Comparative in vitro activity of a new quinolone, fleroxacin, against respiratory pathogens from patients with cystic fibrosis.

We evaluated fleroxacin, a newer fluoroquinolone, against isolates from sputum from patients with cystic fibrosis. These isolates included rough and mucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Selected isolates were tested by the broth microdilution method to examine the influence of various pHs, inoculum sizes, and biological fluids (serum or sputum from patients with cystic fibrosis). Fleroxacin MICs for 50 and 90% of isolates of P. aeruginosa were 2.0 and 4 micrograms/ml, those for P. cepacia were 2 and 16 micrograms/ml, those for S. aureus were 0.5 and 1 microgram/ml, those for H. influenzae were 0.06 and 0.06 micrograms/ml, and those for E. coli were 0.01 and 0.03 micrograms/ml, respectively. Fleroxacin activity against mucoid P. aeruginosa was similar to the activities of enoxacin and ofloxacin but eightfold lower than that of ciprofloxacin. It was twofold more active than norfloxacin and enoxacin but was twofold less active than ciprofloxacin, ofloxacin, and nafcillin against S. aureus. Fleroxacin inhibitory activity against P. cepacia was two- to fourfold lower than that of ciprofloxacin but eightfold greater than those of the other quinolones tested. Alterations in pH, diluent, and inoculum size did not significantly affect fleroxacin activity. These results, combined with available pharmacokinetic and tissue distribution data, support the need for clinical evaluation of fleroxacin in pulmonary infections in patients with cystic fibrosis.

In vitro activity of E-1040, a 3-substituted cephalosporin, against pathogens from cystic fibrosis sputum.

On the basis of preliminary in vitro data, we evaluated E-1040, a new cephalosporin, against 188 cystic fibrosis (CF) sputum isolates obtained from 26 CF centers in the United States. These isolates included mucoid and nonmucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. In addition to MICs measured under standard conditions, selected isolates were tested at various pH values, inoculum sizes, and diluent (CF serum and sputum) conditions. E-1040 activities (MICs for 50 and 90% of the strains) against the isolates were as follows: P. aeruginosa (mucoid and nonmucoid), 1 and 4 micrograms/ml; P. cepacia, 4 and 16 micrograms/ml; S. aureus, 8 and 8 micrograms/ml; H. influenzae, 1 and 4 micrograms/ml; and E. coli, less than or equal to 0.12 and less than or equal to 0.12 microgram/ml. E-1040 activity against mucoid P. aeruginosa was 4-fold greater than that of aztreonam, 16-fold greater than that of ceftazidime, and 32-fold greater than that of piperacillin. E-1040 was similar to other broad-spectrum cephalosporins against S. aureus, H. influenzae, and E. coli. Bactericidal activity was less than or equal to 1 dilution of MIC for 88% of the strains, although kinetic studies with mucoid strains of P. aeruginosa demonstrated effective killing only at eight times the MIC. Variations in pH from 5 to 8, in inoculum size from 10(3) to 10(7) CFU/ml, and in diluent (CF serum or CF sputum) did not affect E-1040 activity.