In this episode, I’ll discuss the impact of achieving an aggressive PK/PD target for beta-lactams in critically ill patients.
Therapeutic drug monitoring for beta-lactams has not yet made it to the mainstream in all hospitals, but data continues to accumulate that I believe will eventually compel clinicians to check blood levels of beta-lactams in select patients.
Investigators recently published in the journal Critical Care a systematic review and meta-analysis looking at the effect of achieving an aggressive PK/PD target for beta-lactams compared to a conservative one. For purposes of the analysis an aggressive target was considered as having 100% of the dosing interval have a level greater than 4 times the MIC.
21 observational studies representing nearly 5000 patients were included in the analysis. The authors found that attaining an aggressive PK/PD target was significantly associated with higher clinical cure rate with an odds ratio of 1.69 and lower risk of beta-lactam resistance development with an odds ratio of 0.06.
In addition, the authors identified 3 significant independent predictors of failure in attaining aggressive PK/PD targets: male gender, BMI above 30, and augmented renal clearance.
In Table 4 of the article, the authors outline a predictive risk scoring system that attempts to outline a specific patient’s individual risk for not obtaining an aggressive PK/PD target.
The authors concluded:
Attaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.
Unfortuantely this meta-analysis consisted of entirely observational studies, most of which were retrospective in nature. This limits the applicability of these findings to clinical practice as the level of evidence is still low. Until validation in a prospective cohort, this data will likely not make it to routine clinical practice.
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