Skip to main content
SpringerLink
Log in

Acute kidney injury associated with concomitant vancomycin and piperacillin/tazobactam administration: a systematic review and meta-analysis

  • Nephrology - Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

As a tricyclic glycopeptide antibiotic used to treat acute infections, Vancomycin (VAN) is often administered with piperacillin/tazobactam (PT) to treat various infections in clinical practice. However, whether the combination of these two drugs, compared to VAN alone, can cause an increased risk of acute kidney injury (AKI) remains controversial.

Objectives

This study aims to identify the correlation between the development of AKI and the combined use of VAN and PT.

Methods

We conducted a meta-analysis of eight observational cohort studies (a total of 10727 participants received VAN and PT versus VAN and other β-lactams). PubMed, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI) Database, Wan Fang Digital Periodicals Database (WFDP), and China Science Citation Database (CSCD) were searched through April 2017 using “vancomycin” and “piperacillin” and “tazobactam” as well as “acute kidney injury” or “acute renal failure” or “AKI” or “ARF” or “nephrotoxicity.” Two reviewers extracted the data and assessed the risk of bias.

Results

A correlation was found between the development of AKI and concurrent use of VAN and PT compared with concomitant VAN and β-lactams (OR 1.57; 95% CI, 1.13–2.01; I2 = 76.4%, p < 0.001). Similar findings were obtained in an analysis of studies comparing concurrent VAN and PT use with concurrent VAN and β-lactam (cefepime) use (OR 1.50; 95% CI, 1.07–1.93; I2 = 80.5%, p < 0.001). Exclusion of fair-quality and low-quality articles did not change the results (OR 1.49; 95% CI, 1.06–1.92; I2 = 84.1%, p < 0.001).

Conclusions

Regarding β-lactam therapy in clinical practice, an elevated risk of AKI due to the combined use of VAN and PT should be considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Moellering RC Jr (2006) Vancomycin: a 50-year reassessment. Clin Infect Dis 42(Suppl 1):S3–S4

    Article  PubMed  Google Scholar 

  2. Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W, Macleod A (2007) Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol 18(4):1292–1298

    Article  CAS  PubMed  Google Scholar 

  3. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N et al (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2(3):431–439

    Article  PubMed  Google Scholar 

  4. Fang Y, Ding X, Zhong Y, Zou J, Teng J, Tang Y, Lin J, Lin P (2010) Acute kidney injury in a Chinese hospitalized population. Blood Purif 30(2):120–126

    Article  PubMed  Google Scholar 

  5. Murugan R, Kellum JA (2011) Acute kidney injury: what’s the prognosis? Nat Rev Nephrol 7(4):209–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Elyasi S, Khalili H, Dashti-Khavidaki S, Mohammadpour A (2012) Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review. Eur J Clin Pharmacol 68(9):1243–1255

    Article  CAS  PubMed  Google Scholar 

  7. Bamgbola O (2016) Review of vancomycin-induced renal toxicity: an update. Ther Adv Endocrinol Metab 7(3):136–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jeon N, Staley B, Klinker KP, Castillo JH, Winterstein AG (2017) Acute kidney injury risk associated with piperacillin/tazobactam compared with cefepime during vancomycin therapy in hospitalised patients: a cohort study stratified by baseline kidney function. Int J Antimicrob Agents 50(1):63–67

    Article  CAS  PubMed  Google Scholar 

  9. Lau WK, Mercer D, Itani KM, Nicolau DP, Kuti JL, Mansfield D, Dana A (2006) Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection. Antimicrob Agents Chemother 50(11):3556–3561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hammond DA, Smith MN, Painter JT, Meena NK, Lusardi K (2016) Comparative incidence of acute kidney injury in critically Ill patients receiving vancomycin with concomitant piperacillin-tazobactam or cefepime: a retrospective cohort study. Pharmacotherapy 36(5):463–471

    Article  CAS  PubMed  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. LeCleir LK, Pettit RS (2017) Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with vancomycin and tobramycin in pediatric cystic fibrosis patients. Pediatr Pulmonol 52(8):1000–1005

    Article  PubMed  Google Scholar 

  13. Moenster RP, Linneman TW, Finnegan PM, Hand S, Thomas Z, McDonald JR (2014) Acute renal failure associated with vancomycin and beta-lactams for the treatment of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime. Clin Microb Infect 20(6):O384–O389

    Article  CAS  Google Scholar 

  14. Navalkele B, Pogue JM, Karino S, Nishan B, Salim M, Solanki S, Pervaiz A, Tashtoush N, Shaikh H, Koppula S et al (2017) Risk of acute kidney injury in patients on concomitant vancomycin and piperacillin-tazobactam compared to those on vancomycin and cefepime. Clin Infect Dis 64(2):116–123

