ECFS 2020 - Optimizing pharmaceutical care in cystic fibrosis

European Cystic Fibrosis Society   45  CHAPTER 3 Pharmacokinetics/pharmacody- namics guided approach to antibacterial administration in cystic fibrosis Authors Elio Castagnola, Giuliana Cangemi, Alessio Mesini, Francesca Mattioli 1 General concepts of pharma- cokinetics/pharmacodynamics Antibiotic resistance is a major problem in modern medicine. “Standard” therapeutic regimens do not always achieve plasma concentrations capable to guarantee pathogen eradication, while minimizing undesirable effects. Pharmacokinetic (PK) principles can help predict antimicrobial effi- cacy and therefore the pharmacodynamic (PD) response [1]. An antibiotic’s effective- ness is related both to patient’s exposure to the drug, defined by different PK properties such as maximum plasma concentration (Cmax), area under plasma concentration curve over 24 hours as a function of time (AUC), minimum pre-dose concentration (Cmin) [2], and to microorganism suscepti- bility, estimated in vitro by the minimal drug concentration inhibiting the bacterial growth (minimum inhibitory concentration [MIC]). PK/PD parameters normalized to MIC can be used to manage difficult to treat infec- tions [3]. The antibacterial effect of antibiotics depends on the antibiotic concentration or the time of exposure of the bacteria to the drug [4]. Time-dependent antibiotics (beta-lac- tams, macrolides, tetracyclines, glycopep- tides) are characterized by an in vivo activity related to the proportion of time that drug plasma levels persist above the MIC during the administration interval (% t>MIC), and to the fact that Cmin can be higher than the MIC. To reduce the risk of resistance selec- tion and to maximize therapeutic effec- tiveness, a drug plasma concentration 4-5 times above MIC, or at least at MIC level, is desirable at the end of dose interval. There- fore, the total daily dose should ideally be administered in 3-4 doses, each infused over 2-3 hours, or over 24 hours (continuous infusion). This method of administration is important mainly for time-dependent anti- biotics which have no post-antibiotic effect (PAE). PAE is defined as the persistent suppression of bacterial growth even when