In this episode, I’ll discuss an article that suggests the vancomycin – piperacillin-tazobactam AKI interaction is just pseudotoxicity.
For many years there have been publications suggesting an association between the combination of vancomycin and piperacillin-tazobactam and the development of acute kidney injury. Studies that draw this conclusion typically compare a vancomycin + piperacillin-tazobactam cohort to a vancomycin + cefepime cohort.
A group of authors felt that existing evidence was unclear on whether the association represents true kidney injury or what they call a pseudotoxicity which is characterized by isolated effects on creatinine secretion and not other outcomes. They designed, performed, and have now published in Intensive Care Medicine a study that attempts to resolve this question by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, BUN, and hard outcomes like dialysis and mortality.
The study involved almost 800 critically ill septic patients who were in a prospective cohort and were treated for at least 48 hours with vancomycin + piperacillin–tazobactam or vancomycin + cefepime.
Measurements included 3 kidney function biomarkers (creatinine, cystatin C, and blood urea nitrogen (BUN)) which were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day 14, and mortality through day 30.
While the authors corroborated previous studies with their finding that vancomycin + piperacillin–tazobactam was associated with a higher percentage increase of creatinine at day 2, the alternative biomarkers (cystatin C and BUN) did not have significant differences between groups.
Likewise the clinical outcomes of dialysis and mortality did not differ between groups.
The authors thereby conclude that the study results show they were correct in their hypothesis that vancomycin + piperacillin–tazobactam effects on creatinine represent pseudotoxicity rather than acute kidney injury. The authors believe this is further supported because both piperacillin and tazobactam are substrates for organic anion transporters that have been implicated in the tubular handling of creatinine, and vancomycin suppresses the same transporter subtypes that piperacillin and tazobactam are substrates of.
If this is the case, efforts to avoid this commonly requested combination of antibiotics may be unneccesary.
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