High fluoroquinolone MIC is associated with fluoroquinolone treatment failure in urinary tract infections caused by fluoroquinolone susceptible Escherichia coli

Pinyo Rattanaumpawan, Irving Nachamkin, Warren B. Bilker, Jason A. Roy, Joshua P. Metlay, Theoklis E. Zaoutis, Ebbing Lautenbach, on behalf of the CDC prevention epicenters program

Suboptimal clinical response to fluoroquinolone (FQ) therapy has been clearly documented in patients with Salmonella typhi infection with reduced FQ susceptibility. However, the clinical impact of reduced FQ susceptibility on other infections including E. coli urinary tract infections (UTIs) has never been evaluated. We conducted a retrospective cohort study of female patients with fluoroquinolone susceptible E. coli (FQSEC) UTIs who received FQ therapy at outpatient services within University of Pennsylvania Health System, Philadelphia. Exposed patients were those with high MIC-FQSEC UTIs (the levofloxacin MIC > 0.12 but ≤ 2 mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC ≤ 0.12 mg/L). The primary treatment outcome was treatment failure within 10 weeks after initiation of FQ therapy. From May 2008 to April 2011, we enrolled 29 exposed patients and 246 unexposed patients. Two patients in each group experienced treatment failure; exposed vs. unexposed (6.9 vs. 0.8%; p = 0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI -0.03-0.15; exact-p = 0.06] and 8.48 [95% CI 1.24-57.97; exact-p = 0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20-42.10; MH-p = 0.04). Our study demonstrated the negative impact of reduced FQ susceptibility on the treatment response to FQ therapy in FQSEC UTIs. This negative impact may be more intensified in other serious infections. Future studies in other clinical situations should be conducted to fill the gap of knowledge.