FINAL DIAGNOSIS: - Invasive Mycobacterium Haemophilum
Biological testing strongly suggests the diagnosis of infection with Mycobacterium Haemophilum. Ribosomal DNA sequencing from dual databanks confirms this typing as designated in the figures below.
Following his initial surgery the patient was started on an empiric antibiotic regimen of clarithromycin and moxifloxacin. One month later the patient was admitted for a second debridement of his hand wound. At a subsequent office visit he admitted a recent 20 lb weight loss. Blood testing revealed near lymphocytopenia with a CD4 count of 212 x109/L. At that time the patient refused an HIV test citing a recent negative test at an outside hospital. Two weeks later infectious disease supplemented his antibiotic therapy with rifampin and doxycycline. He continues to be followed by infectious disease.
Mycobacterium haemophilum is a fastidious, slow growing, non-tuberculous member of the family Mycobacteriaceae. Like nearly all mycobacterium, M. haemophilum are small, aerobic, non-motile, slightly curved bacilli. They do not absorb crystal violet due to their characteristic cell wall but are instead acid fast and stain by way of the Ziehl-Neelsen, Fite, and Kinyoun methods. M. haemophilum was first described in 1978 causing cutaneous lesions in a patient with Hodgkin's disease (1). Infection with M. Haemophilum most often results in solitary or multiple tender cutaneous lesions clustered on the extremities and, frequently overlying joints. M. Haemophilum grows optimally at the relatively lower temperatures found in such locations (2). Septic arthritis and tenosynovitis should also be considered in unexplained monoarticular or oligoarticular arthralgias in the appropriate patient populations. Skin biopsy or arthrocentesis may reveal acid fast bacilli in such cases. Culture and identification is required, however, to distinguish M. Haemophilum from M. Tuberculosis, M. Leprae, M. Marinum, M. Fortuitum, M. Ulcerans, and M. Avium complex which are all capable of producing a somewhat similar clinical picture (3).
M. Haemophilum is classified as a slow grower and can take 2-3 weeks or longer to form visible colonies on supplemented media. Optimal growth occurs at 30-32ºC with CO2, similar to M. Marinum, and M. Ulcerans (7). Supplementation of growth media requires ferric iron compounds for growth such as the hemin found in chocolate agar, or an X-factor strip (8). It is inactive for many of the common tests used to distinguish mycobacterial species. However, nicotinamindase and pyrazimindase tests are positive.
Infections with M. Haemophilum have rarely been reported in the United States, Canada, Australia and Europe (3). Most members of the Mycobacteriaceae family are found environmentally in the soil and aquatic habitats but M. Haemophilum has never been isolated from a non-human source (4,5). Several studies have examined its prevalence in urban locations and patient populations. Generally, M. Haemophilum has proven exceedingly difficult to locate and isolate. This is mostly due to its slow growth, and fastidious nature. Such growth occurs most often in patients who are immunosuppressed with depressed CD4 lymphocyte counts. This population includes patients with AIDS, transplant recipients, dialysis users, and lymphoma patients. M. Haemophilum infection has also been reported in immunocompetent children with lymphadenitis (6). M. Haemophilum's mode of transmission and incidence are essentially unknown, though new DNA based techniques of identification are providing new information in this regard.
Little is known of the susceptibility of M. Haemophilum. No standardized methods currently exist for determining bacterial resistance. This makes recommendations for empiric therapy difficult. Several studies suggest the in-vitro effectiveness of rifampin, rifabutin, amikacin, ciprofloxacin, and clarithromycin (9,10,11). Doxycycline and sulfonamides have demonstrated mixed utility (10,11). Ethambutol and pyrazinamide, however, has been shown to universally ineffective (10,11). Nevertheless, antibiotic treatment, even in immunosuppressed patients, has been successful in many cases with multiple drug regimens consisting of the aforementioned agents. In cases of immunocompetent patients, surgical resection can be sufficient without antibiotic therapy.
Contributed by Chris Gilbert, MD, William Pasculle, ScD, and Karin Byers, MD