Antibiotics in critically ill patients - a systematic review of the pharmacokinetics of beta-Lactams.
Crit Care. 2011 Sep 13;15(5):R206
Authors: Goncalves-Pereira J, Povoa P
Abstract
ABSTRACT: INTRODUCTION: Several reports showed a marked heterogeneity of antibiotic pharmacokinetics (PK) in patients admitted to Intensive Care Units (ICU) that may potentially impact on outcomes. Therefore, the pharmacodynamic parameter of efficacy of beta-lactam antibiotics, that is, the time that its concentration is over bacteria minimal inhibitory concentration (T>MIC), cannot be safely extrapolated from healthy population PK data. METHODS: A full review of published studies addressing the PK of intravenous beta-lactam antibiotics given to infected ICU patients was performed. Selection was accomplished by a comprehensive bibliographic search through PubMed and bibliographic references from relevant reviews from January 1966 to December 2010. Only English language studies addressing beta-lactam antibiotics with at least 5 published studies were selected. Pharmacokinetic studies of patients on renal replacement therapy were excluded. RESULTS: A total of 57 studies addressing 6 different beta-lactam antibiotics (meropenem, imipenem, piperacillin, cefpirome, cefepime and ceftazidime) were selected. Significant PK heterogeneity was noted with a broad, more than 2-fold, variation both of volume of distribution (Vd) and of drug clearance (Cl). Correlation of antibiotic Cl with creatinine clearance (Cr Cl) was usually reported. Consequently, in ICU patients, beta-lactam antibiotic half-life and T>MIC were virtually unpredictable, especially in those with normal renal function. A better pharmacodynamic profile was usually obtained by prolonged or even continuous infusion. Tissue penetration was also found to be compromised in critically ill patients with septic shock. CONCLUSIONS: The PK of beta-lactam antibiotics is heterogeneous and largely unpredictable in ICU patients. Consequently the dosing of antibiotics should be supported by PK concepts, including data from ICU PK studies and therapeutic drug monitoring.
PMID: 21914174 [PubMed - as supplied by publisher]