UMEM Educational Pearls

Title: Beta-Lactams in Critically Ill Patients: Current Dosing May be Inadequate

Category: Pharmacology & Therapeutics

Keywords: beta-lactam, piperacillin/tazobactam, critically ill (PubMed Search)

Posted: 9/27/2014 by Bryan Hayes, PharmD (Updated: 10/4/2014)
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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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