Risk of Acute Kidney Injury in Combat-Injured Patients Associated With Concomitant Vancomycin and Extended-Spectrum β-Lactam Antibiotic Use

Abstract

Background:

Multidrug-resistant infections complicating combat-related trauma necessitate the use of broad-spectrum antimicrobials. Recent literature posits an association between vancomycin (VANC) and piperacillin–tazobactam (VPT) combination therapy and acute kidney injury (AKI). We examined whether therapy with VPT was associated with an increased risk of AKI compared to VANC and other broad-spectrum β-lactam antibiotics (VBL) following combat-related injuries.

Methods:

Patients within the Trauma Infectious Disease Outcomes Study (TIDOS) who received ≥48 hours concomitant VPT or VBL started within 24 hours of each other were assessed. Exclusion criteria were receipt of renal replacement therapy and baseline creatinine >1.5 mg/dL. Acute kidney injury was defined by meeting any of the Risk, Injury, Failure, Loss, End Stage Renal Disease (RIFLE), AKIN, or VANC consensus guidelines criteria 3 to 7 days after therapy initiation. Variables significantly associated with AKI were used in inverse probability treatment weighting to perform univariate and subsequent logistic regression multivariate modeling to determine significant risk factors for AKI.

Results:

Sixty-one patients who received VPT and 207 who received VBL were included. Both groups had a median age of 24 years and initial median creatinine of 0.7 mg/dL. The VBL patients were more likely to have sustained blast injuries (P = .001) and received nephrotoxic agents (amphotericin [P = .002] and aminoglycosides [P < .001]). In the VBL group, AKI incidence was 9.7% compared to 13.1% in the VPT group (P = .438). Multivariate analysis identified a relative risk of 1.727 (95% CI: 1.027-2.765) for AKI associated with VPT exposure. Acute kidney injury severity generally met RIFLE Risk criteria and was 1 day in duration. Only 1 patient had persistent renal dysfunction 30 days after therapy completion.

Conclusion:

In this young and previously healthy, severely ill combat-injured population, VPT was associated with nearly twice the risk of AKI compared to VBL. Nevertheless, AKI was of low severity, short duration, and had high rates of renal recovery.

Keywords

acute kidney injury combat trauma antibiotics

Get full access to this article

View all access options for this article.

References

Tribble

Conger

Fraser

, et al. Infection-associated clinical outcomes in hospitalized medical evacuees after traumatic injury: trauma infectious disease outcome study. J Trauma. 2011;71(suppl 1):S33–S42.

Murray

Wilkins

Molter

, et al. Infections in combat casualties during operations Iraqi and enduring freedom. J Trauma. 2009;66(4 Suppl):S138–S144.

Campbell

Whitman

, et al. Multi-drug–resistant gram-negative infections in deployment-related trauma patients. Surg Infect (Larchmt). 2017;18(3):357–367.

Kaye

Pogue

. Infections caused by resistant gram-negative bacteria: epidemiology and management. Pharmacotherapy. 2015;35(10):949–962.

Mende

Stewart

Shaikh

, et al. Microbiology of combat-related extremity wounds: trauma infectious disease outcomes study. Diagn Microbiol Infect Dis. 2019;94(2):173–179.

Heitkamp

Mende

Demons

Tribble

Tyner

. Association of Enterococcus spp. with severe combat extremity injury, intensive care, and polymicrobial wound infection. Surg Infect (Larchmt). 2018;19(1):95–103.

Karino

Kaye

Navalkele

, et al. Epidemiology of acute kidney injury among patients receiving concomitant vancomycin and piperacillin-tazobactam: opportunities for antimicrobial stewardship. Antimicrob Agents Chemother. 2016;60(6):3743–3750.

Kim

Kandiah

Patel

, et al. Risk factors for kidney injury during vancomycin and piperacillin/tazobactam administration, including increased odds of injury with combination therapy. BMC Res Notes. 2015;8:579.

Hammond

Smith

Hayes

Lusardi

Bookstaver

. Systematic review and meta-analysis of acute kidney injury associated with concomitant vancomycin and piperacillin/tazobactam. Clin Infect Dis. 2017;64(5):666–674.

10.

Burgess

Drew

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

11.

Buckley

Hartsock

Berry

, et al. Comparison of acute kidney injury risk associated with vancomycin and concomitant piperacillin/tazobactam or cefepime in the intensive care unit. J Crit Care. 2018;48(1):32–38.

12.

Hammond

Smith

Painter

Meena

Lusardi

. Comparative incidence of acute kidney injury in critically ill patients receiving vancomycin with concomitant piperacillin-tazobactam or cefepime: a retrospective cohort study. Pharmacotherapy. 2016;36(5):463–471.

13.

Gomes

Smotherman

Birch

, et al. Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime. Pharmacotherapy. 2014;34(7):662–669.

