Epidemiologic Notes and Reports Mycobacterium haemophilum Infections -- New York City Metropolitan Area, 1990 - 1991

During September 1990-March 1991, clinicians at a New York City (NYC) hospital diagnosed Mycobacterium haemophilum infections in four patients. Two cases occurred in persons with acquired immunodeficiency syndrome (AIDS), and two occurred in persons who had received bone marrow transplants and were on therapy to prevent a graft-versus-host reaction. In April 1991, three additional M. haemophilum infections in persons with AIDS were identified in the NYC area. Because M. haemophilum infection rarely has been recognized, intensive case finding was initiated in NYC as a result of these reports.

Cases were identified by review of hospital microbiology laboratory records and by reports from infectious disease and laboratory specialists. From April 24 through September 1, 13 persons with M. haemophilum infection were identified at seven hospitals in the NYC area. All 13 mycobacterial isolates were confirmed at CDC as M. haemophilum by routine biochemical tests and tests for typical mycolic acid patterns by high-performance liquid chromatography (HPLC).

Among these 13 patients, the earliest onset of symptoms occurred in August 1989. M. haemophilum was diagnosed in four persons in 1990 and in nine persons in 1991. Nine (69%) patients were male; 12 were white and one was black, including one Hispanic. The mean age of patients at the time of diagnosis was 34 years (range: 27-51 years). Eleven patients had AIDS; the other two patients were the bone marrow transplant recipients. For patients with AIDS, the mean duration of AIDS at the time of M. haemophilum illness was 15.9 months (range: 0-43.4 months).

Initial signs and symptoms included multiple cutaneous ulcerating lesions, which were most frequently found on the extremities, often overlying joints (11 patients); upper respiratory complaints (three); and joint effusions (two). M. haemophilum was isolated from cutaneous lesions (11 patients), bone (five), sputum (four), synovial fluid (two), blood (one), and lung biopsy tissue (one). For seven patients, M. haemophilum was isolated from multiple sites. By September 1, two of the 13 patients had died; for one of the two, pulmonary disease with cavitary lesions from M. haemophilum was the cause of death.

Among the NYC cases, M. haemophilum was first isolated using growth conditions for fungi. Some clinical specimens were tested specifically for M. haemophilum. For other specimens, testing was done only after bacilli were observed on acid-fast smears but growth was not detected by standard mycobacterial culture procedures. Media used to grow the organism included Middlebrook 7H10 agar with hemin supplied by an x-factor strip, brain-heart infusion broth with 5% sheep blood, chocolate agar, and Middlebrook 7H10 agar supplemented with hemoglobin.

The mean time from initiation of laboratory evaluation to final diagnosis of M. haemophilum infection was 124 days (range: 14-495 days). Once identified, treatment regimens varied but included combinations of isoniazid, rifampin, ethambutol, minocycline, doxycycline, clarithromycin, ciprofloxacin hydrochloride, amikacin sulfate, clofazimine, streptomycin, and pyrazinamide. Drug susceptibility for nine of the M. haemophilum isolates varied from 0 to 100% (Table 1). Reported by: D Armstrong, MD, T Kiehn, PhD, N Boone, M White, MD, K Pursell, MD, Memorial-Sloan Kettering Cancer Center, S Lewin, MD, EM Sordillo, MD, N Schneider, MH Grieco, MD, St. Luke's/Roosevelt Hospital, V LaBombardi, PhD, R Yarish, MD, St. Vincent's Hospital, D Larone, PhD, M Tapper, MD, Lenox Hill Hospital, KR Ong, MD, Commission on Disease Intervention, New York City Dept of Health; DL Morse, MD, State Epidemiologist, New York State Dept of Health. J Kocher, MD, Englewood Hospital, Englewood; KC Spitalny, MD, State Epidemiologist, New Jersey State Dept of Health. Respiratory Diseases Br, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: M. haemophilum was first described as a human pathogen in 1978 (1). Through 1989, only 18 cases of infection with this organism have been reported: seven of these patients were from the United States (2-6), and 11 were from Australia, Canada, and France. Since 1989, in addition to the New York specimens, CDC has identified 10 isolates of M. haemophilum from eight patients. These patients were from Connecticut, Florida, Georgia, Pennsylvania, Texas, and Virginia.

