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Background: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers., Methods: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose., Results: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis., Conclusions: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.

Study Objectives: To compare the safety and efficacy of oral azithromycin and levofloxacin in the treatment of outpatients with acute bacterial exacerbations of chronic bronchitis (ABECB)., Design: Randomized, double-blinded, double-dummy, multicenter trial with 1:1 treatment allocation., Setting: Outpatient treatment setting., Patients: Two hundred thirty-five male or female outpatients between the ages of 35 and 75 years who had received a clinical diagnosis of ABECB., Interventions: Blinded treatment with either oral azithromycin, 500 mg on day 1 and 250 mg per day for days 2 to 5, or, oral levofloxacin, 500 mg q24h for 7 days., Results: Both treatments were well-tolerated, with the majority of adverse events being GI in nature. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 89% of patients receiving azithromycin and in 92% of patients receiving levofloxacin by day 4 of therapy. At day 24, the posttherapy visit, favorable responses were approximately 82% and 86%, respectively, for patients in the two treatment groups. The bacterial eradication rates of respiratory pathogens were 96% for azithromycin and 85% for levofloxacin., Conclusions: Despite increasing concerns over macrolide resistance and a higher incidence of Gram-negative pathogens, a standard 5-day course of oral azithromycin was clinically and bacteriologically equivalent to a 7-day course of oral levofloxacin in the treatment of patients with ABECB.

Study Objectives: The objectives of this study were to characterize the single-dose and steady-state plasma pharmacokinetics of IV levofloxacin and IV alatrofloxacin, and to compare the results to pneumococcal isolate sensitivities in order to estimate the clinical efficacy of current community-acquired pneumonia treatment regimens against pneumococcal infections., Design: Two-way, open-label, randomized, crossover study., Participants: Each of 12 healthy volunteer subjects received IV levofloxacin, 500 mg qd for 7 days, and IV alatrofloxacin, 200 mg qd for 7 days. The two regimens were separated by a 2-week washout period., Measurements and Results: Plasma concentration profiles were collected around the first and final doses of both regimens and were assayed for their respective quinolone concentrations. When the peak concentrations for both agents were compared to standard twofold dilution minimum inhibitory concentration (MIC) values for pneumococcal isolates, it was discovered that the breakpoint MIC value at which each compound would no longer achieve a peak plasma concentration/MIC ratio of at least 12:1 was 0.5 mg/L for levofloxacin and 0.25 mg/L for alatrofloxacin., Conclusions: Based on the MIC that inhibits 90% of isolates of Streptococcus pneumoniae for both of these agents (1.0 to 2.0 mg/L for levofloxacin and 0.125 to 0.25 mg/L for trovafloxacin), our results indicate that although the once-daily regimen of alatrofloxacin appears to be appropriate for this pathogen, a more aggressive regimen may need to be investigated to optimize the clinical and microbiological effects of levofloxacin.