Case Presentation: A 28-year-old female from Mexico with AIDS and prior Mycobacterium bovis (M. bovis) infection treated with rifampin, isoniazid, ethambutol (RIE), complicated by lumbar osteomyelitis due to suspected medication non-adherence, presented with acute onset headache and photophobia. On admission, CD4 T-cell count was 28/μL and HIV viral load was 75,200 copies/mL. Cerebral spinal fluid (CSF) showed neutrophilic pleocytosis, prompting initiation of RIE, vancomycin, cefepime and dexamethasone, later followed by antiretroviral therapy. Despite treatment, CSF analysis 1 week later showed persistent neutrophilic pleocytosis; therefore, Rifampin dosage was increased. MRI lumbar spine showed improvement of prior spinal lesions. Fevers and headache returned with worsening neutrophilic pleocytosis on day 15, with CSF studies now positive for MTB with Rifampin resistance. Meropenem, cycloserine, and levofloxacin were added with improvement in neutrophilic pleocytosis on day 21. Rifampin was eventually stopped and pt was transitioned to Bedaquilline, linezolid, moxifloxacin, and isoniazid.
Discussion: Human tuberculosis (TB) caused by M. bovis accounts for 1-2% of annual TB cases in the United States (1). A high prevalence of M. bovis has been reported in San Diego, accounting for 5.4% of all TB cases in California in 2011 (2-3). Risk factors include Hispanic ethnicity, extrapulmonary disease, and immunosuppressed status (3). M. bovis has increased propensity for extrapulmonary manifestations, frequently the central nervous system. This case highlights the challenges of drug-resistant M. bovis meningitis, specifically in diagnosing M. bovis relapse due to nonadherence, microbiologic resistance, and being an immune reconstitution inflammatory syndrome (IRIS) mimicker. Neutrophilic pleocytosis can occur in early phases but typically converts to lymphocyte pleocytosis within 7 days (4–6). In our patient, neutrophil predominance persisted over 2 weeks, which was suggestive of IRIS (7). The improvement of her spinal lesions and symptoms following RIE and steroids, with negative microbiological studies early on supported IRIS rather than resistant mycobacterium as well. While we did not check CSF inflammatory markers, calprotectin was found to be significantly higher in TB meningitis (TBM) with IRIS than TBM without IRIS (7). If calprotectin was low in our patient, it may have prompted us to broaden antibiotics to cover resistant M. bovis sooner, however that change was not made until after testing was positive for rifampin resistance on day 17.
Conclusions: This case reflects the diagnostic challenges of drug-resistant mycobacterial infection, when microbiologic data reporting is delayed. The presentation of persistent neutrophilic pleocytosis and patient’s immunocompromised status with risk for IRIS further complicated the diagnosis. Given the higher prevalence of M. bovis in Southern California and management of CNS infection in the inpatient setting, hospitalists should be aware of the atypical presentations of M. bovis. Given the high fatality rate and neurological complications if not treated, hospitalists should consider having a lower threshold to broaden treatment for resistant mycobacterium in the setting of persistent neutrophilic pleocytosis and prolonged non-response to current treatment. Further studies in imaging and CSF analysis could be utilized to help with the diagnostic challenges of drug-resistant M. bovis when microbiological data is unavailable.
