ArticleThe Journal of infectious diseases2025
Population Pharmacokinetic Modeling of Cefepime, Meropenem, and Piperacillin-Tazobactam in Patients With Cystic Fibrosis.
Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Antimicrobial Pharmacokinetic and Pharmacodynamic Considerations in Special Populations: A Call to Action.Open forum infectious diseases · 2026Review
- An Unexpected Inverse Relationship Between Biofilm Formation and Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2026Article
- Inclusion of Women, Children, the Elderly, and Individuals With Underlying Medical Conditions: Prioritizing Vulnerable Populations in Clinical Research.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
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Authors and funding
17 authors.
Funding
Abstract
backgroundPatients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. Management of these infections is increasingly challenging due to decreased antimicrobial susceptibility to β-lactam antibiotics. The pharmacokinetics (PK) of these agents are inadequately characterized in patients with CF.
methodsThis study enrolled 155 pediatric and adult participants with CF who were receiving the following β-lactam antibiotics: cefepime (n = 82), meropenem (n = 42), or piperacillin-tazobactam (n = 31). Opportunistic blood samples were obtained during hospitalization. Population PK analysis was conducted via nonlinear mixed effects modeling. Clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for different dosing regimens.
resultsEstimated creatinine clearance and total or lean body weight affected the PK of cefepime and meropenem. No covariates were identified for piperacillin and tazobactam. In the cefepime group, a 3-hour infusion achieved a higher PTA than a 0.5-hour infusion for all participants. Estimated breakpoints-the respective minimum inhibitory concentration up to which ≥90% of patients are predicted to reach a PK/pharmacodynamic target-were 2- to 4-fold higher in pediatric participants receiving a 3- vs 0.5-hour infusion. In the meropenem group, increased creatinine clearance led to reduced PTA. In the piperacillin-tazobactam group, total daily dose and mode of administration were principal drivers of PTA.
conclusionsStandard dosing regimens fail to achieve specific minimum inhibitory concentration targets in patients with CF. Therefore, clinicians should incorporate local antibiograms and PK models to determine optimal dosing. Further PK optimization to account for interindividual differences could be achieved by real-time β-lactam therapeutic drug monitoring.
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