Optimizing beta-lactam pharmacodynamics against Pseudomonas aeruginosa in adult cystic fibrosis patients

J Cyst Fibros. 2016 Sep;15(5):660-3. doi: 10.1016/j.jcf.2016.04.002. Epub 2016 May 4.


Background: Patients with cystic fibrosis (CF) exhibit increased clearance of beta-lactams. The purpose of this study was to predict the probability of beta-lactam target attainment (PTA) against Pseudomonas aeruginosa in adult CF patients based on local microbiological data.

Methods: CF-specific pharmacokinetic parameters were obtained from published data for aztreonam, cefepime, ceftazidime, meropenem and piperacillin-tazobactam. Pharmacodynamic modeling was used to determine the PTA for bolus, prolonged infusion, and continuous infusion regimens.

Results: Prolonged infusion of meropenem 2g every 8h performed the best among all regimens tested, with a PTA of 83%. The PTA was increased with both prolonged and continuous infusion; however, no regimen reached the target PTA of >90% against P. aeruginosa in CF patients at our institution.

Conclusions: Prolonged and continuous infusion provided higher PTA than bolus for all regimens. Further investigation of novel regimens in CF patients is needed.

Keywords: Beta-lactam; Continuous-infusion; Pharmacodynamics; Pharmacokinetics; Prolonged infusion; Pseudomonas aeruginosa.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / classification
  • Anti-Bacterial Agents / pharmacokinetics
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / microbiology
  • Drug Administration Routes
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Microbial Sensitivity Tests / methods
  • Models, Theoretical
  • Pseudomonas Infections / diagnosis
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • Respiratory Tract Infections / diagnosis
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / microbiology
  • beta-Lactams* / administration & dosage
  • beta-Lactams* / classification
  • beta-Lactams* / pharmacokinetics


  • Anti-Bacterial Agents
  • beta-Lactams