Clinical trial NCT00376376: Urinary Bactericidal Activity of 4 Doses of Levofloxacin Against Fluoroquinolone-Resistant E. Coli
Official title: Urinary Bactericidal Activity of 4 Doses of Levofloxacin (250, 500, &750, and 1000 mg) Against Fluoroquinolone-Resistant E. Coli
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Keywords: levofloxacin
pharmacodynamic
bactericidal
Lead sponsor: Michigan State University
Sponsor class: OTHER
Collaborators: name: PriCara, Unit of Ortho-McNeil, Inc.
First posted: 2006-09-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility 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

Primary outcomes:
measure: evaluate the Urine Bactericidal Activity (UBA) of different doses and urine levels of levofloxacin against drug-resistant bacteria.
Secondary outcomes:
Other outcomes:
Locations:
city: East Lansing
country: United States
facility: Michigan State University- Dept. of Medicine
state: Michigan
Study officials:
affiliation: Michigan State University
name: Gary E. Stein, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Michigan State University
name: Daniel Havlichek, M.D.
role: PRINCIPAL_INVESTIGATOR
References: