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Treatment of lung infection with Mycobacterium kansasii and other less common nontuberculous mycobacteria in adults

Treatment of lung infection with Mycobacterium kansasii and other less common nontuberculous mycobacteria in adults
Literature review current through: Jan 2024.
This topic last updated: Jan 10, 2024.

INTRODUCTION — Treatment of nontuberculous mycobacterial (NTM) infection of the lung is dependent upon a number of factors, including the species of the infecting organism. Depending on the geographic area, the most common slow growing NTM to cause lung disease are Mycobacterium avium complex (MAC), Mycobacterium kansasii, Mycobacterium malmoense, and Mycobacterium xenopi [1-4].

The treatment of lung infections due to M. kansasii and other non-MAC slow growing nontuberculous mycobacteria will be reviewed here. Management of pulmonary infections due to MAC and to rapidly growing mycobacterium (Mycobacterium abscessus, Mycobacterium fortuitum complex, and Mycobacterium chelonae) are discussed separately. (See "Treatment of Mycobacterium avium complex pulmonary infection in adults" and "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum".)

The epidemiology, microbiology, clinical manifestations, and diagnosis of NTM infection are discussed elsewhere. (See "Overview of nontuberculous mycobacterial infections" and "Epidemiology of nontuberculous mycobacterial infections" and "Diagnosis of nontuberculous mycobacterial infections of the lungs".)

M. KANSASII — M. kansasii was first described by Buhler and Pollack in 1953 as a cause of progressive lung disease [5]. In the United States, M. kansasii is the second most common slow growing nontuberculous mycobacterial (NTM) cause of pulmonary disease after MAC.

Rationale for treatment — Antimycobacterial treatment is indicated for most patients diagnosed with M. kansasii lung disease because untreated M. kansasii usually leads to chronic progressive lung disease [6]. Furthermore, outcomes are generally good with treatment of M. kansasii, with rare treatment failures and uncommon relapse. Thus, the benefits of treatment outweigh potential risks in most individuals.

Susceptibility testing — M. kansasii is a yellow pigmented mycobacterium that is typically inhibited by rifampin, rifabutin, isoniazid, ethambutol, ethionamide, cycloserine, sulfamethoxazole, clofazimine, linezolid, aminoglycosides, macrolides, and later generation fluoroquinolones [7-12]. We routinely have M. kansasii isolates tested for susceptibility to rifampin (which also corresponds to susceptibility to rifabutin) and macrolides. If rifampin resistance is detected, susceptibility testing of other potential agents (isoniazid, ethambutol, rifabutin, aminoglycosides, sulfonamides, and moxifloxacin) should be performed.

Resistance to rifampin has been described in patients who had prior rifampin exposure, particularly HIV-infected individuals [13], and has been associated with treatment failure. Rifampin resistance has also been associated with resistance to other agents, including isoniazid and ethambutol [7]. Isoniazid is generally less active against M. kansasii than against Mycobacterium tuberculosis (ie, minimum inhibitory concentration (MIC) to isoniazid is usually higher for M. kansasii) [13]; however, M. kansasii is usually susceptible to the serum levels of isoniazid achieved with typical dosing, and reported low level resistance to isoniazid (eg, at 0.2 or 1 mcg/mL) is not associated with clinical failure with isoniazid if rifampin is also used in the regimen [2].

Regimen selection

Drug-susceptible isolates — For most patients with M. kansasii, we suggest treatment with one of the following combination regimens:

One of the following daily dosed regimens:

Preferred daily regimen:

-Azithromycin 250 to 500 mg daily (or clarithromycin 1000 mg daily) PLUS

-Rifampin 450 (for patients <45 kg) or 600 mg (for patients >45 kg) daily PLUS

-Ethambutol 15 mg/kg daily

Alternative daily regimen:

-Isoniazid 300 mg daily PLUS

-Rifampin 450 (for patients <45 kg) or 600 mg (for patients >45 kg) daily PLUS

-Ethambutol 15 mg/kg daily

OR

An intermittently dosed regimen:

Azithromycin 500 mg (or clarithromycin 1000 mg) three times weekly PLUS

Rifampin 450 (for patients <45 kg) or 600 mg (for patients >45 kg) three times weekly PLUS

Ethambutol 25 mg/kg three times weekly

For individuals without cavitary disease, either an intermittently dosed regimen or a daily dosed regimen can be used; for those with cavitary disease, we favor a daily dosed regimen because of a lack of data on intermittently dosed regimens in that population [4].

