Is there an association between vancomycin-piperacillin-tazobactam and renal failure?

Is there an association between vancomycin-piperacillin-tazobactam and renal failure?

The CAMERA-2 study, a randomized controlled clinical trial that included approximately 350 patients and evaluated monotherapy versus combination therapy for the treatment of MRSA, was stopped early because it showed that the combination of a beta lactam (mainly piperacillin – tazobactam) to vancomycin could be extremely nephrotoxic. Since then, the scientific community has focused on studying and better understanding this association, since it is a regimen commonly used in intensive care because it has coverage for MRSA and Pseudomonas. A recent prospective study by Miano et al was the first to assess the risk of acute kidney injury caused by the association vancomycin-piperacillin-tazobactam.

methods

It included 739 patients from a sepsis database who had used vancomycin + cefepime or vancomycin + tazocin for 48 hours. They evaluated renal function biomarkers (creatinine, cystatin C and urea) before treatment and 48 hours after. In addition, they evaluated acute kidney injury and dialysis on the 14th day of follow-up and mortality on the 30th day.

Results

The vancomycin-piperacillin-tazobactam arm had 297 patients and 442 vancomycin-cefepime. However, only 192 patients could assess the value of cystatin C. The arm that used tazocin was associated with a greater percentage increase in creatinine in the second day (8.04% – 95%CI 1.21-15.34) and higher incidence of acute kidney injury (RR 1.34 – 95%CI 1.01-1.78). However, this was not accompanied by a change in renal function biomarkers or clinical outcome. Cystatin C dosage, for example, was similar in the two regimens (1.51 for the vancomycin-tazocin arm and 1.52 for the vancomycin-cefepime arm). These results led the authors to the theory that this association would actually cause renal pseudotoxicity. That is, the increase in serum creatinine would occur due to an impairment of tubular creatinine secretion.

Considerations

In fact, the inhibition of anion transporters caused by piperacillin-tazobactam could affect the renal excretion of creatinine, which would lead to a serum increase of the substance of sufficient magnitude to obtain a diagnosis of acute kidney injury by the KDIGO criteria. Still, there is no impact on glomerular filtration rate and, therefore, a pseudonephrotoxicity that would not lead to severe acute kidney injury requiring renal replacement therapy.

Before reaching a definitive conclusion on the subject, some other aspects need to be raised. First, the studies published so far still have observational designs and this one is no exception. The rule. Second, the study published by Miano et al It is unicentric and limited in terms of sampling, as only 192 patients had cystatin C measurement. It is important to note that cystine C is an interesting alternative to creatinine, but it still represents a functional biomarker with significant limitations as it is affected by numerous conditions and medications ( such as neoplasms, diabetes mellitus and corticosteroids). In Miano’s analysis et almore than 50% of the patients used corticosteroids, which could increase the production of cystatin C. Finally, acute kidney injury can occur in up to seven days and the evaluation was performed after 48 hours of antimicrobial regimen.

Read too: Do cumulative doses of topical antibiotic powder increase risk of acute renal failure?

practical message

In any case, this new study demonstrated the complementary value and practicality of the use of several functional biomarkers with different potentials and confounders not only for research but also for the clinic, and it was also a step towards resolving the doubts about the adverse effects of complex associations. of antimicrobials.

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