ESBL-producing Organism Research Articles

Efficacy of noncarbapenem therapy for the treatment of ceftriaxone-resistant Enterobacterales outside the urinary tract.

To determine the safety of noncarbapenem versus carbapenem antibiotics for treatment of adults with documented infection caused by ceftriaxone-resistant infections outside the urinary tract. Retrospective cohort of adult patients with a documented infection caused by an extended-spectrum β-lactamase (ESBL)-producing organism isolated between January 2018 and October 2021. An academic tertiary-care center. Adult patients with a documented infection caused by an ESBL-producing organism outside the urinary tract. The primary outcome was a composite of treatment failure defined as 30-day mortality, 30-day readmission, microbiological recurrence, and/or clinical worsening requiring antibiotic change. Secondary outcomes included differentiation of primary composite components and postantibiotic Clostridioides difficile infection (CDI). This study included 130 patients. The primary source of infections were bloodstream (67.7%) and caused by Escherichia coli (81.5%). Overall, 101 patients received carbapenem therapy and 29 received noncarbapenem therapy (NCT). NCT was comprised of mainly fluoroquinolones (18 of 29) followed by cefepime (7 of 29). Patients receiving NCT had shorter hospital stays (median, 7 days vs 9 days) and were more often discharged on antibiotics (79.3% vs 50.5%). We did not detect a significant difference in the primary composite outcome of treatment failure for carbapenem (23.8%) versus noncarbapenem treatment (24.2%; P = .967). Secondary outcomes included a numerically higher 30-day mortality rate in the noncarbapenem group compared to the carbapenem group: 4 (13.8%) of 29 versus 4 (3.9%) of 101. We did not detect a difference in rates of CDI. Noncarbapenem therapy may play a role for certain patients with infections caused by ESBL-producing organisms.

1177. Mind the GAPP: Global Arrivals and Pre-treated Patients screening at a children’s cancer center

Abstract Background Clinical and laboratory evaluation for infectious diseases prior to initiation of cancer-directed therapy creates opportunities for risk assessment, infection prevention and targeted treatment. The need may be greater for patients from outside the United States (US) where the epidemiology of infectious diseases may differ. We created the Global Arrivals and Pretreated Patients (GAPP) program to address this need at a referral hospital for children with cancer and blood disorders. Methods Patients accepted for treatment at our hospital are referred to GAPP for the following reasons: 1) residence in the continental US for 1 year or less, 2) travel outside the continental US within 3 months of referral 3) hospitalization outside the continental US, or 4) clinician request. GAPP evaluation includes review of history and laboratory studies, and recommendations for screening tests and management. Results Between March 21, 2019 and May 2, 2022, 35 patients were evaluated; 9 (26%) with solid or CNS tumors, 25 (71%) with hematological malignancies and 1 (3%) with immune thrombocytopenic purpura. Of these, 20/35 (57%) were from Latin America, and 10/35 (29%) from Eastern Europe. Most patients (29/35 [83%]) were seen within 2 weeks of arrival to the institution. Evaluation prompted isolation precautions in 2/35 (6%) for communicable respiratory illness and in 4/35 (11%) for ESBL-producing organism on perianal screen. Additionally, 13 patients were under-immunized (mostly non-immune to hepatitis B [7/35, 20%] or varicella zoster virus [8/35, 22%]), and 9/35 (26%) had an exposure-related risk. Finally, parasitic infection prompted specific management in 4 patients; 3/35 (9%) had positive serology for Toxoplasma gondii requiring appropriate prophylaxis, and 1/35 (3%) was treated for cryptosporidiosis. Conclusion Screening new arrivals to the US prior to administration of immunosuppressive therapy is feasible and may identify risk factors for illness during therapy as well as opportunities for infection prevention, immunization, and treatment or suppression of existing infections. Providers focusing on acute hematologic or oncologic illness may otherwise miss this quality improvement opportunity in a patient group at high risk of poor infectious outcomes. Disclosures Randall Hayden, MD, Inflammatix: Advisor/Consultant|Quidel Corporation: Advisor/Consultant|Roche Diagnostics: Advisor/Consultant|T2 Diagnostics: Advisor/Consultant Gabriela Maron, MD, Astellas Inc,: Grant/Research Support|SymBio Pharmaceuticals: Grant/Research Support Joshua Wolf, MBBS, PhD, Karius: Grant/Research Support|Merck: Participation in industry sponsored research.

