• Nontuberculous mycobacterial pulmonary infections (1/3)

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    Journal ListJ Thorac Disv.6(3); 2014 MarPMC3949190
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    J Thorac Dis. 2014 Mar; 6(3): 210–220.
    doi: 10.3978/j.issn.2072-1439.2013.12.24
    PMCID: PMC3949190

    Nontuberculous mycobacterial pulmonary infections

    Margaret M. Johnsoncorresponding author1 and John A. Odell2
    Author information ► Article notes ► Copyright and License information ► This article has been cited by other articles in PMC.
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    Abstract
    Pulmonary infections due to nontuberculous mycobacteria (NTM) are increasingly recognized worldwide. Although over 150 different species of NTM have been described, pulmonary infections are most commonly due to Mycobacterium avium complex (MAC),
    Mycobacterium kansasii, and Mycobacterium abscessus. The identification of these organisms in pulmonary specimens does not always equate with active infection; supportive radiographic and clinical findings are needed to establish the diagnosis. It is
    difficult to eradicate NTM infections. A prolonged course of therapy with a combination of drugs is required. Unfortunately, recurrent infection with new strains of mycobacteria or a relapse of infection caused by the original organism is not uncommon.
    Surgical resection is appropriate in selected cases of localized disease or in cases in which the infecting organism is resistant to medical therapy. Additionally, surgery may be required for infections complicated by hemoptysis or abscess formation.
    This review will summarize the practical aspects of the diagnosis and management of NTM thoracic infections, with emphasis on the indications for surgery and the results of surgical intervention. The management of NTM disease in patients with human
    immunodeficiency virus (HIV) infections is beyond the scope of this article and, unless otherwise noted, comments apply to hosts without HIV infection

    KEYWORDS : Nontuberculous mycobacterium (NTM), mycobacterium avium intracellulare (MAI), bronchiectasis, mycobacterium abscessus, hot tub lung
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    Introduction
    Historically, human infections due to Mycobacterium were due almost exclusively to Mycobacterium tuberculosis (TB); the extensive societal impact of this infection is legendary. More recently, other species of mycobacterium causing clinical disease have
    been identified and, in many geographical regions, cause greater disease burden than TB. These organisms are referred to by a variety of collective names—anonymous or atypical mycobacteria, mycobacteria other than tuberculosis (MOTT) and nontuberculous
    mycobacteria (NTM). In this paper, the acronym NTM is used to collectively describe NTM organisms.

    Similar to TB, NTM infections can occur throughout the body. However, pulmonary infections, lymphadenitis, and skin and soft tissue infections are the most commonly described attributable human infections (1). Both host factors and organism
    characteristics influence the susceptibility and manifestations of infection (1).

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    Overview of atypical mycobacteria
    Mycobacteria are aerobic, non-motile organisms that appear positive with acid-fast alcohol stains (2). They have a lipid rich, hydrophobic cell wall, which is substantially thicker than most other bacteria (2). The thickness and composition of the cell
    wall renders mycobacteria impermeable to hydrophilic nutrients and resistant to heavy metals, disinfectants, and antibiotics (3).

    NTM are ubiquitous in the environment with the heaviest concentrations found in soil and water sources. They are associated with biofilm formation (4), which contributes to disinfectant and antibiotic resistance (3,5). The hydrophobicity of NTM results
    in preferential aerosolization from water (6), and many of these organisms are resistant to high temperature and are relatively resistant to low pH (7,8).

    Given these characteristics of NTM it is not surprising that drinking water, household plumbing, peat rich soils, brackish marshes, and drainage water are reservoirs of NTM (9). Water systems in hospitals, hemodialysis centers, and dental offices have
    particularly high rates of mycobacterium colonization (10). When sampling a potential source for NTM colonization, biofilms should be included in the sampled specimens given the organisms’ predilection for biofilm adherence (11-13).

    Currently, there are more than 150 species of Mycobacterium and it is likely that more will be discovered. The rapid increase in identified species in recent years is due to improved culturing techniques and more precise differentiations of species.
    Species differentiation improved dramatically with the development of molecular techniques that enabled the detection of differences in the 16S rRNA gene (14). This gene is highly conserved amongst species and slight differences characterize different
    species. A full listing of recognized NTM can be found at www.bacterio.cict.fr/m/mycobacterium.html.

    Although mycobacterium organisms other than TB were identified soon after Koch’s identification of TB in 1882, it was not until the 1950’s when they were recognized to cause human disease (15). Historically, different classification systems have been
    proposed, but NTM are most commonly classified by growth rate—either slowly growing or rapidly growing (Table 1). By far, the most common organism associated with pulmonary disease is the Mycobacterium avium complex (MAC), a slow growing NTM that
    encompasses many subspecies including avium, silvaticum, hominissuis, and paratuberculosis, as well as the species intracellulare, arosiense, chimaera, colombiense, marseillense, timonense, bouchedurhonense, and ituriense. Mycobacterium kasassii, also a
    slow growing organism, is the second most common cause of pulmonary infections in the United States and is responsible for pockets of infection in England (16,17) M. abscessus, is the most commonly isolated rapidly growing NTM and is the third most
    common cause of lung disease (16). Although most NTM lung infections are caused by these three organisms, it is important to recognize that many other NTM may cause pulmonary disease in both immunocompetent and immunocompromised hosts. Thus, the
    pathogenic significance of a NTM specimen must be determined in the context of a patient’s clinical presentation (18,19).

    Table 1
    Table 1
    Atypical Mycobacteria causing lung disease (not complete list; other species may cause disease).
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    Epidemiology
    Over the last three decades, it has been suggested that the incidence of both NTM laboratory isolation and disease prevalence is increasing. This change has been attributed, in part, to improved culturing techniques, coupled with greater disease
    awareness and a true increase in disease prevalence. However, it is challenging to accurately characterize the incidence and prevalence of NTM pulmonary infections since isolation of the organism does not universally indicate clinical infection.
    Additionally, NTM infections, unlike TB, do not require public health reporting, which hinders an accurate understanding of epidemiology. Furthermore, nearly all epidemiologic data is reported from the United States, Japan, and Europe, and thus, may not
    be reflective of changes in prevalence worldwide.

    When similar culture techniques are employed, environmental recovery is similar in various geographical regions (20). In Western societies, most laboratories report a dramatically greater prevalence of NTM than TB (21). However, not all positive NTM
    cultures represent infection. A recent analysis showed that approximately half of those with positive NTM respiratory cultures fulfilled clinical criteria for active infection (22). In Kendall and Winthrop’s review, the prevalence of NTM pulmonary
    infections based on laboratory records coupled with clinical characteristics varied between 4.1 and 14.1 per 100,000 patient years (23). In patients greater than 65 years the prevalence was 47 per 100,000 patient years (24). Women are also more likely to
    have NTM disease than men (24), the disease prevalence increases with age (25), and it is more common in the West and Southeast (24). In the United States, Caucasians account for 90% of cases followed by Asians/Pacific Islanders and Blacks (24).

    In a review from Oregon, NTM pulmonary infections were associated with more densely populated areas, suggesting that urban municipal water supply exposure predisposed individuals to disease (26). However, in Japan, NTM was more commonly found in farmers
    and gardeners than in urban patients with bronchiectasis, suggesting a greater etiologic role for exposure to soil than water sources (27).

    Skin testing for MAC antigens suggests that exposure to MAC is not uncommon and varies greatly geographically. Early studies of United States Navy recruits demonstrated reactivity to MAC antigens in 10-20% of recruits from northern and western areas of
    the United States, but over 70% of recruits from the southeast demonstrated MAC antigen reactivity (28).

    Currently, greater than 90% of NTM cultures in the United States are from pulmonary secretions (29). At the height of the human immunodeficiency virus (HIV) epidemic, NTM was more commonly cultured from blood due to disseminated infections, but anti-
    retroviral therapy and appropriate prophylaxis have substantially decreased the incidence of disseminated disease in this population (30).

    For reasons that are not fully understood, some pathogenic NTM organisms tend to cluster in specific geographical distributions. In the United States, M. kansasii is most commonly seen in southern and central regions (16). However, even outside of
    geographically endemic areas for M. kansasii, disease prevalence is high in areas with a substantial HIV disease (31). M. abscessus is most commonly identified in the southeastern United States from Florida to Texas. However, it has also been identified
    outside of this region.

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    NTM culture and Identification
    When NTM are sought, care must be taken when processing samples. Specimens from non-sterile sites, such as sputum, require decontamination to avoid overgrowth by bacteria or fungi. NTM are not visible on routine Gram stain, so the fluorochrome technique
    for staining is recommended (2). Culturing specimens in both broth and solid media is recommended. Broth cultures offer the advantage of greater yield and more rapid growth, but they are more susceptible to bacterial overgrowth. Growth of specimens on
    solid media allows an opportunity to visualize characteristics of colony growth (32). Cultured NTM should be identified to the species level to guide decisions regarding clinical relevance and appropriate therapy. Speciation of NTM can be achieved with
    polymerase chain reactions, gene probe assays, and high-performance liquid chromatography (33).

    When NTM is cultured from a human sample such as sputum, its clinical significance needs to be determined. In some instances the mycobacterial organisms are pathogenic; but in others they are commensal. Many NTM are less virulent than M tuberculosis.
    Additionally, since NTM are so commonly identified in water systems (9), it is important to assure that NTM in a clinical specimen, especially when present in low concentration, is not the result of contamination from water sources.

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    Mechanism of infection
    The mode of transmission to humans has not been defined. In many instances the Koch postulates do not prevail. Unlike TB, person-to-person transmission has not been convincingly demonstrated. Although animals may serve as a reservoir for NTM, animal to
    human transmission is not thought to occur. However, shared drinking water systems with animals may serve as a source of infection (34).

    Although the exact route of NTM infection is not established with certainty, based on NTM environmental distribution, it is very likely that the organism is ingested, inhaled, or implanted. Cervical lymphadenitis due to NTM occurs more frequently in
    children, coincident at the time that they are exploring outdoors and there is trauma to gums due to erupting teeth (35). Thus, it is assumed that NTM enter the tissues via the mouth. Previous infections leading to cervical lymphadenitis were most often
    due to Mycobacterium scrofulaceum; now most are due to MAC (35).

    Aerosolization of droplets small enough to enter the alveoli is the likely route of acquisition of pulmonary disease. Bathroom showers have been implicated as a primary source of exposure to aerosolized NTM (36). Households with water heater temperatures
    ≤50 °C are more likely to demonstrate colonization of their water supply with NTM than those with water heater temperature ≥55 °C (37). Potting soils, particularly those enriched with peat, have a high concentration of NTM and dust generated from
    soil may produce particles small enough particles to enter the alveoli (38). However, a case controlled cohort study by Dirac et al. looked at “aerosol-generating activities in the home and found that the only activity predictive of the development of
    NTM lung disease was the use of a spray bottle for watering plants (39).

    Contamination of hospital water supplies, medical equipment, including bronchoscopes and endoscopes, and contaminated dialysis solutions, has led to both NTM colonization and nosocomial outbreaks of disease. The site of disease is dependent upon the
    exposure, but cutaneous abscesses, pulmonary disease, meningitis, and surgical site infections have all been described (10). It is hypothesized that regulations to limit hospital water system temperatures to prevent scalding hinder the control of NTM (40)
    . Advances in DNA techniques have allowed easier and more rapid identification of the source of NTM in the setting of nosocomial outbreaks. However, recognition of nosocomial outbreaks is highly dependent upon clinical suspicion and investigation.

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    Susceptibility to NTM infection
    Nearly everyone is presumed exposed to NTM, yet most do not develop clinical signs of infection. The factors predisposing to infection are not well understood, but likely are due to an interaction between host defense mechanisms and the load of clinical
    exposure.

    Disseminated disease is most commonly seen in association with profound immunosuppression. In HIV infected patients, dissemination does not typically occur unless the CD-4+ T-lymphocyte count is below 50/uL (41). Structural lung disease, such as chronic
    obstructive pulmonary disease (COPD), silicosis, pneumoconiosis or prior TB infection, predisposes to pulmonary infection. Nodular bronchiectasis is very strongly associated with NTM infections.

    NTM infections are of particular importance in patients who are awaiting or have undergone lung transplantation and those with cystic fibrosis (CF) (42,43). The manifestations of infection are protean and may affect soft tissues, bones, and joints, as
    well as the lung (44). As in other populations, isolation of NTM organisms is not uncommon among transplant patients, but most have transient colonization and do not require treatment. Knoll et al., reviewed lung transplant recipients from 1990-2005 (45).
    NTM, especially, M. avium was commonly found in the respiratory secretions of this cohort, but a minority of patients fulfilled criteria for active pulmonary infections (45). However, lung transplant patients with NTM after transplantation have a higher
    mortality (46). In a multi-centered cohort study of 1,582 patients with CF, 6.6% demonstrated sputum positivity for NTM, while 3.3% fulfilled bacteriologic criteria for disease (47). A prior multicenter study showed a 13% prevalence of NTM sputum
    positivity (48). Molecular typing of the organisms suggested neither person-to-person transmission nor nosocomial spread was common. In study groups, M. avium and M. abscessus were most commonly identified.

