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Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases

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Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases American Thoracic Society Documents An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases David E. Griffith, Timothy Aksamit, Barbara A. Brown-Elliott, Antonino Catanzaro, Charles Daley, Fred Gordin, Steven M. Holland, Robert Horsburgh, Gwen Huitt, Michael F. Iademarco, Michael Iseman, Kenneth Olivier, Stephen Ruoss, C. Fordham von Reyn, Richard J. Wallace, Jr., and Kevin Winthrop, on behalf of the ATS Mycobacterial Diseases Subcommittee This Official Statement of the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) was adopted by the ATS Board Of Directors, September 2006, and by the IDSA Board of Directors, January 2007 CONTENTS Health Care– and Hygiene-associated Disease and Disease Prevention Summary NTM Species: Clinical Aspects and Treatment Guidelines Diagnostic Criteria of Nontuberculous Mycobacterial M. avium Complex (MAC) Lung Disease Key Laboratory Features of NTM M. kansasii Health Care- and Hygiene-associated M. abscessus Disease Prevention M. chelonae Prophylaxis and Treatment of NTM Disease M. fortuitum Introduction M. genavense Methods M. gordonae Taxonomy M. haemophilum Epidemiology M. immunogenum Pathogenesis M. malmoense Host Defense and Immune Defects M. marinum Pulmonary Disease M. mucogenicum Body Morphotype M. nonchromogenicum Tumor Necrosis Factor Inhibition M. scrofulaceum Laboratory Procedures M. simiae Collection, Digestion, Decontamination, and Staining M. smegmatis of Specimens M. szulgai Respiratory Specimens M. terrae complex Body Fluids, Abscesses, and Tissues M. ulcerans Blood M. xenopi Specimen Processing Other NTM Species/Pathogens Smear Microscopy Research Agenda for NTM Disease Culture Techniques Summary of Recommendations Incubation of NTM Cultures NTM Identification Antimicrobial Susceptibility Testing for NTM SUMMARY Molecular Typing Methods of NTM Diagnostic Criteria of Nontuberculous Mycobacterial Clinical Presentations and Diagnostic Criteria Lung Disease Pulmonary Disease Cystic Fibrosis The minimum evaluation of a patient suspected of nontubercu- Hypersensitivity-like Disease lous mycobacterial (NTM) lung disease should include the fol- Transplant Recipients lowing: (1) chest radiograph or, in the absence of cavitation, Disseminated Disease chest high-resolution computed tomography (HRCT) scan; (2) Lymphatic Disease three or more sputum specimens for acid-fast bacilli (AFB) analysis; Skin, Soft Tissue, and Bone Disease and (3) exclusion of other disorders, such as tuberculosis (TB). Clinical, radiographic, and microbiologic criteria are equally im- portant and all must be met to make a diagnosis of NTM lung disease. The following criteria apply to symptomatic patients with radiographic opacities, nodular or cavitary, or an HRCT scan that shows multifocal bronchiectasis with multiple small nodules. This document has an online supplement, which is accessible from this issue’s These criteria fit best with Mycobacterium avium complex (MAC), table of contents at www.atsjournals.org M. kansasii, and M. abscessus. There is not enough known about Am J Respir Crit Care Med Vol 175. pp 367–416, 2007 DOI: 10.1164/rccm.200604-571ST most other NTM to be certain that these diagnostic criteria are Internet address: www.atsjournals.org universally applicable for all NTM respiratory pathogens. 368 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 175 2007 Clinical. Health Care– and Hygiene-associated Disease Prevention 1. Pulmonary symptoms, nodular or cavitary opacities on Prevention of health care–related NTM infections requires that chest radiograph, or an HRCT scan that shows multifocal surgical wounds, injection sites, and intravenous catheters not bronchiectasis with multiple small nodules. be exposed to tap water or tap water–derived fluids. Endoscopes and cleaned in tap water and clinical specimens contaminated with 2. Appropriate exclusion of other diagnoses. tap water or ice are also not acceptable. Microbiologic. Prophylaxis and Treatment of NTM Disease 1. Positive culture results from at least two separate expecto- 1. Treatment of MAC pulmonary disease. For most patients rated sputum samples. (If the results from the initial spu- with nodular/bronchiectatic disease, a three-times-weekly tum samples are nondiagnostic, consider repeat sputum regimen of clarithromycin (1,000 mg) or azithromycin (500 AFB smears and cultures.) mg), rifampin (600 mg), and ethambutol (25 mg/kg) is recommended. For patients with fibrocavitary MAC lung or disease or severe nodular/bronchiectatic disease, a daily 2. Positive culture results from at least one bronchial wash regimen of clarithromycin (500–1,000 mg) or azithromycin or lavage. (250 mg), rifampin (600 mg) or rifabutin (150–300 mg), or and ethambutol (15 mg/kg) with consideration of three- 3. Transbronchial or other lung biopsy with mycobacterial times-weekly amikacin or streptomycin early in therapy is histopathologic features (granulomatous inflammation or recommended. Patients should be treated until culture AFB) and positive culture for NTM or biopsy showing negative on therapy for 1 year. mycobacterial histopathologic features (granulomatous in- 2. Treatment of disseminated MAC disease. Therapy should flammation or AFB) and one or more sputum or bronchial include clarithromycin (1,000 mg/d) or azithromycin washings that are culture positive for NTM. (250 mg/d) and ethambutol (15 mg/kg/d) with or without rifabutin (150–350 mg/d). Therapy can be discontinued 4. Expert consultation should be obtained when NTM are with resolution of symptoms and reconstitution of cell- recovered that are either infrequently encountered or that mediated immune function. usually represent environmental contamination. 3. Prophylaxis of disseminated MAC disease. Prophylaxis 5. Patients who are suspected of having NTM lung disease but should be given to adults with acquired immunodeficiency who do not meet the diagnostic criteria should be followed syndrome (AIDS) with CD4ϩ T-lymphocyte counts less until the diagnosis is firmly established or excluded. than 50 cells/␮l. Azithromycin 1,200 mg/week or clarithro- 6. Making the diagnosis of NTM lung disease does not, per mycin 1,000 mg/day have proven efficacy. Rifabutin se, necessitate the institution of therapy, which is a decision 300 mg/day is also effective but less well tolerated. based on potential risks and benefits of therapy for individ- 4. Treatment of M. kansasii pulmonary disease. A regimen ual patients. of daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d). Patients should be treated until Key Laboratory Features of NTM culture negative on therapy for 1 year. 1. The preferred staining procedure is the fluorochrome 5. Treatment of M. abscessus pulmonary disease. There are method. Specimens should be cultured on both liquid no drug regimens of proven or predictable efficacy for and solid media. Species that require special growth con- treatment of M. abscessus lung disease. Multidrug regi- ditions and/or lower incubation temperatures include mens that include clarithromycin 1,000 mg/day may cause M. haemophilum, M. genavense, and M. conspicuum. These symptomatic improvement and disease regression. Surgi- species can cause cutaneous and lymph node disease. cal resection of localized disease combined with multidrug 2. In general, NTM should be identified to the species level. clarithromycin-based therapy offers the best chance for Methods of rapid species identification include commercial cure of this disease. DNA probes (MAC, M. kansasii, and M. gordonae) and 6. Treatment of nonpulmonary disease caused by RGM high-performance liquid chromatography (HPLC). For (M. abscessus, M. chelonae, M. fortuitum). The treatment some NTM isolates, especially rapidly growing mycobac- regimen for these organisms is based on in vitro susceptibil- terial (RGM) isolates (M. fortuitum, M abscessus, and ities. For M. abscessus disease, a macrolide-based regimen M. chelonae), other identification techniques may be nec- is frequently used. Surgical debridement may also be an essary including extended antibiotic in vitro susceptibility important element of successful therapy. testing, DNA sequencing or polymerase chain reaction 7. Treatment of NTM cervical lymphadenitis. NTM cervical (PCR) restriction endonuclease assay (PRA). lymphadenitis is due to MAC in the majority of cases and 3. Routine susceptibility testing of MAC isolates is recom- treated primarily by surgical excision, with a greater than mended for clarithromycin only. 90% cure rate. A macrolide-based regimen should be con- sidered for patients with extensive MAC lymphadenitis or 4. Routine susceptibility testing of M. kansasii isolates is rec- poor response to surgical therapy. ommended for rifampin only. 5. Routine susceptibility testing, for both taxonomic identifi- cation and treatment of RGM (M. fortuitum, M abscessus, INTRODUCTION and M. chelonae) should be with amikacin, imipenem This is the third statement in the last 15 years dedicated entirely (M. fortuitum only), doxycycline, the fluorinated quinolones, to disease caused by NTM (1, 2). The current unprecedented a sulfonamide or trimethoprim-sulfamethoxazole, cefoxitin, high level of interest in NTM disease is the result of two major clarithromycin, linezolid, and tobramycin (M. chelonae recent trends: the association of NTM infection with AIDS only). and recognition that NTM lung disease is encountered with American Thoracic Society Documents 369 increasing frequency in the non-AIDS population. Furthermore,
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