Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis

Luther, Megan K.; Timbrook, Tristan T; Caffrey, Aisling R.; Dosa, David; Lodise, Thomas P.; LaPlante, Kerry L.

doi:10.1097/ccm.0000000000002769

Cited by 196 publications

(110 citation statements)

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“…One of the studies evaluated the brief (Ͻ72 h) use of combination therapy in critically ill patients (24). Recent meta-analyses were also unable to adequately assess the interaction of VPT in the critically ill patient population due to a lack of adequate data (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

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Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam, Cefepime, or Meropenem

Blevins

Lashinsky

McCammon

et al. 2019

Antimicrob Agents Chemother

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Critically ill patients are frequently treated with empirical antibiotic therapy, including vancomycin and β-lactams. Recent evidence suggests an increased risk of acute kidney injury (AKI) in patients who received a combination of vancomycin and piperacillin-tazobactam (VPT) compared with patients who received vancomycin alone or vancomycin in combination with cefepime (VC) or meropenem (VM), but most studies were conducted predominately in the non-critically ill population. A retrospective cohort study that included 2,492 patients was conducted in the intensive care units of a large university hospital with the primary outcome being the development of any AKI. The rates of any AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, were 39.3% for VPT patients, 24.2% for VC patients, and 23.5% for VM patients (P < 0.0001 for both comparisons). Similarly, the incidences of stage 2 and stage 3 AKI were also significantly higher for VPT patients than for the patients in the other groups. The rates of stage 2 and stage 3 AKI, respectively, were 15% and 6.6% for VPT patients, 5.8% and 1.8% for VC patients, and 6.6% and 1.3% for VM patients (P < 0.0001 for both comparisons). In multivariate analysis, the use of vancomycin in combination with piperacillin-tazobactam was found to be an independent predictor of AKI (odds ratio [OR], 2.161; 95% confidence interval [CI], 1.620 to 2.883). In conclusion, critically ill patients receiving the combination of VPT had the highest incidence of AKI compared to critically ill patients receiving either VC or VM.

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Section: Discussionmentioning

confidence: 99%

“…ill patient populations, but limited studies in the critically ill population have failed to demonstrate an increased risk of AKI with VPT (14,24,(26)(27)(28)(29).…”

mentioning

confidence: 99%

Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam, Cefepime, or Meropenem

Blevins

Lashinsky

McCammon

et al. 2019

Antimicrob Agents Chemother

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“…[ 37 ] The analysis we have performed is in agreement with recent reports of piperacilln/tazobactam associations vAKI, which has only been recently identified. [ 38 , 39 ] The strength of the associations of nafcillin and clindamycin with vAKI warrant that the use of nafcillin or clindamycin with vancomycin should be investigated further.…”

Section: Resultsmentioning

confidence: 99%

Vancomycin associated acute kidney injury in pediatric patients

et al. 2018

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IntroductionVancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI.Methods and materialsA 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI.ResultsA total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67–11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3–7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28–0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1–3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6–8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05)ConclusionsModerate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.

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“…The proposed mechanism of the cefepime-associated AKI was interstitial nephritis and direct cytotoxic damage with dose-dependent manner [ 7 , 8 , 9 ]. Although two meta-analyses have showed that piperacillin-tazobactam plus vancomycin led to a higher risk of AKI than cefepime plus vancomycin, the difference was not significant in critically ill patients [ 30 , 31 ]. This finding might reflect that AKI might be substantial depending on the morbidity of the patients and severity of the infection.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Cystatin C-Guided Renal Dose Adjustment of Cefepime Treatment in Hospitalized Patients with Pneumonia

Kim

et al. 2020

JCM

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Cystatin C (CysC) may estimate renal function more accurately than serum creatinine (SCr). The clinical impact of renal dose adjustment of cefepime according to CysC rather than SCr has remained uncertain. We investigated the efficacy and safety of CysC-guided cefepime dosing compared with SCr-guided dosing in hospitalized patients with pneumonia. All adults hospitalized with pneumonia between July 2016 and December 2018 who used cefepime for at least 3 days were enrolled. Mortality, acute kidney injury (AKI), cefepime-induced encephalopathy (CIE), and Clostridium difficile infection were compared between the CysC-guided and SCr-guided groups. One hundred and ninety patients were divided into two groups: 129 and 61 received cefepime based on CysC and SCr, respectively. In-hospital mortality did not significantly differ between the groups (12% versus 31%; hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.31–1.77; p = 0.50). CysC-guided cefepime dosing decreased the risk of AKI (13% versus 61%; HR 0.18; 95% CI, 0.07–0.44; p < 0.001) and CIE (2% versus 11%; HR 0.11; 95% CI, 0.03–0.47; p = 0.003) compared with SCr-guided dosing. There was no significant difference in the risk of Clostridium difficile infection. CysC-guided dosing of cefepime was associated with decreased risk of the cefepime-associated morbidities including AKI and CIE without increasing mortality among the hospitalized patients with pneumonia.

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Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis

Cited by 196 publications

References 58 publications

Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam, Cefepime, or Meropenem

Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam, Cefepime, or Meropenem

Vancomycin associated acute kidney injury in pediatric patients

Efficacy and Safety of Cystatin C-Guided Renal Dose Adjustment of Cefepime Treatment in Hospitalized Patients with Pneumonia

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