In vitro pharmacodynamics of levofloxacin and other aerosolized antibiotics under multiple conditions relevant to chronic pulmonary infection in cystic fibrosis

Abstract

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.

FIG. 1.

Geometric mean log CFU/ml versus time for P. aeruginosa isolates from patients with CF. (A) Nonmucoid strain PA 1042 with MICs in the susceptible range for all antibiotics (levofloxacin MIC, 2 μg/ml; tobramycin MIC, 0.5 μg/ml; aztreonam MIC, 0.5 μg/ml); (B) mucoid strain PA 881 with MICs representing the MIC₅₀s for all antibiotics (levofloxacin MIC₅₀, 4 μg/ml; tobramycin MIC₅₀, 2 μg/ml; aztreonam MIC₅₀, 2 μg/ml); (C) nonmucoid strain PA 876 with MICs representing the MIC₉₀s for all antibiotics (levofloxacin MIC₉₀, 8 μg/ml; tobramycin MIC₉₀, 32 μg/ml; aztreonam MIC₉₀, >128 μg/ml); (D) nonmucoid strain PA 861 with MICs also in the resistant range for all antibiotics (levofloxacin MIC, 32 μg/ml; tobramycin MIC, 16 μg/ml; aztreonam MIC, 128 μg/ml). Thick lines, growth controls; squares, levofloxacin (□, 0.2 mg/ml; ▪, 2.0 mg/ml); diamonds, tobramycin (⋄, 0.2 mg/ml; ♦, 2.0 mg/ml); circles, aztreonam (○, 0.2 mg/ml; •, 2.0 mg/ml). The limit of detection was 2 log CFU/ml.