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MYCOBACTERIUM SPP.

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Mycobacterium spp. - excluding M. tuberculosis, and members of the Mycobacterium tuberculosis complex (M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, “Mycobacterium canettii”)

SYNONYM OR CROSS REFERENCE: Atypical mycobacteria, non-tuberculous mycobacteria (NTM), mycobacteria other than tubercle bacilli (MOTT) (1-3). There are well over 100 species of Mycobacteria but most common species include: M. avium Complex (MAC), M. kansasii, M. haemophilum, M. xenopi, M. malmoense, M. asiaticum, M. simiae, M. szulgai, M. marinum, M. ulcerans, M. genavense (slow growers); M. fortuitum, M. chelonae, M. abscessus (rapid growers) (4).

CHARACTERISTICS: The Mycobacterium genus belongs to the family Mycobacteriaceae and consists of many species, some of which are pathogenic to humans (3). They are aerobic, non-spore forming, non-motile, slightly curved or straight rods (0.2 to 0.6 μm by 1.0 to 10 μm) which may branch. They can grow on simple substrates such as amino acids and glycerol (3). Different species have different temperatures of growth with a range of <30-45 °C (3). They can either grow slowly (require 7 days for growth) or rapidly (requiring less than 7 days for growth) when subcultured on Löwenstein-Jensen media (3). They belong to two groups: slow growers (further divided into photochromogens, scotochromogens, nonphotochromogens), and rapid growers (4, 5).

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Non-tuberculous mycobacteria (NTM) infections occur mainly in immunosuppressed individuals, although immunocompetent patients can also be affected (4, 6). Non tuberculous mycobacteria cause many different diseases in humans:

Pulmonary disease: Pulmonary diseases are caused mainly by M. kansasii, MAC, and rarely by M. malmoense, M. xenopi, M. asiaticum, M. simiae and M. szulgai (1). Pulmonary disease may show different clinical patterns: tuberculosis like infiltrates, nodular bronchiectasis, solitary nodules, and diffuse infiltrates (3, 6).

Lymphadenitis: caused mainly by MAC, M. scrofulaceum, M. haemophilum, M. fortuitum, M. kansasii (1).

Cutaneous and soft tissue infections (skin ulcers): Cutaneous or skin infections may be associated with M. marinum, M. ulcerans, M. fortuitum, and M. chelonei (1). M. marinum can cause cutaneous infection on exposure of broken skin to contaminated freshwater fish tanks (7). The disease is characterized by a formation of a single papulonodular lesion confined to one extremity, which with time may become ulcerative (7). M. ulcerans causes cutaneous skin ulcers which may vary from a localized nodule to widespread ulcerative or non-ulcerative disease including osteomyelitis (3).

Other infections associated with NTM include enteritis, musculoskeletal disease, bursitis, CNS disease, corneal infections, and otitis media (3, 4). Disseminated infection and bacteremia may also occur (6). Disseminated infection occurs mainly in immunosuppresed individuals, and may involve liver, spleen, bone marrow (6). Patients with disseminated infection present with nonspecific symptoms such as fever, malaise, weight loss, anorexia, abdominal pain and night sweats (6).

EPIDEMIOLOGY: Worldwide. Altered local or systemic immunity (such as HIV infection) is the greatest risk factor for acquiring NTM infections (2). In British Columbia, Canada from 1996-2006, incidence of all isolated NTM ranged from 3.4-9.1/100,000, M. avium Complex (MAC) accounted for 2.6–6.7 and non-MAC accounted for < 0.7 of the total sample (including both NTM and M. tuberculosis isolates) (8). A similar study conducted in 2000-2003 in New York city, USA, reported the estimated incidence of NTM positive cultures (without HIV infection) and diseases (caused due to NTM infection) to be 17.7, 2.7, and 2.0 per 100,000 persons, respectively (9). A 2008 study reported that isolation prevalence of all NTM species in Ontario, Canada, increased from 9.1/100 000 in 1997 to 14.1/100 000 by 2003 (10).

HOST RANGE: Humans, domestic and wild animals (3).

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Nosocomial, direct contact with a contaminated environment (3).

INCUBATION PERIOD: Infection with M. marinum has an incubation period of about 2-3 weeks (11).

COMMUNICABILITY: No evidence of person-to-person transmission of the infection.

SECTION III - DISSEMINATION

RESERVOIR: Ubiquitous in nature - soil, water, humans, domestic, and wild animals (3).

ZOONOSIS: Yes for some species: M. marinum from pet fish, M. avium complex from swine, and from other domestic and wild animals (3, 7).

VECTOR: None.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY/RESISTANCE: Combinational drug therapy is used as different species are susceptible and resistant to different drugs (6). Drug susceptibility tests are performed on isolated organisms to guide proper therapy (6). M. kansasii is susceptible to first line tuberculosis drugs (rifampin, isoniazid, pyrazinamide and ethambutol).

DRUG RESISTANCE: M. marinum is resistant to pyrazinamide (11), and MAC organisms, unlike M. kansasii, are resistant to first line tuberculosis drugs (6).

SUSCEPTIBILITY TO DISINFECTANTS: Mycobacteria are more resistant to disinfectants than vegetative bacteria (12, 13). Atypical mycobacteria are generally susceptible to sodium hydroxide, chlorine dioxide, ethylene oxide, 0.35% peracetic acid, and orthophthalaldehyde (2, 13-15). 70% ethanol can be used for surface disinfection (13). Some atypical mycobacteria such as M. marinum, M. smegmatis, and M. fortuitum are highly susceptible to 2% alkaline glutaraldehyde, whereas others such as M. gordonae, M. avium complex, M. xenopi, M. chelonae are resistant to it (13, 16, 17).

PHYSICAL INACTIVATION: Mycobacteria are easily inactivated by heat (> 65 °C for at least 30 min) and by UV light but not by freezing or desiccation (3).

SURVIVAL OUTSIDE HOST: Mycobacteria are able to survive for weeks to months on inanimate objects if protected from sunlight (3). NTM species are widely distributed in nature and have been found in natural water, tap water, soil, water used in showers and surgical solutions (2).

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Diagnosis of NTM infection can be done via culture of clinical specimens and identification using phenotypic characteristics (growth rate, colony pigmentation and biochemical tests); histopathological examination to demonstrate the presence of granuloma in aspirates or biopsies; serotyping methods; isoenzyme and protein electropherogram based methods; and PCR, DNA fingerprinting and identification using gene probes (2).

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: A combination of several antibiotics over long periods of time is recommended for treatment of NTM infections (6). The most important antibiotics used in antimycobacterial therapy include: rifampin, isoniazid, ethambutol, macrolides (clarithromycin, azithromycin), quinolones (ciprofloxacin, moxifloxacin, gatifloxacin), aminoglycosides (streptomycin, amikacin) and linezolid (6). Surgery may be useful in removing debridement in soft tissue diseases caused by NTM species, and in managing cervical lymphadenitis (2, 6). Surgery can also be used along with antibiotic therapy to reduce the bacterial load and to cure life threatening symptoms such as hemoptysis (6).

IMMUNIZATION: None.

PROPHYLAXIS: The public health service of USA has recommended the use of rifabutin for preventing and delaying the onset of bacteremia caused by M. avium complex infection in HIV infected patients (2, 18).

SECTION VI - LABORATORY HAZARD

LABORATORY-ACQUIRED INFECTIONS: 40 cases of non pulmonary tuberculosis due to laboratory or autopsy room accidents have been reported. These infections may have been caused by Mycobacterium spp. other than M. tuberculosis/bovis (1). A case has been described of an infection in a male research laboratory worker who accidentally inoculated his thumb with a viable suspension of M. marinum (19).

SOURCE/SPECIMENS: NTM can be isolated from sputa, exudates from lesions, tissues, environmental samples (soil, water), and from wounds (1). MAC has also been isolated from blood, and stool specimens of infected individuals (3).

PRIMARY HAZARDS: Direct contact of skin or mucous membranes with the infectious material, accidental parenteral inoculation of the bacteria, and ingestion of the bacteria (1).

SPECIAL HAZARDS: Exposure to infectious aerosols generated during manipulation of broth cultures or tissue homogenates may cause pulmonary disease in laboratory personnel (1).

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk group 2 (20). Note that this risk group applies to Mycobacterium spp. excluding M. tuberculosis, and members of the Mycobacterium tuberculosis complex (M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, Mycobacterium canettii) as a whole, and may not apply to every species within the genus.

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures. Note that these containment requirements apply to Mycobacterium spp. (excluding M. tuberculosis, and members of the Mycobacterium tuberculosis complex (M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, M. canettii) as a whole, and may not apply to every species within the genus.

PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes (21).

OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities (21).

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (21).

DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism before disposing by autoclave, chemical disinfection, gamma irradiation, or incineration.

STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labelled.

SECTION IX - REGULATORY AND OTHER INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: September 2011

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada

Although the information, opinions and recommendations contained in this Pathogen Safety Data sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©

Public Health Agency of Canada, 2011

Canada

REFERENCES:

  1. Agent Summary Statements:Bacterial Agents. (1999). In J. Y. Richmond, & R. W. Mckinney (Eds.), Biosafety in Microbiological and Biomedical Laboratories (BMBL) (4th ed., pp. 88-117). Washington, D.C.: Centres for Disease Control and Prevention.

  2. Katoch, V. M. (2004). Infections due to non-tuberculous mycobacteria (NTM). Indian Journal of Medical Research, 120(4), 290-304.

