In vitro activity, postantibiotic effect and human monocyte activity of grepafloxacin against Legionella species

Abstract

Objective: To determine the in vitro antimicrobial activity, postantibiotic effect (PAE) and human monocyte activity of grepafloxacin compared with sparfloxacin, ciprofloxacin, clarithromycin, erythromycin and rifampicin against 181 strains of Legionella pneumophila, nine strains of L. micdadei, 10 strains of L. dumoffii, seven strains of L. longbeachae and seven other Legionella strains. Methods: MICs were determined by standard agar dilution using buffered yeast extract (BYE) agar. PAE and human monocyte activity were determined by standard culture techniques. Results: Grepafloxacin, sparfloxacin and rifampicin were the most active agents against L. pneumophila (MIC90 ≤ 0.016 mg/L for most strains tested). Grepafloxacin was more active than erythromycin against L. dumoffii and L. longbeachae and more active than both erythromycin and clarithromycin against L. micdadei and isolates of other Legionella spp. The PAE of grepafloxacin against erythromycin-susceptible L. pneumophila (2.62 h) was higher than that of sparfloxacin (0.88 h), erythromycin (0.93 hours) and clarithromycin (0.72 h). Against erythromycin-resistant L. pneumophila, the PAE of grepafloxacin (4.18 h) was higher than those of all the other antibiotics tested. Grepafloxacin, sparfloxacin, ciprofloxacin and clarithromycin inhibited the growth of all L. pneumophila strains and other erythromycin-resistant Legionella spp. in human monocytes. However, only grepafloxacin and ciprofloxacin prevented regrowth or killed L. pneumophila after removal of extracellular antibiotic. Conclusions: Grepafloxacin showed effective antibacterial activity against the Legionella spp. tested, and has a PAE and activity within human monocytes that suggest it may be useful in the treatment of lower respiratory tract infections caused by Legionella spp.