14.

Navalkele

Pogue

Karino

, et al. Risk of acute kidney injury in patients on concomitant vancomycin and piperacillin-tazobactam compared to those on vancomycin and cefepime. Clin Infect Dis. 2017;64(2):116–123.

15.

Jeon

Staley

Klinker

Hincapie Castillo

Winterstein

. 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. 2017;50(1):63–67.

16.

Moenster

Linneman

Finnegan

Hand

Thomas

McDonald

. Acute renal failure associated with vancomycin and beta-lactams for the treatment of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime. Clin Microbiol Infect. 2014;20(6):O384–O389.

17.

Al Yami

. Comparison of the incidence of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or with meropenem. J Infect Public Health. 2017;10(6):770–773.

18.

Blevins

Lashinsky

McCammon

Kollef

Micek

Juang

. Incidence of acute kidney injury in critically ill patients receiving vancomycin with concomitant piperacillin/tazobactam, cefepime, or meropenem. Antimicrob Agents Chemother. 2019;63(5):e02658–e02668.

19.

Schreier

Kashani

Sakhuja

, et al. Incidence of acute kidney injury among critically ill patients with brief empiric use of antipseudomonal beta-lactams with vancomycin. Clin Infect Dis. 2019;68(9):1456–1462.

20.

Peyko

Smalley

Cohen

. 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. 2017;30(2):209–213.

21.

Giuliano

Patel

Kale-Pradhan

. Is the combination of piperacillin-tazobactam and vancomycin associated with development of acute kidney injury? a meta-analysis. Pharmacotherapy. 2016;36(12):1217–1228.

22.

Rutter

Burgess

Talbert

Burgess

. Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: a retrospective cohort analysis. J Hosp Med. 2017;12(2):77–82.

23.

Davies

Efird

Guidry

, et al. Top guns: the “maverick” and “goose” of empiric therapy. Surg Infect (Larchmt). 2016;17(1):38–47.

24.

Molina

Barletta

Hall

Yazdani

Huang

. The risk of acute kidney injury in critically ill patients receiving concomitant vancomycin with piperacillin-tazobactam or cefepime. J Intensive Care Med. 2019. [Epub ahead of print]. doi:10.1177/0885066619828290

25.

Bellomo

Ronco

Kellum

Mehta

Palevsky

, Acute Dialysis Quality Initiative Workgroup. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute dialysis quality initiative (ADQI) group. Crit Care. 2004;8(4):R204–R212.

26.

Mehta

Kellum

Shah

, et al. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.

27.

Rybak

Lomaestro

Rotschafer

, et al. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases society of America, the American society of health-system pharmacists, and the society of infectious diseases pharmacists. Clin Infect Dis. 2009;49(3):325–327.

28.

Ganesan

Shaikh

Bradley

, et al. Classification of trauma-associated invasive fungal infections to support wound treatment decisions. Emerg Infect Dis. 2019;25(9):1639–1647.

29.

Min

Box

Lane

, et al. 714: Acute kidney injury in patients receiving concomitant vancomycin and piperacillin/tazobactam. Crit Care Med. 2011;39(12):200.

30.

Hellwig

Hammerquist

Loecker

Shields

. 301: retrospective evaluation of the incidence of vancomycin and/or piperacillin-tazobactam induced acute renal failure. Crit Care Med. 2011;39(12):79.

31.

Luther

Timbrook

Caffrey

Dosa

Lodise

LaPlante

. Vancomycin plus piperacillin-tazobactam and acute kidney injury in adults: a systematic review and meta-analysis. Crit Care Med. 2018;46(1):12–20.

32.

Watkins

Deresinski

. Increasing evidence of the nephrotoxicity of piperacillin/tazobactam and vancomycin combination therapy-what is the clinician to do? Clin Infect Dis. 2017;65(12):2137–2143.

33.

Leblanc

Kellum

Gibney

Lieberthal

Tumlin

Mehta

. Risk factors for acute renal failure: inherent and modifiable risks. Curr Opin Crit Care. 2005;11(6):533–536.

34.

Pereira

Rodrigues

Godinho

, et al. Acute kidney injury in patients with severe sepsis or septic shock: a comparison between the ‘risk, injury, failure, loss of kidney function, end-stage kidney disease’ (RIFLE), acute kidney injury network (AKIN) and kidney disease: improving global outcomes (KDIGO) classifications. Clin Kidney J. 2017;10(3):332–340.

35.

van den Akker

Egal

Groeneveld

. Invasive mechanical ventilation as a risk factor for acute kidney injury in the critically ill: a systematic review and meta-analysis. Crit Care. 2013;17(3): R98.

36.

Muriithi

Nasr

Leung

. Utility of urine eosinophils in the diagnosis of acute interstitial nephritis. Clin J Am Soc Nephrol. 2013;8(11):1857–1862.