Retrospective Cohort Study of the Incidence of Acute Kidney Injury with Vancomycin Area under the Curve-Based Dosing with Concomitant Piperacillin-Tazobactam Compared to Meropenem or Cefepime

Kiley, Patrick S; Pearston, Aaron P.; Hodge, Laura; Kaplan, Marcus C; Baczek, Stephanie M; Stanley, James S; Wilson, Tyler J.; Soriano, Kristina M; Yao, Andrew; Shaeffer, Zachary A; Talt, Irene E; Cohen, Joshua; Ingemi, Amanda I.

doi:10.1128/aac.00040-22

Cited by 9 publications

(9 citation statements)

References 13 publications

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“…Compared with previous literature, the baseline patient characteristics of our population including VPT regimens, concomitant nephrotoxins, baseline renal function, and severity of illness were all mostly similar. 7,8,11,12,25 We think this study adds to the body of literature, as data from other studies are scarce regarding VPT administration in obese patients. For example, Karas et al evaluated incidence of Note.…”

Section: Discussionmentioning

confidence: 84%

“…Our incidence of AKI in patients managed with the AUC guided approach was also noted to be similar to other recent studies evaluating VPT therapy with AUC guided dosing, although these studies were small and without an obese population. 7,8,25 Future research should evaluate AUC guided vancomycin dosing along with use of extended antibiotic infusions (vancomycin and piperacillin-tazobactam), as these strategies may prove to be pharmacokinetically superior for obese patients and in reducing AKI. 1,14 Our study has limitations, including that it was a small retrospective study with mostly male veteran patients, which may limit the external validity and application of our findings to other patient populations.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity

et al. 2023

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Background: Increasing evidence suggests that administration of combination vancomycin and piperacillin-tazobactam (VPT) increases the incidence of acute kidney injury (AKI) beyond that of vancomycin alone. But these investigations have not evaluated AKI risk specifically in an increasingly prevalent obese population in whom VPT pharmacokinetics are altered. Objective: To evaluate AKI risk with VPT administration to patients with obesity. Methods: We conducted a multicenter retrospective study of obese patients admitted to 2 separate academic teaching hospitals from January 2010 to December 2021, who received VPT, or vancomycin plus either cefepime, meropenem, or ceftazidime. The primary outcome evaluated AKI when patients were treated with or without VPT. Results: A total of 227 patients were evaluated (114 in VPT, vs 113 in control group). Overall, body mass index (35.6 kg/m2 ± 4.8vs 36.1 kg/m2 ± 5.2; P = .44) was similar between the VPT and control groups respectively. Total vancomycin dose on day 1 of antibiotic therapy (3,432 mg ± 935 vs 2,732 mg ± 912; P < .01) and nephrotoxin administration (75.4% vs 62.8%; P = .04) were higher in the VPT group. Incidence of AKI was higher in the VPT group (37.7%vs 14.2%; P = .01) and on regression analysis VPT was predictive of developing AKI (OR = 3.9; 95% CI = 2.0-7.7; P < .01). Conclusion and Relevance: In this retrospective study, the incidence of AKI was increased in obese patients receiving therapy with VPT. Vancomycin combination therapy with ceftazidime, cefepime, and meropenem appeared to be safe and was associated with less nephrotoxicity. Cautious use of VPT and further investigation with larger studies are warranted in this area.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity

et al. 2023

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“…Our findings are consistent with previous studies demonstrating higher rates of AKI with VPT as compared to vancomycin alone or vancomycin plus other BLs with short-term use. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] The mechanism by which VPT increases AKI risk has not been clearly defined. Increased rates of nephrotoxicity have been seen with antistaphylococcal penicillin compared to cefazolin when combined with vancomycin for MRSA bacteremia.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11][12][13][14][15][16][17] Vancomycin plus piperacillin/tazobactam (VPT) has been associated with an increased risk of acute kidney injury (AKI) compared to vancomycin plus an alternative antipseudomonal beta-lactam (BL) such as cefepime or meropenem. [12][13][14][15][16][17][18][19][20] AKI has been shown to occur faster with VPT compared to vancomycin alone or vancomycin plus cefepime or meropenem. 12,16,21 In contrast, other studies have not found an increased rate of AKI with VPT compared to vancomycin plus cefepime or meropenem in critically ill populations after adjustment for relevant confounders.…”

