Group II. Scotochromogenic Mycobacterium (M. scrofulaceum, M. szulgai, M. gordonae)

Authors: Perez-Velez CMKasperbauer SHIseman MD.

Scotochromogenic mycobacteria compose group II in the Runyon classification of mycobacteria, and are characterized by the fact that they do not typically require light to produce pigmented colonies. They are slowly growing mycobacteria, that is, they require more than 7 days to reach mature growth. Members include Mycobacterium flavescens, M. gordonae, M. marinum, M. scrofulaceum, M. szulgai, M. xenopi. This chapter will only discuss M. scrofulaceum (the most common cause of cervical lymphadenitis in children exposed to nonchlorinated tap water), M. szulgai (a species which when isolated from patients usually implies clinical disease), and M. gordonae (the most common mycobacterial contaminant of cultures).

M. Scrofulaceum

In 1952, Prissick and Masson described, from Canada, a pigmented Mycobacterium species that caused cervical lymphadenitis in children, and in 1956 they named this organism scrofulaceum, derived from the term scrofula (“brood sow”), in reference to the fact that cervical lymphadenitis in children is the most common clinical syndrome that it causes (61).

M. Szulgai

The first recognized case of disease due to M. szulgai, named after the Polish microbiologist T. Szulga, dates back to 1962, in a patient with olecranon bursitis. Ten years later, it was identified and reported from the United Kingdom in 1972 by Marks, Jenkins and Tsukamura (58).

M. Gordonae

 M. gordonae (formerly identified as M. aquae) was reported from Mexico in 1962 by Bojalil, Cerbon and Trujillo, and was named in honor of Ruth E. Gordon (7).

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On microscopy, scotochromogenic mycobacteria are gram-positive, non-motile, and moderate-to-long acid-fast rods. When cultured on conventional solid media, they share the attribute of forming yellow to orange pigmented colonies when grown even in darkness. They are slow-growing mycobacteria, that is, colony formation requires seven days or more.

M. scrofulaceum

Colonies of M. scrofulaceum grow slowly (4-6 weeks) at various temperatures (21°, 31°, 37° C). They are typically smooth, buttery in consistency, and globoid, with pigmentation ranging from light yellow to deep orange. M. scrofulaceum may be difficult to differentiate from other NTM by conventional means and may require molecular methods (e.g., DNA probes or 16S rRNA gene sequencing) (89). The distinction between M. scrofulaceum and M. parascrofulaceum is particularly challenging given that the biochemical and culture tests, as well as the high performance liquid chromatography (HPLC) of mycolic acids, are not discriminative. It is estimated that approximately 10% of strains initially identified as M. scrofulaceum actually belong to the species M. parascrofulaceum (93). Therefore, genetic sequencing of strains identified as M. scrofulaceum by biochemical testing or by HPLC is recommended.

M. szulgai

M. szulgai is scotochromogenic at 37°C but photochromogenic at 25°C. It usually grows within 10-25 days, producing smooth or rough pigmented colonies, at 37°C. In some strains, a period of exposure to light may be required before orange pigment is produced. Based on 16S rRNA gene sequences, M. szulgai is most closely related to M. malmoense; nonetheless, the two species are not difficult to distinguish phenotypically.

M. gordonae

M. gordonae is readily recognized by the smooth, deeply yellow-orange pigmented colonies that grow usually within 10-15 days at 37° C.


General Reservoirs

All three of these scotochromogenic mycobacteria have been recovered from water, and this is presumed to be a common source of infection.

Predisposing Conditions

Risk factors predisposing to disease due to M. scrofulaceum, M. szulgai, and M. gordonae are probably similar to those of other mycobacteria, and are related to the patient’s immune status and/or underlying abnormalities of a specific organ system. For example, the lungs, one of the organs most affected by nontuberculous mycobacteria (NTM) are predisposed to infection by any one of the following conditions:

  • Cystic fibrosis (mucoviscidosis) and variants (69)
  • Ciliary disorders (e.g., primary ciliary dyskinesia (67); Young syndrome)
  • Inflammatory lung disease (e.g., rheumatoid arthritis; Sjogren’s syndrome; ankylosing spondylitis; relapsing  polychondritis; systemic lupus erythematosus; inflammatory bowel disease)
  • Alpha-1 antitrypsin anomalies (with or without alpha-1 antitrypsin deficiency) (10)
  • Chronic obstructive pulmonary disease
  • Pneumoconiosis (62)
  • Pulmonary alveolar proteinosis (101)
  • Connective tissue disorders with airway abnormalities (e.g., Marfan syndrome) (33)
  • Post-infectious pulmonary sequelae (e.g., tuberculosis  (4); histoplasmosis; coccidioidomycosis; measles;necrotizing pneumonia; recurrent respiratory infections predisposed by primary or secondary immunodeficiency)
  • Postinflammatory pneumonitis (pulmonary aspiration syndrome (49); toxic inhalation; thermal injury)
  • Congenital anatomic defects (bronchial cartilage disorders; pulmonary sequestration; Swyer-James syndrome; yellow-nail syndrome)
  • Postobstructive disorders (right middle lobe syndrome; tumor; foreign body; hypertrophic adenopathy)
  • Allergic bronchopulmonary mycosis (57)

M. scrofulaceum


M. scrofulaceum is found in water, including both natural surface water (rivers, lakes), as well as swimming pools and aquaria (25). It is also found in aerosols (100), soil, house dust, vegetation, and animal and human feces (73).


