Interim Laboratory Biosafety Guidance for Extensively
Drug-Resistant (XDR) Mycobacterium tuberculosis strains
The recent emergence of a new Mycobacterium tuberculosis
strain that causes extensively drug-resistant tuberculosis (XDR
TB) has prompted the issuance of these interim guidelines
for clinical and research laboratories handling XDR TB
strains.
XDR TB stems from poor general TB control and the consequent
development of multidrug-resistant TB (MDR TB). The current
definition of XDR TB is “XDR TB is TB showing resistance to at least
rifampicin and isoniazid, which is the definition of MDR TB, in
addition to any fluoroquinolone, and to at least 1 of the 3
following injectable drugs used in anti-TB treatment: capreomycin,
kanamycin and amikacin.” 1
Currently, no differences in modes of infection, pathogenesis,
transmissibility, or other risk assessment factors have been
demonstrated for XDR-TB strains other than its increased resistance
to antibiotic treatment. At the time of this writing, the emergence
of XDR TB is a recent phenomenon; evidence indicating that XDR TB
may be a much higher risk organism from a laboratory safety
perspective may yet emerge. In that event, laboratory facilities
must reevaluate their own site-specific risk assessments in order to
determine if additional safety measures, beyond those described in
this document, are required.
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Occupational Infections
The risk of occupational infections from XDR TB strains has not
been shown to differ from that of non-resistant M. tuberculosis
strains. As described in the 5th edition of “Biosafety in
Microbiological and Biomedical Laboratories” (BMBL), M.
tuberculosis
infections are a proven hazard to laboratory personnel as well as
others who may be exposed to infectious aerosols in the laboratory,
autopsy rooms, and other healthcare facilities.2 The incidence of
tuberculosis in laboratory personnel working with M. tuberculosis
has been reported to be three times higher than that of those not
working with the agent. Naturally or experimentally infected
non-human primates are a proven source of human infection.
Experimentally infected guinea pigs or mice do not pose the same
hazard because droplet nuclei are not produced by coughing in these
species; however, litter from infected animal cages may become
contaminated and serve as a source of infectious aerosols.
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Laboratory Safety
Like other strains of M. tuberculosis, XDR tubercle bacilli may
be present in sputum, gastric lavage fluids, cerebrospinal fluid,
urine, and in a variety of tissues.2 Exposure to
laboratory-generated aerosols is the most important hazard
encountered. Tubercle bacilli may survive in heat-fixed smears and
may be aerosolized in the preparation of frozen sections and during
manipulation of liquid cultures. Because of the low infective dose
of M. tuberculosis (i.e., ID50 <10 bacilli), sputa and other
clinical specimens from suspected or known cases of tuberculosis
must be considered potentially infectious and handled with
appropriate precautions. Accidental needle-sticks are also a
recognized hazard.
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Containment Recommendations
Clinical specimens
Most laboratories handling clinical specimens of suspected
tuberculosis will not know if an XDR TB strain is present until
after testing is completed on the materials. Initially, BSL-2
practices and procedures, containment equipment, and facilities are
required for non-aerosol-producing manipulations of clinical
specimens such as preparation of acid-fast smears.2 All
aerosol-generating activities must be conducted in a biological
safety cabinet (BSC). Use of a slide-warming tray, rather than a
flame, is recommended for fixation of slides. Liquefaction and
concentration of sputa for acid-fast staining may be conducted
safely on the open bench by first treating the specimen in a BSC
with an equal volume of 5% sodium hypochlorite solution (undiluted
household bleach) and waiting 15 minutes before processing.
If samples are being received from a known or highly suspected
source of XDR TB, BSL-2 with full BSL-3 practices are highly
recommended for manipulations of the clinical specimens, including
additional personal protective equipment (PPE) and autoclaving of
waste before leaving the laboratory (see 5th edition BMBL for full
description of BSL-3 practices).
Laboratory activities with known XDR TB strains
Research activities on XDR TB strains, especially protocols
involving aerosolization of infectious materials, should only be
undertaken if absolutely necessary. Researchers and institutions
should review protocols to determine if less resistant strains of M.
tuberculosis can be used instead of XDR TB strains.
BSL-3 practices, containment equipment, and facilities with
enhancements are required for laboratory activities in the
propagation and manipulation of cultures of XDR TB. BSL-3
enhancements must include the use of respiratory protection,
the implementation of specific procedures and use of specialized
equipment to prevent and contain aerosols, and the autoclaving of
laboratory waste before removal from the laboratory. The use of
Powered Air-Purifying Respirators (PAPRs) or higher level of
protection is highly recommended. Loose fitting PAPRs can be used;
however a site and procedure specific risk assessment should be
conducted to determine the exact type of respiratory protection
used. An OSHA respiratory protection program will be required for
individuals required to wear respirators.
Disinfectants proven to be tuberculocidal should be used. (See
Appendix B in the 5th edition BMBL for additional information.)
Vertebrate Biological Safety Level (ABSL) 3 is required for
animal studies using non-human primates experimentally or naturally
infected with XDR-TB. Animal studies using guinea pigs or mice can
be conducted at ABSL-2.
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References
- Extensively drug-resistant tuberculosis (XDR-TB):
recommendations for prevention and control. Wkly Epidemiol Rec. 2006
Nov 10;81(45):430-2.
-
CDC/NIH Biosafety in Microbiological and Biomedical
Laboratories, 5th Edition. (2007) Retrieved March 1, 2007.
Last Reviewed: 05/18/2008 Content Source: Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
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