    Interleukin-12 (IL-12) and interferon-gamma (INF-γ) are crucial elements of the host defense response to NTM. Defects in these pathways increase susceptibility to NTM infections (49). Abnormalities in IFN-γ receptors have been described in association
    with NTM infections in both individuals and familial clusterings of disease (15). However, therapy with aerosolized IFN-γ has been clinically unrewarding.

    Increasing therapeutic use of tumor necrosis factor-alpha (TNF-α) receptor antagonist drugs, especially in rheumatoid arthritis and other connective tissue diseases, has been associated with a concomitant increase in NTM infections. In a review of cases
    reported to the FDA, Winthrop et al., founds that most cases of NTM infection were due to lung infections, but there were significant extra-pulmonary sites of involvement as well (50). M. avium was responsible for half of the cases. In a review of 8,000
    users of anti-TNF-α agents, the rate of NTM infections was 74/100,000 person years (51).

    Measures taken may reduce exposure to NTM, and may be warranted in patients with recognized risk factors such as immunosuppression or structural lung disease. Bathroom showers with large diameter water streams have been suggested as preferable to one
    producing a fine mist. However, a prospective study examining risk factors for NTM lung infection was unable to correlate infection with shower exposure (52). It is presumed beneficial to use a bathroom vent that can exhaust the aerosol rapidly. Higher
    water temperatures with water heater temperatures greater than 55 °C are associated with lower NTM recovery. Thus, increasing the water heater temperature may be advantageous. Additionally, access to well water rather than use of a piped supply might
    reduce NTM levels.

    Filtration of water has theoretical advantages in reducing the passage of NTM, but these filters are expensive and require replacement regularly (53). Chemical disinfection of water also has potentially negative ramifications by changing the microbial
    flora. Avoidance of hot tubs, especially in enclosed areas, may be beneficial.

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    Diagnosis of NTM pulmonary infections
    Unlike TB, the isolation of NTM in pulmonary specimens does not equate with disease.

    In an effort to standardize the definition of NTM infection, the American Thoracic Society (ATS) and the Infectious Disease Society of America (IDSA) jointly published guidelines in 2007 (16). The diagnosis of NTM pulmonary infection requires the
    presence of symptoms, radiologic abnormalities, and microbiologic cultures in conjunction with the exclusion of other potential etiologies. Clinical symptoms vary in scope and intensity but chronic cough, often with purulent sputum, is common. Hemoptysis
    may also be present. Systemic symptoms including malaise, fatigue, and weight loss may occur often in association with advancing disease. As demonstrated in Figures 1,​,22,​,33,​,4,4, various radiographic patterns may be seen in patients with NTM
    pulmonary infections. Fibrocavitary disease is commonly identified on chest roentgenograms. Characteristic findings include thin walled cavities with an upper lobe distribution and surrounding pleural abnormalities. There is no radiographic finding to
    reliably differentiate fibrocavitary NTM from TB. NTM in conjunction with nodular bronchiectasis may be visible on chest radiograph, but is best appreciated on high resolution chest computed tomography (HRCT). Characteristic findings include clusters of
    small nodules usually less than 0.5 mm—the so-called tree-in-bud sign. Larger nodules, with or without cavitation, may occur, which are suspicious for malignancy. Uptake of 18F fluorodeoxyglucose (FDG) on PET scan has been described in nodules due to
    NTM (54). Infected areas of lung parenchyma may demonstrate atelectasis or cystic or saccular bronchiectasis.

    Figure 1
    Figure 1
    Tree-in bud opacities, most prominent in the right middle lobe due to mycobacterium avium intracellulare (MAI) infection.
    Figure 2
    Figure 2
    Cavitating nodule in the right lower lobe due to Mycobacterium avium complex (MAC).
    Figure 3
    Figure 3
    Extensive right middle lobe disease with parenchymal destruction due to Mycobacterium avium complex (MAC). After a prolonged course with multiple drug therapy, she underwent a right middle lobectomy with a video-assisted thoracoscopy.
    Figure 4
    Figure 4
    “Hot Tub Lung”-Diffuse consolidation due to hypersensitivity pneumonitis (HP) after repeated exposure to Mycobacterium avium complex (MAC) in an indoor hot tub. Surgical lung biopsy demonstrated granulomatous inflammation. The patient ...
    Because NTM are ubiquitous in the environment, especially in water sources, a single positive pulmonary specimen does not fulfill microbiologic criteria for infection. Confirmatory microbiologic findings requires culture growth of NTM from either one
    bronchoalveolar lavage, two sputum samples, or culture from respiratory tissue demonstrating granulomatous histopathology.

