBL-PE to decrease the incidence of carbapenem resistance. Conclusions Ceftazidime/avibactam and ceftolozane/tazobactam can be used as carbapenem sparers in the treatment of ESBL-PE to decrease the incidence of carbapenem resistance.

Dynamics of Resistance Plasmids in Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae during Postinfection Colonization.

Extended-spectrum β-lactamase-producing Enterobacteriaceae (EPE) are a major cause of bloodstream infections, and the colonization rate of EPE in the gut microbiota of individuals lacking prior hospitalization or comorbidities is increasing. In this study, we performed an in-depth investigation of the temporal dynamics of EPE and their plasmids during one year by collecting fecal samples from three patients initially seeking medical care for urinary tract infections. In two of the patients, the same strain that caused the urinary tract infection (UTI) was found at all consecutive samplings from the gut microbiota, and no other EPEs were detected, while in the third patient the UTI strain was only found in the initial UTI sample. Instead, this patient presented a complex situation where a mixed microbiota of different EPE strain types, including three different E. coli ST131 variants, as well as different bacterial species, was identified over the course of the study. Different plasmid dynamics were displayed in each of the patients, including the spread of plasmids between different strain types over time and the transposition of blaCTX-M-15 from the chromosome to a plasmid, followed by subsequent loss through homologous recombination. Small cryptic plasmids were found in all isolates from all patients, and they appear to move frequently between different strains in the microbiota. In conclusion, we could demonstrate an extensive variation of EPE strain types, plasmid composition, rearrangements, and horizontal gene transfer of genetic material illustrating the high dynamics nature and interactive environment of the gut microbiota during post-UTI carriage.

Temporal Dynamics and Risk Factors for Bloodstream Infection With Extended-spectrum β-Lactamase-producing Bacteria in Previously-colonized Individuals: National Population-based Cohort Study.

Little is known of the long-term risks of bloodstream infection (BSI) with extended spectrum β-lactamase-producing Enterobacteriaceae (EPE) in previously-colonized individuals. We investigated EPE-BSI risks and associated risk factors during 6 years following EPE colonization. We performed a population-based cohort study in Sweden using national health registers. Subjects were followed from their first EPE finding in feces (n = 5513) or urine (n = 17189). The effects of co-morbidity, sociodemography, and outpatient antibiotic dispensation on EPE-BSI risks were assessed. The EPE-BSI risks were compared to those of 45161 matched population-based reference subjects. The cumulative 6-year EPE-BSI incidences were 3.8%, 1.6%, and 0.02% in the urine, feces, and reference cohorts, respectively. The incidences decreased exponentially during the first 6-12 months. Among EPE-exposed subjects, urological disorders were associated with the highest adjusted cause-specific hazard ratio (aCSHR) for subsequent EPE-BSIs (3.40, 95% confidence interval 2.47-4.69). The aCSHRs were between 1.62-2.20 for male sex, immunosuppression, diabetes, malignancy, lung disease, baseline urine source, and Klebsiella pneumoniae, compared to the Escherichia coli baseline sample. Antibiotics with selective activity against gram-negative bacilli-but mostly not EPE (trimethoprim-sulfamethoxazole, fluoroquinolones, oral cephalosporins, and penicillins with extended spectrums)-and pivmecillinam were associated with doubled EPE BSI risk during the 3 months after antibiotic dispensation in EPE-colonized subjects. EPE in urine or feces is a substantial risk factor for subsequent EPE-BSIs, but the risk declines rapidly during the first year after detection. In EPE-colonized individuals, specific risk factors can be used to identify subgroups for targeted interventions, such as eradication therapy.

Subsequent infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in patients with prior infection or fecal colonization.

In clinical practice, there is a growing need to assess the impact of prior colonization or infection with extended-spectrum β-lactamase-producing Enterobacteriaceae (EPE) on new EPE infections. We have investigated the frequency of, and duration to, a subsequent EPE infection in patients with prior fecal carriage or infection with EPE. Culture data for 3272 EPE-positive patients in Western Sweden during 2004-2014 were evaluated. The median follow-up time was 3.7years. The first recorded EPE-positive fecal screen, or clinical (urine, blood) culture, and subsequent EPE-positive clinical samples were analyzed, focusing on the first and last recurrence of EPE infection. ESBL Escherichia coli dominated (95%). Almost all (94%) patients initially positive in fecal screen (n = 1436) and 72 and 71% of those initially positive in urine (n = 1717) and blood (n = 119) had no further EPE clinical isolates. Subsequent EPE bacteremia was only detected in 0.7, 1.6, and 4.2% of the respective patient group. Recurrent EPE-positive urine cultures occurred in 27% (460/1717), most (75%) within 6months, and rarely (13%) after 1year. Repeated EPE-positive clinical samples were significantly (p < 0.01) more common in patients > 65years and in men with ESBL Klebsiella pneumoniae. In our low-endemic setting, subsequent EPE infections in previously colonized patients were rare. On the other hand, in patients previously EPE-positive in urine or blood, subsequent EPE urinary tract infections were common, especially within 6months and in patients > 65years old.

Outcome of Bacteremia Caused by Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae After Solid Organ Transplantation

IntroductionAlthough infection with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) has been recognized as an important cause of morbidity after solid organ transplantation, there are limited data on the outcome of this complication among transplant recipients. The objective of this study was to describe the outcome and factors associated with mortality among recipients of abdominal solid organ transplants with bloodstream infection caused by ESBL-E. Patients and MethodsThis study was a retrospective analysis of a case series of patients who had bacteremia caused by ESBL-E after undergoing renal or liver transplantation between January 2000 and September 2008 at a university-affiliated hospital in Rio de Janeiro, Brazil. The primary end point of the study was death within 30 days of the diagnosis of bacteremia. ResultsDuring the study period, 997 subjects underwent kidney (759 patients) or liver (238 patients) transplantation. Fifty-four episodes of bacteremia caused by ESBL-E were diagnosed in 39 patients (4%). Mortality after the first episode of ESBL-E bacteremia was 26% (10 deaths). In multiple logistic regression analysis, the Pitt bacteremia score (P = .005) and being on mechanical ventilation at the time of infection diagnosis (P = .02) were the only variables associated with mortality. Thirteen episodes of recurrent bacteremia occurred in 8 (28%) of the 29 patients who survived the first episode. Two (25%) of these 8 patients died during the course of a recurrent episode. ConclusionsBacteremia caused by ESBL-E was associated with high mortality and high risk of recurrence. Factors associated with clinical severity at the time of infection diagnosis were the main predictors of mortality.

The crisis of antimicrobial resistance: current status and future strategies

The continuous emergence of new antimicrobial resistance in major human pathogens is a serious threat to clinical medicine, that increases mortality, morbidity, length of hospitalization, and the cost of healthcare. This review article focuses on the current status of antimicrobial resistance and future strategies to overcome antimicrobial resistance. In the community, multidrugresistant Streptococcus pneumoniae, community-associated methicillin-resistant Staphylococcus aureus (MRSA), and extended-spectrum β-lactamaseproducing Enterobacteriaceae are major issues. In the hospital, an increasing prevalence of multidrug-resistant or pan-drug resistant gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are emerging problems, while MRSA still remains the major cause of nosocomial infections. Strategies to control antimicrobial resistance include effective antimicrobial treatment, vaccination, infection control and appropriate policies and regulations. Continuous surveillance activities both in Korea and in an international setting are essential. Control of antimicrobial resistance should be a national priority based on a multisectoral approach, and international collaboration.