title: High fluoroquinolone MIC is associated with fluoroquinolone treatment failure in urinary tract infections caused by fluoroquinolone susceptible Escherichia coli.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. pinyohiso@hotmail.com.|Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. pinyohiso@hotmail.com.
authors.forename: Pinyo
authors.identifier: http://orcid.org/0000-0002-2964-6732
authors.initials: P
authors.lastname: Rattanaumpawan
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Irving
authors.initials: I
authors.lastname: Nachamkin
authors.affiliation: Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Warren B
authors.initials: WB
authors.lastname: Bilker
authors.affiliation: Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roy
authors.affiliation: Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Metlay
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Theoklis E
authors.initials: TE
authors.lastname: Zaoutis
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ebbing
authors.initials: E
authors.lastname: Lautenbach
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015331:Cohort Studies; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010045:Outpatients; D015143:Philadelphia; D012189:Retrospective Studies; D017211:Treatment Failure; D014552:Urinary Tract Infections / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
keywords: Escherichia coli; Fluoroquinolone resistance; Urinary tract infection