M. scrofulaceum is a very uncommon isolate from humans. In national surveys of nontuberculous mycobacteria isolates in the United States between 1979 and 1983, M. scrofulaceum accounted for 2-4% of isolates, and the majority of reports were from the South Atlantic region  (3268). Clinical disease due to M. scrofulaceum was considered present in 22% (47/ 214) of isolates, and the mean age was 38.5 years, the lowest for all of the nontuberculous mycobacteria species reported (68). Using skin test reactions to PPD sensitins derived from M. scrofulaceum, different studies from the Netherlands (9), Czechoslovakia (88), Greece (17) and Kenya (52) measured human exposure to the organism and demonstrated that there is an uneven geographic distribution. Prevalence does appear to be influenced by exposure to implicated water sources, and one of the reasons why it is thought that the prevalence has significantly dropped is chlorination of tap water. As clean water acts have been implemented in such countries as the United States (since 1975), the United Kingdom, and Australia, there has been a shift in the species of Mycobacterium causing cervical lymphadenitis, from M. scrofulaceum (the most common species recovered from cervical lymphadenitis in children prior to 1978) to M. avium (102). M. scrofulaceum is five times more susceptible to chlorine than is M. avium (73).

Predisposing Conditions

Exposure to waters containing M. scrofulaceum is probably the major risk factor for cervical lymphadenitis in children (103). An unusually high incidence (14%) of M. scrofulaceum pulmonary disease has been reported in HIV-uninfected South African gold miners, suggesting an increased susceptibility to this Mycobacterium among this population (14). In patients with AIDS, M. scrofulaceum accounts for approximately 2% of mycobacterial infections (89), and—like other immunodeficiencies—can predispose to both pulmonary and disseminated disease (82). Trauma to skin or to a joint is a risk factor for M. scrofulaceum cutaneous or articular disease, respectively.

M. szulgai


M. szulgai has been recovered from surface water (Rio Grande River) (73), from hospital tap water  (11)and from swimming pool water (92). Human-to-human transmission has never been reported.


M. szulgai accounts for less than 0.5% of all human isolates of nontuberculous mycobacteria (60). Due to difficulties in its identification, there is probably an underestimation of this species, but even in laboratories implementing identification approaches appropriate to its recognition (such as lipid analyses or 16S rDNA sequencing), it is rarely recovered. Among over a thousand nontuberculous mycobacteria isolated in one laboratory, only two were identified as M. szulgai (92). As of 2003, there were only 53 cases reported (81). Most patients have been males (83%) and middle-aged (mean 50 years, range 26-62) (24). M. szulgai disease has now been reported in all continents, and there does not appear to be geographic clustering of cases.

Predisposing Conditions

The majority of patients with pulmonary disease are men greater than 50 years of age with risk factors including chronic alcohol abuse, smoking, COPD, and a history of pulmonary tuberculosis (81). One reported case of pulmonary disease involved a patient with AIDS (66). In immunocompromised patients (with HIV disease, malnutrition, cancer, or immunosuppression from cancer chemotherapy or for organ transplantation), disseminated disease can develop (26).

M. gordonae


M. gordonae is ubiquitous in the environment. It can be found in soil, but it is especially isolated from water, such as freshwater, public swimming pools, whirlpools, aquaria, water treatment plants, pipeline, potable water sources, ice machines, and tap water (a.k.a., "the tap water bacillus") including hospital tap water (73).


M. gordonae is a rare cause of human disease. A retrospective survey of nontuberculous mycobacteria isolates in clinical laboratories in fourteen countries found that M. gordonae was the second most frequent nontuberculous mycobacteria isolate (59). Of the group of Mycobacterium species to rarely cause human infection, M. gordonae is the one most frequently isolated in the laboratory. However, the majority of cultures yielding M. gordonae reflect contamination rather than human disease or colonization. Evidence demonstrating invasive disease (e.g., AFB and granulomas on histopathology; isolation from tissue culture) should be pursued to determine the clinical significance.

Predisposing Conditions

Even though it is almost always considered nonpathogenic, M. gordonae can produce invasive disease on rare occasion, especially in selected immunocompromised hosts such as patients with AIDS (3,5340), immunosuppression (e.g., steroid therapy), carcinoma, peritoneal dialysis, transplantation, or in early childhood.

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M. scrofulaceum, M. szulgai, and M. gordonae are known to cause several different clinical syndromes, both localized (especially pulmonary) and disseminated disease.

M. scrofulaceum

Lymph Node Disease

M. scrofulaceum most commonly causes a granulomatous cervical lymphadenitis (single or clustered, unilateral, minimally tender, submandibular lymph node that gradually enlarges over weeks) with few if any constitutional symptoms. It affects children predominantly between the ages of 1 and 5 years; it rarely presents in adults.

Pulmonary Disease

M. scrofulaceum can also cause a pulmonary disease, most often in adults, that is clinically indistinguishable from other mycobacterial pulmonary pathogens. A progressive bronchopulmonary disease with cavitary lesions has been reported in adults with pneumoconiosis (15).

Skin Disease 

M. scrofulaceum can cause a nodular cutaneous disease. In an immunosuppressed patient, M. scrofulaceum infection caused a red nodule on the finger (46). Cutaneous abscesses developed in a man with systemic lupus erythematosus (SLE) (64). Progressive sporotrichoid lesions on the hands of a 77-year-old woman who regularly cleaned fish aquariums has been reported (84).

