Emergency Department Urinary Tract Infections Caused by Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae: Many Patients Have No Identifiable Risk Factor and Discordant Empiric Therapy Is Common.

STUDY OBJECTIVE: Community-onset urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, which are resistant to ceftriaxone and usually coresistant to fluoroquinolones, are increasing worldwide. We investigate and describe in detail UTIs caused by ESBL-producing Enterobacteriaceae in our emergency department (ED), and determine the proportion that occurred in patients without health care-associated risk factors and who received discordant initial antibiotic therapy. METHODS: At an urban public hospital in Northern California, microbiology staff prospectively reviewed ED urine culture results weekly for 1 year and presumptively identified ESBL-producing isolates by ceftriaxone plus ceftazidime resistance. For isolates associated with a clinical UTI, patient demographic and case clinical features were abstracted retrospectively. Health care-associated infections were defined by standard risk factors plus aged 65 years or older, bladder catheter, urologic procedure, functional dependence, or antibiotics in the previous 90 days. Community-associated infections were defined by absence of these. A subset of community-associated ESBL-producing Escherichia coli isolates underwent genotyping. Electronic health record query was used to determine the denominator of ED UTI patients who underwent urine culture during the study period. RESULTS: Between August 2016 and July 2017, there were 1,045 unique ED patients diagnosed with a UTI, whose specimens underwent culture. There were 62 ESBL-producing isolates (5.9%; 95% confidence interval [CI] 4.6% to 7.5%). Selected characteristics of the entire ESBL UTI cohort were median age 50 years, 37 (60%) patients were women, 28 (44%) Hispanic, 11 (18%) had been hospitalized in the previous 3 months, 19 (31%) had pyelonephritis, 49 (79%) of isolates were E coli, 44 (71%) were levofloxacin-resistant, and 24 (23%) nitrofurantoin-resistant. Initial antibiotic choice was discordant with isolate susceptibility in 26 of 56 cases (46%; 95% CI 33% to 60%), and the initial oral antibiotic prescred was discordant in 19 of 41 cases (46%; 95% CI 31% to 63%). Twenty-seven infections (44%; 95% CI 31% to 57%) were categorized as community-associated. Eight patients with community-associated infection were women younger than 50 years, with no comorbidities and no more than 1 UTI in the previous year. Of 12 community-associated E coli isolates tested, all were confirmed to harbor ESBL genes; the CTX-M1 ß-lactamase gene was found in 8 (67%); 4 belong to genotype ST131. CONCLUSION: At this single Northern California ED, greater than 5% of culture-proven UTI were caused by ESBL-producing Enterobacteriaceae, and in nearly half of cases there was no identifiable health care-associated risk factor. Levofloxacin co-resistance and discordant antibiotic therapy were common.

A Dual Enzyme-Based Biochemical Test Rapidly Detects Third-Generation Cephalosporin-Resistant CTX-M-Producing Uropathogens in Clinical Urine Samples.

Extended-spectrum ß-lactamase (ESBL)-producing Gram-negative bacteria (GNB) are increasingly identified as the cause of both community and healthcare-associated urinary tract infections (UTIs), with CTX-Ms being the most common ESBLs identified. CTX-M-producing GNB are resistant to most ß-lactam antibiotics and are frequently multidrug-resistant, which limits treatment options. Rapid diagnostic tests that can detect ESBL-producing GNB, particularly CTX-M producers, in the urine of patients with UTIs are needed. Results from such a test could direct the selection of appropriate antimicrobial therapy at the point-of-care (POC). In this study, we show that a chromogenic, dual enzyme-mediated amplification system (termed DETECT [dual-enzyme trigger-enabled cascade technology]) can identify CTX-M-producing GNB from unprocessed urine samples in 30 minutes. We first tested DETECT against a diverse set of recombinant ß-lactamases and ß-lactamase-producing clinical isolates to elucidate its selectivity. We then tested DETECT with 472 prospectively collected clinical urine samples submitted for urine culture to a hospital clinical microbiology laboratory. Of these, 118 (25%) were consistent with UTI, 13 (11%) of which contained ESBL-producing GNB. We compared DETECT results in urine against a standard phenotypic method to detect ESBLs, and polymerase chain reaction and sequencing for CTX-M genes. DETECT demonstrated 90.9% sensitivity and 97.6% specificity (AUC, 0.937; 95% confidence interval, 0.822-1.000), correctly identifying 10 of 11 urine samples containing a clinically significant concentration of CTX-M-producing GNB (including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis). Our results demonstrate the clinical potential of DETECT to deliver diagnostic information at the POC, which could improve initial antibiotic selection.