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    Common clinical scenarios of NTM pulmonary infections
    There are two commonly encountered patterns of NTM pulmonary infections. Upper lobe fibrocavitary disease historically had been most well described. It commonly occurs in patients with COPD or other structural lung diseases including silicosis,
    pneumoconiosis, or prior TB infections. Similar to the historical demographics of COPD, infected patients were often older males with a history of underlying lung disease.

    In 1989, Prince et al., described a cohort of 21 patients, 19 of whom were women, with NTM pulmonary infections without known underlying lung disease. They presented with slowly progressive nodular opacities on chest radiograph (55). This report led to
    the subsequent recognition of NTM infections in association with nodular bronchiectasis. The prototypical patient is an older thin female, often with pectus excavatum, scoliosis, and mitral valve prolapse (56). In these patients, it is uncertain if the
    NTM infection lead to the development of bronchiectasis, or is a consequence of it.

    A presentation suggestive of hypersensitivity pneumonitis (HP) has been reported to occur after exposure to aerosolized MAC, most often in association with indoor hot tub use (57,58). HP has also been suggested to occur in workers exposed to metalworking
    fluid (59). However, it is often challenging to demonstrate growth of NTM in the workplace (60). Patients with HP often present acutely ill with fevers and pulmonary symptoms in conjunction with various chest radiograph abnormalities. A favorable
    response to strict avoidance of exposure to the antigen, with or without adjunctive corticosteroid therapy suggests that this is a hypersensitivity reaction rather than true infection (57,58).

    Co-infection with different strains of NTM or different organisms is reported. MAC and M. abscessus infections may co-exist, making eradication even more challenging.

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    Treatment of NTM pulmonary infections: medical therapy
    There are numerous clinical challenges regarding the treatment of NTM pulmonary infections. The duration and toxicity of antimycobacterial therapy must be balanced against the often indolent clinical course and the patients other co-morbidities. It is
    often appropriate to observe a patient’s clinical course before embarking on therapy. There is currently a paucity of data on the natural history of untreated NTM infections adding to the difficulties of clinical decision-making. Kikuchi et al, have
    demonstrated that specific genotypic patterns of MAC may predict clinical behavior (61). If confirmed by subsequent investigations, these data may augment clinical decision making on directed drug therapy.

    Once a decision is made to begin targeted NTM therapy, recommendations for medical therapy are limited by a paucity of adequately powered randomized controlled trials. Often consensus opinion, in conjunction with in vitro susceptibility testing results,
    guides therapeutic recommendations. The choice of agents and duration of therapy is based upon the specific organism and extent or disease.

    Patients with advanced lung disease in need of transplantation present particular challenges when they develop NTM pulmonary infections. It is debated if listing for transplant should be deferred until completion of therapy. Because of the long duration
    of therapy for NTM, it is the authors’ opinion that listing these patients for bilateral lung transplants should not be delayed, as the involved lungs will be resected at the time of transplantation. Directed NTM therapy should be initiated and
    continued in the post-transplant period, although the duration of post-transplant therapy is not well defined.

    Recommended antibiotic therapy for the most common causes of pulmonary infections is outlined below. For details regarding therapy of other NTM infections, the reader is referred to the ATS consensus statement (16). Monitoring patients for signs of drug
    toxicity is required during therapy (Table 2). Attention to adequate nutritional intake and weight stability is important as gastrointestinal side-effects, such as nausea and vomiting, are commonly seen in conjunction with the macrolide agents, rifampin,
    and rifabutin. It is especially important that weight is monitored in patients with nodular bronchiectasis given the propensity of these patients to be quite thin.

