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  • Title: Urinary bactericidal activity of single doses (250, 500, 750 and 1000 mg) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli.
    Author: Stein GE, Schooley SL, Nicolau DP.
    Journal: Int J Antimicrob Agents; 2008 Oct; 32(4):320-5. PubMed ID: 18715762.
    Abstract:
    Increasing resistance to fluoroquinolones in uropathogens has become a clinical concern. The purpose of this study was to analyse the urinary bactericidal activity (UBA) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli. Ten healthy adult subjects (aged 23-60 years) received single doses of levofloxacin (250, 500, 750 and 1000 mg) and then blood and urine samples were collected in intervals (0-1.5, 1.5-4, 4-8, 8-12 and 12-24h) over 24h. Both serum and urine concentrations were measured by a validated high-performance liquid chromatography assay. Bactericidal titres in urine were determined against E. coli isolates with minimum inhibitory concentrations of 0.125, 4, 8, 16, 32 and 64microg/mL for levofloxacin. The mean serum pharmacokinetic parameters for these doses of levofloxacin were similar to previously published values. The mean peak urinary concentrations (0-1.5h) were 210, 347, 620 and 536microg/mL for the 250, 500, 750 and 1000 mg dose, respectively. Each dose of levofloxacin exhibited early (0-1.5h time period) bactericidal activity in urine in virtually all subjects against E. coli strains with MICs<or=32microg/mL. Moreover, high-dose (750 mg and 1000 mg) levofloxacin provided prolonged (8-12h time period) bactericidal activity in 9/10 subjects against E. coli isolates with MICs up to 32microg/mL. In summary, this ex vivo investigation found that high-dose levofloxacin can produce early and prolonged UBA against fluoroquinolone-resistant strains of E. coli. Patient outcome studies are needed to determine whether these findings translate into clinical cures.
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