Previous reports of infections with M. haemophilum have most commonly described cutaneous lesions in persons on immunosuppressive therapy following renal transplantation (7,8). In addition, infections in persons with AIDS (3,4) and cases of cervical lymphadenitis in immunocompetent children have been reported (6). Much remains unknown about the organism, including its reservoir, its mode of transmission, and the spectrum of human disease associated with infection.

The incidence of M. haemophilum infection is also unknown; the relative rarity of the organism's isolation from clinical specimens may be because of its specific growth requirements. M. haemophilum will grow on egg- or agar-based media only if supplemented with 0.4% hemoglobin, 60 uM hemin, or 15 mg/mL ferric ammonium citrate (9). The temperature growth range is 25-35 C, but the optimum incubation temperature is reported to be 32 C (10). Because of these growth requirements, the organism would not be isolated using routine culture techniques for other mycobacteria such as M. tuberculosis. The cases in the NYC area and the eight other cases with isolates submitted to CDC suggest that infections with M. haemophilum may occur more commonly than is recognized or that they are increasing in incidence.

Because the number of immunocompromised persons is increasing, the incidence of M. haemophilum infections is likely to increase. Clinicians should consider this pathogen in any immunocompromised patient who has cutaneous ulcerating lesions, joint effusions, or osteomyelitis. Lesions can be screened for mycobacteria using an acid-fast stain. If acid-fast bacilli are seen, M. haemophilum should be considered. Appropriate media and incubation conditions include Lowenstein-Jensen medium with ferric ammonium citrate (9) or Middlebrook 7H10 agar with an x-factor strip (11). Specimens should be incubated for at least 6 weeks at 32 C. Definitive identification of cultured isolates can be made through biochemical profiles and mycolic acid patterns shown by HPLC.

Optimal strategies to treat M. haemophilum infections are unclear because the small number of reported cases has not permitted comparisons of therapeutic modalities. For the same reason, characteristic drug-susceptibility patterns have not been defined. In addition, the relation between in vitro drug susceptibilities and clinical response is not known for this organism. These issues may be resolved as additional cases are identified through enhanced clinical awareness and appropriate testing.

References

1. Sompolinsky D, Lagziel A, Naveh D, Yankilevitz T. Mycobacterium haemophilum sp. nov., a new pathogen of humans. Int J Syst Bacteriol 1978;28:67-75.

2. Davis BR, Brumbach J, Sanders WJ, Wolinsky E. Skin lesions caused by Mycobacterium haemophilum. Ann Intern Med 1982;97:723-4.

3. Males BM, West TE, Bartholomew WR. Mycobacterium haemophilum infection in a patient with acquired immune deficiency syndrome. J Clin Microbiol 1987;25:186-90.

4. Rogers PL, Walker RE, Lane HC, et al. Disseminated Mycobacterium haemophilum infection in two patients with the acquired immunodeficiency syndrome. Am J Med 1988;84:640-2.

5. McBride ME, Rudolph AH, Tschen JA, et al. Diagnostic and therapeutic considerations for cutaneous Mycobacterium haemophilum infections. Arch Dermatol 1991;127:276-7.

6. Saubolle MA, Rudinsky M, Merritt ES, Williams J, Raines JM, Dimler M. Mycobacterium haemophilum infection in two otherwise normal pediatric patients (Abstract). In: Program and abstracts of the 91st annual meeting of the American Society for Microbiology. Washington, DC: American Society for Microbiology, 1991:391.

7. Mezo A, Jennis F, McCarthy SW, Dawson DJ. Unusual mycobacteria in 5 cases of opportunistic infections. Pathology 1979;11:377-84.

8. Gouby A, Branger B, Oules R, Ramuz M. Two cases of Mycobacterium haemophilum infection in a renal-dialysis unit. J Med Microbiol 1988;25:299-300.

9. Dawson DJ, Jennis F. Mycobacteria with a growth requirement for ferric ammonium citrate, identified as Mycobacterium haemophilum. J Clin Microbiol 1980;11:190-2.

10. Wayne LG, Kubica GP. Genus Mycobacterium. In: Sneath PHA, Mair NS, Sharpe ME, Holt JG, eds. Bergey's manual of systematic bacteriology. Baltimore: Williams & Wilkins, 1986:1436-57.

11. Vadney FS, Hawkins JE. Evaluation of a simple method for growing Mycobacterium haemophilum. J Clin Microbiol 1985;22:884-5.

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