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

November 25, 2008 updated by: Michigan State University

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • East Lansing, Michigan, United States, 48824
        • Michigan State University- Dept. of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michigan State University

Collaborators

PriCara, Unit of Ortho-McNeil, Inc.

Investigators

  • Principal Investigator: Gary E. Stein, Pharm.D., Michigan State University
  • Principal Investigator: Daniel Havlichek, M.D., Michigan State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Study Completion

November 1, 2006

Study Registration Dates

First Submitted

September 13, 2006

First Submitted That Met QC Criteria

September 13, 2006

First Posted (Estimate)

September 14, 2006

Study Record Updates

Last Update Posted (Estimate)

November 27, 2008

Last Update Submitted That Met QC Criteria

November 25, 2008

Last Verified

November 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MSU 06-496F

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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