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The role of the species Mycobacterium haemophilum as a pathogenic non-tuberculous microorganism is becoming better defined with the use of specific detection methods. However, epidemiological investigations of this species are still scarce. We analysed the genetic diversity of M. haemophilum by amplified fragment length polymorphism (AFLP) typing and compared isolates from different parts of the world. In total, 128 isolates, including 41 from the USA, 51 from Australia, 28 from Europe and eight from Israel were compared using AFLP methodology. Two restriction enzymes (MseI and EcoRI) and one selective primer were applied and provided a high discriminatory power. Clusters of isolates with identical AFLP patterns, which could indicate a possible common source, were observed from the Netherlands, New York and Australia. No clear clustering on the basis of continental origin was observed; however, types were restricted to geographical areas and not found on other continents. A high genetic stability within the species was demonstrated by the long-term existence of a single type.

Mycobacterium haemophilum, a recently described pathogen, can cause an array of symptoms in immunocompromised patients. To date, 90 patients with this infection have been described worldwide. We report our institution's experience with 23 patients who were treated from 1990 through 2000. Fourteen patients had undergone bone marrow transplantation, 5 were infected with human immunodeficiency virus, 3 had hematologic malignancies, and 1 had no known underlying immunosuppression. Clinical syndromes on presentation included skin lesions alone in 13 patients, arthritis or osteomyelitis in 4 patients, and lung disease in 6 patients. Although patients with skin or joint involvement had favorable outcomes, 5 of 7 patients with lung infection died. Prolonged courses of multidrug therapy are required for treatment. A diagnosis of M. haemophilum infection must be considered for any immunocompromised patient for whom acid-fast bacilli are identified in a cutaneous, synovial fluid or respiratory sample or for whom granulomas are identified in any pathological specimen.

Mycobacterium haemophilum is an emerging pathogen in immunocompromised patients. We report the clinical and histologic findings of 16 skin biopsies from 11 patients with culture-proven infections by M. haemophilum. The patients had leukemia or non-Hodgkin's lymphoma. Ten of them had undergone bone marrow transplantation. When the skin biopsy specimens were taken, a portion of the skin was simultaneously submitted to a microbiology laboratory for cultures. The remaining skin was processed routinely. Acid-fast bacilli were found in 11 of 16 lesions. The number of histologically detectable organisms was typically low: nine biopsies had fewer than three bacilli per 50 oil immersion fields. The most common histologic pattern was a mixed suppurative and granulomatous reaction (7 of 16 biopsies). Four biopsies showed well-formed epithelioid granulomas. Two showed necrosis, one of which was ulcerated. One lesion was a subcutaneous abscess. Two biopsies showed a mixed lichenoid and granulomatous dermatitis. In one of them, the granulomatous reaction was focal and small. One biopsy lacked a granulomatous tissue reaction altogether; it showed an interface dermatitis, a perivascular and periadnexal lymphocytic infiltrate, and necrotizing lymphocytic small vessel vasculitis. A subsequent biopsy from the same patient additionally showed a focal granulomatous reaction. Our observation that infections by M. haemophilum can present with nongranulomatous or pauci-granulomatous reactions without necrosis is of note. Failure to suspect mycobacterial infection in such reactions contributes to probable underreporting of M. haemophilum and to misdiagnoses. Furthermore, our findings emphasize the importance of simultaneous biopsies for culture and histology in immunocompromised patients.

We present a case of a pulmonary nodular lesion in an immunocompetent patient documented at open lung biopsy to be due to Mycobacterium haemophilum. This organism has recently been recognized as a cause of disease in immunocompromised patients, presenting predominantly as skin lesions, arthritis, and rarely pneumonia. Because this mycobacterium is fastidious and difficult to grow without the use of special media and conditions, our case raises the possibility that M. haemophilum could be an underrecognized cause of granulomatous pulmonary lesions and should be considered particularly in cases where smears for acid-fast bacteria are positive but cultures are negative.

Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.

The purpose of this study was to describe the clinical presentation, treatment, and outcome of Mycobacterium haemophilum infection in patients undergoing bone marrow transplantation at a cancer center. Bone marrow transplant recipients with M haemophilum infection were identified upon culture of the organism by implementing the organism's unique requirements for growth. This report of the patients' clinical and immunologic course is based on a retrospective chart review. Two distinctly different presentations of M haemophilum infection were observed. Three patients presented with cutaneous lesions, typical of those seen in previous reports of the infection. Two others developed pulmonary disease only. All patients received directed therapy against M haemophilum, but respiratory failure developed in the patients with pneumonia and they died. The remaining 3 patients survived and are free of infection. These are the only reported cases of M haemophilum infection in bone marrow transplant recipients. Early diagnosis obtained through biopsy and special request for culture conditions conducive to the growth of the organism may decrease morbidity and mortality, particularly in patients with pulmonary disease.

Mycobacterium haemophilum is emerging as a pathogen of immunocompromised patients particularly those with AIDS and organ transplants. Infection has also occurred in healthy children. Adults usually present with cutaneous manifestations, septic arthritis or occasionally pneumonia. Children have perihilar, cervical or submandibular adenitis. The organism grows on mycobacterial media supplemented with ferric ammonium citrate or hemin, incubated at 30 degrees C to 32 degrees C, two to three weeks after inoculation. The most active antimicrobial agents in vitro are amikacin, ciprofloxacin, clarithromycin, rifabutin and rifampin. Development of resistance to the rifamycins has been demonstrated after patients were treated for several months with several antimycobacterial agents, including the rifamycins. Treatment for several months with at least two agents demonstrated to have low MICs for the organism has been shown to be effective.

Mycobacterium haemophilum is an emerging opportunistic pathogen, and since 1989, infections caused by this organism have been identified more frequently in the New York City area than in any other region of the United States. A DNA fingerprinting method, based on restriction fragment length polymorphisms (RFLPs) was developed. A genomic library of M. haemophilum isolate 1A was constructed; screening the library yielded a recombinant strain that incorporated a genetic element present in multiple copies in the M. haemophilum genome. This clone was used to produce a probe for RFLP analyses of PvuII digests of genomic DNA. We used this probe to determine the RFLP patterns of 43 clinical isolates of M. haemophilum from 28 patients. A total of six distinct patterns were observed. Two patterns, designated types 1 and 2, accounted for 91% of the infections in patients from the New York City area. Two isolates from Arizona had identical patterns but were distinct from those of New York isolates, and an isolate from Israel, the type strain, had another distinct pattern (type 6). The type 6 pattern was also seen in a recent isolate from Norway. All of the type 1 isolates and 60% of the type 2 isolates were recovered from patients with AIDS in the New York City area. This molecular subtyping method should provide a useful tool for epidemiological studies and may help identify the associated risk factors, vehicles, and possible reservoirs of this newly emerging pathogen.