Pharmacodynamically Guided Levofloxacin Dosing for Pediatric Community-Acquired Pneumonia

Abstract

Background.: Oral levofloxacin is recommended as a preferred treatment for infection with Streptococcus pneumoniae with a penicillin minimum inhibitory concentration (MIC) of ≥4 µg/mL and as an alternative for infection with S pneumoniae with a penicillin MIC of ≤2 µg/mL. To investigate the current dosing recommendations and create a pharmacodynamically guided regimen, a Monte Carlo simulation was performed.

Methods.: The simulation included a previously published 1-compartment model, and incorporated a formula that takes into account age-appropriate weights for hospitalized patients. Three different dosing regimens, including community-acquired pneumonia guideline dosing, inhalational anthrax dosing, and a pharmacodynamically guided regimen, were assessed. The probability of target attainment was described as the proportion of patients who achieve an unbound-drug area under the concentration-time curve over 24 hours divided by the MIC above 33.7 µg/mL per hour. Microbiologic data from 2 stand-alone pediatric tertiary care centers were included.

Results.: Guideline-recommended doses of levofloxacin seem to produce suboptimal exposure in patients aged 5-14 years for pneumococci with an MIC of 1 µg/mL. Anthrax dosing was suboptimal in patients aged <5 years and in those aged >15 years. The pharmacodynamically guided regimen maintained a probability of target attainment of >90% for all age groups without producing peak concentrations higher than those previously described. None of the regimens attained the pharmacodynamic targets for a levofloxacin MIC of 2 µg/mL.

Conclusions.: Current dosing recommendations were found to be suboptimal for specific age groups. A pharmacodynamically guided levofloxacin dosing regimen was determined, but it will need to be studied clinically for safety and tolerability.

Keywords: Monte Carlo method; Streptococcus pneumoniae; levofloxacin; pneumonia.