Beta-lactam antimicrobials (penicillins, cephalosporins, and carbapenems) are frequently used for empiric and targeted therapy in critically ill patients. They display time-dependent killing, meaning the time the antibiotic concentration is above the minimin inhibitory concentration (MIC) is associated with improved efficacy.
Two new pharmacodynamic/pharmacokinetic studies suggest that current beta-lactam antimicrobial dosing regimens may be inadequate.
- In patients from 68 ICUs across 10 countries, use of intermittent infusions (compared to extended and continuous infusions) and increasing creatinine clearance were risk factors for MIC target non-attainment. [1]
- A second group specifically investigated the pulmonary penetration of piperacillin/tazobactam in critically ill patients and found that intrapulmonary exposure is highly variable and unrelated to plasma exposure and pulmonary permeability. [2]
Antimicrobial dosing in critically ill patients is complex. Current dosing of beta-lactams may be inadequate and needs to be studied further with relation to clinical outcomes.
References
- De Waele JJ, et al. Risk factors for target non-attainment during empirical treatment with beta-lactam antibiotics in critically ill patients. Intensive Care Med 2014;40(9):1340-51. [PMID 25053248]
- Felton TW, et al. Pulmonary penetration of piperacillin and tazobactam in critically ill patients. Clin Pharmacol Ther 2014;96(4):438-48. [PMID 24926779]
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