  3. Pfyffer, G. E. (2007). Mycobacterium: General Characteristics, Laboratory Detection, and Staining Procedures. In P. R. Murray (Ed.), Manual of Clinical Microbiology (9th ed., pp. 543-572). Washington D.C.: ASM Press.

  4. Brown-Elliot, B. A., & Wallace, R. J. (2007). Mycobacterium: Clinical and Laboratory Characteristics of Rapidly Growing Mycobacteria. In P. R. Murray (Ed.), Manual of Clinical Microbiology (9th ed., pp. 589-600). Washington, D.C.: ASM Press.

  5. Vincet, V., & Gutiérrez, M. C. (2007). Mycobacterium: Laboratory Characteristics of Slowly Growing Mycobacteria. In P. R. Murray (Ed.), Manual of Clinical Microbiology (9th ed., pp. 573-588). Washington, D.C.: ASM Press.

  6. Esteban, J., & Ortiz-Perez, A. (2009). Current treatment of atypical mycobacteriosis. Expert Opinion on Pharmacotherapy, 10(17), 2787-2799.

  7. Lewis, F. M. ., Marsh, B. ., & von Reyn, C. . (2003). Fish Tank Exposure and Cutaneous Infections Due to Mycobacterium marinum: Tuberculin Skin Testing, Treatment, and Prevention. Clinical Infectious Diseases, 37(3), 390-397. Retrieved from http://dx.doi.org/10.1086/376628

  8. Hernandez-Garduno, E., Rodrigues, M., & Elwood, R. K. (2009). The incidence of pulmonary non-tuberculous mycobacteria in British Columbia, Canada. International Journal of Tuberculosis & Lung Disease, 13(9), 1086-1093.

  9. Bodle, E. E., Cunningham, J. A., Della-Latta, P., Schluger, N. W., & Saiman, L. (2008). Epidemiology of nontuberculous mycobacteria in patients without HIV infection, New York City. Emerging Infectious Diseases, 14(3), 390-396.

  10. Marras, T. K., Chedore, P., Ying, A. M., & Jamieson, F. (2007). Isolation prevalence of pulmonary non-tuberculous mycobacteria in Ontario, 1997–2003. Thorax, 62(8), 661-666.

  11. Krauss, H., Schiefer, H. G., Weber, A., Slenczka, W., Appel, M., von Graevenitz, A., Enders, B., Zahner, H., & Isenberg, H. D. (2003). Bacterial Zoonoses. In H. Krauss, H. G. Schiefer, A. Weber, W. Slenczka, M. Appel, A. von Graevenitz, B. Enders, H. Zahner & H. D. Isenberg (Eds.), Zoonoses: Infectious Diseases Transmissible from Animals to Humans (Third ed., pp. 216-217). Washington, D.C.: ASM Press.

  12. Best, M., Sattar, S. A., Springthorpe, V. S., & Kennedy, M. E. (1990). Efficacies of selected disinfectants against Mycobacterium tuberculosis. Journal of Clinical Microbiology, 28(10), 2234-2239.

  13. Lauzardo, M. and Rubin, J. (1996). Mycobacterial Disinfection. In S. S. Block (Ed.), Disinfection, Sterilization, and Preservation (5th ed., pp. 513-528). Philadelphia P.A.: Lipincott Williams and Wilkins.

  14. Griffiths, P. A., Babb, J. R., & Fraise, A. P. (1999). Mycobactericidal activity of selected disinfectants using a quantitative suspension test. Journal of Hospital Infection, 41(2), 111-121.

  15. Walsh, S. E., Maillard, J. Y., Russell, A. D., & Hann, A. C. (2001). Possible mechanisms for the relative efficacies of ortho-phthalaldehyde and glutaraldehyde against glutaraldehyde-resistant Mycobacterium chelonae. Journal of Applied Microbiology, 91(1), 80-92.

  16. Dauendorffer, J. N., Laurain, C., Weber, M., & Dailloux, M. (2000). Evaluation of the bactericidal efficiency of a 2% alkaline glutaraldehyde solution on Mycobacterium xenopi. Journal of Hospital Infection, 46(1), 73-76.

  17. Collins, F. M. (1986). Bactericidal activity of alkaline glutaraldehyde solution against a number of atypical mycobacterial species. Journal of Applied Bacteriology, 61(3), 247-251.

  18. Gordin, F., & Masur, H. (1994). Prophylaxis of Mycobacterium avium complex bacteremia in patients with AIDS. Clinical Infectious Diseases, 18(Suppl 3), S223-6.

  19. Chappler, R. R., Hoke, A. W., & Borchardt, K. A. (1977). Primary inoculation with Mycobacterium marinum. Archives of Dermatology, 113(3), 380.

  20. Human Pathogens and Toxins Act. S.C. 2009, c. 24. Government of Canada, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009, (2009).

  21. Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.