Pharmacokinetics and pharmacodynamics of antibiotics in cystic fibrosis: a narrative review

Cystic fibrosis affects several organs, predisposing patients to severe bacterial respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus . Cystic fibrosis is also associated with a wide spectrum of pathological changes that can significantly affect the absorption, distribution, metabolism, and/or elimination of several drugs, including antibacterial agents. Therefore, awareness of the pharmacokinetic derangements in patients with cystic fibrosis is mandatory for the optimisation of antibiotic therapy. This review discusses the basic principles of pharmacokinetics and the pathophysiology of the pharmacokinetics changes associated with cystic fibrosis; it also provides an update of available data for the most widely used antibiotics. Evidence accumulated in the last few years has clearly shown that a significant number of cystic fibrosis patients treated with conventional dosing schemes have subtherapeutic antibiotic concentrations, increasing their risk of therapeutic failure and/or the emergence of resistant pathogens. Some proposals to optimise antibiotic therapies in this clinical setting based on therapeutic drug monitoring are also discussed. (c) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Automated summary

Cystic fibrosis can lead to severe bacterial respiratory infections and pathological changes affecting drug absorption, distribution, metabolism, and elimination. It is crucial to be aware of pharmacokinetic derangements in cystic fibrosis patients to optimize antibiotic therapy. Recent evidence shows that many cystic fibrosis patients treated with conventional dosing schemes have subtherapeutic antibiotic concentrations, increasing the risk of treatment failure and the emergence of resistant pathogens.