Long-term outcomes of inappropriate antibiotic therapy for upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a retrospective cohort study

Abstract

Background: To evaluate the short- and long-term outcomes of different antimicrobial treatment options for upper urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

Methods: We retrospectively analyzed patients with a first episode of febrile UTI and positive urine culture with ESBL-producing E. coli or K. pneumoniae during 2012-2015. We compared outcomes among patients who received: (1) definitive treatment with a carbapenem (CP), (2) a microbiologically appropriate intravenous non-carbapenem agent (NCA), (3) a non-appropriate antimicrobial (NAA), and (4) an intravenous NAA followed by an oral NCA (NAA-PO).

Results: The majority of patients received empirical therapy with NAA (165/178, 93%), and definitive treatment with NCA (n=43), NAA (n=50), and NAA-PO (n=59). The NCA group had significantly higher SIRS score than the NAA-PO group (2.18 versus 1.76, P=0.018), but no differences were found between the NCA and NAA groups (2.18 and 1.92, P=0.15). Clinical cure at discharge from the index hospitalization was high (97-100%) in all 3 groups. The NCA group had longer length of stay as compared with the NAA-PO and NAA groups (8.7days versus 5.39 and 5.24days, P<0.0001) and a lower rate of early (48-72h) improvement (79% versus 96-100%, P=0.0002). Among re-admitted patients, re-admission with ESBL-related bloodstream infection was significantly higher in the NAA group as compared to the NAA-PO and NCA groups (33% versus 4% and 0%, respectively, P=0.02). Death rate within 60days was also higher in the NAA and NCA groups as compared with the NAA-PO group (P=0.048).

Conclusions: Inappropriate antimicrobial therapy for febrile non-bacteremic UTI with ESBL-producing enterobacteriaceae is associated with favorable short-term outcomes, but also with a long-term risk of relapsed bacteremic UTI. Definitive treatment with appropriate carbapenem-sparing antimicrobial agents effectively prevents late relapses.

Keywords: Extended spectrum beta lactamase (ESBL); Inappropriate; Long-term; Outcome; Therapy; Urinary tract infection (UTI).