Acute renal failure associated with vancomycin and β-lactams for the treatment of osteomyelitis in diabetics: piperacillin–tazobactam as compared with cefepime

Abstract

Few data are available on the nephrotoxic potential of vancomycin when combined with certain β-lactam antibiotics for the treatment of osteomyelitis (OM). A retrospective cohort study was conducted of all diabetic patients with OM treated with vancomycin plus piperacillin-tazobactam (VPT) or vancomycin plus cefepime (VC) for at least 72 h at a VA Medical Center between 1 January 2006 and 31 December 2011. All patients with a creatinine clearance (CrCl) of ≤ 40 mL/min, a blood urea nitrogen/serum creatinine (SCr) ratio of ≥ 20 : 1 or an absolute neutrophil count of <500 cells/mm(3) were excluded. The primary outcome was development of acute renal failure (ARF), defined as an increase in SCr of 0.5 mg/dL or 50% of baseline. One hundred and thirty-nine patients met the inclusion criteria; 109 in the piperacillin-tazobactam group and 30 in the cefepime group. Among patients receiving VPT, 29.3% (32/109) developed ARF, as compared with 13.3% (4/30) receiving VC (p 0.099). Among patients receiving high-dose therapy (≥ 18 g of piperacillin-tazobactam daily or ≥ 3 g of cefepime daily), 37.5% (9/24) receiving VPT and 17.6% (3/17) receiving VC developed ARF (p 0.29). A multiple logistic regression analysis identified weight and average vancomycin trough as the only significant predictors of ARF; the choice of VPT as therapy yielded an OR of 3.45 (95% CI 0.96-12.40; p 0.057). The authors were unable to detect a statistically significant difference in ARF between groups; however, the power requirement was not met. Further study with a larger patient population seems warranted.

Effect of piperacillin/tazobactam restriction on usage and rates of acute renal failure

“…A previous study completed at the VA St Louis Health Care System revealed high rates of PT prescribing with increasing cases of acute renal failure (ARF) (defined as a 50 % increase or 0.5 mg dl 21 increase in serum creatinine from baseline) (Moenster et al, 2014). Based on these data, the decision was made on 15 July 2012 to place PT on 72 h restriction, meaning that any inpatient provider could order the antibiotic, but each order would be given a 72 h stop date.…”

Acute renal failure after high-dose antibiotic bone cement: case report and review of the literature

“…45 This finding with piperacillin-tazobactam is not surprising as its nephrotoxicity risk appears to be more significant than previously appreciated. [46][47][48][49] We do not believe that the tobramycin was the cause of the AKI alone in our case, but rather a contributing factor. Our patient experienced significant post-operative hypotension for a brief time period and was also on intravenous vancomycin.…”

A Case of Acute Kidney Injury with Vancomycin and Piperacillin/Tazobactam

“…One study comparing the use of vancomycin with piperacillin/ tazobactam and vancomycin with cefepime found higher incidence of acute renal failure in patients given both vancomycin and piperacillin/tazobactam than with cefepime; however, no statistical significance was demonstrated [8]. Because both antibiotics are eliminated through renal mechanisms and show nephrotoxicity individually, it is predicted that the concomitant use of vancomycin and piperacillin/tazobactam can cause a higher incident of nephrotoxicity than when used as monotherapy [1,2,8].…”

“…Acute renal failure can be defined as serum creatinine (SCr) increase by 0.5 mg/dL or increase by 50% from baseline [8]. In a person without any kidney disease, serum creatinine is constant with very small variability [9].…”