Text Size

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

This study has been completed.
Sponsor:
Collaborator:
PriCara, Unit of Ortho-McNeil, Inc.
Information provided by:
Michigan State University
ClinicalTrials.gov Identifier:
NCT00376376
First received: September 13, 2006
Last updated: November 25, 2008
Last verified: November 2008
History of Changes
  Purpose

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.


Condition Intervention
Healthy Volunteers
 Drug: levofloxacin at 250, 500, 750, and 1000 mg doses

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Urinary Bactericidal Activity of 4 Doses of Levofloxacin (250, 500, &750, and 1000 mg) Against Fluoroquinolone-Resistant E. Coli

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Michigan State University:

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

Estimated Enrollment: 10
Study Start Date: September 2006
Estimated Study Completion Date: November 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00376376

Locations
United States, Michigan
Michigan State University- Dept. of Medicine
East Lansing, Michigan, United States, 48824
Sponsors and Collaborators
Michigan State University
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
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00376376     History of Changes
Other Study ID Numbers: MSU 06-496F
Study First Received: September 13, 2006
Last Updated: November 25, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Michigan State University:
levofloxacin
pharmacodynamic
bactericidal

Additional relevant MeSH terms:
Ofloxacin
Fluoroquinolones
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
 Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on May 16, 2013