Do Vancomycin Serum Levels Predict Failures of Vancomycin Therapy or Nephrotoxicity in Cancer Patients?

Abstract

The purpose of this study was to determine if patients with high vancomycin (VAN) serum levels experience more toxicity than underdosed patients with lower (VAN) levels, and whether low VAN serum levels cause therapeutic failures in patients with gram-positive bacteremia. In 198 cancer patients trough and peak serum levels of VAN were measured. Acute toxicity (Red Man syndrome) appeared in 3 patients (1.5%). Patients previously or currently treated with other nephrotoxic compounds (134 patients) presented the same incidence of nephrotoxicity as those receiving VAN for the first time in monotherapy (64 patients). VAN did not increase the toxicity when patients were dosed simultaneously or previously with aminoglycosides or amphotericin B. Our second observation, when studying serum levels in our 198 patients was that high VAN trough serum levels (trough > 15 microg/mL) were associated with significantly more nephrotoxicity (33.3% vs. 11.1%, P < 0.03) than low levels in the subgroups of either pretreated patients or unpretreated with other nephrotoxic drugs. None of 198 patients who had trough levels below 15 microg/mL had peak levels exceeding 40 microg/mL. This suggests that only serum monitoring of trough levels may predict nephrotoxicity. A case control study was conducted to compare a group of 22 VAN failures with 22 successfully treated patients matched in underlying disease and neutropenia who were treated in the same period, under the same antibiotic policy, at the same cancer center, for gram-positive bacteremia. Persisting, enterococcal, or mixed enterococcal plus staphylococcal bacteremia were the only statistically significant risk factors which predicted therapy failure in cancer patients. Neither peak nor trough VAN serum levels predicted failure or cure of gram-positive bacteremia in cancer patients.

Systematic Review and Meta-Analysis of Vancomycin-Induced Nephrotoxicity Associated with Dosing Schedules That Maintain Troughs between 15 and 20 Milligrams per Liter

“…The definition of nephrotoxicity was identical (increase in serum creatinine [S CR ] of 0.5 mg/dl, equivalent to 44.2 mol/liter or 50% from baseline on 2 consecutive measurements) in all but three studies ( Table 1). Of the three dissimilar studies, one used the Acute Kidney Injury Network classification of nephrotoxicity (23), one employed the Risk-Injury-Failure-Loss-End-stage-renal disease (RIFLE) classification of nephrotoxicity (39), and one used a nonstandardized definition of nephrotoxicity (increase in S CR by 20% from baseline or Ն110 mol/liter or a decrease of creatinine clearance by Ͻ0.7 ml/s, equivalent to 42 ml/min) (31).…”

Retrospective Analysis of Vancomycin Nephrotoxicity in Elderly Chinese Patients

“…Vancomycin remains a first-line antibiotic treatment for infections caused by MRSA and is often used to treat other gram-positive infections [2]. Pharmacological studies have determined that the best parameters to predict the efficacy and safety of vancomycin activity are the minimum trough concentration and MIC [20]. Although vancomycin has been associated with nephrotoxicity, causality has not been firmly established [21], especially in patients who are more than 60 years old.…”

Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high-dose therapy

“…Studies that evaluated vancomycin by continuous infusion were excluded owing to insufficient data on its safety and efficacy for serious infections involving MRSA. Seven studies with analysis performed on the nephrotoxic potential of high-dose intermittent vancomycin therapy in adult patients have been published in the English literature [9][10][11][12][13][14][15]. Given the paucity of published literature, five studies presented in abstracts were also included [16][17][18][19][20] where relevant data were discussed, and the authors of each respective study were contacted to obtain more details about the study.…”