Presence of infection influences the epithelial lining fluid penetration of oral levofloxacin in adult patients

Although epithelial lining fluid (ELF) is the presumed site for pulmonary infections, most antibiotic penetration studies are conducted in uninfected patients or healthy volunteers. Levofloxacin concentrations in plasma and ELF were collected from two previous studies involving 18 infected patients with acute exacerbations of chronic bronchitis and 15 uninfected elderly patients undergoing diagnostic bronchoscopy. Concentration data were population modelled using the BigNPAG algorithm, and a 5000-patient Monte Carlo simulation was conducted to simulate ELF exposure for a dosing regimen 750 mg every 24 h for five doses in plasma and ELF of infected versus uninfected patients. Mean ± S.D. model parameters for plasma in infected patients were similar to uninfected patients (volume of central compartment, 68.4 ± 36.3 vs. 50.2 ± 17.3 L; clearance, 6.0 ± 2.5 vs. 6.8 ± 3.3 L/h; and absorption rate, 5.4 ± 2.5 vs. 4.7 ± 2.7 h−1), resulting in similar simulated AUC in plasma (infected, 140.5 ± 54.8 vs. uninfected, 133.7 ± 61.6 μg h/mL). The volume of ELF was 57.2 ± 25.0 and 14.8 ± 9.0 L in infected and uninfected patients, respectively, resulting in a lower simulated AUCELF exposure for infected patients (189.1 ± 210.5 vs. 461.0 ± 558.7 μg h/mL). Penetration ratios for infected and uninfected patients were, respectively, 1.4 ± 1.8 and 3.5 ± 3.7, with median values of 0.9 and 2.4. ELF penetration in infected patients was approximately one-half that of uninfected adults. These data highlight the importance of confirming exposure in infected patients to further support dosage regimen selection.