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September 10, 2018
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NEPHROTOXICITY
Although the mechanism underlying renal toxicity from vancomycin is not fully understood,
experimental studies supported proinflammatory oxidation, mitochondrial dysfunction and
cellular apoptosis as the principal modes of injury.
Oxidative phosphorylation by vancomycin induces free oxygen radicals and thereby reduces
the activity of defensive antioxidative enzymes including superoxide dismutase and catalases.
Superoxide production by vancomycin causes depolarization of mitochondrial membrane
potential with a release of cytochrome C, and a subsequent activation of both caspases 9 and 3.
The latter is involved in apoptotic cell death.
https://en.wikipedia.org/wiki/Vancomycin
https://www.idstewardship.com/drugs/vancomycin/
1
https://theodora.com/drugs/zosyn_zosyn_in_galaxy_containers_wyeth.html
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VANCOMYCIN + ZOSYN
MECHANISM?
1. Navalkele B, et al. - October 2016
"AKI rates were significantly higher in the vanc + pip-tazo than the vanc + cefepime group (81/279 (29%) vs. 31/279 (11%), p<0.0001.) "
2. Lorenz M, et al. - 2016
"Overall, 11.8% (22/186) of patients who received therapy with pip-tazo + vancomycin developed AKI, compared with 1.7% (1/56) who received pip-tazo monotherapy (P < 0.0001)."
3. McQueen KE, et al. - 2016
Nephrotoxicity developed in 3 of 79 patients (3.8%) in the vancomycin group and in 25 of 106 patients (23.6%) on combination therapy (p = 0.0001).
4. Karino S, et al. - 2016
Overall, AKI occurred in 105/320 (33%) of the cohort receiving combination therapy. There were similar rates in those receiving intermittent (53/160 (33.1%)) and extended infusions (52/160 (32.5%)) of pip-tazo.
5. Peyko V, et al. - 2016
The incidence of AKI was significantly higher in the pip-tazo + vancomycin group (37.3%) compared with the cefepime or meropenem + vancomycin group (7.7%; χ2 = 7.80, P = .005).
https://kmir.com/2018/04/19/desert-regional-medical-center-penalized-for-two-2015-deaths/
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PERFORMED BY CHART REVIEW
RESULTS
3,4
According to the RIFLE (Risk, Injury, Failure, Loss, End Stage Renal Disease) criteria, the terms risk, injury, and failure were defined as follows:
https://emedicine.medscape.com/article/1925597-overview
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0.78 x 1.5 (risk) = 1.17
0.78 x 2 (injury) = 1.56
http://www.enzolifesciences.com/browse/toxicology/assessment-of-kidney-injury---nephrotoxicity/
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2
1. Limit nephrotoxic agents
2. Continually reassess patients
3. Target lower troughs if possible
4. Vanco + Cefepime + Metronidazole (optional)
1.Bhagyashri Navalkele et al; Risk of Acute Kidney Injury in Patients on Concomitant Vancomycin and Piperacillin–Tazobactam Compared to Those on Vancomycin and Cefepime; Clinical Infectious Diseases; 2016.
2. Olson Logan; Vancomycin and Piperacillin/Tazobactam. Combination Therapy: The Renal Wringer?, Mayo Clinic; 2016
3. Rutter W; Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime; 2017
4. Hayes et al; Piperacillin/Tazobactam and Risk of Acute Kidney Injury with Vancomycin; Academic Life in Emergency Medicine; 2016.
5. Does Piperacillin-Tazobactam Cause Renal Failure?; PulmCC.org; 2018
6. Hammond et al; Systematic Review and Metaanalysis of Acute Kidney Injury Associated With Concomitant Vancomycin and Piperacillin/Tazobactam; Clinical Infectious Disease; 2017.