Influence of β-Lactam Infusion Strategy on Acute Kidney Injury

Abstract

Limited literature is available assessing nephrotoxicity with prolonged ␤-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged ␤-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: ␤-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P ϭ 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged ␤-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI.

Incidence of Acute Kidney Injury among Patients Treated with Piperacillin-Tazobactam or Meropenem in Combination with Vancomycin

“…Further work to identify optimal handling of concomitant nephrotoxins is needed. Duration of beta-lactam infusion was not assessed in this study; however, previous studies demonstrate that AKI incidence is not associated with duration of infusion (13,16,17). Despite the rigorous study design, there is a possibility of uncontrolled confounding as unknown confounders may remain.…”

Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review

“…Beta-lactam infusion strategy does not seem to alter the risk of nephrotoxic AKI with beta-lactams [44] and specifically with PT therapy in combination with vancomycin. In a matched-cohort of 2,390 patients receiving intravenous beta-lactam antibiotics, Cotner et al [45] showed that extended infusion was not a risk factor for AKI with any antipseudomonal agent. Similarly, 2 retrospective studies confirmed the absence of effect between the infusion strategy and the incidence of AKI in patients receiving PT in combination with vancomycin [38, 46].…”

Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity—A Pharmaco-Toxicological Screening

“…Acute interstitial nephritis is most often associated with nafcillin and methicillin. Eosinophiluria, accompanied by fever and rash, is a hallmark of antibiotic-induced acute allergic interstitial nephritis [ 81 , 82 ].…”