Does Piperacillin-Tazobactam Increase the Risk of Nephrotoxicity when Used with Vancomycin: A Meta-Analysis of Observational Trials

Mellen, Chadwick K.; Ryba, Jennifer E.; Rindone, Joseph P.

doi:10.2174/1574886311666161024164859

Cited by 21 publications

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“…Several studies have shown that combining PT and vancomycin leads to an increased risk of AKI, compared to the combinations of other β-lactams with vancomycin [ 7 – 10 ]. Multiple meta-analyses have confirmed this association among adult and pediatric patients [ 11 – 15 ]. This finding has been specifically demonstrated among critically ill patients who have a higher baseline risk of AKI [ 10 , 12 ].…”

Section: Discussionmentioning

confidence: 92%

“…These studies found that the combination of PT and vancomycin is an independent risk factor for AKI after adjustment for potential confounders. Later, several meta-analyses confirmed the increased risk of AKI when PT was combined with vancomycin in both adult and pediatric populations [ 11 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Because vancomycin was a common factor when comparing PT plus vancomycin to other β-lactams plus vancomycin, it appears that vancomycin is not the cause of increased nephrotoxicity. Additionally, in some of these studies, the risk of AKI was higher with the combination of PT plus vancomycin compared to vancomycin alone [ 12 , 14 , 15 ]. A finding which raises a concern about the renal safety of PT monotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the risk of acute kidney injury with the use of piperacillin/tazobactam among adult critically ill patients

et al. 2020

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Purpose Piperacillin/tazobactam (PT), when combined with vancomycin, is associated with an increased risk of acute kidney injury (AKI). It is not known whether PT alone is associated with a higher incidence of AKI compared to other β-lactams among critically ill patients. The objective of this study was to compare the incidence of AKI associated with the use of PT to other β-lactams among adult critically ill patients Methods This retrospective study was conducted in the surgical and the medical intensive care units at two hospitals within Hamad Medical Corporation (HMC) in Qatar and included adult critically ill patients who received at least one dose of anti-pseudomonal β-lactams. The primary outcome was acute kidney injury, defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multiple logistic regression with adjustment for pre-specified potential confounders was used for the primary outcome analysis. Results A total of 669 patients were included in the analysis: 507 patients in the PT group and 162 patients in the control (meropenem/cefepime) group. AKI occurred in 136 (26.8%) members of the PT group and 38 (23.5%) members of the control group [odds ratio (OR) 1.2; 95% confidence interval (CI) 0.79–1.8]. The results were not significantly altered after adjusting for the pre-specified potential confounders (adjusted OR 1.38; 95% CI 0.88–2.15). Conclusion In this study, PT was not associated with a higher risk of AKI compared to cefepime or meropenem among adult critically ill patients.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of the risk of acute kidney injury with the use of piperacillin/tazobactam among adult critically ill patients

et al. 2020

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“…In this study, we found age was correlated with VA-AKI, yet compared with new-borns and infants age group, older age group had less OR for development of VA-AKI. Concomitant administration of diuretics, PTZ and meropenem could increase the incidence of nephrotoxicity [22,26,27], except concomitant NSAIDs seems to have a protective role for VA-AKI. In each age group, VA-AKI incidence was lower in patients with concomitant NSAIDs.…”

Section: Discussionmentioning

confidence: 99%

Vancomycin-associated acute kidney injury in Hong Kong in 2012–2016

et al. 2020

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Background:To study the incidence of vancomycin-associated acute kidney injury (VA-AKI) in Hong Kong and identify risk factors for VA-AKI. Method: Patients with vancomycin prescription and blood level measurement in 2012-2016 were identified using the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. Acute kidney injury was defined using KDIGO criteria. Patients without creatinine measurements, steady-state trough vancomycin level or who had vancomycin treatment < 3 days were excluded. Results were analyzed using SPSS version 22.0. Logistic regression was used to identify the predictors for VA-AKI. Odds ratio and 95% confidence interval were estimated. Results: One thousand four hundred fifty patients were identified as VA-AKI from 12,758 records in Hong Kong in 2012-2016. The incidence was respectively 10.6, 10.9, 11.3, 12.2, 11.2% from 2012 to 2016. The incidence of VA-AKI was 16.3, 12.2, 11.3 and 6.2% in patients aged 1-12, 12-60, elderly aged > 60 and newborn and infants, respectively. Baseline creatinine, serum trough vancomycin level, systematic disease history including respiratory failure, hypertension, congestive heart failure, chronic renal failure, anemia and type II diabetes, and concomitant diuretics, piperacillin-tazobactam (PTZ) and meropenem prescription were significantly higher in VA-AKI patients older than 12 years. Logistic regression showed that older age group, higher baseline creatinine, serum trough vancomycin level, respiratory failure, chronic renal failure and congestive heart failure, concomitant diuretics, PTZ and meropenem prescription, and longer hospital stay were all associated with increased risk of VA-AKI. Conclusion: The incidence of VA-AKI in Hong Kong is low but shows no decline. Patients with higher baseline creatinine, multi-organ diseases and multiple drugs administration should have their vancomycin level monitored to decrease the risk of VA-AKI.

