title: Levofloxacin penetrates human monocytes and enhances intracellular killing of Staphylococcus aureus and Pseudomonas aeruginosa.
abstract: Intracellular bacteria often cause relapsing and refractory infections. However, these infections can be treated effectively with antibiotics such as ofloxacin which penetrate into the cells containing bacteria. As levofloxacin, the levorotatory isomer of ofloxacin, has enhanced antibacterial activity, we tested the levofloxacin concentration in human monocytes and the effects of intracellular levofloxacin on monocyte killing of Staphylococcus aureus strain ATCC 29213 and Pseudomonas aeruginosa strain PA1348A. Human monocytes were incubated with levofloxacin at various pH values and temperatures. Following incubation, the monocytes were separated from incubation media, and intracellular (C) and extracellular (E) levofloxacin concentrations were determined. Mean C/E ratios after 15 min of incubation with 6 and 12 mg/L levofloxacin at pH 7.4 were 6.4 and 7.1, respectively. C/E ratios were similar at pH 7.4 and 8.0, but decreased at lower pH values. To study the effects of levofloxacin on intracellular killing of S. aureus and P. aeruginosa, opsonized bacteria were added to monolayers of monocytes. Following phagocytosis, monocytes were incubated with various concentrations of levofloxacin, ciprofloxacin and rifampicin, alone or in combination. Levofloxacin (2.5 and 4 mg/L) significantly reduced the survival of cell-associated S. aureus and was more effective than ciprofloxacin at similar concentrations (P < 0.01). Enhanced killing of cell-associated P. aeruginosa by levofloxacin (0.5 and 1.0 mg/L) was also observed. Activities of levofloxacin and ciprofloxacin against cell-associated P. aeruginosa were similar. Addition of rifampicin did not augment the bactericidal activity of levofloxacin. Since levofloxacin is concentrated in human monocytes and increases their bactericidal activity against intracellular bacteria, it should be considered for treatment of infections caused by susceptible intracellular bacteria.
authors.affiliation: Infectious Disease Section, Stratton VA Medical Center, Albany Medical College, Albany, NY 12208, USA. smith.raymond@albany.va.gov
authors.forename: R P
authors.initials: RP
authors.lastname: Smith
authors.forename: A L
authors.initials: AL
authors.lastname: Baltch
authors.forename: M A
authors.initials: MA
authors.lastname: Franke
authors.forename: P B
authors.initials: PB
authors.lastname: Michelsen
authors.forename: L H
authors.initials: LH
authors.lastname: Bopp
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D064704:Levofloxacin; D009000:Monocytes / Q000378:metabolism* / Q000382:microbiology; D015242:Ofloxacin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013696:Temperature
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin