Urinary Bactericidal Activity of 4 Doses of Levofloxacin Against Fluoroquinolone-Resistant E. Coli
Condition: Healthy Volunteers
Study type: Interventional

Summary: 
      Single-dose studies of a fluoroquinolone are indicative of their antimicrobial activity since
      little accumulation occurs with multiple doses. Single-dose studies have been utilized to
      determine drug concentrations and time kill activity in serum, urine, and respiratory
      tissues.

      The purpose of this study is to evaluate the Urine Bactericidal Activity (UBA) of
      levofloxacin (250, 500, 750, and 1000 mg) against FQ-resistant, ESBL positive E. coli
      isolates. In addition, a susceptibility breakpoint concentration in the urine can also be
      established for each dose of levofloxacin. Furthermore, urine concentrations and serum
      pharmacokinetic parameters of levofloxacin can be determined.
    

Detailed description: 
      Subjects: -10 healthy (from medical history) adult male or female volunteers

        -  Normal body weight (within 20 %)

        -  Age range: 18-60

        -  Not taking any other restricted medications (ie. antibiotics)

      Drug : all drugs are a single dose given after a 12 hour fast

        -  1000 mg.levofloxacin

        -  750 mg. levofloxacin

        -  500 mg levofloxacin

        -  250 mg levofloxacin

      Levofloxacin Pharmacokinetic Study:

      A serum sample will be obtained prior to and at 1.5 (peak), 4.0, 8.0, 12 (50% of interval)
      and 24 (100% of interval) hours after each single dose of levofloxacin (6 time points).

      Levels will be determined by an HPLC assay.

      Urine Pharmacodynamic Study:

      A urine sample will be obtained prior to and at 1.5 (peak), 4, 8, 12 (50% of interval), and
      24 (100% of interval) hours after a single dose of each dose of levofloxacin.

      A urine pH will be run on each sample.

      All urine levels will be determined by a validated HPLC assay.

      Study Isolates: E. coli (TRUST isolates):

      Levofloxacin MICs:

        -  0.125 (sensitive)

        -  4.0 (intermediate)

        -  8.0 (resistant)

        -  16.0 (resistant)

        -  32.0 (resistant)

        -  64.0 (resistant)

      This MIC range of E. coli isolates should be able to define a levofloxacin susceptibility
      breakpoint for urinary pathogens at each dose studied.

      Urine Cidal Activity: Urine samples will be tested against each of the study isolates. A
      maximum urine cidal titer will be determined for each urine. The median titer at each time
      period (10 subjects) will determine the urine cidal activity.

      The duration of cidal activity for each isolate will be determined and plotted. A 12-h
      duration will be considered the minimum time necessary for prolonged Urine Bactericidal
      Activity (MIC breakpoints).

      Safety: All patients will be monitored for side effects during the study.
    

Intervention name(s): levofloxacin at 250, 500, 750, and 1000 mg doses
Intervention type(s): Drug
Intervention MeSH terms: Levofloxacin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: levofloxacin; pharmacodynamic; bactericidal