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.
A piperacillin/tazobactam (PT) restriction was initiated at our institution on 15 July 2012 requiring clinical pharmacy or infectious diseases approval for durations exceeding 72 h. A retrospective review was undertaken to determine whether this restriction decreased PT usage and/or rates of acute renal failure (ARF) (defined as a 50 % increase or 0.5 mg dl 21 increase in serum creatinine from baseline). Patients prescribed at least 1 day of PT with a creatinine clearance of $39 ml min 21 at the time of initiation in the 3 months prior to the restriction were compared with patients in the 5 months after restriction implementation. Overall, 115 unique patients were included in the pre-implementation group and compared with 117 unique patients in the post-implementation group. The pre-implementation group received a mean of 5.22 days of PT, compared with 4.71 days in the post-implementation group (P50.224). Ten per cent (12/115) of patients in the pre-implementation group developed ARF compared with 9.17 % (11/120) of patients in the post-implementation group (P50.0309). Ninety-five patients in the pre-implementation group and 91 in the post-implementation group received combination therapy with vancomycin. ARF occurred in 11.6 % (11/95) of those in the pre-implementation group and 12.1 % (11/91) in the post-implementation (P.0.05). Overall, 11.8 % (22/186) of patients who received therapy with PT and vancomycin developed ARF, compared with 1.7 % (1/56) who received PT monotherapy (P,0.0001). This restriction resulted in a numeric reduction in the number of PT days in the post-implementation group and a significant reduction in the rate of ARF.
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