    Article  CAS  PubMed  Google Scholar 

  15. 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 Practice 30(2):209–213

    Article  Google Scholar 

  16. Rutter WC, Cox JN, Martin CA, Burgess DR, Burgess DS (2017) Nephrotoxicity during vancomycin therapy in combination with piperacillin-tazobactam or cefepime. Antimicrob Agents Chemother 61(2):e02089-16

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mullins BP, Kramer CJ, Bartel BJ, Catlin JS, Gilder RE (2018) Comparison of the nephrotoxicity of vancomycin in combination with cefepime, meropenem, or piperacillin/tazobactam: a prospective, multicenter study. Ann Pharmacother. https://doi.org/10.1177/1060028018757497

    Article  PubMed  Google Scholar 

  18. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  PubMed Central  Google Scholar 

  19. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  20. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  PubMed  Google Scholar 

  22. Brummett RE (1981) Effects of antibiotic-diuretic interactions in the guinea pig model of ototoxicity. Rev Infect Dis 3(Suppl):S216–S223

    Article  PubMed  Google Scholar 

  23. Farber BF, Moellering RC Jr (1983) Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrob Agents Chemother 23(1):138–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stevens DL (2006) The role of vancomycin in the treatment paradigm. Clin Infect Dis 42(Suppl 1):S51-57

    Google Scholar 

  25. Bagga A, Bakkaloglu A, Devarajan P, Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Joannidis M et al (2007) Improving outcomes from acute kidney injury: report of an initiative. Pediatr Nephrol 22(10):1655–1658

    Article  PubMed  Google Scholar 

  26. Hellwig T, Hammerquist R, Loecker B, Shields J (2011) 301: retrospective evaluation of the incidence of vancomycin and/or piperacillin-tazobactam induced acute renal failure. Crit Care Med 39(12):79

    Google Scholar 

  27. Le Moyec L, Racine S, Le Toumelin P, Adnet F, Larue V, Cohen Y, Leroux Y, Cupa M, Hantz E (2002) Aminoglycoside and glycopeptide renal toxicity in intensive care patients studied by proton magnetic resonance spectroscopy of urine. Crit Care Med 30(6):1242–1245

    Article  PubMed  Google Scholar 

  28. Nishino Y, Takemura S, Minamiyama Y, Hirohashi K, Tanaka H, Inoue M, Okada S, Kinoshita H: Inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat. Redox report: communications in free radical research 2002, 7(5):317–319

  29. Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr T, Andersen MH, Thornberg KJ, Løken J, Steensen M, Fox Z (2012) Kidney failure re lated to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial. BMJ Open 2(2):e000635

    Article  PubMed  PubMed Central  Google Scholar 

  30. Burgess LD, Drew RH (2014) Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam. Pharmacotherapy 34(7):670–676

    Article  CAS  PubMed  Google Scholar 

  31. Hundeshagen G, Herndon DN, Capek KD, Branski LK, Voigt CD, Killion EA, Cambiaso-Daniel J, Sljivich M, De Crescenzo A, Mlcak RP et al (2017) Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients. Crit Care 21(1):318

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hammond DA, Smith MN, Li C, Hayes SM, Lusardi K, Bookstaver PB (2017) Systematic review and meta-analysis of acute kidney injury associated with concomitant vancomycin and piperacillin/tazobactam. Clin Infect Dis 64(5):666–674

    CAS  PubMed  Google Scholar 

  33. Giuliano CA, Patel CR, Kale-Pradhan PB (2016) Is the combination of piperacillin-tazobactam and vancomycin associated with development of acute kidney injury? A meta-analysis. Pharmacotherapy 36(12):1217–1228

    Article  CAS  PubMed  Google Scholar 

  34. Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical practice 120(4):c179-184

    Google Scholar 

  35. Bonazza S, Bresee LC, Kraft T, Ross BC, Dersch-Mills D (2016) Frequency of and risk factors for acute kidney injury associated with vancomycin use in the pediatric intensive care unit. J Pediatr Pharmacol Ther 21(6):486–493

    PubMed  PubMed Central  Google Scholar 

  36. Agbabiaka TB, Savovic J, Ernst E (2008) Methods for causality assessment of adverse drug reactions: a systematic review. Drug Saf 31(1):21–37

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by Key Project of Natural Science of University of Anhui Province (Grant Number KJ 2015A007) and National Natural Science Fund of China (Grant Number 71503006).

Author information

Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Xiao-Yu Chen, Ri-Xiang Xu, Xin Zhou, Yang Liu & Xue-Feng Xie

  2. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Cheng-Yang Hu

Authors
  1. Xiao-Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ri-Xiang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cheng-Yang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xue-Feng Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xue-Feng Xie.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, XY., Xu, RX., Zhou, X. et al. Acute kidney injury associated with concomitant vancomycin and piperacillin/tazobactam administration: a systematic review and meta-analysis. Int Urol Nephrol 50, 2019–2026 (2018). https://doi.org/10.1007/s11255-018-1870-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-018-1870-5

Keywords

Search

Navigation