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.

Half of all empiric antibiotics ordered in critically ill patients are continued for at least 72 hours in absence of adjudicated infection. Additional studies are needed to confirm these findings and determine the risks and benefits of prolonged empiric therapy in the critically ill.

A 59-year-old woman with metastatic breast cancer experienced a poor response to increasing doses of hydromorphone, possibly related to the neuropathic nature of her pain. Ultimately, the cost of this treatment was more than $1000 per day. Administration of methadone, initially as an adjuvant and eventually as the sole analgesic, at a much smaller dose than expected resulted in very satisfactory analgesia, without the development of serious side effects. In addition, the cost of treatment decreased to less than $25 per day. This case illustrates the rationale and advantages for the use of methadone. Intraindividual variability in the response to various opioids is a factor to be considered when selecting analgesics. Methadone is a useful second-line or third-line opioid for the patient who is highly tolerant to other opioids, as it may demonstrate incomplete cross-tolerance with other agonist opioids. Switching of the opioid to methadone may be a worthwhile option to consider in managing patients who are highly tolerant to other opioids.

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