What are the risk factors for recurrent UTI with repeated ESBL-producing Enterobacteriaceae? A retrospective cohort study

IntroductionA previous study has shown that two-thirds of patients with urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae experience recurrence with the same bacteria on subsequent UTI episodes. However, little is known about which patients suffer from UTI due to ESBL-producing Enterobacteriaceae repeatedly. This study aimed to investigate the risk factors for recurrent UTI due to repeated ESBL-producing organism infections. MethodsThis retrospective, single-center, observational cohort study screened all patients with UTI caused by ESBL-producing strains between January 2012 and April 2019. Among the patients who were followed up, patients who experienced UTI recurrence were enrolled and divided into two groups: ESBL recurrence group and non-ESBL recurrence group. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between patient characteristics and the development of recurrent UTI caused by ESBL-producing Enterobacteriaceae. ResultsA total of 330 patients were followed up after the diagnosis of UTI caused by ESBL-producing organisms. Among the patients, 115 (34.8%) experienced UTI recurrence, and 71 (61.7%) of them experienced subsequent recurrent UTI due to ESBL-producing organisms. Patient's age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00–1.04; P = 0.046) and recurrent UTI history (HR, 1.69; 95% CI, 1.05–2.72; P = 0.031) were significantly associated with an increased risk of recurrence with ESBL-producing Enterobacteriaceae. ConclusionThese findings showed that a history of previous frequent UTI recurrence is the risk factor for recurrence of UTI due to repeated ESBL producing Enterobacteriaceae infections.

CTX-M-type Extended-Spectrum β-Lactamases Producing Enterobacteriaceae Isolated from Urine in a Tertiary Care Hospital, Kathmandu, Nepal

Background: Despite the global increase of CTX-M type Extended-Spectrum-β-Lactamases (ESBLs) in recent years among Enterobacteriaceae isolates from urinary tract infections, little data is available from Nepal. Objective: This study was conducted to detect the genes encoding extended-spectrum β-lactamases among Enterobacteriaceae isolated from the urine samples from Nepal. Methods: A total of 148 Enterobacteriaceae isolates were obtained from urine samples in Annapurna Neurological Institute and Allied Sciences from July 2016 to June 2017. ESBL production was detected according to the Clinical and Laboratory Standards Institute (CLSI) recommended method. PCR and sequencing were used for the detection of ESBL genes. Results: Overall, 24.3% (36/148) of the study isolates were positive for ESBL production. E. coli was the predominant ESBL-producing organism (28.8%). ESBL-producing organisms showed a high rate of resistance to ceftazidime (58.4%), cefepime (91.7%), aztreonam (83.4%), and ciprofloxacin (80.6%). Also, 30.6% of ESBL-producing organisms were multi-drug resistant. All ESBL producers were CTX-M positive; other ESBL genes were not detected. The majority of the ESBL positive organisms produced CTX-M-15 (n= 31) and few organisms (n= 5) were CTX-M-27 producers. Conclusion: The present study shows that the predominant CTX-M type ESBL in our hospital setting is CTX-M-15.

Emergence of Extended-Spectrum β-Lactamase-Producing Pathogens in Community-Acquired Urinary Tract Infections Among Infants at a Pediatric Emergency Department.

