title: Effects of Urine Matrix and pH on the Potency of Delafloxacin and Ciprofloxacin against Urogenic Escherichia coli and Klebsiella pneumoniae.
abstract: OBJECTIVE
  We assessed the effects of the urine matrix and its varying pH on the potency of the novel broad-spectrum fluoroquinolone delafloxacin and of ciprofloxacin against 16 urogenic Enterobacteriaceae in the urine of patients with suspected urinary tract infection.
  
  
  METHODS
  We determined minimum inhibitory concentrations in broth and urine using microdilution in 9 Escherichia coli and 7 Klebsiella pneumoniae specimens. The change in potency between broth and urine was calculated.
  
  
  RESULTS
  Against 16 highly ciprofloxacin resistant Enterobacteriaceae with a broth minimum inhibitory concentration of 32 mg/l or greater the minimum inhibitory concentration in delafloxacin in broth was 2 mg/l (1 and 0 isolates of E. coli and K. pneumoniae, respectively), 4 mg/l (3 and 0), 8 mg/l (3 and 1), 16 mg/l (2 and 4) and 32 mg/l (0 and 2). Across the 143 collected urines pH ranged from 4.7 to 9.0 with 71% at pH 6.5 or less. The delafloxacin minimum inhibitory concentration measured in 80% urine from 100 unique patient samples (pH 5.0 to 8.3) was 2 mg/l or less (18% and 0.8% for E. coli and K. pneumoniae, respectively), 4 mg/l (23% and 6%), 8 mg/l (21% and 18%), 16 mg/l (23% and 33%) and 32 mg/l or greater (15% and 42%). For E. coli and K. pneumoniae combined the median changes in the delafloxacin minimum inhibitory concentration were a 1 doubling dilution decrease at pH 6.0 or less, no change at pH 6.1 to 7.0 and a 1 doubling dilution increase at pH 7.1 or greater. Unlike delafloxacin, ciprofloxacin showed a 1 doubling dilution increase for E. coli and no change for K. pneumoniae at pH 7.0 or less with no change observed at pH 7.1 or greater.
  
  
  CONCLUSIONS
  Most urines collected from patients with urinary tract infection had a pH of 6.5 or less. Delafloxacin broth minimum inhibitory concentrations were twofold to fivefold doubling dilutions lower than those of ciprofloxacin. In contrast to ciprofloxacin, the potency of delafloxacin was further enhanced in the acidic environment commonly observed in the setting of urinary tract infection.
authors: Center for Anti-Infective Research and Development, Hartford, Connecticut.
authors: Wonhee
authors: W
authors: So
authors: Center for Anti-Infective Research and Development, Hartford, Connecticut.
authors: Jared L
authors: JL
authors: Crandon
authors: Center for Anti-Infective Research and Development, Hartford, Connecticut; Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut. Electronic address: david.nicolau@hhchealth.org.
authors: David P
authors: DP
authors: Nicolau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology / Q000652:urine; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007710:Klebsiella Infections; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000302:isolation & purification*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D016482:Urinalysis; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000652:urine; D014556:Urine / Q000737:chemistry / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; C477891:delafloxacin
keywords: Enterobacteriaceae; ciprofloxacin; fluoroquinolones; hydrogen-ion concentration; urinary tract infections