Disseminated Disease

There have also been rare cases of disseminated disease, including one in an immunocompetent man (41), one in an immunosuppressed child  (45), and others in patients with AIDS (82).

M. szulgai

Pulmonary Disease

Most case reports of M. szulgai disease have been chronic pulmonary disease (at least 35 reported in the literature), which can present with a variety of patterns, but the majority consist of apical cavitary lesions (81). The most common clinical manifestations have been chronic cough, expectoration (sometimes hemoptysis), low-grade fever, weight loss, and fatigue. The most frequent radiological findings have been unilateral or bilateral apical lesions, consisting of thin-walled cavities with upper-lobe infiltrates in more than half of cases (105). The clinical presentation is indistinguishable from that caused by M. tuberculosis (18), or M. kansasii.

Skin Disease 

M. szulgai cutaneous disease can potentially present with various manifestations, and all appear to be related to an immunocompromising factor; immunosuppression, immunodeficiency, young age, or a break in epithelial integrity. Multifocal cellulitis, nodules, and abscesses were caused by M. szulgai, in a 29-year-old woman on long-term corticosteroid therapy for sarcoidosis (90). Multiple inflammatory skin lesions and osteomyelitis of the right ankle, due to M. szulgai, was reported in a 51-year-old man who had received corticosteroid therapy for several months to treat desquamate interstitial pneumonitis (16). A subcutaneous nodule on the forearm of a 41-year-old woman with systemic lupus erythematosus on chronic corticosteroid therapy grew M. szulgai from the culture of the aspirate (83). A vesiculopustular cellulitis on the foot was caused by M. szulgai in a 4 year-old boy who had undergone bone marrow transplantation with marrow from a matched unrelated donor (27). Multiple severe ulcerations spreading proximally in a sporotrichoid pattern, with more scattered lesions on the legs, in a 27-year-old male with an immunodeficiency of unknown etiology, were due to M. szulgai that was isolated from both skin and bone marrow cultures (47). A carbuncle (subcutaneous abscesses) over the angle of the jaw was reported in a 6-month-old girl (13).

Soft Tissue Infection

There have been at least three cases of olecranon bursitis reported, with no mention of a predisposing factor (57). A 28 year-old male, with no apparent underlying condition, presented with a tuberculoid tenosynovitis of the hand associated with carpal tunnel syndrome (86) and septic arthritis in an HIV patient during immune reconstitution (30).

Bone Disease

At least two cases have been reported in patients with AIDS (5674), and another in a 68-year-old woman on chronic immunosuppressive therapy (42). Multifocal osteomyelitis has been reported in an 18-year-old male with a lymphocyte dysfunction (36). Most cases of M. szulgai osteomyelitis are in patients who are immunocompromised, and are due to hematogenous or contiguous spread, sometimes with extensive dissemination.

Lymph Node Disease

A case of cervical lymphadenitis in a 9 year-old boy was included in the case series that first reported M. szulgai as a pathogen (58).

Kidney Disease

Renal, and probably bone, M. szulgai disease was reported in a patient with HIV infection (79).

Ocular Disease

A cluster of seven cases of M. szulgai keratitis were reported to occur after LASIK due to contamination of the surgical incision site with organisms from the ice used to cool the lavage syringe (39). M. szulgai keratitis generally has a delayed onset (6-14 weeks; average 10 weeks) after LASIK  (44).

Disseminated Disease

M. szulgai disseminated disease is quite rare and usually involves bone and joints (sometimes multifocally), skin, lymph nodes, and/or kidney. As it is invariably associated with an immunocompromising state, it is more difficult to treat and cure (2636).

M. gordonae

Pulmonary Colonization

Colonization can occur in patients with underlying pulmonary disease, in whom M. gordonae is repeatedly isolated, but the lung disease cannot be attributed to it  (23).

Pulmonary Disease

There are sporadic cases of progressive pulmonary disease due to M. gordonae (32021,98).

Peritoneal Disease

M. gordonae peritonitis in patients undergoing peritoneal dialysis has been reported (375598). Contaminated water supplies have been implicated in such cases.

Ocular Disease

Chronic keratitis has been reported in a man who was hit in the eye with some vegetable matter while gardening (63).

Cardiovascular Disease

M. gordonae prosthetic (porcine) valve endocarditis has been reported in the immediate post-operative period (54).

Disseminated Disease

M. gordonae disseminated disease has been reported in a small number of patients (40, 5398). In a review of 24 cases that met criteria for M. gordonae disease, five had disseminated disease, with involvement of lungs and liver in four patients, bone marrow in three patients, kidney in two patients, and CNS in two patients. Four of the five patients had no identifiable immunocompromising factor, and the other had AIDS (98).


M. gordonae is a frequent contaminant of tap water. It is probable that some patients’ respiratory specimen cultures have been positive for M. gordonaeas a result of contamination from tap water ingested by patients before expectoration, tracheal suctioning, or bronchoscopy. As with other nontuberculous mycobacteria, small pseudo-outbreaks (i.e., outbreaks of "pseudoinfections") have been reported with M. gordonae. In several outbreaks, water used in cleaning bronchoscopes was contaminated with M. gordonae, leading to "false-positive" culture results (35,43,72,85). In one case, gargled tap water, as a preparatory step in obtaining sputum specimens, was contaminated with M. gordonae, leading to false-positive cultures (false in the sense that no true infection or colonization was present but the cultures were positive) (2).  A nosocomial pseudoinfection from contaminated tap water in an ice machine has also been reported (70). M. gordonae has also been recovered from commercial antimicrobial solution used to suppress growth on nonmycobacterial species and facilitate the detection of mycobacteria in the laboratory (91) and topical anesthetics.

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Diagnostic Criteria

The following ATS/IDSA criteria for the diagnosis of nontuberculous mycobacteria lung disease are primarily based onMycobacterium avium complex (MAC), M. kansasii, and M. abscessus (34). Knowledge of M. gordonae, M. scrofulaceum, and M. szulgai pulmonary disease is quite limited to be certain that these criteria apply to them as well, but they are probably appropriate.


The patient has symptoms and signs of a chronic pulmonary disease.


A chest radiograph shows nodular opacities or cavitations, and/or a high resolution chest CT shows bronchiectasis with nodules or cavitary lesioins.


Colonization of asymptomatic individuals and environmental contamination of specimens can yield positive cultures of nontuberculous mycobacteria in the absence of clinical infection. Therefore, culture isolation of a scotochromogenic mycobacterium from at least two separate expectoration samples, or from at least one bronchial wash or lavage, or from a lung biopsy, is recommended. Exclusion of other reasonable causes (e.g., tuberculosis, fungal disease, malignancy, etc.).

Microbiological Laboratory Procedures

In order to attain microbiologic confirmation of mycobacterial disease, attention to detail in regards to specimen collection methods is as important as the use of sensitive and specific microbiological tests.

Specimen Collection

Given that nontuberculous mycobacteria are environmental mycobacteria, the collection of all specimens should avoid potential sources of contamination, especially tap water, because environmental mycobacteria are often present. It therefore may be better to have patients avoid rinsing their mouths with, or drinking, tap water (or other beverages made from tap water) for several hours before collection of respiratory samples, in order to avoid contamination. Sputum may need to be induced with hypertonic saline nebulizations. As much body or abscess fluid as possible should be collected (using sterile technique) and submitted for AFB staining and mycobacterial culturing. Swabs are not recommended for sample collection because they often contain limited culture material, and are prone to desiccation.

Specimen Processing

Digestion and decontamination procedures should be performed on specimens collected from nonsterile body sites.

Smear Microscopy

The preferred technique for staining clinical specimens is the fluorochrome method. The Ziehl-Neelsen and Kinyoun staining methods are acceptable but less sensitive alternatives.

Culture Techniques

Specimens should be cultured on both a rapid detection liquid (broth) media and solid media (egg-based and/or agar-based). Supplementation is not required for the growth of M. gordonae, M. scrofulaceum, and M. szulgai. Quantitative or semi-quantitative reporting of the number of colonies on solid media should be performed to aid in diagnosis and for monitoring of therapeutic response.

Incubation of Cultures

M. gordonae, M. scrofulaceum, and M. szulgai do not require special growth conditions or lower incubation temperatures.


Conventional biochemical tests can be inadequate for the identification of some scotochromogenic mycobacteria. In fact, M. szulgai was first distinguished from other nontuberculous mycobacteria by the use of thin-layer chromatographic analysis of its cell wall lipids (58).


Three chromatographic methods (high-performance liquid, gas-liquid, and thin-layer) can be used to identify M. gordonae, M. scrofulaceum, and M. szulgai after a bacterial harvest is obtained.

Molecular Markers

There are no molecular markers commercially available for M. scrofulaceum or for M. szulgai, but there is a commercial hybridization DNA probe assay to identify M. gordonae (AccuProbe® Mycobacterium gordonae Culture Identification Test, GenProbe) that rapidly identifies the species. PCR amplification followed by hybridization has been reported to be useful for M. scrofulaceum (19). Such molecular markers are useful in molecular epidemiological studies of outbreaks of nontuberculous mycobacteria infections, as was the case in an outbreak in France of bronchoscopes contaminated with nontuberculous mycobacteria, including M. gordonae (95).


Transbronchial or other lung biopsy is not required for diagnosis, but if performed would reveal granulomatous inflammation (resembling that of tuberculosis) or a positive AFB stain.

Immunological Testing

Standardized, specific antigens for M. gordonae, M. scrofulaceum, or M. szulgai are not commercially available for skin testing or for interferon gamma release assays. Skin testing with M. scrofulaceum sensitin has been used in research studies intending to measure sensitization to this Mycobacterium. Patients with nontuberculous mycobacteria disease can have skin indurations to PPD-tuberculin skin testing probably due to the presence of antigens in the tuberculin that are shared by some nontuberculous mycobacteria.

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The specific pathogenic mechanisms of disease caused by M. scrofulaceum, M. szulgai, and M. gordonae have not been fully elucidated. Nonetheless, certain principles regarding the pathogenesis of disease caused by other nontuberculous mycobacteria (including M. avium, M. intracellulare, M. kansasii, M. chelonae, M. fortuitum, and M. abscessus) very likely apply to these scotochromogenic mycobacteria. The ubiquitous presence of environmental mycobacteria results in humans being frequently exposed (estimated to be 50-500 bacilli per day) (73).