Extended-spectrum β-lactamase (ESBL)-producing pathogens are common among adults and are associated with extended and multiple hospitalizations. They cause urinary tract infections (UTIs) among children with known risk factors such as urinary tract abnormalities and antimicrobial prophylaxis. The emergence of UTIs caused by ESBL-producing organisms among infants has not been well characterized. We sought to describe the incidence and current clinical management of infants who were diagnosed with UTIs caused by ESBL-producing organisms at a pediatric emergency department (ED). In addition, we sought to describe risk factors associated with inpatient hospitalization for UTIs caused by ESBL-producing organisms. We retrospectively identified infants who were treated in the ED from 2013 to 2017 and who had positive urinalyses and urine cultures positive for greater than 50,000 colony-forming unit per milliliter of a single ESBL-producing urinary pathogen. We abstracted details of clinical management and known previous risk factors, including prior neonatal intensive care unit hospitalization stay, prior UTI caused by an ESBL-producing organism, and known urologic abnormalities. Forty-five UTIs caused by ESBL-producing organisms occurred in 43 patients (mean age of 5.9 months and 59% female)-ESBL Escherichia coli represented the majority (42/45). The incidence of UTIs caused by ESBL-producing organisms ranged from 0.9% to 4.5% during the 5-year study period. The 13 patients (26%) admitted from the ED were significantly younger than discharged patients (1.9 vs 6.7 months, P = 0.016) and more likely to have had prior neonatal intensive care unit hospitalizations (50% vs 15.6%, P = 0.0456). Of the 33 visits (77%) resulting in initial outpatient management, 5 were followed by readmission for parenteral antibiotic treatment. Of those who were readmitted, 40% (n = 2) were afebrile at the time of admission. The remainder (28/33) completed outpatient oral antibiotic courses guided by susceptibilities. Two patients (4%) had negative repeat urine cultures despite in vitro resistance to initial antibiotic coverage. Extended spectrum β-lactamase-producing organisms are an increasing cause of UTIs in infants presenting at a pediatric ED, and outpatient management may be reasonable for infants older than 2 months.

1576. Re-Evaluation of cefepime or piperacillin-tazobactam to Decrease Use of Carbapenems in ESBL-Producing Enterobacterales BloodStream Infections (REDUCE-BSI)

BackgroundThe ideal therapy for treatment of bloodstream infections (BSI) due to ESBL-producing organisms is widely debated. Although prior studies have demonstrated efficacy of non-carbapenems (CBPNs) for ESBL infections, results from the MERINO study group found increased mortality associated with piperacillin/tazobactam (PT) when compared with meropenem for treatment of ESBL BSI. The goal of this study was to investigate patient outcomes associated with the use of CBPN-sparing therapies (PT and cefepime (CEF)) for ESBL BSI. The primary outcome was in-hospital mortality between non-CBPN (PT and CEF) and CBPN groups. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and development of resistance.MethodsThis was a retrospective observational study of patients admitted to the hospital from May 2016 - May 2019 with a positive blood culture for an ESBL-producing organism. Patients receiving meropenem, ertapenem, PT, or CEF were included. Patients were excluded if < 18 years old, receiving antibiotics for < 24 hours, treated for a polymicrobial BSI, or receiving concomitant antibiotic therapy for another gram-negative (non-ESBL) infection.ResultsOne hundred and fourteen patients were analyzed; 74 (65%) patients received CBPN therapy compared with 40 (35%) patients that received a non-CBPN (CEF N=30, PT N=10). There were no statistically significant differences in baseline characteristics between groups. The overall in-hospital mortality rate was 6% (N=7). Eight percent of patients (N=6) in the CBPN arm died compared to 3% (N=1) of patients in the non-CBPN arm, P = 0.42. No difference in mortality was detected between groups when evaluating subgroups with Pitt bacteremia score ≥4 (N=25), requiring ICU admission (N=50), non-genitourinary source (N=50), or by causative organism (N=76 E. coli; N=38 Klebsiella spp.). There was no difference between groups for secondary outcomes.ConclusionCEF and PT are reasonable options for the treatment of ESBL BSI and did not result in increased mortality or decreased clinical efficacy when compared to CBPNs in this cohort.Disclosures All Authors: No reported disclosures

Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum β-Lactamase-Producing Organisms?

Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing organisms. We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain. There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09). TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Clinical Features and Outcomes in ESBL-Producing Microorganisms in Renal Transplant Recipients with Urinary Tract Infections

: Multidrug-resistant organisms have become an increasing challenge in the management of both solid and non-solid organ transplants. This is especially true with extended spectrum beta-lactamases (ESBL) and carbapenem-resistant Enterobacteriaceae (CRE) infections. We performed a retrospective study of 62 renal transplant recipients at a tertiary care center in El Paso, Texas. In our study population, 43% of patients had a positive urine culture and were treated for a UTI. 30% of those UTIs were caused by an ESBL-producing organism. Of note, 43% of the patients who developed a UTI also had a recurrent episode. Notably, one patient had 25 recurrences of UTIs caused by ESBL producing E. coli. K. pneumoniae and E. coli were the most commonly cultured non-ESBL-producing bacteria (40.7%). E. coli was the most frequently cultured ESBL-producing bacteria (62.5%), while K. pneumoniae was the second most frequently cultured ESBL-producing bacteria (37.5%). There were three transplant rejections; two had ESBL UTIs and one had 11 recurrent UTIs prior to rejection. Diabetes, the length of ureteral stents, and higher troughs of immunosuppressant therapy were observed to be correlated with higher rates of UTIs in our patient population. Our findings are consistent with reports published in current literature regarding rates of UTIs among renal transplant recipients. Due to increasing prevalence of multi-drug resistant organisms and increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE), it becomes imperative for clinicians to include CRE in the differential diagnosis when evaluating renal transplant recipients with recurrent UTIs. More importantly, CRE must be considered when evaluating renal transplant recipients with recurrent UTIs caused by ESBL producing organisms.

Psychoactive drug prescription and urine colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae.

BackgroundThe worldwide dissemination of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a major health concern. Previous studies have shown that psychoactive drugs have intrinsic antimicrobial activity and may play a role in the dissemination of antibiotic resistance. The objective of this study was to assess the association between prescriptions for psychoactive drug and urine colonization with ESBL-producing Enterobacteriaceae.SubjectsNinety-five patients were included; 19 cases (urine colonization with an ESBL-producing Enterobacteriaceae) and 76 controls (urine colonization with non ESBL-producing Enterobacteriaceae); and were matched for age and gender.MethodsA retrospective 1:4 matched case–control study design was used. All patients colonized with an Enterobacteriaceae isolate in Nantes University Hospital from March to November 2014, were screened before inclusion in the study. Prescriptions data for psychoactive drugs were collected from the electronic medical records. Univariate and multivariate conditional logistic regression analyses were performed.ResultsThirty-seven patients (38.9%) were treated with psychoactive drugs, of whom 10 (52.6%) were in the ESBL-producing group and 27 (35.5%) were in the non-ESBL group. Mean (SD) age was 71.2 (23.1) years. In multivariate analyses, previous antimicrobial therapy within 6 months (OR=7.12, 95% CI 1.15–44.18; p=0.035) and previous colonization with an ESBL-producing organism (OR=44.87, 95% CI 1.26–1594.19; p=0.037) were associated with urine colonization with ESBL-producing Enterobacteriaceae.ConclusionsOur findings revealed that a history of previous antimicrobial therapy and previous colonization with ESBL-producing organisms are important risk factors in an elderly population. Psychoactive drugs were not associated with urinary carriage of ESBL-producing Enterobacteriaceae. Further studies are required to explore the relationship between psychoactive drugs and colonization with ESBL-producing Enterobacteriaceae.

Association of systemic antimicrobials with the expression of beta-lactamases in bacteria cultured from urological patients

BackgroundPatients with abnormalities of the genitourinary tract are at high risk for infections with antimicrobial-resistant pathogens. MethodsAll urine cultures ordered by members of the Division of Urology from four quarterly one-week periods were included. All gram-negative bacilli isolated were analyzed using the Check-Points Check-MDR CT103XL assay to identify the presence of genes associated with resistance to beta-lactam antibiotics. Association between the days of antibiotics and the presence of an ESBL-producing organism was determined. ResultsOne hundred eleven positive cultures were included in this analysis, of which 5 (4.5%) contained ESBL-producing species. Days of systemic antibiotics within 30 days of urine culture was associated with an increased risk of isolating an ESBL-producing pathogen. ConclusionThe overall prevalence of ESBL-producing organisms is low in this cohort. The number of days of systemic antibiotics within 30 days of a urine culture was significantly associated with increased risk of isolating an ESBL-producing organism.