Section: Comparative Renal Risk Of Long-term Use Of Beta-lactams In C...mentioning

confidence: 99%

Comparative renal risk of long-term use of beta-lactams in combination with vancomycin across the continuum of care

Dolly,

Rivera,

Jensen

et al. 2023

Therapeutic Advances in Infection

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Background: Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin–tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed. Results: AKI occurred in 14.4% of patients in the VPT group ( n = 15/104) compared to 5.5% in the other BL group ( n = 40/722) ( p < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7–12.0) days in the VPT group and 10.9 (5–22.7) days in the other BL group ( p = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33–4.65), p = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group ( n = 15/104) and 5.3% in the other BL group ( n = 11/208) ( p = 0.006). Receipt of VPT [HR: 2.55 (1.36–4.78), p = 0.004] and acyclovir [HR: 2.38 (1.19–4.74), p = 0.014) remained significantly associated with AKI in the multivariable model. Conclusion: Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy.

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“…These findings differ from a recent investigation of critically ill paediatric patients, which showed that those with piperacillin-associated AKI had greater estimated AUC and the highest C min in the first 24 h. 36 Unfortunately, this study did not also evaluate concomitant vancomycin exposure in those patients with AKI, therefore the impact of combination therapy on AUC cannot be deduced. Kiley et al 37 investigated the incidence of AKI with vancomycin+piperacillin/tazobactam versus vancomycin+cefepime/meropenem. This study varied from those previously published due to the utilization of an AUC-based strategy to estimate vancomycin exposure between groups.…”

Section: Discussionmentioning

confidence: 99%

Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy

Venugopalan,

Maranchick,

Hanai

et al. 2023

JAC-Antimicrobial Resistance

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Objectives Acute kidney injury (AKI) is a well-documented adverse effect observed with piperacillin/tazobactam in combination with vancomycin. The pharmacokinetics of these antibiotics when given in combination have not been previously evaluated. The purpose of this study was to compare the exposure of vancomycin + piperacillin/tazobactam in patients with and without AKI. Methods Ninety adult patients, who received at least 72 h of vancomycin + piperacillin/tazobactam combination therapy and had available serum concentrations of vancomycin and piperacillin were included in the study. Nephrotoxicity was defined as a 1.5-fold increase in serum creatinine within 7 days from baseline. Median daily AUCs were calculated in those with nephrotoxicity (vancomycin + piperacillin/tazobactam ‘N’) versus those without nephrotoxicity (vancomycin + piperacillin/tazobactam ‘WN’) during the first 7 days of combination therapy. Results The overall incidence of AKI in those receiving vancomycin + piperacillin/tazobactam was 20% (18/90). The median daily vancomycin AUCs did not differ between the vancomycin + piperacillin/tazobactam ‘WN’ and vancomycin + piperacillin/tazobactam ‘N’ groups. Although not statistically significant, the median daily vancomycin AUCs in the vancomycin + piperacillin/tazobactam ‘N’ group were numerically greater on Day 5 and trended downwards thereafter. For the piperacillin group, the median daily AUCs did not vary between groups, except on Day 7 where the vancomycin + piperacillin/tazobactam ‘WN’ group had statistically greater median piperacillin AUC than the vancomycin + piperacillin/tazobactam ‘N’ group (P = 0.046). Conclusions Utilizing serum creatinine-defined AKI, our study did not find any significant differences in vancomycin and piperacillin/tazobactam exposure between the groups with and without nephrotoxicity. These data indicate that vancomycin + piperacillin/tazobactam should not be avoided due to the risk of overexposure; instead, clinicians should continue to use these therapies cautiously.

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Retrospective Cohort Study of the Incidence of Acute Kidney Injury with Vancomycin Area under the Curve-Based Dosing with Concomitant Piperacillin-Tazobactam Compared to Meropenem or Cefepime

Abstract: Acute kidney injury (AKI) is a complication associated with vancomycin. Previous studies demonstrated that the combination of vancomycin and piperacillin-tazobactam increases the risk of AKI compared to vancomycin with meropenem or cefepime.

Cited by 9 publications

References 13 publications

The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity

The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity

Comparative renal risk of long-term use of beta-lactams in combination with vancomycin across the continuum of care

Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy

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