Human-mycobacterial interaction is complex. It can result in colonization, in which case there is no tissue invasion, and which can be transient (probably in the majority of interactions), intermittent, or permanent (where there is no invasiveness). It can result in infection, in which case there was an immune response, but no overt manifestations whether clinical, radiological, or histopathological. It can also result in disease (tissue invasion), in which case there are one or more overt manifestations. However, only a very small proportion of human-mycobacteria interactions progress to disease. The type of interaction that ensues depends on several factors, including the immunocompetence of the human host, the route of entry of the Mycobacterium (e.g., inhalation of aerosol; oral ingestion; penetration through skin break), the physiological state of the bacteria (e.g., planktonic, aggregates, inside of protozoa) (73), the species of Mycobacterium (e.g., M szulgai is more likely to cause disease than M. gordonae, one of the least pathogenic mycobacteria), the virulence of the Mycobacterium (e.g., the degree of catalase activity), and the number of mycobacteria introduced (the “inoculum”).

               Immunocompromised states predisposing to the development of mycobacterial disease include

  • a primary or acquired immunodeficiency (e.g., AIDS)
  • damage to tissue (bronchiectatic airway; break in skin)
  • immunosuppression (with corticosteroids, TNF-blockers, or other immunomodulators) for autoimmune  disease, transplantation, or severe allergic disease, certain malignancies, dialysis, and early childhood.

M. scrofulaceum

Cervicofacial lymphadenitis due to M. scrofulaceum or other mycobacteria is thought to occur as a result of the ingestion of the bacilli in contaminated material. In children (the most affected age group), organisms may be introduced into the oral cavity by exploratory mouthing of contaminated objects and may then enter the body through oral mucosal breaks caused, for example, by teething or trauma (1).

M. szulgai

M. szulgai is notably pathogenic and when isolated it usually implies disease. Like most other nontuberculous mycobacteria,M. szulgai strains are typically positive for catalase, a virulence factor in these organisms.

M. gordonae

M. gordonae is one of the least pathogenic mycobacteria, usually only causing disease in immunocompromised hosts.

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Because of their limited association with human disease, large numbers of the scotochromogenic mycobacteria have not been subjected to in vitro susceptibility testing.

Combination Activity (In Vitro & In Vivo)

Synergistic or additive effects of combination drugs have not been studied systematically for scotochromogenic mycobacteria.

M. scrofulaceum

 Antimicrobial susceptibility data for M. scrofulaceum are lacking. Clarithromycin has good in vitro activity against tested isolates (75). However, there is no published clinical experience. The in vitro antimicrobial susceptibility patterns of M. scrofulaceumisolates typically resemble those of MAC (28).  Fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin) and linezolid have exhibited excellent in vitro activity against M. scrofulaceum (78). 

M. szulgai

Most strains of M. szulgai are susceptible in vitro to most primary antituberculosis agents, and are generally more susceptible to standard antimycobacterial agents than M. scrofulaceum and MAC. They are typically inhibited by clarithromycin, ethambutol, rifampin, streptomycin, amikacin, capreomycin, and high-concentrations of isoniazid (81831). Clarithromycin has good in vitroactivity against tested isolates (76), however, there is no published clinical experience. Susceptibility to fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) and to macrolides has been reported (42665, 9294). Susceptibility to cefoxitin has been described (38). Partial resistance to isoniazid is common. Most strains are resistant in vitro to pyrazinamide, para-aminosalicylate sodium (PAS), cycloserine, and kanamycin  (831). 

M. gordonae

Although there are few antimicrobial susceptibility data published, the antimicrobial medications most consistently active in vitro include ethambutol, rifampin, rifabutin, clarithromycin, linezolid, fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), and clofazimine (8,78).  M. gordonae has variable susceptibility to aminoglycosides (98104).  There are reports of successful or partially successful treatment of M. gordonae pulmonary disease with clarithromycin (5077). The majority of isolates tested have been resistant to pyrazinamide and isoniazid.

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Since these scotochromogenic organisms are rare human pathogens and the disease is usually indolent, controlled studies of drug treatment versus no treatment have never been performed. Likewise, superiority has not been established for any particular combination or regimen. Nonetheless, from the limited cases reported and by extrapolation from the experience with related mycobacterial disease, the following broad guidelines are offered for therapy for pulmonary disease. For patients with extrapulmonary or disseminated disease, the decision to treat is easier given the recovery of the organism from normally sterile sites. This is particularly true in cases of immunocompromised hosts.

Drugs of Choice and Alternative Drugs for Combination Therapy

Suggested drugs of choice and alternative medications for combination therapy to treat scotochromogenic mycobacterial disease are noted in Table 1 along with their recommended dosages.

Selection of Drugs for Combination Therapy

Antimicrobial agents should be selected on the basis of in vitro susceptibility as well as previously reported therapeutic efficacy.

Number of Drugs for Combination Therapy

Chemotherapeutic regimens with three or more drugs are generally indicated to maximize antimicrobial effect and to lessen the likelihood of acquired drug resistance.

Duration of Treatment

If the patient improves on such treatment, medication should be continued for a minimum of 6 months, generally 12 months, and possibly up to 24 months, depending on the extent and severity of disease, degree of immunosuppression, mycobacterial agent, response to therapy, and the adverse effects of the medications.

Therapeutic Drug Monitoring

Therapeutic drug monitoring (also known as applied pharmacokinetics) is available for most antimycobacterial agents, including clarithromycin, azithromycin, ethambutol, rifampin, rifabutin, amikacin, streptomycin, ciprofloxacin, moxifloxacin, clofazimine, and isoniazid. In order to optimize therapeutic effectiveness while at the same time avoiding concentration-related toxicities, therapeutic drug monitoring is recommended. Given the variable minimum inhibitory concentrations (MICs) shown by nontuberculous mycobacteria for certain antimycobacterial agents (including aminoglycosides), the metabolic interactions with concomitant medications (e.g., rifamycins with certain antiretroviral drugs), and the typically prolonged treatment courses of 6 to 18 months (sometimes longer), therapeutic drug monitoring takes on greater relevance.

