Systematic Review and Meta-Analysis of Acute Kidney Injury Associated with Concomitant Vancomycin and Piperacillin/tazobactam

Abstract

Concomitant vancomycin and piperacillin/tazobactam may be associated with increased acute kidney injury (AKI) compared to vancomycin without piperacillin/tazobactam. A systematic search of Medline, Cochrane Library, and Scopus through October 2016 using ["vancomycin" and "piperacillin" and "tazobactam"] and ["AKI" or "acute renal failure" or "nephrotoxicity"] and registered meta-analysis (PROSPERO: CRD42016041646) with relevant scenarios was performed. From 307 results, fourteen observational studies totaling 3549 patients were analyzed. Concomitant vancomycin and piperacillin/tazobactam was associated with AKI in unadjusted (odds ratio (OR) 3.12, 95% confidence interval (CI) 2.04-4.78) and adjusted (aOR 3.11, 95% CI 1.77-5.47) analyses. Similar findings were seen assessing studies in adults (aOR 3.15, 95% CI 1.72-5.76), children (OR 4.55, 95% CI 2.71-10.21), and when <50% of patients received care in an intensive care unit (aOR 3.04, 95% CI 1.49-6.22) but not ≥50% (aOR 2.83, 95% CI 0.74-10.85). Increased AKI with concomitant vancomycin and piperacillin/tazobactam should be considered when determining beta-lactam therapy.

Pharmacists' perceptions and practice changes resulting from emergence of the vancomycin‐piperacillin/tazobactam nephrotoxicity phenomenon

“…Respondents who believed in the association between combination VPT and AKI most commonly perceived that the odds of AKI development were slightly higher (OR 1‐2) in acutely ill patients and significantly higher (OR > 2) in critically ill patients. Systematic review and meta‐analyses had been published on the topic prior to this survey, which have suggested that the ORs in acutely ill patients were approximately three and there were no differences in AKI development in critically ill patients . Subsequent data have been published that support these findings .…”

“…Alternatively, this may represent an uncertainty with comprehending odds rather than the probability of an event occurring . Regardless, practitioners should recognize that published data do not suggest an association between combination VPT and AKI development in critically ill patients . This may be because these patients are at greater risk for AKI than acutely ill patients and that one additional risk factor is not very impactful.…”

“…Respondents perceived that approximately half of patients who developed AKI from combination VPT would require RRT or progress to CKD, though one‐quarter were unsure of this rate of disease progression. These perceptions likely reflect the challenges of assessing this outcome because many patients in these studies were not followed after hospital discharge, expired while receiving the combination, and had other potential etiologies of progression of their renal dysfunction, which led most studies to not reporting this outcome . Consequently, neither of the meta‐analyses published at the time analyzed this outcome because of the dearth of available data .…”

“…Additionally, AKI may result in increased costs between $11 016 and $42 077 per hospitalization, depending on severity and need for renal replacement therapy (RRT) . AKI may develop as a sequela of other disease states (eg, sepsis) or be drug induced . Earlier detection of AKI may reduce mortality and receipt of RRT through improved preventative and treatment measures .…”

“…Initial studies observed the association in acutely ill patients, though data in critically ill patients found no such association . Recent meta‐analyses have continued to suggest that the association exists in the acutely ill (adjusted odds ratio [aOR] 3.04, 95% confidence interval [CI] 1.49‐6.22) but not in the critically ill (aOR 2.83, 95% CI 0.74‐10.85 and OR 1.32, 95% CI 0.73‐2.38) . Subsequently, multiple variables have been investigated in observational studies to determine their predictive or confounding natures …”