M. kansasii treatment outcomes are generally good, with rare treatment failures and uncommon relapse [14]. There have been no randomized comparative trials evaluating treatment of M. kansasii lung disease, so recommendations are based on observational data as well as understanding of in vitro susceptibility.

Several studies have suggested good efficacy of the combination of a macrolide, rifampin, and ethambutol. In a prospective study of 18 patients, a thrice-weekly clarithromycin, ethambutol, and rifampin-containing regimen, given for an average of 13.5 months, was effective, with no relapses during a mean follow-up of 46 months [15]. A larger retrospective study treated 56 patients with the same three-drug regimen administered daily for a median duration of 21 months; all patients were cured, but relapse rates were not reported [9]. A retrospective study from Korea reported similar treatment outcomes between 49 patients treated with a macrolide-based versus an isoniazid-based regimen [16]. Other preclinical studies support the efficacy of macrolide-containing regimens. In a murine model, clarithromycin was the most active single agent, followed by rifampin and gatifloxacin [17]. Clarithromycin plus rifampin was the most active combination. The fluoroquinolone moxifloxacin also has good in vitro activity against M. kansasii, although there are no clinical studies evaluating its use [11,12,18].

Most observational data have evaluated the combination of isoniazid, rifampin, and ethambutol, given for 9 to 18 months, which had traditionally been the most commonly used regimen [19-24]. In two studies that evaluated a 12-month treatment with this combination (supplemented for the first two to three months with parenteral streptomycin) cure was reported in 83 to 89 percent of patients with relapse rates of 2.5 to 6.6 percent [19,23].

In other studies, M. kansasii infection has been associated with a more rapid culture conversion compared with other slowly growing NTM, and cure rates have ranged from 52 to 100 percent [21,22,24]. When non-mycobacterial deaths and patients lost to follow-up were excluded from the analysis, the cure rate was essentially 100 percent. In an observational study evaluating a two-drug regimen (rifampin and ethambutol) for nine months, cure rates were similarly high, but there was a somewhat higher relapse rate of 10 percent [20].

Rifampin-resistant isolates — Rifampin should not be used in patients with infection with rifampin-resistant isolates. Instead, a regimen consisting of at least three drugs should be selected based on results of susceptibility testing. Data informing the selection of one alternative regimen over another are extremely limited.

For such cases, we prefer a regimen that includes either a macrolide (azithromycin or clarithromycin) or moxifloxacin plus ethambutol and isoniazid. The excellent in vitro activity of clarithromycin and moxifloxacin against M. kansasii [12] suggests that multidrug regimens containing these agents and other drugs based on in vitro susceptibilities are likely to be effective for treatment of a patient with rifampin-resistant M. kansasii disease.

Other options include a regimen of high-dose isoniazid (900 mg/day), ethambutol, trimethoprim-sulfamethoxazole, and streptomycin. This regimen was associated with sputum clearance in 90 percent of treatment courses in a small study [13].

Linezolid has good in vitro activity (MIC range ≤0.25 to 2 mcg/mL), but there is no clinical experience in treating M. kansasii disease [10,12].  

Treatment duration — Treatment should be continued for 12 months [4]. The high cure rates with rifampin-based regimens suggest that a shorter regimen may eventually be available. However, to date, regimens of less than 12 months duration have had unacceptably high relapse rates [25] or lower cure rates [22] than three-drug regimens (sometimes supplemented with streptomycin) given for 12 or more months.

Role of surgery — In contrast to M. avium complex lung disease, the role of surgical intervention in the treatment of M. kansasii lung disease is minimal because of its high response to medical therapy. In very rare instances, surgical intervention may be useful for patients with fibrocavitary disease who fail therapy. Surgical treatment should only be undertaken by a team with substantial experience in treating NTM lung disease.

