Abstract
Vancomycin (VAN) is a broad-spectrum antibiotic against Gram-positive cocci used empirically with other broad-spectrum antibiotics, such as piperacillin/tazobactam (TZP), cefepime, or meropenem (MEM). Conflicting literature on the rates of acute kidney injury (AKI) of VAN with TZP is reported, and studies on AKI rate with MEM are limited. This study aimed to evaluate AKI rates in patients receiving VAN with either TZP or MEM. This was a retrospective cohort study of patients received either VAN-TZP or VAN-MEM for ≥ 72 h. Patients with a baseline serum creatinine (SCr) of ≥ 1.5 mg/dL were excluded. The primary outcome was rate of AKI as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. SCr was recorded at baseline and 3–5 days post antibiotics initiation. 158 patients were included, 77 in the VAN-TZP group versus 81 in the VAN-MEM group. While the percentage of patients meeting AKI definition was numerically higher in the VAN-MEM group, the difference was not significant (10.4% vs. 21%; P = 0.07). As such, change in SCr was not significantly different between the two groups (− 7.4 vs. − 6.1%; P = 0.7). In-hospital mortality was higher in the VAN-MEM group (23.4% vs. 39.5%; P = 0.03) possibly because the majority of this group’s patients were critically ill. This study showed that combining MEM with VAN did not offer the benefit of a lower rate of AKI compared with a combination with TZP. Therefore, patients with no risk factors for infections resistant to TZP can continue to receive TZP with VAN without risking AKI development.
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References
Hazlewood KA, Brouse SD, Pitcher WD, Hall RG (2010) Vancomycin-associated nephrotoxicity: grave concern or death by character assassination? Am J Med 123(2):182. https://doi.org/10.1016/j.amjmed.2009.05.031
Klein EY, Sun L, Smith DL, Laxminarayan R (2013) The changing epidemiology of methicillin-resistant Staphylococcus aureus in the United States: a national observational study. Am J Epidemiol 177(7):666–674. https://doi.org/10.1093/aje/kws273
Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL (2009) Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis 49(4):507–514. https://doi.org/10.1086/600884
van Hal SJ, Paterson DL, Lodise TP (2013) Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother 57(2):734–744. https://doi.org/10.1128/AAC.01568-12
Carreno JJ, Kenney RM, Lomaestro B (2014) Vancomycin-associated renal dysfunction: where are we now? Pharmacotherapy 34(12):1259–1268. https://doi.org/10.1002/phar.1488
Luther MK, Timbrook TT, Caffrey AR, Dosa D, Lodise TP, LaPlante KL (2018) Vancomycin plus piperacillin–tazobactam and acute kidney injury in adults: a systematic review and meta-analysis. Crit Care Med 46(1):12–20. https://doi.org/10.1097/CCM.0000000000002769
Al Yami MS (2017) Comparison of the incidence of acute kidney injury during treatment with vancomycin in combination with piperacillin–tazobactam or with meropenem. J Infect Public Health 10(6):770–773. https://doi.org/10.1016/j.jiph.2016.11.007
Rutter WC, Burgess DS (2018) Incidence of acute kidney injury among patients treated with piperacillin–tazobactam or meropenem in combination with vancomycin. Antimicrob Agents Chemother 62:7. https://doi.org/10.1128/AAC.00264-18
Gomes DM, Smotherman C, Birch A, Dupree L, Della Vecchia BJ, Kraemer DF, Jankowski CA (2014) Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin–tazobactam or cefepime. Pharmacotherapy 34(7):662–669. https://doi.org/10.1002/phar.1428
Information P (2019) MERREM®, meropenem for intravenous injection. AstraZeneca Inc, Wilmington, DE
Robertson AD, Li C, Hammond DA, Dickey TA (2018) Incidence of acute kidney injury among patients receiving the combination of vancomycin with piperacillin–tazobactam or meropenem. Pharmacotherapy 38(12):1184–1193. https://doi.org/10.1002/phar.2179
Blevins AM, Lashinsky JN, McCammon C, Kollef M, Micek S, Juang P (2019) Incidence of acute kidney injury in critically ill patients receiving vancomycin with concomitant piperacillin–tazobactam, cefepime, or meropenem. Antimicrob Agents Chemother 63:5. https://doi.org/10.1128/AAC.02658-18
Thabit AK, Crandon JL, Nicolau DP (2015) Antimicrobial resistance: Impact on clinical and economic outcomes and the need for new antimicrobials. Expert Opin Pharmacother 16(2):159–177. https://doi.org/10.1517/14656566.2015.993381
Avedissian SN, Pais GM, Liu J, Rhodes NJ, Scheetz MH (2019) Piperacillin–tazobactam added to vancomycin increases risk for AKI: fact or fiction? Clin Infect Dis. https://doi.org/10.1093/cid/ciz1189
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, Herzog CA, Joannidis M, Kribben A, Levey AS, MacLeod AM, Mehta RL, Murray PT, Naicker S, Opal SM, Schaefer F, Schetz M, Uchino S (2012) Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2(1):1–138. https://doi.org/10.1038/kisup.2012.1
Peyko V, Smalley S, Cohen H (2017) Prospective comparison of acute kidney injury during treatment with the combination of piperacillin–tazobactam and vancomycin versus the combination of cefepime or meropenem and vancomycin. J Pharm Pract 30(2):209–213. https://doi.org/10.1177/0897190016628960
Baldwin DS, Levine BB, McCluskey RT, Gallo GR (1968) Renal failure and interstitial nephritis due to penicillin and methicillin. N Engl J Med 279(23):1245–1252. https://doi.org/10.1056/NEJM196812052792302
Kang S, Park J, Yu YM, Park MS, Han E, Chang MJ (2019) Comparison of acute kidney injury and clinical prognosis of vancomycin monotherapy and combination therapy with beta-lactams in the intensive care unit. PLoS ONE 14(6):e0217908. https://doi.org/10.1371/journal.pone.0217908
Pais GM, Liu J, Avedissian SN, Hiner D, Xanthos T, Chalkias A, d’Aloja E, Locci E, Gilchrist A, Prozialeck WC, Rhodes NJ, Lodise TP, Fitzgerald JC, Downes KJ, Zuppa AF, Scheetz MH (2020) Lack of synergistic nephrotoxicity between vancomycin and piperacillin/tazobactam in a rat model and a confirmatory cellular model. J Antimicrob Chemother. https://doi.org/10.1093/jac/dkz563
Girling BJ, Channon SW, Haines RW, Prowle JR (2020) Acute kidney injury and adverse outcomes of critical illness: correlation or causation? Clin Kidney J 13(2):133–141. https://doi.org/10.1093/ckj/sfz158
Acknowledgement
We acknowledge the Information Technology Department of King Abdulaziz University Hospital for providing the patients list. The study abstract was published in the abstract book of the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2020.
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The study protocol was approved by the Biomedical Ethics Committee of the Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia (reference No. 500-18).
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Tookhi, R.F., Kabli, N.A., Huntul, M.A. et al. Impact of combining vancomycin with piperacillin/tazobactam or with meropenem on vancomycin-induced nephrotoxicity. Intern Emerg Med 16, 975–979 (2021). https://doi.org/10.1007/s11739-020-02624-5
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DOI: https://doi.org/10.1007/s11739-020-02624-5