M. scrofulaceum

 Due to the lack of antimicrobial susceptibility data and the controversy over standard treatment regimens, susceptibility testing on confirmed disease-producing isolates of M. scrofulaceum is recommended, in order to guide antibiotic selection (78). There are no prospective studies on the treatment of disease caused by M. scrofulaceum. Retrospective case series suggest that antimicrobial therapy alone has very limited benefit and that complete surgical resection provides cure (24).

Initial Empiric Therapy

An empiric three-drug regimen consisting of clarithromycin plus rifampin plus ethambutol is probably adequate for localized disease and for uncomplicated noncavitary pulmonary disease.

Duration of Treatment

At least 12 months, dependent on therapeutic response and immune status. For pulmonary disease, the cure rate was greater than 56% with a mean treatment duration of 17 months (39).

M. szulgai

Therapeutic regimens have included isoniazid, rifampin, ethambutol, and streptomycin (225796). A patient with AIDS and with pulmonary disease due to M. szulgai responded to treatment with isoniazid, rifampin, ethambutol, and pyrazinamide (the isolate was resistant to isoniazid, kanamycin, capreomycin, and cycloserine, and susceptible to rifampin, ethambutol, and ciprofloxacin) (66). A combination of rifampin, ethambutol, and ciprofloxacin for one year successfully treated a 59-year-old male who developed disseminated disease after being immunosuppressed for a misdiagnosis of interstitial lung disease (26).  Moxifloxacin is more active than ciprofloxacin in vitro, however experience in long-term treatment is limited (5). Clinical improvement and cure of pulmonary disease can be anticipated when treatment includes at least 3 drugs to which the isolate is susceptible in vitro, and attains culture conversion within a mean of three months. In 17 of 21 reported cases of pulmonary disease in which response to treatment was described, antimicrobial therapy was adequate when more than two agents were prescribed. There were more relapses with a two-drug regimen (57).

Initial Empiric Therapy

An empiric regimen consisting of ethambutol, rifampin, and a macrolide (e.g., clarithromycin or azithromycin). A fluoroquinolone (e.g., ciprofloxacin), or isoniazid, could be substituted or added if necessary. In cases of severe disease (e.g., cavitary lesions; disseminated infection), an aminoglycoside (e.g., amikacin) should be considered as an additional agent.

Duration of Treatment

The optimal duration of treatment has not been established. The ATS/IDSA practice guidelines recommend the use of 3-4 agents for 12 months after the first negative culture for pulmonary disease, and for 4-6 months for extrapulmonary disease  (34).

M. gordonae

There are no prospective studies, and there are no retrospective case series of significance, to provide guidance on the medical treatment of disease caused by M. gordonae. Antimicrobial susceptibility testing may help guide the selection of a long-term regimen.

Initial Empiric Therapy

An empiric three-drug regimen consisting of clarithromycin, ethambutol, and rifampin is probably adequate.

Duration of Treatment

The optimal duration of treatment has not been established and depends on the clinical syndrome and the underlying immunocompromising predisposing condition that is usually present.

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Surgery should be considered for patients with localized disease, especially when response to chemotherapy alone is usually poor. Pulmonary disease associated with cavitary lesions and/or severe bronchiectasis may require surgical resection of an affected segment or lobe.

M. scrofulaceum

Cervical adenitis due to M. scrofulaceum usually responds poorly to just antimicrobial therapy and thus surgical resection of the lymph node, and of sinus tracts if present, is recommended and is usually curative (99). Incision and drainage is not recommended due to risk of fistulae developing. However, this experience predated the antimycobacterial use of newer macrolides (and fluoroquinolones) which have potent in vitro activity. There is a single case report of successful use of combination regimen consisting of isoniazid, rifampin, ethambutol, and ofloxacin.

M. szulgai

A 48-year-old male with persistent pulmonary disease despite three years of antimycobacterial therapy with three agents (isoniazid, rifampin, and ethambutol) had a favorable outcome after undergoing surgical resection of diseased lung (94). Bursa excision appeared to have cured an olecranon bursitis in a 42 year-old male with no reported predisposing condition (58). Antimicrobial therapy in addition to surgical drainage of infected joints in a patient with septic polyarthritis lead to significant clinical improvement. For keratitis, excision of infected areas (i.e., lamellar keratectomy or penetrating keratoplasty) or corneal transplantation may be required for up to 50-60% of patients (39).

M. gordonae

Surgical debridement is recommended for soft tissue disease.

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Patients receiving antimicrobial therapy should be monitored with a combination of clinical, imaging, laboratory, and microbiological parameters.

Clinical Findings

 Resolution of immunological (e.g., fever, night sweats) and constitutional (fatigue, malaise, loss of appetite, weight loss) symptoms, as well as of the clinical manifestations of the organ system(s) involved, is reassuring of a therapeutic response.

Imaging Studies

 In cases of extrapulmonary disease, such as intrathoracic or intraabdominal lymphadenitis, osteomyelitis, and kidney disease, follow-up imaging studies may be helpful to assess response to antimicrobial therapy.

Laboratory Studies

 Inflammatory markers, although nonspecific, may serve as markers for the monitoring of a therapeutic response, assuming they are elevated initially. However, the lack of an elevation does not assure the absence of active disease.

Microbiological Studies

 In cases of cardiovascular, renal, CNS, or joint disease, collecting new samples of blood, urine, cerebrospinal fluid, or synovial fluid, respectively, is very important to demonstrate clearance of the infection from these sterile spaces. Culture conversion is a useful milestone to determine the total duration of treatment.

Pulmonary Disease

Pulmonary disease is most easily assessed due to the relatively precise, quantitative, and reproducible findings on radiographic and sputum microbiological studies.

Imaging Studies

Chest radiographs or computed tomographic (CT) scans provide ready information about the locale, extent, and character of the pulmonary processes. Mycobacterial diseases inevitably cause irreversible lung damage with scarring, so the purpose of monitoring therapy is not to await normalization but to establish that the patient is improving.

Microbiological Studies

 Bacteriology is a traditional endpoint for anti-tuberculosis therapy and is often adopted for the treatment of NTM diseases. However, unlike pulmonary tuberculosis (wherein negative sputum cultures are vital to assure safety from human-to-human transmission), an acceptable response to therapy of nontuberculous mycobacteria pulmonary disease may include clinical and radiological improvement, without necessarily conversion to culture negativity (although conversion to smear negativity is an attainable goal). Certainly negative cultures are a favorable sign, but some patients on treatment never achieve this endpoint. The decision whether to reinforce the drug regimen or consider surgical resection in this setting is complex and should be undertaken only with experienced consultants.


No vaccines have been shown to be efficacious in the prevention of any nontuberculous mycobacteria diseases. Limited data from Sweden suggest that, following termination of universal BCG vaccination, cervical lymphadenitis due to nontuberculous mycobacteria occurred with increasing frequency among the unvaccinated children (48). From this, some people have inferred that BCG vaccination protected children against cervical node infection by nontuberculous mycobacteria. While this is a plausible theory, neither the absolute increase in nontuberculous mycobacteria adenitis nor a causal relationship between withdrawal of the vaccine have been proven.

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 In patients with acquired immunodeficiency syndrome (AIDS) with CD4+ T-lymphocyte counts less than 50 cells/uL, prophylaxis for MAC disseminated disease is recommended with a macrolide (azithromycin 1200 mg per week or clarithromycin 1000 mg per day) or with rifabutin (300 mg per day). On the basis of similarity of susceptibility to antimycobacterial drugs, such regimens may prevent disease due to M. scrofulaceum, M. szulgai, or M. gordonae infection.

Infection Control

Tap water may contain environmental mycobacteria. Prevention of healthcare- and hygiene-related nontuberculous mycobacteria infections, including M. scrofulaceum, M. szulgai, and M. gordonae, requires that surgical wounds, injection sites, and intravenous catheters not be exposed to tap water or tap water-derived fluids. Endoscopes should not be cleaned with tap water, and clinical specimens should not be exposed to tap water or ice. Sterile protocol should be adhered to during laser in situ keratomileusis (LASIK) (29).

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Deciding whether an isolate is truly causing invasive disease, is simply colonizing, or is a contaminant, is not always easy. Culture isolation of M. szulgai usually implies the presence of invasive disease (2226). The vast majority of clinical isolates of M. gordonae are contaminants.


Due to the lack of controlled studies, treatment of patients with infections due to these uncommon pathogens is problematic. Also, determining if surgery is indicated may be a challenge. Therefore, for all but the most straightforward cases which enjoy a prompt and uncomplicated response to therapy, it is recommended that these patients be evaluated by experienced consultants in referral centers early in the course of the disease. Early errors in management may result in irreparable problems including acquired drug resistance and/or disease progression.

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Table 1:  Suggested Drugs for Scotochromogenic Mycobacterial Diseases 

Primary Agents  Alternatives
Macrolides:  clarithromycin*; azithromycin Aminoglycosides:  amikacin; streptomycin
Rifamycins*:  rifampin; rifabutin Fluoroquinolones:  ciprofloxacin, levofloxacin, moxifloxacin
Ethambutol Riminophenazine:  clofazimine
  Oxazolidinone:  linezolid

*Note predictable drug interaction between clarithromycin and the rifamycins; rifampin > rifabutin induces the catabolism

of clarithromycin resulting in substantially reduced bioavailability (97). The clinical significance of this has not been established,

but given the preeminent activity of clarithromycin against many NTMs, I would recommend checking drug levels and/or

dosing clarithromycin in the high range.  Conversely, clarithromycin inhibits the catabolism of the rifamycins resulting in a

variety of clinical complications including uveitis, pseudo jaundice, arthralgias/myalgias, and a drug-induced lupus syndrome (6).

