Vancomycin-Induced Severe Neutropenia in a Patient With Osteomyelitis: A Case Report

Vancomycin is a glycopeptide antibiotic with activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). We present a 52-year-old Caucasian HIV-positive male patient who initially presented to an outside hospital with altered mental status and drainage of purulence from his submental area and was started empirically on IV meropenem and IV vancomycin. He was nonadherent on antiretroviral therapy (ART) with elvitegravir/cobicistat/emtricitabine/tenofovir. His CD4 count was 1,063 cells/mm³ (64%) and undetectable viral load. A maxillofacial scan revealed findings suggestive of chronic osteomyelitis of the mandible for which surgical debridement was performed with positive cultures for methicillin-resistant Staphylococcus epidermidis (MRSE). He was transferred to our facility for further care on hospital day six. His intravenous vancomycin was continued, while IV meropenem was stopped. At our facility, his baseline serum creatinine (SCr) was reported at 0.51 mg/dL, and his white blood cell count (WBC) and absolute neutrophil count (ANC) were 9,900 cells/mm³ and 6,000 cells/µL, respectively. After 13 days of treatment, notable neutropenia and nephrotoxicity occurred. On day 14 of therapy, the WBC and ANC decreased acutely to 1,600 cells/mm³ and 900 cells/µL, respectively; the SCr increased acutely to 1.23 mg/dL; and a vancomycin trough level resulted in 34.7 mg/L. The corresponding vancomycin area under the curve (AUC) was 852 mg/L, which exceeds the recommended AUC goal range of 400-600 mg/L. The vancomycin AUC was within a goal range four days prior, and there was no evidence of nephrotoxicity or neutropenia at that time. Despite vancomycin dosage reductions and holding ART, neutropenia persisted. He was eventually switched to daptomycin, and neutropenia resolved after one week. The patient received vancomycin for 13 days before experiencing neutropenia. In this patient's case, concurrent acute kidney injury and supratherapeutic vancomycin concentrations may have contributed to neutropenia. Of note, his other medication known to cause potential neutropenia was discontinued, which included elvitegravir/cobicistat, emtricitabine, and tenofovir alafenamide. While literature demonstrates a prolonged duration of vancomycin treatment with neutropenia, his case is unique because it illustrates an association between neutropenia and vancomycin exposure. Vancomycin-induced neutropenia could be multifactorial, relating not just to duration but also to supratherapeutic vancomycin levels. This report aims to describe a unique case of vancomycin-induced neutropenia in a patient who exhibited persistent supratherapeutic drug levels in addition to a prolonged course of treatment.