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Atypical Mycobacteria ATYPICAL MYCOBACTERIA Chris A. Gentry, Pharm.D. Reviewed by Michelle M. Chapman, Pharm.D., FCCP, BCPS; and David E. Nix, Pharm.D., FCCP, BCPS The epidemiology of mycobacterial infections has been Learning Objectives dynamic over the past several decades. In the developed world, tuberculosis has been on the decline because of the 1. Classify the atypical mycobacteria by microbiological maturation of infection control measures and the characteristics, epidemiology, pathogenesis, sites of development of effective antituberculosis pharmacotherapy. infection, and general pharmacotherapy Atypical mycobacteria, although recognized soon after the 2. Given a specific history of present illness, devise a discovery of M. tuberculosis in the 19th century, were not diagnostic strategy for a suspected atypical deemed significant pathogens until the mid-20th century mycobacterial infection. with the emergence of pulmonary infection in patients with 3. Distinguish between infection control measures preexisting lung disease. Subsequently, the acquired necessary for atypical mycobacterial infections and immune deficiency syndrome (AIDS) epidemic brought tuberculosis. forth drastic increases in the occurrence of certain 4. Evaluate the potential for successful outcomes opportunistic infections. One of the most common systemic associated with various pharmacotherapeutic strategies opportunistic infections was disseminated disease due to for infections due to atypical mycobacteria. MAC. Many established atypical mycobacterial infections 5. Given pertinent clinical and laboratory data, construct a also grew in prevalence over the past few decades, and pharmacotherapy plan for a patient with an infection several new species emerged with variable ability to cause due to atypical mycobacteria. human disease. 6. Develop a treatment monitoring plan for a patient with Atypical mycobacteria have caused many types of an atypical mycobacterial infection. infections, including pneumonia, lung abscess, pleural space 7. Justify the patient populations that may benefit from infection, lymphadenitis, skin and soft tissue infection preventive measures. (including postoperative wound infection), meningitis, gastrointestinal infection, joint space infection, osteomyelitis, disseminated infection, and even intravenous catheter-related infection. Although most mycobacterial Introduction infections are community acquired, nosocomial infection and nosocomial outbreaks have occurred, most often Infections from Mycobacterium species have a variety of originating from contaminated water supplies that led to clinical presentations. The most notorious species of this central venous catheter, wound, or pulmonary infections. genus is Mycobacterium tuberculosis, which is responsible Infections with atypical mycobacteria are not limited to for millions of cases of tuberculosis worldwide each year immunocompromised patients. Before AIDS-associated (about 4 million cases were reported to the World Health disseminated MAC disease, the most common presentation Organization in 2001). Mycobacterium tuberculosis of atypical mycobacteria in the developed world was lung overshadows most other mycobacterial species, termed infection in relatively immunocompetent individuals with “atypical mycobacteria”. The most common atypical chronic lung diseases. mycobacteria that cause disease in the United States are This chapter focuses on the bacteriology, Mycobacterium avium complex (MAC), Mycobacterium pathophysiology, epidemiology, common disease states, fortuitum complex, and Mycobacterium kansasii. diagnostic principles, and pharmacotherapeutic Pharmacotherapy Self-Assessment Program, 5th Edition 99 Atypical Mycobacteria M. tuberculosis, atypical mycobacteria typically take 2 or Abbreviations in this more weeks to grow on standard agar. Some confusion exists regarding the taxonomy of rapid-growing Chapter mycobacteria. Mycobacterium chelonae and M. abscessus often are referred together as the M. chelonae/abscessus AFB Acid-fast bacilli complex, although not because they often are present in the AIDS Acquired immune deficiency syndrome same infection (in contrast to MAC). In addition, ATS American Thoracic Society M. fortuitum and M. fortuitum group often are referred to CYP Cytochrome P450 interchangeably. Mycobacterium fortuitum has several HIV Human immunodeficiency virus common morphological characteristics with other rapid- MAC Mycobacterium avium complex growing mycobacteria (e.g., Mycobacterium peregrinum, M. fortuitum third biovariant, and Mycobacterium management of atypical mycobacteria. The chapter mucogenicum), and these organisms are referred to as the highlights recent advancements, though relatively few, in M. fortuitum group. Some clinical laboratories