OTHER NONTUBERCULOUS MYCOBACTERIA — Other slowly growing nontuberculous mycobacteria (NTM), including M. malmoense, Mycobacterium simiae, Mycobacterium szulgai, and M. xenopi, can also cause chronic lung disease. It is difficult to make generalities about the therapy of disease caused by these organisms because there have been few randomized trials for the treatment of most of these organisms. In addition, for most of these organisms, there is not a demonstrable correlation between in vitro susceptibility to a specific drug and in vivo response. As with M. avium complex (MAC), more effective drugs are needed to improve outcomes.

M. malmoense — M. malmoense was first isolated in 1977 from respiratory specimens in four patients from Malmo, Sweden [26]. The organism is considered the second most pathogenic NTM after MAC in some parts of Northern Europe [27,28]. However, the clinical significance of M. malmoense is variable; in the Netherlands, 70 to 80 percent of isolates are considered clinically significant [29], whereas in the United States, M. malmoense is rarely a pathogen [30]. Disease typically occurs in a patient with underlying lung disease.

In vitro susceptibility — M. malmoense is a slowly growing non-pigmented mycobacteria that grows optimally at a pH of 6.0 [31]. Determination of drug susceptibility has been variable with poor correlation with clinical outcomes [32-34]. The initial strains were reported to be susceptible to ethambutol, ethionamide, kanamycin, and cycloserine and resistant to isoniazid, streptomycin, rifampin, and p-amino-salicylic acid. However, more recent data using an agar dilution method described susceptibility to rifampin, rifabutin, clarithromycin, cycloserine, clofazimine, and prothionamide [35]. Isolates were usually resistant to isoniazid, streptomycin, amikacin, and ciprofloxacin.

Regimen selection — The optimal treatment regimen is uncertain [36]. We suggest a three-drug combination consisting of the following:

Azithromycin 250 to 500 mg daily (or clarithromycin 1000 mg daily) PLUS

Rifampin 450 to 600 mg daily PLUS

Ethambutol 15 mg/kg daily

For patients with more severe disease, such as fibrocavitary disease, we also include one of the following agents:

Moxifloxacin 400 mg daily OR

Amikacin 15 mg/kg intravenously three times weekly

Treatment should be continued until sputum cultures are consecutively negative for at least 12 months.

Evidence supporting treatment regimens for pulmonary disease due to M. malmoense is limited mainly to two randomized pragmatic multicenter trials conducted by the British Thoracic Society [32,37]. In these studies, although not directly compared, certain three-drug regimens were associated with lower treatment failure and relapse rates than two-drug regimens (5 percent versus 12 percent). Among three-drug regimens, a macrolide-containing regimen compared with a fluoroquinolone-containing regimen resulted in a higher proportion of patients alive and cured at five years and was better tolerated. However, many of the differences in outcomes between the different arms of the two studies were modest and not statistically significant. Importantly, development of drug resistance was not reported.

In the one trial [37], clarithromycin, rifampin, plus ethambutol was compared with a regimen of ciprofloxacin, rifampin, and ethambutol. Overall, the macrolide-containing regimen had slightly better outcomes, with 38 percent alive and cured at given years compared with 20 percent with the ciprofloxacin regimen. Treatment failure occurred in 5 percent of patients in both study groups. All-cause mortality was high; 42 percent in the clarithromycin group versus 56 percent in the ciprofloxacin arm.

In a previous trial, treatment with rifampin plus ethambutol (two-drug regimen) was statistically equivalent to treatment with rifampin plus ethambutol plus isoniazid (three-drug regimen), with 38 and 44 percent of patients alive and cured at five years, respectively [32]. Treatment failure occurred in 12 percent of patients in the two-drug arm versus 9 percent in the three-drug arm. All-cause mortality was 33 to 35 percent in both arms whereas mycobacterial-related deaths occurred in 2 percent of the two-drug arm versus 6 percent in the three-drug arm.

In a retrospective study of 30 patients from the Netherlands with pulmonary M. malmoense disease, the overall clinical response to treatment (with various, usually macrolide-containing regimens) was good; 70 percent had an adequate response, 17 percent suffered a failure or relapse, and 13 percent died [29].

M. simiae — M. simiae was reported in 1965 by Karassova after the organism was isolated from rhesus monkeys [38]. The organism is typically found in water and has been reported most commonly from arid areas such as the desert southwestern United States and Israel [2]. In various cohorts, including from the US and Netherlands, fewer than 25 percent of M. simiae isolates are thought to be clinically significant [39-42]. Thus, when M. simiae is isolated in clinical samples, it more often a contaminant than a true pathogen. When it is a true pathogen, however, it is extremely difficult to treat effectively due to high levels of in vitro resistance.

In vitro susceptibility — M. simiae typically displays high levels of in vitro resistance to antimycobacterial drugs. In vitro resistance has been reported for rifampin, rifabutin, ethambutol, isoniazid, streptomycin, amikacin, and ethionamide, and resistance to clarithromycin and ciprofloxacin has been reported in over 70 percent of isolates [35,43]. Among 29 isolates from the Netherlands, most were susceptible to clofazimine, cycloserine, and prothionamide [35]. No synergy can be demonstrated between rifampin and ethambutol [34]; however, in vitro synergy was described between clofazimine and amikacin [44].

Regimen selection — The optimal treatment regimen is uncertain. We suggest a three-drug combination consisting of the following:

Azithromycin 250 to 500 mg daily (or clarithromycin 1000 mg daily) PLUS

Moxifloxacin 400 mg daily PLUS

Trimethoprim-sulfamethoxazole 1 DS tablet twice daily

For patients with fibrocavitary disease, because of the high level of in vitro resistance and documented in vitro synergy between clofazimine and amikacin [44], we supplement the regimen with clofazimine or clofazimine plus amikacin, if feasible based on availability and expected toxicity. In the United States, clofazimine is not commercially available but  through an expanded-access program or single-patient investigational new drug application.

Treatment should be continued until sputum cultures are consecutively negative for at least 12 months.

To date, although many regimens have been tried, there are no predictably effective drug combinations for treating M. simiae, and treatment outcomes have varied significantly between reports. Limited evidence suggests that the regimen suggested above is promising. In a study from Iran, treatment with clarithromycin, ofloxacin, and trimethoprim-sulfamethoxazole was effective in 24 of 26 patients with M. simiae pulmonary disease [45]. There were no recurrences in the cured patients during two years of follow-up. Treatment with a similar regimen (substituting moxifloxacin for ofloxacin) at the time of lung transplant for a patient with a chronic M. simiae infection resulted in good outcomes, with negative cultures at one year [46]. Similarly, in a patient with HIV/AIDS, the combination of clarithromycin, ethambutol, and ciprofloxacin successfully treated M. simiae infection [47].

In a study of 102 patients with pulmonary M. simiae in Israel, all were treated with rifampin (600 mg), clarithromycin (1000 mg), ethambutol (25 mg/kg for the first two months, then 15 mg/kg) [48]. Patients were treated for at least 12 months of negative cultures. There were no failures or relapses reported; there were five non-mycobacterial deaths during a median of 24 months of follow-up. However, others have described much poorer treatment outcomes with similar regimens, which is consistent with our clinical experience [2].

Preclinical studies have also suggested possible effective regimens. In an intravenous murine model, a combination of rifampin, clofazimine, and amikacin demonstrated activity against two strains of M. simiae [49]. In a disseminated murine model, ofloxacin and clarithromycin plus ethambutol were more active than clarithromycin alone [50].

M. szulgai — M. szulgai was first described in 1972 in seven patients with pulmonary and extrapulmonary disease [51]. Pulmonary M. szulgai disease is rare, but M. szulgai isolates are often clinically significant. Among 21 patients with M. szulgai isolation in the Netherlands, 76 percent were felt to be clinically significant [39]. Similarly, in a previous study from the United States, 57 percent of patients with M. szulgai were thought to be significant [52]. However, in South Korea, only 43 percent of patients had clinically significant disease [53]. Disease occurs most commonly in patients with underlying lung disease, and the presentation is similar to pulmonary tuberculosis.

In vitro susceptibility — M. szulgai is often susceptible to a broad array of antibiotics including rifampin, rifabutin, ethionamide, prothionamide, aminoglycosides, fluoroquinolones, macrolides, cycloserine, and clofazimine. The organism is usually resistant to isoniazid in vitro [35].

Regimen selection — The optimal regimen is uncertain, but most patients respond well to multidrug therapy. We suggest the following three-drug combination regimen:

Azithromycin 250 to 500 mg daily (or clarithromycin 1000 mg daily)

Rifampin 450 to 600 mg daily (or rifabutin 300 mg daily)

Ethambutol 15 mg/kg daily

Based on in vitro drug susceptibility test results, later generation fluoroquinolones such as moxifloxacin can be substituted for one of the above drugs.

Treatment should be continued until sputum cultures are consecutively negative for at least 12 months. Although shorter regimens may be possible, the number of patients described with regimens less than 12 months is too small to draw definitive conclusions.

Although the optimal treatment regimen has not been identified through randomized trials, most patients can be treated successfully with a macrolide-containing regimen that includes more than two drugs [39,54-57]. In a study that included 12 patients who were treated for M. szulgai infection, patients responded well to multiple treatment regimens, usually including rifampin, ethambutol, and either clarithromycin or ciprofloxacin [39]. In a small retrospective study from South Korea, the median duration of treatment was 8 months and all 9 patients that were treated responded well with no relapses after a median follow-up of 41 months [53]. Eight of nine patients were treated with isoniazid, rifampin, and ethambutol and one with azithromycin, rifampin, and ethambutol.

M. xenopi — M. xenopi was identified in 1959 from lesions on the skin of a South African toad [58]. The organism is one of the most common causes of pulmonary disease due to an NTM in some parts of Canada and Europe [3,27,59,60]. In the Netherlands, approximately 50 percent of isolates are reported to be clinically significant and most patients have underlying lung disease or other co-morbidities [61]. Based on a study from France, approximately one-third of patients present with cavitary disease, one-third with a solitary nodule, and one-third with an infiltrative form that is associated with a higher mortality rate [62]. Prognosis of patients with M. xenopi infection is poor with mortality rates ranging from 51 to 69 percent at five years [32,62].

In vitro susceptibility — Drug susceptibility results may be difficult to interpret and reports on susceptibility are not entirely consistent. Furthermore, there is poor correlation between in vitro activity and clinical outcomes.

In a study of 35 isolates in Italy, approximately 75 percent were susceptible to rifampin, isoniazid, ethambutol, and streptomycin [63]. Among 50 isolates from the Netherlands, most were susceptible to rifampin, rifabutin, streptomycin, amikacin, ciprofloxacin, clarithromycin, cycloserine, clofazimine, and prothionamide, but were resistant to isoniazid and ethionamide [35].

In another study from France, clarithromycin and moxifloxacin had the lowest minimum inhibitory concentration (MIC) values with all combinations tested showing synergism; amikacin-containing regimens demonstrated the greatest synergist activity [64].

Time-kill kinetics demonstrate similar activity of clarithromycin and moxifloxacin [65].

Regimen selection — The optimal treatment for M. xenopi has not been established [2]. Treatment of pulmonary disease is associated with high all-cause mortality and there is poor correlation between in vitro activity and clinical outcomes. We suggest use of at least three drugs, including:

Azithromycin 250 to 500 mg daily (or clarithromycin 1000 mg daily) or moxifloxacin 400 mg daily PLUS

Rifampin 450 to 600 mg daily (or rifabutin 300 mg daily) PLUS

Ethambutol 15 mg/kg daily

Either a macrolide or moxifloxacin-based regimen can be used. We use whichever drug has the best in vitro activity on susceptibility testing of the isolate, recognizing the limitations of such testing with M. xenopi.

For patients with fibrocavitary disease, we add amikacin, 15 mg/kg administered intravenously three times weekly.

Treatment should be continued until sputum cultures are consecutively negative for at least 12 months.

Our recommendations differ slightly from the British Thoracic Society guidelines, which recommend a four-drug regimen, including a macrolide, ethambutol, rifampin, with either a fluoroquinolone or isoniazid [66]. For patients with extensive fibrocavitary disease, a four-drug regimen is reasonable, and we would use a fluoroquinolone instead of isoniazid given the much better in vitro activity of the fluoroquinolones against M. xenopi [35].

A randomized, placebo-controlled study comparing macrolide- and fluoroquinolone-based regimens has been completed in France, but results are not yet available. Otherwise, evidence supporting the use of different regimens for M. xenopi come mainly from observational studies [14,60]. In a systematic review that included 48 studies and 1255 subjects, the overall treatment success at the end of therapy was 80 percent, with a 15 percent relapse rate; thus, 65 percent had a sustained, disease-free outcome [60]. Multiple drug regimens were used in these studies. INH-containing and aminoglycoside-containing regimens were associated with worse short- and long-term success whereas fluoroquinolone-containing regimens were associated with better long-term success.

Data from other studies have not suggested superiority of particular regimens. Two trials of two- and three-drug regimens reported overall poor results [32,37]. As an example, in a trial conducted by the British Thoracic Society that compared clarithromycin and ciprofloxacin, each in combination with rifampin and ethambutol, only 18 and 12 percent of patients, respectively, were alive and cured at five years [37]. In a retrospective study of 136 patients with pulmonary infection caused by M. xenopi, median survival was 10 months in untreated patients compared with 32 months in treated patients, and combination therapy with a rifamycin-containing regimen was associated with improved survival rates [62]. However, since these outcomes were not adjusted for comorbidity, the differences in survival cannot be definitively attributed to treatment. In a report on 49 patients with M. xenopi lung disease in the Netherlands, multiple different treatment regimens were used, but no specific drug combination showed consistently superior results [61].

Preclinical studies have also been used to inform appropriate regimen selection. In an intravenous mouse model, multiple different clarithromycin-containing regimens including clarithromycin alone showed more activity than a combination of isoniazid, rifampin, and ethambutol [67]. Azithromycin was demonstrated to be more active than clarithromycin in beige mice, and both macrolides were comparable to or better than rifampin, ethambutol, or clofazimine [68]. The combination of ethambutol and rifampin plus either clarithromycin or moxifloxacin had significant bactericidal activity after 12 weeks of therapy in a nude mouse aerosol model [64]. Amikacin-containing regimens had the highest efficacy against M. xenopi in this model.

MONITORING

Monitoring for side effects — Patients should be evaluated clinically for evidence of drug-related toxicity every one to two months while on therapy. This includes testing of the complete blood count, blood urea nitrogen (BUN), creatinine, and liver enzymes. For patients receiving aminoglycosides, audiograms and vestibular assessment should be performed routinely with the frequency of monitoring depending on the dose used and whether the patient has pre-existing hearing loss. Other specific testing depends on the drugs included in the regimen. As an example, color discrimination and visual acuity should be evaluated regularly in patients on ethambutol or linezolid.

Gastrointestinal intolerance – clarithromycin, azithromycin, fluoroquinolones, isoniazid, ethambutol, rifabutin, rifampin, or clofazimine

Abnormal liver function tests – clarithromycin, azithromycin, isoniazid, moxifloxacin, rifabutin, or rifampin

Low white blood cell count – rifabutin, rifampin, linezolid

Impaired visual acuity or color vision – ethambutol, linezolid

Decreased auditory function – aminoglycosides, azithromycin, or clarithromycin

Vestibular toxicity – aminoglycosides

Decreased renal function – aminoglycosides

Peripheral neuropathy – isoniazid, ethambutol, aminoglycosides, linezolid

Prolonged QTc – fluoroquinolones, macrolides, clofazimine

Decisions on dose modifications or drug discontinuations in the setting of toxicity are complex and depend on the type and severity of the toxicity and the importance of the offending drug in the patient's regimen. The threshold to discontinue a macrolide because of mild or moderate transaminitis is generally higher than that for discontinuation of ethambutol in the setting of objective visual deficits. Similarly, the decision to stop an aminoglycoside must be weighed against the risks and benefits to the patient. Consultation with an expert in nontuberculous mycobacterial infections is advised in such situations.

Monitoring for clinical response — The duration of treatment for most NTM-related pulmonary disease is determined by the microbiologic response to therapy, with the aim of achieving 12 months of negative sputum cultures. Therefore, we typically obtain acid-fast bacillus (AFB) sputum cultures every one to two months to monitor treatment efficacy and less often once sustained conversion has been documented. If the patient is not productive of sputum, we recommend a sputum induction with hypertonic saline. The likelihood of conversion to negative cultures is unlikely within the first few months of therapy for most pulmonary nontuberculous mycobacteria (NTM) species. However, earlier documentation of sputum conversion allows optimization of treatment duration, which is based on the length of time with negative cultures.

Lack of microbiological response after six months of therapy warrants evaluation for adherence to the drug regimen, susceptibility testing, and possible assessment of serum drug concentrations.

Therapeutic drug monitoring — The role of TDM in the management of patients with NTM infections remains unclear. (See "Treatment of Mycobacterium avium complex pulmonary infection in adults", section on 'Therapeutic drug monitoring'.)

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

After Mycobacterium avium complex (MAC), the most common slow-growing nontuberculous mycobacteria (NTM) to cause lung disease are Mycobacterium kansasii, Mycobacterium malmoense, and Mycobacterium xenopi, depending on the geographic area. (See 'Introduction' above.)

Untreated M. kansasii infection usually leads to chronic progressive lung disease, and treatment outcomes are generally good, with rare treatment failures and uncommon relapse. (See 'Rationale for treatment' above.)

For patients with M. kansasii lung disease, we suggest treatment with azithromycin, rifampin, and ethambutol (Grade 2C). Rifampin should not be used in patients with infection with rifampin-resistant isolates. Instead, a regimen consisting of at least three drugs (such as a macrolide or moxifloxacin plus ethambutol and isoniazid) should be selected based on susceptibility testing results. (See 'Regimen selection' above.)

For lung disease caused by other slowly growing NTM, including M. malmoense, Mycobacterium simiae, Mycobacterium szulgai, and M. xenopi, only limited clinical evidence informs the choice of an antimycobacterial regimen. Furthermore, for most of them, in vitro susceptibility to a specific drug does not correlate with in vivo responses.

The clinical significance of M. malmoense is geographically variable; it is a relatively frequent pathogen in Northern Europe but is rarely so in the United States. For M. malmoense infection, we suggest a macrolide plus rifampin plus ethambutol (Grade 2C). An additional agent is warranted for severe or fibrocavitary disease. (See 'M. malmoense' above.)

M. simiae, when isolated in clinical samples, is more often a contaminant than a true pathogen. When it does cause symptomatic infection, however, it is extremely difficult to treat effectively. For M. simiae infection, we suggest a macrolide plus moxifloxacin plus trimethoprim-sulfamethoxazole (Grade 2C). Additional agents are warranted for severe or fibrocavitary disease. (See 'M. simiae' above.)

Pulmonary M. szulgai disease is rare, but M. szulgai isolates are often clinically significant. Most infections respond well to multidrug therapy. For M. szulgai infection, we suggest a macrolide plus rifampin plus ethambutol (Grade 2C). (See 'M. szulgai' above.)

M. xenopi is one of the most common causes of NTM pulmonary disease in some parts of Canada and Europe; prognosis is poor. For M. xenopi infection, we suggest using at least three drugs, including a macrolide and/or moxifloxacin plus rifampin plus ethambutol (Grade 2C). An additional agent is warranted for severe or fibrocavitary disease. (See 'M. xenopi' above.)

For most NTM lung disease, treatment is continued until sputum cultures are consecutively negative for at least 12 months. Pulmonary disease caused by M. kansasii is treated for a fixed duration of 12 months. (See 'Treatment duration' above and 'Other nontuberculous mycobacteria' above.)

We typically obtain sputum cultures every one to two months following treatment initiation to monitor treatment response. Patients should also be evaluated clinically for evidence of drug-related toxicity every one to two months while on therapy. This generally includes testing of the complete blood count, blood urea nitrogen (BUN) and creatinine, liver enzymes, as well as color discrimination and visual acuity. (See 'Monitoring' above.)

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Topic 107702 Version 10.0

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