Antibiotic Susceptibilities and Appropriateness of Initial Drug Selection for Community-Acquired Urinary Tract Infections (UTI) Caused by Extended-Spectrum Β-Lactamase (ESBL)-Producing Pathogens

BACKGROUND: Community-acquired (CA) UTI caused by ESBL-producing pathogens pose challenges related to initial antibiotic (AB) selection. Better characterization of AB susceptibilities in CA ESBL infections may improve empiric drug selection for outpatient therapy. The objectives of this study were to describe AB susceptibilities of isolates in CA ESBL UTI and provide recommendations for appropriate treatment at our institution. METHODS: Adult patients with CA ESBL UTI (cystitis) from 2009 through 2013 were retrospectively matched 1:1 with a control group of non-ESBL CA UTI based on age within 5 years, gender, and organism. The primary outcome in this phase of the study was description of AB susceptibilities in CA ESBL UTI vs. controls. Secondary outcomes were comparison of appropriate initial AB therapy (defined as concordance of initial AB with in vitro susceptibilities) and development of recommendations for initial antibiotics for CA UTI. RESULTS: Eighty-five patients were matched into each of the ESBL and non-ESBL CA UTI groups. E. coli was the pathogen in 94% of ESBL UTIs and 96% of controls. Patients with ESBL UTI most often received ceftriaxone or oral β-lactam (BL, 31%), fluoroquinolone (FQ, 27%), trimethoprim/sulfamethoxazole (TMP/SMX, 14%), or nitrofurantoin (NF, 14%); controls were similar. Besides non-carbapenem BLs, ESBL producers were significantly more resistant to FQs (78% resistant), NF (16%), TMP/SMX (60%), gentamicin (33%), and doxycycline (78%) vs. controls (P < 0.01 for each). Ertapenem and amikacin had 100% and 96% susceptibility, respectively. Initial AB were discordant in 64% of ESBL UTI vs. 14% of controls (OR 11.0, 95% CI 5.0–24.3; P < 0.0001). FQs and TMP/SMX were discordant in 83% and 42% of ESBL UTI, respectively, while NF was concordant in 100% of patients with ESBL UTI and 89% of controls. CONCLUSION: Patients with CA ESBL UTI were significantly more likely to receive inappropriate initial AB therapy. Although ESBL-producing strains were resistant to multiple AB classes, NF retained activity against 84% of ESBL isolates and was associated with appropriateness of initial therapy in 100% of patients with ESBL UTI. Nitrofurantoin is an appropriate oral option for treatment of CA UTI, even in patients with ESBL infection. DISCLOSURES: D. N. Fish, Merck & Co.: Grant Investigator, Research grant M. Barron, Merck & Co.: Grant Investigator, Research grant