Urinary bactericidal activity of single doses (250, 500, 750 and 1000 mg) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli

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 12–24 h) over 24 h. 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 64 μg/mL for levofloxacin. The mean serum pharmacokinetic parameters for these doses of levofloxacin were similar to previously published values. The mean peak urinary concentrations (0–1.5 h) were 210, 347, 620 and 536 μg/mL for the 250, 500, 750 and 1000 mg dose, respectively. Each dose of levofloxacin exhibited early (0–1.5 h time period) bactericidal activity in urine in virtually all subjects against E. coli strains with MICs ≤ 32 μg/mL. Moreover, high-dose (750 mg and 1000 mg) levofloxacin provided prolonged (8–12 h time period) bactericidal activity in 9/10 subjects against E. coli isolates with MICs up to 32 μg/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.