Piperacillin-Tazobactam Versus Carbapenems for the Treatment of Nonbacteremic Urinary Tract Infections due to Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae.

Background: Carbapenems are the drug of choice for treatment of infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Current evidence regarding piperacillin-tazobactam (PTZ) as an effective treatment alternative remains controversial. The purpose of this study was to determine the efficacy of PTZ versus carbapenems for treatment of nonbacteremic urinary tract infections (UTIs) due to ESBL-producing Enterobacteriaceae. Methods: A retrospective cohort study of patients treated for ESBL-related UTIs was conducted at three medical centers in the greater Middle Tennessee area. Patients were included if they were ≥ 18 years old, had a positive urine culture with an ESBL-producing organism, and received ≥ 48 hours of treatment with PTZ or carbapenem. Patients with bacteremia as well as those with isolates resistant to the treatment regimen selected were excluded. The primary objective was to determine the difference in clinical response between PTZ and carbapenem for treatment of ESBL-related UTIs. Clinical response was defined as absence of all of the following: (1) repeat admission for UTI caused by the same organism within 6 months, (2) repeat urine culture within 6 months showing growth of the same organism, or (3) a change in antimicrobial regimen due to subjective failure as determined by the ordering provider. Results: A total of 180 patients were included in the analysis (PTZ = 39; carbapenem = 141). There was no difference in clinical response between patients receiving PTZ and carbapenem (74.4% versus 80.9%; P = .38). Conclusion: PTZ may be an effective alternative to carbapenems for treatment of nonbacteremic UTIs due to ESBL-producing Enterobacteriaceae.

1588. Clinical Prediction Tool for Extended-Spectrum Β Lactamase-Producing Enterobacteriaceae as the Etiology of Bacteremia in Solid Organ Transplant Recipients

BackgroundMultidrug-resistant Gram-negative bacterial infections have emerged as a significant cause of morbidity among solid-organ transplant (SOT) recipients, leading to challenges in selection of empiric antibiotic therapy. As such, we developed a predictive tool to determine whether these patients are high or low risk for extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EB) bacteremia at the time of positive blood culture.MethodsAll SOT recipients admitted to the Hospital of the University of Pennsylvania with blood cultures positive for EB between January 2007 and July 2016 were included in the source cohort. Multivariate logistic regression was used to determine predictors of ESBL-EB bacteremia. Manual forward selection was utilized to maximize area under the receiver operating characteristic curve (AUC), with sequential addition of covariates until achieving an AUC increase of <1%. A scoring system was developed based on the adjusted odds ratios for each covariate. Interval validity was assessed using the Hosmer-Lemeshow statistic, sensitivity, specificity, and the bootstrapping technique.ResultsOver the study period, there were 287 SOT recipients admitted with an EB bacteremia, of which 51 were due to an ESBL-producing organism. The final model that predicted presentation with ESBL-EB bacteremia included: identification of an ESBL-EB on culture in the previous 12 months, trimethoprim-sulfamethoxazole exposure in the prior 6 months, receipt of a kidney transplant, and fluoroquinolone exposure in the prior 6 months. This model achieved an AUC of 0.85, sensitivity of 54.9%, specificity of 96.6%, and Hosmer–Lemeshow statistic of 0.26 (Figure 1). Based on the adjusted odds ratios for each factor, scores of +3, +1, −1, and +1 were assigned to each covariate, respectively. With this scoring system, the maximum attainable score was 5, with any score of ≥3 deemed to be predictive of ESBL-EB bacteremia. After bootstrapping, the adjusted AUC remained at 0.85.ConclusionThe presence of ESBL-EB organism as the etiology of bacteremia in SOT recipients can be predicted using the above scoring system. This tool will inform judicious empiric antibiotic use in this population at the time of positive blood culture. Disclosures All authors: No reported disclosures.

Augmenting the Guidelines: Screening Patients for CRE Carriage Prior to Endoscopic Retrograde Cholangiopancreatography (ERCP) as Surveillance and Risk Mitigation Strategy

Introduction: Outbreaks of Carbapenem Resistant Enterobacteriaceae (CRE) due to contaminated duodenoscopes continue to be reported despite adherence to optimal reprocessing practices. Frequent culturing of devices can be labor intensive and adds challenges in maintaining workflow. Our study hypothesizes that reliable and timely detection of CRE colonization among patients can help inform surveillance practices, such that a duodenoscope is assessed for microbial contamination only after use on CRE colonized persons. Methods: In a prospective observational study, screening for CRE via dual rectal swab occurred immediately prior to ERCP. All swabs were tested for CRE using PCR and culture methods. Bacterial culture swabs were plated on Hardy Chrome CRE media. Subsequent positive growth was cultured to a Mac-Conkey plate. Duodenoscope reprocessing occurred per the manufacturer's instructions. Results: During the six-month study period, 111 samples were collected from 97 patients. Median age of the study cohort was 65 years (range 37-91); 57 % were women. The most common underlying diagnoses were pancreatic (58%) and colon cancer (10%) [Table 1]. 24 (25%) patients had undergone ERCP at another institution in the past and 19 patients previously had ERCP at our institution. Three (3%) patients had detectable MDR colonization on screening, one each with CRE (KPC; detected by PCR only) and ESBL producing organism, a third patient was co-colonized with ESBL and CRE (OXA-48). Three patients (3%) developed bloodstream infection within 30 days following the ERCP procedure, none were CRE. The blood isolates included Streptococus species and Enterobacter, none were MDR. No patient to patient transmission of CRE was detected during the study period. Conclusion: In a large tertiary care referral cancer center, we found a low prevalence of CRE colonization in our patient population. This is despite the diverse referral pattern of our patient population, high rate of previous device exposure, and geographic location in a CRE endemic area. These findings support a potential approach to screen patients for CRE thus limiting the number of duodenoscopes that need to be screened for potential CRE contamination. This strategy may serve as a useful adjunct to the recent new multisociety duodenoscope surveillance sampling and culturing protocol and may streamline workflow practices at large volume endoscopy centers.1065 Figure 1 No Caption available.

Epidemiological Analysis of Extended-Spectrum Beta-Lactamase-Producing Bacterial Infections in Adult Live Donor Liver Transplant Patients.

Introduction:Bacterial infections are a leading cause of morbidity and mortality in patients receiving solid-organ transplants. Extended-spectrum beta-lactamases (ESBL) pathogens are the most important pathogenic bacteria infecting these patients.Aim:This study aims to evaluate for the incidence and characteristics of ESBL-positive organism, to look for the clinical outcomes in ESBL-positive infected cases, and to evaluate and draft the antibiotic policy in posttransplant patients during the first 28 days posttransplant.Materials and Methods:This is a retrospective data analysis of liver transplant recipients infected with ESBL culture-positive infections. All the culture sites such as blood, urine, and endotracheal tube aspirates were screened for the first ESBL infection they had and noted. This data were collected till day 28 posttransplant. The antibiotic susceptibility pattern and the most common organism were also noted.Results:A total of 484 patients was screened and 116 patients had ESBL-positive cultures. Out of these, 54 patients had infections and 62 patients were ESBL colonizers. The primary infection site was abdominal fluid (40.7%), with Klebsiella accounting for most of the ESBL infections. Colistin was the most sensitive antibiotic followed by tigecycline. The overall mortality was 11.4% and 31 out of 54 ESBL-infected patients died.Conclusions:Infections with ESBL-producing organism in liver transplant recipients has a high mortality and very limited therapeutic options.

