<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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&nbsp;&gt;&nbsp;0.12 but&nbsp;≤&nbsp;2&nbsp;mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC&nbsp;≤&nbsp;0.12&nbsp;mg/L). The primary treatment outcome was treatment failure within 10&nbsp;weeks after initiation of FQ therapy.</p>

<p><strong>RESULTS: </strong>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&nbsp;=&nbsp;0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI -0.03-0.15; exact-p&nbsp;=&nbsp;0.06] and 8.48 [95% CI 1.24-57.97; exact-p&nbsp;=&nbsp;0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20-42.10; MH-p&nbsp;=&nbsp;0.04).</p>

<p><strong>CONCLUSION: </strong>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.</p>

<p><strong>OBJECTIVES: </strong>The prevalence of high-MIC fluoroquinolone-susceptible Escherichia coli (FQSEC) has been increasing. These isolates are one step closer to full fluoroquinolone (FQ) resistance and may lead to delayed response to FQ therapy. Our study aimed to investigate the epidemiology of high-MIC FQSEC in ambulatory urinary tract infections (UTIs).</p>

<p><strong>PATIENTS AND METHODS: </strong>A case-control study was conducted at outpatient services within the University of Pennsylvania Health System, Philadelphia. All female subjects with non-recurrent UTI caused by FQSEC (levofloxacin MIC &lt; 4 mg/L) were enrolled. Cases were subjects with high-MIC FQSEC UTI (levofloxacin MIC &gt;0.12 but &lt; 4 mg/L) and controls were subjects with low-MIC FQSEC UTI (levofloxacin MIC ≤0.12 mg/L). Data on microbiology results and baseline characteristics were extracted from electronic medical records.</p>

<p><strong>RESULTS: </strong>During the 3 year study period (May 2008-April 2011), 11 287 episodes of E. coli bacteriuria were identified. The prevalence of FQSEC, FQ-intermediate susceptible E. coli and FQ-resistant E. coli was 75.0%, 0.4% and 24.6%, respectively. A total of 2001 female subjects with FQSEC UTI were enrolled into our study (165 cases and 1836 controls). Independent risk factors for high-MIC FQ susceptibility included Asian race (OR = 2.92; 95% CI = 1.29-6.58; P = 0.02), underlying renal disease (OR = 2.18; 95% CI = 1.15-4.14; P = 0.02) and previous nitrofurantoin exposure (OR = 8.86; 95% CI = 1.95-40.29; P = 0.005).</p>

<p><strong>CONCLUSIONS: </strong>Asian race, underlying renal disease and previous exposure to nitrofurantoin were identified as independent risk factors for high-MIC FQSEC. There may be some factors that are more common in Asians, which may result in the selection of high-MIC FQSEC. Further studies are necessary to explore these findings.</p>