Adverse effects of intravenous vancomycin-based prophylaxis during therapy for pediatric acute myeloid leukemia [PublishAheadOfPrint]

Background Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infection, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk, but might increase risk of renal or liver toxicity, or Clostridium difficile infection (CDI).

Methods A retrospective review was conducted of patients treated for newly diagnosed AML at St. Jude Children's Research Hospital from 2002 to 2008. Nephrotoxicity was classified according to pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (RIFLE) criteria, and hepatotoxicity according to Common Terminology Criteria for Adverse Events criteria. The risks of nephrotoxicity, hepatotoxicity and CDI were compared between patients receiving vancomycin-based prophylaxis, no intravenous prophylaxis, or other prophylaxis. Generalized linear mixed models were used to address potential confounding.

Results 392 chemotherapy courses (108 with no intravenous prophylaxis, 218 with vancomycin-based prophylaxis, and 66 with other prophylaxis) in 111 patients were included. Development of pRIFLE risk, injury, or failure occurred in 190, 44, and 2 courses, respectively. An increase in ≥1, 2, or 3 grades for hepatotoxicity occurred in 189, 52, and 19 courses, respectively. After adjusting for confounders, vancomycin-based prophylaxis was not associated with nephrotoxicity or hepatotoxicity, and reduced the risk of CDI compared to no intravenous prophylaxis (0.9% vs. 6.5%; P= 0.007) or other prophylaxis regimens (0.9% vs. 3.0%; P= 0.23).

Summary Despite concerns about vancomycin toxicity, vancomycin-based prophylaxis in pediatric patients with AML did not increase the risk of nephrotoxicity or hepatotoxicity and reduced CDI. Caution is advised to avoid contributing to antibiotic resistance.

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