In silico and In vitro Activity of Ceftolozane/Tazobactam Against Pseudomonas aeruginosa Collected Across Indian Hospitals

Ceftolozane/tazobactam is a novel antimicrobial agent with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens. In this study, we determined the antimicrobial susceptibility for a total of 149 clinical isolates of P. aeruginosa for the most commonly used antimicrobials including the new agent ceftolozane/tazobactam (C/T). Broth microdilution was performed to determine the minimum inhibitory concentration against various antimicrobials including C/T. Among the β-lactam/β-lactamase inhibitor, overall susceptibility was 67%, 55% and 51% for C/T, Piperacillin/Tazobactam (P/T) and Cefoperazone/Sulbactam, respectively. The variations in the susceptibility rates were noted among the three different β-lactam/β-lactamase inhibitors. Interestingly, 33% susceptibility was noted for C/T against isolates that were resistant to P/T, indicating the higher activity of C/T. This finding suggests about 33% of the P/T-resistant isolates can still be treated effectively with C/T. C/T could be a better alternative for the treatment of ESBL-producing organism, and thereby usage of higher antimicrobials can be minimised.

Extended-spectrum β-lactamase-producing bacteria caused less than 5% of urinary tract infections in a paediatric emergency centre.

The last decade has seen a significant increase in extended-spectrum β-lactamase (ESBL) secreting organisms responsible for paediatric urinary tract infections (UTIs), particularly in community-acquired infections. These expose patients to the risks of antibiotic treatment failure and renal scarring. This prospective study examined the prevalence and risk factors of febrile ESBL UTIs and their treatment in the paediatric emergency department of a university hospital. In this prospective observational study, all children from 0 to 16 years of age with febrile UTIs were included from May 2012 to April 2013. Cases with and without ESBL involvement were compared. Of the 474 diagnosed febrile UTIs, 22 (4.6%) with a 95% confidence interval (95% CI) of 2.9-6.9 were due to an ESBL-producing organism. Escherichia coli was found in 85% of cases. Significant odds ratios (OR) for ESBL urinary tract infections were prior hospitalisation (OR 4.1, 95% CI 1.6-10.8), urinary tract abnormalities (OR 3.9, 95% CI 1.5-10.2) and previous antibiotic treatment (OR 3.1, 95% CI 1.2-8.8). All ESBL urinary tract infections had positive outcomes. The prevalence of febrile ESBL urinary tract infections was less than 5% in a paediatric emergency department. This low rate was not high enough to justify changing our guidelines.

Risk Factors for Community-Acquired Urinary Tract Infection by Extended-Spectrum β-Lactamase–Producing Organisms in Children

The profile of 65 hospitalized children with community-acquired urinary tract infection (UTI) was analyzed to identify the risk factors associated with UTI caused by extended-spectrum β-lactamase (ESBL) producers. Of the 58 subjects with gram-negative organisms, 64.4% were ESBL producers. There were no statistically significant differences in the clinical characteristics of those with UTI caused by ESBL producers and non-ESBL producers. No specific risk factors for infection with ESBL producers were identified in individuals with UTI; the possibility of infection with an ESBL-producing organism must therefore be considered in all cases of UTI, and antibiotic prescribing policies reviewed accordingly.

Predictors of hospital surface contamination with Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: patient and organism factors

BackgroundThe role of the hospital environment in transmission of ESBL-Klebsiella pneumoniae (ESBL-KP) and ESBL-Escherichia coli (ESBL-EC) is poorly defined. Recent data however suggest that in the hospital setting, ESBL-KP is more transmissible than ESBL-EC. We sought therefore to measure the difference in hospital contamination rates between the two species and to identify key risk factors for contamination of the hospital environment with these organisms.MethodsWe systematically sampled 8 surfaces in the rooms and bathrooms of adult patients colonized or infected with ESBL-EC or ESBL-KP throughout their hospital stay. Data were collected on factors potentially affecting contamination rates. Environmental contamination was defined as recovery of an ESBL-producing organism matching the source patient’s isolate. Multivariate logistic regression analysis was performed at the level of the patient visit using generalized estimating equations to identify independent predictors of environmental contamination.Results24 patients (11 with ESBL-KP, 11 ESBL-EC and 2 with both organisms) had 1104 swabs collected during 138 visits. The overall contamination rate was 3.4% (38/1104) and was significantly higher for ESBL-KP than ESBL-EC (5.4% versus 0.4%; p < 0.0001). After multivariate analysis, environmental contamination was found to be negatively associated with carbapenem exposure (OR 0.06 [95% CI 0.01-0.61]; p = 0.017) and positively associated with the presence of an indwelling urinary catheter (OR 6.12 [95% CI 1.23-30.37]; p = 0.027) and ESBL-KP in the source patient (OR 26.23 [95% CI 2.70-254.67]; p = 0.005).ConclusionsContamination of the hospital environment with ESBL-producing Enterobacteriaceae (ESBL-E) is inversely associated with carbapenem exposure. Predictors of hospital contamination with ESBL-E include: indwelling urinary catheters and ESBL-KP. Rooms of patients with ESBL-KP have substantially higher contamination rates than those with ESBL-EC. This finding may help explain the apparently higher transmissibility of ESBL-KP in the hospital setting.

