Risk of Acute Kidney Injury in Patients on Concomitant Vancomycin and Piperacillin–Tazobactam Compared to Those on Vancomycin and Cefepime

Navalkele, Bhagyashri; Pogue, Jason M.; Karino, Shigehiko; Nishan, B; Salim, Madiha; Solanki, Shantanu; Pervaiz, Amina; Tashtoush, Nader; Shaikh, Hamadullah; Koppula, Sunitha; Koons, Jonathan; Hussain, Tanveer; Perry, William; Evans, Richard P.; Martin, Emily T.; Mynatt, Ryan P.; Murray, Kathryn; Rybak, Michael J.; Kaye, Keith S.

doi:10.1093/cid/ciw709

Cited by 164 publications

(159 citation statements)

References 12 publications

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“…In cases 8 and 10, a proton pump inhibitor was deemed unlikely as culprit for the development of AKI, given the absence of evidence for allergic interstitial nephritis by either histology or clinical and laboratorial features. Nonetheless, we cannot discard the possibility that other drugs or agents increased the risk of VA-AKI, as suggested by reports of increased incidence of VA-AKI during co-exposure to piperacillin-tazobactam, aminoglycosides and cephalosporins [16, 36-38]. In our series, co-exposure to piperacillin-tazobactam, cefepime, ceftriaxone and levofloxacin in some of the cases (Table 2) could have played a role in the observed phenotype.…”

Section: Discussionmentioning

confidence: 68%

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine

Obadan

Kaushal

Alzubaidi

et al. 2018

Nephron

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Background: Vancomycin-associated (VA) acute kidney injury (AKI) is being increasingly recognized. A distinct pattern of rapid rise in serum creatinine (sCr) during VA-AKI has occasionally been observed. However, such scenarios remain underreported. Methods: We conducted an online survey at the American Society of Nephrology Communities forum and reviewed publications of VA-AKI via PubMed or Google searching for cases of precipitous AKI (those with rise in sCr ≥1.5 mg/dL/day) attributable to vancomycin. Results: We identified 12 original cases compiled from 6 different hospitals and 4 published cases (n = 16; 38% women, age 43.5 ± 16 years, weight 108 ± 23 kg, body mass index 35 ± 7 kg/m²) of precipitous AKI observed shortly after large cumulative doses of VA (8.8 ± 5 g). The median steepest 24-h rise in sCr was 2.6 mg/dL (range 1.5–3.5 mg/dL) and the slope of the initial 48-h sCr rise was greater than that of a control AKI (non-VA, n = 48) group (2.03 ± 0.1 vs. 0.62 ± 0.0 mg/dL/day; p < 0.0001). The steep rise in sCr in the VA-AKI was not accompanied by anuria. Overt rhabdomyolysis was absent in all cases. Further, in 3 precipitous VA-AKI cases, simultaneous serum cystatin C values did not rise precipitously, suggesting that the reductions in glomerular filtration rate were overestimated by the sCr increase. Conclusions: VA-AKI can manifest with a precipitous rise in sCr shortly after a high cumulative dose of vancomycin. True toxic tubular injury overrepresented by the sCr rise is postulated.

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Section: Discussionmentioning

confidence: 68%

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine

Obadan

Kaushal

Alzubaidi

et al. 2018

Nephron

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“…Most critically ill patients requiring broad-spectrum empirical antibiotics during the trough concentration-guided dosing period would have received piperacillin-tazobactam and been excluded, as this was the institutional antipseudomonal agent of choice during the time of the study. However, due to a piperacillin-tazobactam shortage and institutional data associating it with vancomycin-associated nephrotoxicity, during the AUC-guided dosing period most critically ill patients would have received cefepime and been included in the analysis (23). This is supported by the disproportionate number of patients in the AUC-guided dosing group with a pneumonia indication.…”

Section: Discussionmentioning

confidence: 99%

“…Patients who received vancomycin to treat meningitis, skin and soft tissue infections without concomitant bacteremia, urinary tract infections, or surgical prophylaxis were excluded, as the current DMC vancomycin monitoring guidelines do not recommend AUC 24 targets for these indications. Due to the emerging body of evidence correlating use of the combination of vancomycin and piperacillin-tazobactam with increased nephrotoxicity and a piperacillin-tazobactam shortage, piperacillin-tazobactam use sharply declined during the study period (23,25,26). To account for this potential confounding variable, patients receiving concomitant piperacillin-tazobactam were excluded.…”

Section: Methodsmentioning

confidence: 99%

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

Finch

Zasowski

Murray

et al. 2017

Antimicrob Agents Chemother

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200

180

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Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of Ն400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P ϭ 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P ϭ 0.002). AUCguided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

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“…Numerous risk factors exist for vancomycin-associated nephrotoxicity, including vancomycin trough concentrations3 ≥15 mcg/mL, concomitant exposure to other nephrotoxins, such as aminoglycosides4 and piperacillin/tazobactam5,6,7,8,9,10,11,12,13, duration of exposure,12,14-16, and total daily dose 15,17. Due diligence is necessary when vancomycin is used in patients.…”

Section: Introductionmentioning

confidence: 99%

Effects of staff education and standardizing dosing and collection times on vancomycin trough appropriateness in ward patients

Hammond¹,

Atkinson²,

James³

et al. 2017

Pharm Pract (Granada)

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Background:Many institutions have guidelines for initiation and monitoring, but not timing, of vancomycin.Objective:Our objective was to evaluate vancomycin trough collection appropriateness before and after an initiative to change the dosing and trough collection times in ward patients.Methods:A retrospective cohort study of ward patients from May 2014-16 who received scheduled intravenous vancomycin was performed. Nurse managers and pharmacists provided staff education. Differences between pre- and post-intervention groups were compared using student’s t-test for continuous data and chi-square test for categorical data.Results:Baseline characteristics were similar between the pre-intervention (n=124) and post-intervention (n=122) groups except for weight-based maintenance dose (15.3 mg/kg vs. 16.5 mg/kg, p=0.03) and percentage of troughs collected with morning labs (14% vs. 87%, p<0.001). Patients in the pre- and post-intervention groups received a similar frequency of loading doses (14.5% vs. 16%, p=0.68). There was no significant difference in percentage of vancomycin troughs collected appropriately at 30 (40% vs. 42%, p=0.72), 60 (57% vs. 63%, p=0.35), or 75 (60% vs. 68%, p=0.22) minutes from the scheduled time of the next dose.Conclusion:Staff education and standardizing collection of vancomycin troughs with morning blood collections did not affect the percentage of appropriately collected vancomycin troughs.

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Risk of Acute Kidney Injury in Patients on Concomitant Vancomycin and Piperacillin–Tazobactam Compared to Those on Vancomycin and Cefepime

Abstract: The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination.

Cited by 164 publications

References 12 publications

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

Effects of staff education and standardizing dosing and collection times on vancomycin trough appropriateness in ward patients

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