Disseminated Mycobacterium chimaera Presenting as Vertebral Osteomyelitis

Mycobacterium chimaera, a member of the Mycobacterium avium complex, is a slow-growing, nontuberculous mycobacterium associated with outbreaks in cardiac-surgery patients supported on heart-lung machines. We report a case of an elderly woman on chronic prednisone who presented with a six-month history of worsening chronic back pain, recurrent low-grade fevers, and weight loss. Imaging identified multilevel vertebral osteomyelitis and lumbar soft-tissue abscess. Abscess culture identified M. chimaera.

Prior reports show that, despite antibiotic and surgical treatment, disseminated M. chimaera has a high mortality rate. Even with antibiotic therapy targeted to in vitro sensitivities, medical therapy often fails to result in clearance. The identification of M. chimaera may be missed in the absence of molecular sequencing diagnostics. While this case represents a description of proven M. chimaera osteomyelitis, it is likely that other cases have occurred and been attributed to other MAC species.

Case
A 75-year-old woman with systemic lupus erythematosus was evaluated for two months of chronic, low back pain. She also reported subjective fevers, weight loss, and an initially necrotic, one-centimeter wound on her right calf that developed five months earlier. She had no history of trauma, paraspinal steroid injections, or past cardiac or spine surgery. Medications are significant for prednisone and hydroxychloroquine.
On exam she was afebrile, with normal vitals, mild lumbar tenderness, normal strength, and intact reflexes in the lower extremities and without saddle anesthesia.
MRI with and without contrast of the thoracic and lumbar spine revealed multilevel discitis and prevertebral osteomyelitis at L1-2, L2-3, and L5-S1 ( Figure 1). An abscess located in L5-S1 (Figure 1(a), white arrow) was aspirated. Culture of the abscess revealed polymorphonuclear cells without organisms on conventional and acid-fast bacilli staining. Bacterial and fungal microscopy of the abscess and blood cultures were obtained. Cryptococcal PCR, Coccidioides antibody, and Mycobacterium tuberculosis polymerase chain reaction were negative.
The patient was started on empiric intravenous vancomycin and ertapenem. On day 12, M. chimaera was identified in the abscess aspirate by culture and sequencing. She was then transitioned to clarithromycin, rifampin, and STIR showing high signal consistent with fluid in the L1-2, L2-3, and L5-S1 disc spaces with endplate edema (white arrows). (b) Sagittal T1 fat saturation obtained after contrast shows extensive enhancement centered around the L1-3 and L5-S1 disc spaces consistent with discitis and osteomyelitis (dashed arrows). ethambutol. A new biopsy of the calf wound was positive for M. chimaera. Surgical discectomy, debridement, and fusion were recommended; however, she deferred surgery and was discharged with a prolonged course of antimycobacterials.

Discussion
Disseminated infection with M. chimaera has been previously described following cardiac surgery (range of 5 to 40 months to diagnosis after surgery) as vascular graft infection, prosthetic valve endocarditis, or myocarditis [2,3]. Outbreaks of M. chimaera in patients supported by heart-lung machines have prompted recent investigations identifying water tanks supporting heater-cooler systems as the likely source of infection in these outbreaks [6,7]. M. chimaera can also cause pulmonary infection, similar to M. avium and M. intracellulare [8][9][10][11]. Initial reports suggested that M. chimaera is more virulent than the other MAC species [1]. This has since been called into question by a larger case series in which M. chimaera was more likely to be a colonizer of the respiratory tract and less likely to cause true infection, compared to the other MAC species [11]. In this series, patients with true respiratory infection due to M. chimaera were more likely to be immunosuppressed (53%), suggesting a more opportunistic pattern of infection [11].
Similar to other MAC species, M. chimaera is typically treated with a prolonged course of clarithromycin, ethambutol, and rifampin. Vertebral osteomyelitis caused by MAC or other NTM often requires surgery, due to either neurologic deficits, spinal instability, or failure of medical treatment [12].
Identification of M. chimaera requires sequencing; therefore, nonsequencing methods may fail to identify the correct Mycobacterium species [3,11,13]. A study that retrospectively sequenced samples from patients with diagnosed MAC found that 28% of infections were due to M. chimaera, while 54% and 18% of previously diagnosed MAC infections were due to M. avium and M. intracellulare, respectively [11]. In another retrospective study of patients with prior diagnosis of M. intracellulare, sequencing determined that 143 of the 166 samples attributed to M. intracellulare infection could be reclassified as M. chimaera [13]. Similar to other MAC infections, M. chimaera often presents with fever of unknown origin and weight loss.
The patient in this case presented with a history of chronic nonhealing leg wound months prior to the clinical signs of her vertebral osteomyelitis. Given that the leg wound later grew acid-fast bacilli identified as M. chimaera, her ulcer was likely the first manifestation of the disease, months before diagnosis of spinal involvement. This emphasizes the importance of considering slow-growing NTM species in the evaluation of nonhealing wounds in patients on immunecompromising medications, since conventional pathology and bacterial cultures will fail to make the diagnosis. Unlike many prior descriptions of patients with M. chimaera, our patient did not have a history of recent surgery or heart-lung bypass. Her chronic immunosuppression with prednisone and hydroxychloroquine was a likely predisposing factor to this infection. She had an elevated CRP and anemia similar to other reports, but she did not have pancytopenia or liver and kidney involvement, as described in other patients with disseminated disease after heart surgery [2][3][4]. To our knowledge, this is the first report in the literature of M. chimaera causing vertebral osteomyelitis in a patient without history of cardiac surgery.

Disclosure
All authors had access to data and had a role in writing this manuscript.

Conflicts of Interest
The authors declare no conflicts of interest.