Official Title: “Urinary Bactericidal Activity of 4 Doses of Levofloxacin (250, 500, &750, and 1000 mg) Against Fluoroquinolone-Resistant E. Coli”

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.

Study Type: Interventional

Study Design: Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacodynamics Study

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(s) in this Clinical Trial

• Drug: levofloxacin at 250, 500, 750, and 1000 mg doses

Primary Measures

• evaluate the Urine Bactericidal Activity (UBA) of different doses and urine levels of levofloxacin against drug-resistant bacteria.

Inclusion Criteria:

• 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)

Exclusion Criteria:

• Non-healthy volunteers
• pregnant women
• volunteers on other antibiotics
• body weight over 20% of normal
• Age <18 or >60

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Michigan State University

Overall Clinical Trial Officials and Contacts

Gary E. Stein, Pharm.D. Principal Investigator Michigan State University  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00376376

Study ID Number: MSU 06-496F

ClinicalTrials.gov Identifier: NCT00376376

Health Authority: United States: Institutional Review Board