Urinary Bactericidal Activity of 4 Doses of Levofloxacin Against Fluoroquinolone-Resistant E. Coli

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00376376
• Other study ID #: MSU 06-496F
• Status: Completed
• Phase: N/A
• First received: September 13, 2006
• Last updated: November 25, 2008
• Start date: September 2006
• Est. completion date: November 2006

Study information

• Verified date: November 2008
• Source: Michigan State University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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

Locations

Country	Name	City	State
United States	Michigan State University- Dept. of Medicine	East Lansing	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Michigan State University	PriCara, Unit of Ortho-McNeil, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	evaluate the Urine Bactericidal Activity (UBA) of different doses and urine levels of levofloxacin against drug-resistant bacteria.