title: Comparison of the activity of fluoroquinolones against Mycobacterium avium in cell-free systems and a human monocyte in-vitro infection model.
abstract: Mycobacterium avium frequently causes disseminated infection in advanced AIDS. Some quinolones including ciprofloxacin and sparfloxacin have anti-M. avium activity in cell-free systems in vitro. Acidic conditions within macrophages and variable intracellular drug penetration and compartmentalization may, however, alter the susceptibility of M. avium to these antimicrobial agents in human tissues. We, therefore, tested the activities of 47 quinolones against M. avium in a human monocyte infection model using ciprofloxacin susceptible (MIC = 0.25 mg/L) and resistant (MIC = 4 mg/L) patient isolates. Monocytes from healthy subjects were infected with M. avium and cultured with or without antimicrobials for 8 days. Some quinolones had poor activity against M. avium in the monocyte culture system despite low MICs (< or = 0.25 mg/L); in contrast, some quinolones with MICs > 32 mg/L showed some inhibition of M. avium growth within monocytes at 4 mg/L. Six quinolones synthesized based on structure-activity analysis were more active than ciprofloxacin. These data underscore the importance of evaluating drug activity of new antimicrobial agents against intracellular pathogens in a macrophage model as well as in cell-free systems.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shiratsuchi
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: A J
authors.initials: AJ
authors.lastname: Pearson
authors.forename: N
authors.initials: N
authors.lastname: Venkataprasad
authors.forename: G
authors.initials: G
authors.lastname: Klopman
authors.forename: J J
authors.initials: JJ
authors.lastname: Ellner
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002474:Cell-Free System; D024841:Fluoroquinolones; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones