Disseminated nontuberculous mycobacterial (NTM) infections and NTM bacteremia in children

INTRODUCTION — Nontuberculous mycobacteria (NTM) are a miscellaneous collection of acid-fast bacteria that are widespread in the environment [1]. They have been isolated from numerous environmental sources including water, soil, food products, and domestic and wild animals [2]. Health care-associated transmission has occurred with medical equipment [3-5].

This topic will provide an overview of NTM disseminated infections and bacteremia in children. NTM lymphadenitis, SSTI, and pulmonary infections in children are discussed separately.

●(See "Nontuberculous mycobacterial lymphadenitis in children".)

●(See "Nontuberculous mycobacterial skin and soft tissue infections in children".)

●(See "Nontuberculous mycobacterial pulmonary infections in children".)

MICROBIOLOGY — More than 170 species of have been identified, not all of which have been documented to cause disease in humans [6-9].

●Classification – NTM pathogens are classified as rapidly growing or slowly growing (table 1). Rapidly growing species grow within seven days and include Mycobacterium fortuitum, Mycobacterium abscessus, and Mycobacterium chelonae. Slowly growing species require several weeks to grow and include Mycobacterium avium complex (MAC), Mycobacterium marinum, and Mycobacterium kansasii. (See "Microbiology of nontuberculous mycobacteria", section on 'Classification'.)

●Disease associations – NTM can cause a broad range of infections that vary depending on the particular NTM species and the host. In children, NTM cause four main clinical syndromes: lymphadenopathy, skin and soft tissue infection (SSTI), pulmonary disease (predominantly in children with underlying pulmonary conditions), and disseminated disease (predominantly in children with immune compromise).

M. avium complex (MAC) is the most common cause of disseminated NTM infection in children without central vascular access [10,11]. In children with indwelling vascular catheters, Mycobacterium mucogenicum and other species that are ubiquitous in water supplies have been reported [12-15].

The microbiology, culture requirements, and methods of speciation for NTM are discussed separately. (See "Microbiology of nontuberculous mycobacteria".)

EPIDEMIOLOGY — Estimates of the true burden of NTM infections in children are unavailable; in part because NTM infections may be asymptomatic and because NTM infections are not communicable, reporting of NTM infections is not required in the United States or many other countries [2]. Nonetheless, the overall prevalence of NTM disease appears to be increasing with time (possibly as a result of enhanced detection) [16-20]. One study estimated that disseminated NTM was seen in 3.7 per 100,000 inpatients [21]. (See "Epidemiology of nontuberculous mycobacterial infections".)

Disseminated NTM is rare in immune-competent children. In a prospective surveillance study, only 3 of 192 children with confirmed or probable NTM infection had disseminated disease [22]. Two of the cases occurred in immunocompromised children with intravenous catheter-related bacteremia. Most case series of disseminated NTM describe disseminated M. avium complex (MAC) in children with acquired immunodeficiency virus [23,24]. However, with the advent of potent antiretroviral therapy, the incidence of disseminated MAC in HIV-positive children has declined [11,25,26]. One study estimated that disseminated NTM was seen in 3.7 per 100,000 inpatients [21].

NTM are transmitted through environmental sources. Water (from both natural and treated sources) is a common reservoir [12-14,27-31]. Aquatic transmission of NTM is facilitated by the formation of biofilms, which permit survival under a variety of environmental conditions and, through detachment, allow dissemination of large numbers of organisms [32]. (See "Pathogenesis of nontuberculous mycobacterial infections".)

The respiratory and gastrointestinal tracts are the usual portal of entry for disseminated disease. However, direct inoculation may occur. NTM bacteremia in pediatric oncology patients has been reported after flushing central lines with tap water and when inadequate chlorination allowed proliferation of NTM species in water from hospital faucets [12-14].

The incubation periods are variable [9].

RISK FACTORS — Cases of nontuberculous mycobacteria (NTM) bacteremia or disseminated NTM disease in children have been reported among children with:

●Congenital defects in interferon-gamma and interleukin (IL)-12 synthesis and response pathways, including signal transducer and activator of transcription 1 (STAT1) mutations, and GATA2 mutations, which can be associated with M. avian complex infections and monocytopenia [33-40] (see "Mendelian susceptibility to mycobacterial diseases: Specific defects")

In a retrospective study in HIV-infected adults, disseminated NTM disease was associated with interferon-gamma neutralizing autoantibodies, a risk factor for disseminated NTM disease that is less well appreciated than congenital defects in interferon-gamma synthesis and response pathways [41].

While children with severe combined immunodeficiency, DiGeorge syndrome, chronic granulomatous disease, and hyperimmunoglobulin M syndrome also have defects in portions of the IL-12 pathway, they are not prone to disseminated infection with NTM species [42].

●Chemotherapy for malignancy [43,44]

●Solid organ (particularly organs other than the lungs) or hematopoietic cell transplantation [43,45-48] (see "Nontuberculous mycobacterial infections in solid organ transplant candidates and recipients")

●Intravenous catheter (particularly in immune-compromised patients) [10,15,22,44,49]

●Advanced HIV infection [11,23,24] (see "Mycobacterium avium complex (MAC) infections in persons with HIV")

CLINICAL FEATURES — Disseminated NTM disease occurs almost exclusively in immune-compromised children. Clinical features are nonspecific and may include fever, weight loss, sweating, diarrhea, generalized lymphadenopathy, generalized cutaneous lesions (picture 1), diffuse abdominal tenderness, and hepatosplenomegaly [24,25,46,50-53].

Symptoms and signs reflect the major sites of involvement (eg, bone marrow, lymphoreticular system, gastrointestinal tract, lungs). Skin lesions may be the first manifestation of disseminated infection [54]. Patients with HIV infection who have recently initiated antiretroviral therapy may present with immune reconstitution inflammatory syndrome. (See 'Immune reconstitution inflammatory syndrome' below.)

There is little information about the presenting signs of disseminated NTM in children. However, in one series of 20 HIV-positive children with disseminated M. avium complex (MAC), all 20 had persistent failure to gain weight, 18 had anorexia, 18 had abdominal pain/tenderness, and 16 had persistent or recurrent fever [24]. Fourteen had all four symptoms, and six patients had at least two of the four symptoms. Nine had intermittent diarrhea, three had persistent diarrhea, five had night sweats, and three had joint pain.

LABORATORY FEATURES — Laboratory findings of disseminated NTM disease are nonspecific and may include normocytic anemia, elevated lactate dehydrogenase, and elevated alkaline phosphatase [25,55]. Bacteremia may be intermittent and low grade [50,52,56,57].

DIAGNOSIS — Disseminated NTM disease should be suspected in immune-compromised children with skin lesions or nonspecific symptoms and signs (eg, weight loss, abdominal pain, fever, etc) without other plausible explanations.

Definitive diagnosis disease requires recovery of NTM from blood, bone marrow, liver, visceral lymph nodes, or other normally sterile body site [54,58,59]. Culture is essential to differentiate NTM from Mycobacterium tuberculosis, determine which species of NTM is causing infection, and perform drug-susceptibility testing [53].

More than 90 percent of individuals diagnosed with disseminated M. avium complex (MAC) have positive blood cultures [50]. Multiple blood cultures may be required because NTM bacteremia can be intermittent and low grade [52,56,57,60]. Mycobacterial blood cultures are collected in special media, different from the media used in standard bacterial blood cultures, and must be specifically requested. (See "Microbiology of nontuberculous mycobacteria", section on 'Culture'.)

Although optimal therapy for NTM generally requires identification at the species level, M. abscessus should be identified at the subspecies level. Two of the three subspecies of M. abscessus (subspecies abscessus and subspecies bolletii) have inducible macrolide resistance, whereas M. abscessus subspecies massiliense is macrolide susceptible and is associated with greater treatment success [61]. Identification of children likely to benefit from macrolide therapy is particularly important for M. abscessus, given the limited number of well-tolerated therapy options. (See 'Antimycobacterial therapy' below.)

In patients with suspected disseminated NTM and two negative blood cultures, diagnosis of disseminated NTM disease may require tissue specimens from involved sites (eg, bone marrow, liver, lymph node) for culture, acid-fast stains, and histopathology [50]. Intrathoracic, intra-abdominal, or retroperitoneal adenopathy may be accessible through fine-needle aspiration.

Ophthalmologic examination demonstrating granulomatous choroidal lesions or uveitis supports a diagnosis of disseminated NTM disease [62] but cannot differentiate disseminated NTM disease from miliary tuberculosis or tuberculous meningitis.

Histopathology demonstrating acid-fast bacilli (AFB) or granulomas supports the diagnosis of disseminated NTM disease in children with negative blood cultures. However, these findings do not distinguish NTM from M. tuberculosis, and the absence of these findings does not exclude NTM disease. In one series of immune-compromised (non-HIV) adults with disseminated NTM infection, only one-half had biopsy findings consistent with mycobacterial infection (eg, granulomas), and AFB smears were positive in fewer than 20 percent [63].

POSTDIAGNOSIS EVALUATION — NTM bacteremia in immunocompromised children should prompt evaluation for disease at remote sites; this may include computed tomography of the chest, abdomen, and pelvis. In a small series of pediatric oncology patients, four of five children with vascular catheter-associated NTM bacteremia had pulmonary nodules [43].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of disseminated nontuberculous mycobacterial disease in immune-compromised children includes:

●Disseminated fungal disease (see "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis", section on 'Clinical manifestations')

●Nocardiosis (see "Nocardia infections: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis')

●Actinomycosis

●Miliary tuberculosis (see "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis")

●Metastatic disease (in older patients)

Histopathology and/or microbiology studies are needed to differentiate among the possible etiologies.

TREATMENT

General measures

●Treatment of disseminated NTM in immune-compromised children should be undertaken in consultation with an expert in infectious diseases [9,50,53].

●If bacteremia or disseminated infection is associated with a vascular catheter, the catheter must be removed. It is rare to clear NTM bacteremia with the line in situ [15,64].

There are reports of isolated cases of NTM bacteremia being successfully treated with removal of the vascular catheter without antimycobacterial therapy [14]. However, given the potential for development of pulmonary nodules or other signs of disseminated disease in asymptomatic immunocompromised children [43], we suggest antimycobacterial therapy in addition to removal of the catheter.

Antimycobacterial therapy — Treatment for disseminated NTM infection or bacteremia is usually divided into two phases. The initial phase is more intensive and usually based upon the most likely susceptibility patterns. The continuation phase is less intensive and may be tailored according to susceptibilities, if susceptibilities are available.

Antimicrobial susceptibility — M. avium complex (MAC) is the most common NTM species associated with disseminated NTM disease in children. MAC is generally susceptible to macrolide antibiotics with good correlation between in vitro testing and clinical response [50].

M. mucogenicum is another potential cause of disseminated NTM among children with indwelling vascular catheters [12-14]. In vitro, M. mucogenicum is usually susceptible to macrolides, carbapenems, fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMX), and aminoglycosides [50].

Initial phase — The initial phase of antimycobacterial for disseminated NTM infection or bacteremia is more intensive and usually based upon the most likely susceptibility patterns of the isolate.

For children with disseminated NTM disease or NTM bacteremia, we suggest therapy with at least three drugs to which the isolate is susceptible (or likely susceptible if susceptibility studies are pending) for the first one to two months or until clinical and/or radiographic improvement is noted. A typical regimen may include (table 2):

●A macrolide (azithromycin or clarithromycin)

●Ethambutol

●A rifamycin (rifampin or rifabutin)

Amikacin, streptomycin, or a fluoroquinolone may be substituted for the macrolide or added as a fourth drug for patients who develop breakthrough MAC while receiving MAC prophylaxis or for patients in whom there is concern about macrolide resistance [50].

There are no randomized controlled trials evaluating therapy for disseminated NTM in children. In randomized and observational studies in adults with HIV and disseminated MAC, multidrug regimens that include macrolides have been associated with clinical and microbiologic improvement [65-67]. Monotherapy with clarithromycin reduced bacteremia, but nearly one-half of patients developed clarithromycin resistance, so monotherapy is contraindicated [68]. The addition of rifamycin to multidrug regimens that do not include macrolides is associated with shorter duration of bacteremia [69]. Although this benefit is not clear in macrolide-containing multidrug regimens, the addition of rifamycin appears to be associated with decreased development of macrolide-resistance [66,67]. This is likely due to rifamycins killing subpopulations that are macrolide resistant and macrolides killing subpopulations that are rifamycin resistant.

We generally prefer azithromycin to clarithromycin as the macrolide agent for patients with disseminated NTM infection. Although early studies of macrolides for NTM were conducted with clarithromycin, azithromycin may be preferable for at least two reasons. First, it can be administered once daily, which may increase adherence. Second, there is a potential for drug interaction between clarithromycin and rifamycins. In observational studies, coadministration of clarithromycin and rifamycin decreased serum concentrations of clarithromycin [70,71]. In many cases, the concentration was lower than the minimum inhibitory concentration (MIC) of the organism, which may lead to acquired antibiotic resistance [70]. Clarithromycin also appears to induce greater erythromycin ribosome methyltransferase gene (erm) expression and higher macrolide resistance than azithromycin for M. abscessus [72]. It is unclear the degree to which the benefit of combination therapy outweighs the risk of selecting for clarithromycin resistance. However, using azithromycin rather than clarithromycin permits combination therapy without potentially sacrificing the MIC.

Continuation phase — The continuation phase of antimycobacterial therapy is less intensive than the initial phase. The continuation phase usually begins after one to two months, when the child has demonstrated clinical improvement. The child is transitioned to two drugs, based upon the results of susceptibility studies. If possible, the two-drug regimen should be entirely oral.

Duration — The total duration of therapy usually is 6 to 12 months [50].

Monitoring adverse effects

Drug-specific effects — The antimycobacterial agents that are used to treat disseminated NTM infections and NTM bacteremia often are difficult to tolerate, and some have important toxicities (table 2). It may be challenging to determine which of the multiple medications is responsible for a given reaction. In addition, children with comorbid medical conditions may require additional medications that can interact with antimycobacterial therapy, particularly with rifamycins [17]. They also may have baseline hepatic or renal dysfunction, which may decrease medication tolerance.

Although most adverse effects are monitored clinically by assessing the patient for symptoms (eg, dizziness, vomiting), some specific parameters should be monitored at baseline or periodically as indicated below, even in children without comorbid medical conditions [50].

For children receiving combination rifampin (rifampicin), ethambutol, and macrolide therapy (with or without other agents), we suggest baseline complete blood count (CBC), electrocardiogram (ECG), alkaline phosphatase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Thereafter, the need for subsequent laboratory evaluation should be driven by symptoms and/or examination findings; scheduled laboratory evaluation may not be needed unless patients are receiving other marrow-suppressive or potentially hepatotoxic medications. If the regimen includes other agent(s), the specific parameters for those agents should be monitored as indicated below. Ethambutol is rapidly metabolized in children and ocular toxicity is extremely rare in children with normal renal function [73,74]. For the treatment of M. tuberculosis in children, the World Health Organization recommends vision screening if possible, but unavailability of vision screening is not a contraindication to using ethambutol [75].

For children receiving other regimens, we suggest baseline CBC, alkaline phosphatase, AST, and ALT followed by periodic monitoring of specific parameters for particular agents as follows:

●Rifamycins (rifampin, rifabutin, rifapentine) – Periodic CBC to evaluate granulocytopenia and thrombocytopenia (see "Rifamycins (rifampin, rifabutin, rifapentine)")

●Macrolides (eg, azithromycin, clarithromycin) – Baseline ECG before initiation of therapy to evaluate prolongation of the QT interval; periodic alkaline phosphatase, AST, and ALT during the first three months of therapy to evaluate hepatotoxicity (see "Azithromycin and clarithromycin", section on 'Adverse reactions')

●Isoniazid – Periodic monitoring of AST and ALT may be warranted in children with pulmonary NTM who are at increased risk for liver disease (eg, those with cystic fibrosis) or are receiving other medications that are metabolized in the liver (see "Isoniazid hepatotoxicity")

●Aminoglycosides (including amikacin and streptomycin) – Periodic hearing evaluations and renal function tests to monitor ototoxicity (both sensorineural hearing loss and vestibulitis) and nephrotoxicity; for children receiving amikacin, periodic amikacin levels

●Cefoxitin – Periodic CBC to monitor bone marrow suppression

●TMP-SMX – Periodic CBC to monitor bone marrow suppression

●Linezolid – Periodic CBC to monitor bone marrow suppression; periodic eye examinations by an ophthalmologist to evaluate optic neuritis

Immune reconstitution inflammatory syndrome — Immune reconstitution inflammatory syndrome (IRIS) refers to clinical worsening while receiving effective antimycobacterial chemotherapy and is well described in HIV-infected patients [76]. IRIS can result in worsening of existing symptoms (paradoxical IRIS) or new onset of opportunistic infections after immune reconstitution (unmasking IRIS). The most common symptoms of NTM IRIS include fever, abdominal pain, subcutaneous nodules, and suppurative lymphadenitis.

One series reported NTM-induced IRIS in 9 (5 percent) of 153 HIV-infected children 2 to 26 weeks after initiation of ART; MAC and Mycobacterium scrofulaceum were the most common isolates [77]. Another pediatric series documented IRIS from a number of causes, mycobacterial and otherwise, in up to 20 percent of HIV-infected children initiating ART; IRIS was associated with malnutrition and high viral loads [78].

Although IRIS has been associated with death (primarily from rapidly enlarging lymph nodes causing airway compression or expansile central nervous system lesions causing brainstem herniation), most IRIS cases are mild and can be managed with nonsteroidal anti-inflammatory medications or glucocorticoids [76]. (See "Immune reconstitution inflammatory syndrome".)

Response to therapy — Most patients who are treated for disseminated NTM infection have improvement in fever after two to four weeks and improvement in symptoms after four to six weeks of initial therapy [79]. However, clinical improvement may be delayed in patients with extensive disease or advanced immunosuppression. Patients who do not have clinical improvement after four to eight weeks of initial therapy should have NTM blood culture repeated. Clearance of NTM from the blood may take up to 12 weeks.

Treatment failure — Treatment failure is defined by the absence of a clinical response and persistence of mycobacteremia after 8 to 12 weeks of treatment [53].

For children with treatment failure, susceptibility testing should be repeated on the NTM isolate and a new treatment regimen instituted [53]. This regimen should be determined in consultation with an expert. It should include at least two drugs to which the isolate is susceptible and were not previously used (eg, amikacin, quinolones, streptomycin). In a small case series, interferon alpha therapy was associated with clinical and microbiologic improvement in children with interferon-gamma receptor mutations who failed to respond to initial therapy [80]. (See "Mendelian susceptibility to mycobacterial diseases: Specific defects", section on 'IFN-gamma receptor deficiencies'.)

PREVENTION

HIV-positive children

●Initiation of MAC primary prophylaxis – Primary prevention against M. avium complex (MAC) should be offered to for HIV-infected children with low CD4 cell counts [53]. Given the variation in normal CD4 cell count by age and that disseminated MAC has been seen in young children with high CD4 cell counts, prophylaxis should be offered to:

•Children <1 year: <750 cells/microL

•Children 1 to <2 years: <500 cells/microL

•Children 2 to 5 years: <75 cells/microL

•Children ≥6 years: <50 cells/microL

Before initiation of prophylaxis, a blood culture should be performed to exclude disseminated MAC [50,53]. Primary prophylaxis usually consists of a macrolide, either:

•Azithromycin 20 mg/kg (maximum dose 1200 mg) orally weekly, or

•Clarithromycin 7.5 mg/kg (maximum dose 500 mg) orally twice daily

For patients unable to tolerate macrolides, rifabutin (300 mg orally once daily with food for children older than five years) is a less effective alternative [81,82]. However, it should not be used until M. tuberculosis disease has been excluded (because monotherapy with rifabutin could lead to resistance). M. tuberculosis should be excluded by tuberculin skin test (or interferon-gamma release assays in children ≥2years of age [83]), assessment of M. tuberculosis risk factors, and, for children with acid-fast bacillus-smear positive respiratory specimens, polymerase chain reaction for M. tuberculosis. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

In randomized controlled trials in HIV-positive adults with decreased CD4 counts, the incidence of MAC bacteremia was reduced in patients who received MAC prophylaxis with rifabutin [84]; subsequent trials comparing macrolides and rifabutin found macrolides to be superior [81,82].

●Discontinuation of MAC primary prophylaxis

•Children <2 years of age – Discontinuation of prophylaxis is not recommended for children younger than two years of age [53].