Impact of extended‐spectrum β‐lactamase–producing organisms on clinical and economic outcomes in patients with urinary tract infection

To compare clinical and economic outcomes between patients with urinary tract infection (UTI) due to extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) versus patients with non-ESBL-EK UTI. Eighty-four (3.6%) of 2345 patients admitted between September 1, 2011 and August 31, 2012 with UTI were positive for ESBL-EK. Fifty-five ESBL-EK UTI (cases) and matched controls (non-ESBL-EK UTI) were included in the analysis. Clinical and economic outcomes were compared between cases and controls for statistical significance. Cases were more likely to have diabetes mellitus, a history of recurrent UTIs, recently received antibiotics, recently been hospitalized, and had previous isolation of an ESBL-producing organism compared with controls. Failure of initial antibiotic regimen (62% vs 6%; P < 0.001) and time to appropriate antibiotic therapy (51 vs 2.5 hours; P < 0.001) were greater in cases. The median cost of care was greater (additional $3658; P = 0.02) and the median length of stay (LOS) prolonged for cases (6 vs 4 days; P = 0.02) despite similar hospital reimbursement (additional $469; P = 0.56). Although not significant, infection-related mortality (7.2% vs 1.8%) and 30-day UTI readmission (7.2% vs 3.6%) were higher in ESBL-EK cases. UTI caused by ESBL-EK is associated with significant clinical and economic burden. The cost of care and LOS of patients with ESBL-EK UTI were 1.5 times those caused by non-ESBL-EK. Importantly, the additional cost of care is a liability to the hospital, as this is not offset by reimbursement. Appropriate and timely initial antibiotics may minimize the ESBL-EK impact on outcomes of patients with UTI.

Risk factors associated with preoperative fecal carriage of extended‐spectrum β‐lactamase‐producing Enterobacteriaceae in liver transplant recipients

The aim of the study was to identify risk factors associated with pre-transplant fecal carriage of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in liver transplant recipients. Over a 3-year period (January 2009-December 2011), 317 patients who underwent liver transplantation were screened preoperatively for fecal carriage of ESBL-producing Enterobacteriaceae. Risk factors for fecal carriage were investigated by univariate analysis and stepwise logistic regression. Of the 317 patients screened, 50 (15.7%) harbored an ESBL-producing isolate. Previous infection with an ESBL-producing organism had developed during the last 6 months in 20% of fecal carriers versus in none of the non-carriers. Other variables associated with fecal carriage were a model for end-stage liver disease score ≥25, pre-transplant stay in the intensive care unit ≥48 h, hospital stay ≥10 days in the last 6 months, a history of spontaneous bacterial peritonitis (SBP), exposure to a β-lactam agent in the last month, and prophylaxis with norfloxacin. Independent predictors of fecal carriage in the multivariate logistic regression model were exposure to a β-lactam agent in the month preceding transplantation (odds ratio [OR] = 7.8, confidence interval [CI] = 4-15.5, P < 0.001), and a history of SBP (OR = 2.4, CI = 1.1-4.9, P = 0.02). Previous infection with an ESBL-producing isolate, recent exposure to a β-lactam agent, and a history of SBP are risk factors for preoperative fecal carriage of ESBL-producing Enterobacteriaceae in liver transplant recipients. Patients at risk of fecal carriage should receive intraoperative prophylaxis and, when necessary, empiric postoperative antimicrobial treatment that includes coverage for these organisms.