Table 2:  Recommended Antimycobacterial Dosages   

Drug Age Daily Regimen   Three Times Weekly  
    Target Dose (Range) by Weight Maximum Dose Target Dose (& Range) by Weight Maximum Dose
Clarithromycin (PO) Pediatric§ 15 mg/kg/day div QD  1000 mg  15 mg/kg/day div QD

 1000 mg

  Adult 15 mg/kg/day div QD  1000 mg  15 mg/kg/day div QD

 1000 mg

  Geriatric 15 mg/kg/day div QD  1000 mg  15 mg/kg/day div QD

 1000 mg

Azithromycin (PO) Pediatric§ 5 (5-10) mg/kg/day div QD  500 mg  10 (5-10) mg/kg/day div QD

 600 mg

  Adult 5 (5-10) mg/kg/day div QD  500 mg  10 (5-10) mg/kg/day div QD

 600 mg

  Geriatric 5 (5-10) mg/kg/day div QD  500 mg  10 (5-10) mg/kg/day div QD

 600 mg

Ethambutol† (PO) Pediatric 15 (15-20) mg/kg/day div QD  1000 mg  25 (25-30) mg/kg/day div QD

 2400 mg

  Adult 18 (15-20) mg/kg/day div QD  1600 mg  25 (25-30) mg/kg/day div QD

 2400 mg

  Geriatric 18 (15-20) mg/kg/day div QD  1600 mg  25 (25-30) mg/kg/day div QD

 2400 mg

Rifampin (PO) Pediatric§ 10 (8-12) mg/kg/day div QD  600 mg  10 (8-12) mg/kg/day div QD

 600 mg

  Adult 10 (8-12) mg/kg/day div QD  600 mg  10 (8-12) mg/kg/day div QD

 600 mg

  Geriatric 10 (8-12) mg/kg/day div QD  600 mg  10 (8-12) mg/kg/day div QD

 600 mg

Rifabutin (PO) Pediatric 5 (5-10) mg/kg/day div QD  300 mg  5 (5-10) mg/kg/day div QD

 600 mg

  Adult 5 mg/kg/day div QD  300 mg  5 (5-10) mg/kg/day div QD

 600 mg

  Geriatric 5 mg/kg/day div QD  300 mg  5 (5-10) mg/kg/day div QD

 600 mg

Amikacin† (IV) Pediatric 15(15-22.5) mg/kg†/day div QD  1000 mg  15 (15-22.5) mg/kg/day div QD

 1000 mg

  Adult 15(15-22.5) mg/kg†/day div QD  1000 mg  15 (15-22.5) mg/kg†/day div QD

 1000 mg

  Geriatric 15(15-22.5) mg/kg†/day div QD  1000 mg  15 (15-22.5) mg/kg†/day div QD

 1000 mg

Streptomycin‡ (IV) Pediatric 20 (20-30) mg/kg/day div QD  1000 mg  20 (20-30) mg/kg/day div QD

 1000 mg

  Adult 15 mg/kg/day div QD  1000 mg  15 mg/kg/day div QD

 1000 mg

  Geriatric 10 mg/kg/day div QD  750 mg  10 mg/kg/day div QD

 750 mg

Ciprofloxacin (PO)* Pediatric§ 20 (20-30) mg/kg/day  1500 mg  20 (20-30) mg/kg/day div BID

 1500 mg

  Adult 30 (20-30) mg/kg/day  1500 mg  30 (20-30) mg/kg/day div BID

 1500 mg

  Geriatric 20 (20-30) mg/kg/day  1500 mg  20 (20-30) mg/kg/day div BID

 1500 mg

Clofazimine (PO) ¥ Pediatric 1-2 mg/kg/day div QD  100 mg  No recommendation  
  Adult 1-2 mg/kg/day div QD  100 mg  No recommendation  
  Geriatric 1-2 mg/kg/day div QD  100 mg  No recommendation  
Isoniazid (PO) Pediatric 10 (10-15) mg/kg/day div QD  300 mg  No recommendation  
  Adult 5 (5-10) mg/kg/day div QD  300 mg  No recommendation  
  Geriatric 5 (5-10) mg/kg/day div QD  300 mg  No recommendation  
Linezolid (PO) Pediatric No recommendation  300 mg  No recommendation  
  Adult 600 mg QD¶  1200 mg  No recommendation  
  Geriatric No recommendation  1200 mg  No recommendation  

§ Available in a pediatric suspension formulation.

† Dosage based on ideal body weight:

     Men:  50 kg plus 2.3 kg/in over 5 feet of height.

     Women:  45 kg plus 2.3 kg/in over 5 feet of height.

 ‡ Dosage based on ideal body weight plus 40% of the excess weight.

* Ciprofloxacin is not a drug of first choice in the pediatric population due to reported adverse events related to joints and/or surrounding tissues. 

However, the American Academy of Pediatrics has stated that once risks and benefits have been assessed, it may be justified to use a fluoroquinolone

in mycobacterial infections caused by isolates susceptible to one.

¥ Start clofazimine with dose of 1-2 mg/kg/day up to a maximum of 100 mg once daily, until skin pigmentation appears; then 50 mg once daily;

may reduce to 50 mg thrice weekly after skin bronzing is present.

¶ The recommended frequency of administration of linezolid for acute bacterial infections is 10 mg/kg.  However, for chronic mycobacterial pulmonary

disease such as tuberculosis (and by extrapolation presumably for chronic NTM disease as well), some experts are prescribing it once-daily, as this

frequency appears to also be effective, with the possible advantage of being less likely to cause the long-term use-related adverse effects of neuropathy

(peripheral and optic) and anemia.  However, in one small prospective study of eight patients, the risk of neurotoxicity was not reduced, although it did

reduce hematological adverse effects (105).

What's New

Deresinski S et al. Natural History of Lymphadenitis due to Nontuberculous Mycobacteria (NTM). Clin Infect Dis. 2009 Jan 15;48(2):iv.

van Ingen J, et al.  Clinical Relevance of Mycobacterium szulgai in the Netherlands.  Clin Infect Dis 2008;46:1200-1205.



Clinical Manifestations

Laboratory Diagnosis




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