•Children ≥2 years of age – For children ≥2 years of age who have received ≥6 months of antiretroviral therapy, primary MAC prophylaxis can be discontinued if they have had high CD4+ cell counts for ≥3 consecutive months; high CD4+ cell counts are defined according to age as follows [53]:

-Age 2 through 5 years: ≥200 cells/microL

-Age ≥6 years: ≥100 cells/microL

●Reinitiation of MAC primary prophylaxis – For children who have less optimal virologic control and a subsequent decline in CD4+ cell count, MAC primary prophylaxis should be restarted if:

•CD4+ cell count is <200 cells/microL for children 2 through 5 years of age

•CD4+ cell count is <100 cells/microL for children ≥6 years of age

Other immune-compromised hosts — Whether immune-compromised children who do not have HIV infection should receive prophylaxis for MAC depends upon the underlying disorder.

Given the low incidence of MAC in pediatric hematopoietic stem cell transplantation recipients [85], prophylaxis is not routinely recommended.

Use of macrolide prophylaxis after lung transplantation is controversial. There is evidence that long-term macrolide usage decreases intracellular killing of mycobacteria within macrophages [79]. However, preexisting M. abscessus lung disease in cystic fibrosis patients has been associated with disease recurrence posttransplantation [86].

OUTCOME — The morbidity and mortality for disseminated NTM disease is substantial [24]. The outcome often is related to immune system recovery (eg, initiation of antiretroviral therapy [ART] in HIV-infected children or reduction of immunosuppressive regimen in organ transplant recipients).

After the advent of potent ART, the incidence of disseminated NTM infection among children in the Perinatal AIDS Collaborative Transmission Study declined from 1.3 to 0.2 cases per 100 patient years [11]. Fewer opportunistic infections were associated with increased survival.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Nontuberculous mycobacteria".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology and risk factors – Disseminated nontuberculous mycobacterial (NTM) disease and NTM bacteremia occur in children with congenital or acquired immunodeficiency. (See 'Epidemiology' above and 'Risk factors' above.)

●Microbiology – Mycobacterium avium complex (MAC) is the most common cause of disseminated NTM infection in children without central vascular access. Among children with central vascular access, Mycobacterium mucogenicum and other species that are ubiquitous in water supplies have been reported. (See 'Microbiology' above.)

●Clinical and laboratory features – Clinical and laboratory features are nonspecific and may include fever, weight loss/failure to gain weight, night sweats, generalized lymphadenopathy, skin lesions (picture 1), abdominal tenderness, diarrhea, hepatosplenomegaly, anemia, elevated lactate dehydrogenase, and elevated alkaline phosphatase. Skin lesions may be the first manifestation of disseminated disease. (See 'Clinical features' above and 'Laboratory features' above.)

●Diagnosis – Definitive diagnosis of disseminated NTM disease requires recovery of NTM from blood, bone marrow, liver, visceral lymph nodes, or other normally sterile body site. Mycobacterial blood cultures are collected in special media, different from the media used in standard bacterial blood cultures, and must be specifically requested. (See 'Diagnosis' above.)

●Treatment – Treatment of disseminated NTM is usually undertaken in consultation with an expert in infectious diseases. If NTM bacteremia or disseminated disease is associated with a vascular catheter, the catheter must be removed. (See 'General measures' above.)

•We suggest that disseminated NTM disease be treated initially with at least three drugs to which the isolate is susceptible (or likely to be susceptible if susceptibility testing is pending) (Grade 2C). Appropriate drugs may include macrolides, ethambutol, rifamycins, aminoglycosides, and fluoroquinolones (table 2). The initial regimen is continued for one to two months or until there is clinical and radiographic improvement. (See 'Antimycobacterial therapy' above and 'Initial phase' above.)

•The initial treatment phase is followed by a continuation phase. We suggest that during the continuation phase, children with disseminated NTM infection be treated with two drugs to which the isolate is susceptible (Grade 2C). If possible, both of these drugs should be administered orally. The total duration of therapy is 6 to 12 months. (See 'Continuation phase' above and 'Duration' above.)

●Outcome – Survival of disseminated NTM disease is enhanced by immune system recovery (eg, initiation of antiretroviral therapy in HIV-infected children or reduction of immunosuppressive regimen in organ transplant recipients). (See 'Outcome' above.)