In vitro pharmacodynamics of levofloxacin and other aerosolized antibiotics under multiple conditions relevant to chronic pulmonary infection in cystic fibrosis.
The inhalational administration of antibiotics can provide high concentrations locally in the lungs of cystic fibrosis patients and, thus, can be useful for the treatment of chronic bacterial infections. The present study evaluated the in vitro activities of levofloxacin, ciprofloxacin, tobramycin, amikacin, and aztreonam against clinical isolates of Pseudomonas aeruginosa, Burkholderia cepacia complex, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans, and Staphylococcus aureus from cystic fibrosis patients. Levofloxacin was the most potent antibiotic against all cystic fibrosis isolates tested, with MIC(90)s ranging from 8 to 32 microg/ml. Levofloxacin was more potent than the aminoglycosides and aztreonam against P. aeruginosa biofilms. Time-kill assays with drug concentrations achievable in sputum following aerosol administration showed that levofloxacin had the most rapid rate of killing among mucoid and nonmucoid isolates of P. aeruginosa. In contrast to tobramycin, the bactericidal activity of levofloxacin was not affected by sputum from cystic fibrosis patients. The results of the study show that the high concentrations of levofloxacin readily achievable in the lung following aerosol delivery may be useful for the management of pulmonary infections in patients with cystic fibrosis.
King
Paula
P
Mpex Pharmaceuticals, Inc., 11535 Sorrento Valley Road, San Diego, CA 92121-1309, USA. pking@mpexpharma.com
Lomovskaya
Olga
O
Griffith
David C
DC
Burns
Jane L
JL
Dudley
Michael N
MN
D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects; D002908:Chronic Disease; D002939:Ciprofloxacin / Q000494:pharmacology; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D064704:Levofloxacin; D008171:Lung Diseases / Q000150:complications* / Q000378:metabolism* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D013183:Sputum / Q000382:microbiology
D000336:Aerosols; D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin