title: Pharmacodynamically Guided Levofloxacin Dosing for Pediatric Community-Acquired Pneumonia.
abstract: 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.
  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.
  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.
  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.
authors.affiliation: Division of Pharmacy, Cincinnati Children's Hospital Medical Center, Ohio.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Courter
authors.affiliation: Butler University College of Pharmacy and Health Sciences.|Riley Hospital for Children at Indiana University Health, Indianapolis.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Nichols
authors.affiliation: University of Connecticut School of Pharmacy, Storrs, and.
authors.forename: Christina
authors.initials: C
authors.lastname: Kazazian
authors.affiliation: University of Connecticut School of Pharmacy, Storrs, and.|Connecticut Children's Medical Center, Hartford.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Girotto
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007223:Infant; D064704:Levofloxacin / Q000008:administration & dosage* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin
keywords: Monte Carlo method; Streptococcus pneumoniae; levofloxacin; pneumonia