    Table 2
    Table 2
    Required monitoring for patients on drug therapy for nontuberculous mycobacteria (NTM).
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    M. avium
    Newer macrolide drugs such as azithromycin and clarithromycin are central to drug therapy for MAC lung infections. These agents demonstrate in vitro and clinical activity (62) against MAC, and are able to achieve penetration into phagocytes and tissue (
    63). It is imperative that these agents not be used in isolation due to the substantial possibility of the development of resistance. Combination drug therapy with a macrolide (azithromycin or clarithromycin), rifampin or rifabutin, and ethambutol with
    or without an intravenous aminoglycoside are recommended. Therapy should be continued for at least one year after conversion of sputum cultures from positive to negative (16). The duration of antimicrobial therapy commonly exceeds 18 months or more. In
    patients with nodular bronchiectasis, thrice weekly “triple therapy” with a macrolide, ethambutol, and rifamycin is typically recommended over daily therapy to improve drug tolerability and decrease costs. Aminoglycoside therapy is typically not
    required. Sequential introduction of the drugs over a few weeks may improve patient tolerability. For patients with fibrocavitary disease, previously treated disease, or severe disease daily therapy with the inclusion of either streptomycin or amikacin
    to the aforementioned agents is recommended. Success, defined as sustained eradication of the organism without relapse for several years after the discontinuation of therapy, is only achieved in 55% of patients treated with a macrolide based regimen (15).
    The duration of therapy, the suboptimal efficacy, and morbidity of drug toxicity often leads to reluctance to pursue treatment or discontinuation of therapy. In a meta-analysis of studies examining the efficacy of a macrolide containing antibiotic
    regimen, the patient dropout rate ranged from 11-33% (15). Furthermore, even after completion of recommended therapy, many patients will grow MAC organisms again and require repeated prolonged courses of therapy. In a study of 34 patients treated for 18
    months with combination drug therapy, 11/34 (32%) grew MAC in sputum one year following discontinuation of therapy (64). Early reoccurrence of positive cultures suggests relapsed disease, whereas as later reoccurrence suggests a new infection.

    Recent evidence suggests that macrolide antibiotics may decrease exacerbations and sputum density in patients with bronchiectasis (65,66). It is known that MAC infection following successful MAC therapy treatment with a macrolide containing regimen is
    associated with subsequent macrolide resistant MAC (67). Thus, there is great concern that the use of macrolides in patients with bronchiectasis may render subsequent NTM infections resistant to therapy.

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    M. Kansasii
    Prolonged triple drug therapy including isoniazid (INH), rifampin, and ethanbutol is recommended for treatment of M. kansasii infections. Therapy should be continued for 12 months after sputum conversion to negative. Macrolides such as clarithromycin and
    the fourth generation fluoroquinolone moxifloxacin demonstrate very good in vitro activity against M. kansasii and may be an alternative to INH (68).

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    M. Abscessus
    Lung infections due to M. abscessus are notoriously difficult to treat successfully with drug therapy alone. Chemotherapy in conjunction with surgical resection is often needed in those who can tolerate it. It is important that laboratories specifically
    differentiate infections with M. abscessus, as opposed to reporting a recovered organism as M. chelonae/abscessus, as the potential for success with drug therapy differs.

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    The role of surgery in NTM infections
    The role of surgical intervention in patients with NTM infections has been infrequently studied. Thus, the historical roles of surgery in the management of TB, including diagnostic assistance, an adjuvant treatment option, and the management of
    complications of the disease have been extrapolated to patients with NTM infections. However, the public health implications for TB clearly differ from NTM. Surgical control of the disease is important in TB on both an individual and societal level
    because of the substantial risk of disease transmission to other patients and the development of multidrug resistance. These issues do not pertain to NTM.

    The optimal procedure, the timing of surgical intervention, the value of debulking the most diseased areas, and expected morbidity and mortality of surgery for NTM infections remain as incompletely answered questions.

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    Assistance in making the diagnosis
    NTM can present with various radiographic patterns including a diffuse ground-glass infiltrate, nodules, and mosaic attenuation consistent with patchy air trapping. Given the lack of specificity of these radiographic findings, surgical biopsies or
    resections to identify their etiology may fortuitously establish a diagnosis of NTM. An appreciation of the potential for an underlying infectious etiology of radiographic abnormalities highlights the importance of culturing explanted tissue removed at
    an operative procedure, if a benign diagnosis is provided (69).

    The need for medical therapy after a surgical resection identifying NTM is dependent upon the extent of remaining disease, the immune status of the patient, and the pathogenicity of the organism isolated. Patients with remaining areas of infection
    nodules will presumably benefit from medical treatment post-operatively. The role of post-operative medical therapy and the duration of therapy in patients who have had resection of an isolated solitary nodule are uncertain.

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    The role of surgery in the management of NTM pulmonary infections

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