and research the understanding of these concepts. reports do not pursue the procedures necessary to identify these organisms more specifically than “M. fortuitum group.” For this review, references refer to the specific Pathophysiology species, M. fortuitum, M. chelonae, and M. abscessus, unless noted otherwise. Bacteriology Identification of mycobacteria is made with several The genus Mycobacterium contains several species, microbiological techniques that differ from methodologies many of which have caused human illness. Mycobacterium used for standard bacteria, so clinicians should notify their tuberculosis and three closely related mycobacterial species microbiology laboratory that tests other than those for (M. bovis, M. africanum, and M. microti) cause tuberculous routine bacteria are required. Despite several limitations, disease, composing what is known as the M. tuberculosis staining procedures are still of critical importance in complex. In the United States, tuberculosis cases are mycobacterial infections. Staining procedures for predominantly caused by M. tuberculosis. Mycobacterium mycobacteria take advantage of the low permeability of the bovis and M. africanum are rare causes of disease in the lipid-rich and mycolic acid-containing cell wall for basic United States; M. microti does not cause disease in humans. dyes. Permeability is enhanced by heat or prolonged Mycobacteria other than those that make up the exposure, allowing colorization by the basic dyes. When M. tuberculosis complex are called nontuberculous or stained, mycobacteria retain color despite decolorization atypical mycobacteria. techniques that use acids with or without alcohol Atypical mycobacteria that historically have been (i.e., “acid-fast”). Concentrating the specimen before recognized as causing human disease include MAC, staining typically is recommended to increase sensitivity. M. kansasii, M. fortuitum, Mycobacterium chelonae, The Ziehl-Neelson method is a commonly used staining Mycobacterium abscessus, M. gordonae, M. terrae, technique using basic fuchsin and phenol for colorization, M. leprae, M. szulgae, Mycobacterium ulcerans, hydrochloric acid and ethanol for acid decolorization, and Mycobacterium marinum, and Mycobacterium then counterstaining with methylene blue. Against a blue scrofulaceum. More than 100 species of atypical background, the acid-fast bacilli (AFB) appear as slender mycobacteria have been described. Most have been red rods under microscopy. The Kinyoun stain is similar, implicated in human infection, including more than 20 although it typically is thought to be less effective. Another newly described species since the 1990s (see Table 1-1). method used is fluorescent microscopy, which uses Classification of atypical mycobacteria usually is prolonged exposure to auramine-rhodamine dye (without described by the Runyon criteria. The four groups, heating), decolorization with hydrochloric acid and ethanol, distinguished by in vitro growth characteristics on agar and brief treatment with a potassium permanganate plates, include photochromogens, scotochromogens, solution. Fluorescent microscopy reveals bright yellow nonchromogens, and rapid growers. Photochromogens are rods against a dark background. Fluorescent microscopy is mycobacteria that produce a yellow pigment after being thought to be more sensitive than the Ziehl-Neelson stain, exposed to light. These include the potential pathogens but this characteristic is countered by a greater potential for M. kansasii and M. marinum. Scotochromogens are those a false-positive result. that produce a pigment without exposure to light. These Acid-fast smears are important to rapidly detect the mycobacteria include M. scrofulaceum, Mycobacterium potential presence of a mycobacterial infection, allowing for xenopi, M. gordonae, and M. szulgae. Nonchromogens proper infection control measures to be initiated or usually produce no pigment and include MAC, M. ulcerans, continued (such as respiratory isolation in patients and Mycobacterium malmoense. Mycobacterium fortuitum, suspected of having pulmonary tuberculosis). Other M. chelonae, and M. abscessus are classified as rapidly positive aspects of the acid-fast smear include ease of growing mycobacteria, or “rapid growers,” because of their preparation and the low expense relative to other ability to produce visible growth on standard agar used for identification techniques, a relatively high specificity (some mycobacterial culture within 1 week. In contrast to other bacteria, most notably Nocardia species, also can Gangadharam PR. Microbiology of nontuberculosis mycobacteria. Semin Respir Infect 1996;11:231–43. Atypical Mycobacteria100 Pharmacotherapy Self-Assessment Program, 5th Edition appear acid-fast), the provision of
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