title: Effect of levofloxacin, erythromycin or rifampicin pretreatment on growth of Legionella pneumophila in human monocytes.
abstract: Opsonophagocytic killing of some bacteria (Staphylococcus aureus, Pseudomonas aeruginosa) by phagocytes is enhanced by previous brief exposure of the organism to antibiotics. We studied the regrowth of Legionella pneumophila previously pretreated with levofloxacin, erythromycin and/or rifampicin in human monocytes. The MIC for the L. pneumophila isolate of levofloxacin, erythromycin and rifampicin was 0.03, 0.5 and 0.001 mg/L, respectively. Growth of L. pneumophila from buffered charcoal yeast extract (BCYE) agar for 24 h was subcultured into BYE broth containing from 0 to 4x MIC of levofloxacin, erythromycin or rifampicin. After incubation at 35 degrees C in 5% CO2 for 18 h, the organisms were washed and opsonized with 20% heat inactivated pooled normal human serum. Thereafter, L. pneumophila was exposed to human monocytes (5:1 ratio) previously adhered to wells in tissue culture plates containing RPMI and 10% fetal calf serum. After 0, 24, 48 and 72 h of incubation, quantitative cultures of lysed human monocytes were done on BCYE agar. Our results indicate effective inhibition on L. pneumophila at 0 h regardless of the antibiotic (levofloxacin, rifampicin or erythromycin) or their concentrations (1x, 2x or 4x MIC). At 24, 48 and 72 h, recovery and regrowth of L. pneumophila were both antibiotic- and concentration-dependent. In comparison with controls (no antibiotic pretreatment), peak regrowth of L. pneumophila pretreated with either 1x MIC of levofloxacin or erythromycin was delayed (48 versus 24 h) and reduced (30% of control peak regrowth). Regrowth of L. pneumophila pretreated with 1x MIC of rifampicin continued beyond 72 h. Pretreatment with levofloxacin at 4x MIC caused the greatest degree of growth inhibition (2 log10). In contrast, at 72 h, regrowth of organisms pretreated with 4x MIC of erythromycin or rifampicin was less than peak control (P < 0.01) but greater than that seen with levofloxacin (P < 0.01). The rate and degree of regrowth of L. pneumophila pretreated with combinations of levofloxacin or erythromycin with rifampicin, or levofloxacin with erythromycin (all at 1x MIC) was similar to that seen with single drugs. Thus, significant delay and reduction of regrowth in this phagocytic system occurred with levofloxacin only. Prolonged exposure of the organism at 4x MIC levofloxacin concentrations was effective in suppressing regrowth of pretreated L. pneumophila in human monocytes.
authors.affiliation: Department of Medicine, Stratton VA Medical Center and Albany Medical College, NY 12208, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Smith
authors.forename: A L
authors.initials: AL
authors.lastname: Baltch
authors.forename: M
authors.initials: M
authors.lastname: Franke
authors.forename: W
authors.initials: W
authors.lastname: Hioe
authors.forename: W
authors.initials: W
authors.lastname: Ritz
authors.forename: P
authors.initials: P
authors.lastname: Michelsen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D016952:Legionella pneumophila / Q000187:drug effects*; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000187:drug effects*; D015242:Ofloxacin / Q000494:pharmacology*; D009895:Opsonin Proteins / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D009895:Opsonin Proteins; D004917:Erythromycin; D064704:Levofloxacin; D015242:Ofloxacin; D012293:Rifampin