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“…Vancomycin (VAN) and piperacillin-tazobactam (TZP) are two of the most commonly utilized antibiotics in hospitalized patients (after the class of fluoroquinolones) (1–6). Meta-analyses (7–11) compiling over 25,000 patients suggest that VAN+TZP increases AKI by an absolute of 9% when considered against VAN + relevant comparators with mean odds ratios ranging from 1.6-3.6 fold higher risk (2–6). This suggested synergistic toxicity is very concerning as experts now recommend avoiding VAN+TZP (12, 13) even though VAN+TZP is a cornerstone of antibiotic therapy in numerous national guidelines.…”

Section: Introductionmentioning

confidence: 99%

Urinary biomarker and histopathological evaluation of vancomycin and piperacillin-tazobactam nephrotoxicity in comparison with vancomycin in a rat model and a confirmatory cellular model

Pais

Liu

Avedissian

et al. 2019

Preprint

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word count: 294 34 2 | Page Abstract: 35Introduction: Vancomycin and piperacillin tazobactam (VAN+TZP) are two of the most 36 commonly utilized antibiotics in the hospital setting and are reported in clinical studies to 37 increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic 38 toxicity occurs, only that serum creatinine (SCr) increases with VAN+TZP. The purpose of this 39 study was to assess biologic plausibility by quantifying kidney injury between VAN, TZP, and 40 VAN+TZP treatments using a translational rat model of AKI and rat kidney epithelial cell studies. 41 Methods: (i) Male Sprague-Dawley rats (n=32) received either saline, VAN 150 mg/kg/day 42 intravenously, TZP 1400 mg/kg/day via intraperitoneal injection, or VAN+TZP. Animals were 43 placed in metabolic cages pre-study and on drug dosing days 1-3. Urinary biomarkers and 44 histopathology were analyzed. (ii) Cellular injury of VAN+TZP was assessed in serum-deprived 45 rat kidney cells (NRK-52E) using an alamarBlue® viability assay. Cells were incubated with 46 antibiotics VAN, TZP, cefepime, and gentamicin alone or combined with the same drugs plus 47 VAN 1 mg/mL. 48Results: In the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 49 compared to controls (P<0.001). Elevations were seen only after 3 days of treatment with 50 VAN+TZP (P<0.001 KIM-1, P<0.05 clusterin). Histopathology was only elevated in the VAN 51 group when compared to TZP as a control (P=0.04). Results were consistent across biomarkers 52and histopathology suggesting that adding TZP did not worsen VAN induced AKI and may even 53 be protective. In NRK-52E cells, VAN alone caused moderate cell death with high doses (IC50 54 48.76 mg/mL). TZP alone did not cause cellular death under the same conditions. VAN+TZP 55 was not different from VAN alone in NRK-52E cells (P>0.2). 56Conclusions: VAN+TZP does not cause more kidney injury than VAN alone in a rat model of 57 VIKI or in rat kidney epithelial cells. 58 59 3 | Page

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Does Piperacillin-Tazobactam Increase the Risk of Nephrotoxicity when Used with Vancomycin: A Meta-Analysis of Observational Trials

Abstract: Adding piperacillin-tazobactam to vancomycin increases the risk of nephrotoxicity when compared to vancomycin alone or vancomycin with either cefepime or meropenem.

Cited by 21 publications

References 0 publications

Evaluation of the risk of acute kidney injury with the use of piperacillin/tazobactam among adult critically ill patients

Evaluation of the risk of acute kidney injury with the use of piperacillin/tazobactam among adult critically ill patients

Vancomycin-associated acute kidney injury in Hong Kong in 2012–2016

Urinary biomarker and histopathological evaluation of vancomycin and piperacillin-tazobactam nephrotoxicity in comparison with vancomycin in a rat model and a confirmatory cellular model

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