Case Presentation: A 38 year old Hispanic male was admitted to the hospital with a four day history of fever, headache, shortness of breath and intermittent left forearm and abdominal rash. All signs and symptoms appeared during the administration of vancomycin and ceased after a few hours of finishing the infusion. His history was significant for non healing crush injury of the left foot, later complicated by osteomyelitis. Empiric treatment with intravenous vancomycin and cefepime was started three weeks before. His physical exam was remarkable for fever of 38.3 degree Celsius. Cardiac, respiratory and abdominal exam were unremarkable. No distinct rash could be appreciated at the time of admission. No redness was noticed around the peripherally inserted central catheter (PICC). Last dose of vancomycin was administered six hours before admission. Basic laboratory data showed a white blood cell count of 0.6 x 103 cells/mm3 and neutropenia with an absolute neutrophil count of 0.0 x 103 cells/mm3. Normal hemoglobin: 15.7 g/dl and normal platelet count: 168 103/ul. Complete metabolic panel, blood cultures, chest radiograph and electrocardiogram were unremarkable. Vancomycin trough level was 17. Our main differential diagnosis included vancomycin induced febrile neutropenia. However, cefepime was also considered as a confounding medication and both antibiotics were discontinued. No more fevers were recorded and the patient reported feeling better within 24 hours of drug cessation. ANC improved to 759/mm3 in the next thirty-six hours. In order to continue treatment of osteomyelitis, patient was started on levofloxacin and daptomycin, with good tolerance. ANC increased to 4725/mm3 and the patient was discharged home to continue antibiotic treatment.
Discussion: Vancomycin induced neutropenia is an uncommon but serious adverse reaction associated with increased risk of infections. When it presents with fever, it creates a dilemma regarding persistent or superimposed infection versus drug reaction. The exact mechanism of action is unknown. A direct toxic effect on bone marrow and an immune-mediated reaction have been postulated, supported by bone marrow studies showing maturation arrest and granulocyte specific antibodies respectively.
Conclusions: Based on systematic reviews, vancomycin induced neutropenia is not associated with total dosing or through levels. The onset of neutropenia is most likely related to prolonged exposure, occurring at least twenty days after initiation of treatment. Rapid discontinuation of the offending drug should be considered when patients present with acute onset of febrile neutropenia during prolonged treatment with vancomycin. Based on the Naranjo probability scale, the association of vancomycin with neutropenia in our case was categorized as probable. Cefepime was considered as a potential contributing drug, and as such discontinued.No current guidelines exist describing the frequency and appropriate laboratory studies that should be obtained with prolonged vancomycin treatment.