International Journal of General Medicine Dovepress

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REVIEW

Nontuberculous Mycobacteria Lung Disease

(NTM-LD): Current Recommendations on
Diagnosis, Treatment, and Patient Management
International Journal of General Medicine downloaded from https://www.dovepress.com/ on 28-Oct-2022

Kriti Pathak 1, *, Stephanie Hart 1, *, Leah Lande 1,2

1
Division of Pulmonary and Critical Care Medicine, Lankenau Medical Center, Wynnewood, PA, USA; 2Lankenau Institute for Medical Research,
Wynnewood, PA, USA

*These authors contributed equally to this work

Correspondence: Leah Lande, Tel +1 610-642-3796, Email [email protected]

Abstract: Nontuberculous mycobacteria (NTM) are a group of ubiquitous environmental bacteria that can be found in soil, dust, and
For personal use only.

water. Mycobacterium avium complex (MAC) is the most common pathogen and the one most associated with chronic pulmonary
disease. In recent years, the prevalence of Mycobacterium avium complex-related pulmonary disease (MAC-PD) has increased and is
an emerging public health concern. This is due to a combination of environmental and geographic factors, dynamic changes in
organism virulence and antimicrobial susceptibility, and evolving host susceptibility. Given the dynamic nature of the disease,
management of NTM pulmonary disease (NTM-PD) often includes a multimodal approach including antimicrobial therapy, airway
clearance techniques, limiting environmental exposures, and reducing susceptibility to NTM through prevention of reflux and
maintenance of body weight. This review will explore the most recent concepts in the diagnosis, treatment, and management of
individuals with NTM pulmonary infection.
Keywords: non-tuberculous mycobacteria, Mycobacterium avium complex, MAC, Mycobacterium abscessus, environment,
bronchiectasis

Epidemiology
In the United States over the past two decades, numerous reports have shown that the prevalence rates for NTM infections
are increasing.1 This is likely multifactorial and due to a larger aging population, increasing environmental exposures,
increased incidence of chronic lung disease, and increased physician awareness of NTM.1 There exist over 180 species of
NTM, most of which do not cause clinical disease.2 Progressive pulmonary disease is most commonly caused by
Mycobacterium avium complex, which includes M. avium, M. intracellulare and M. chimera, as well as Mycobacterium
abscessus.3 Individuals who are immunosuppressed or have underlying lung disease such as chronic obstructive pulmonary
disease (COPD), bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, and alpha-1-antitrypsin deficiency are at
increased risk of acquiring NTM.4,5 The disease is also increasing in incidence in individuals without predisposing factors.
Given the ubiquitous nature and the increasing incidence of NTM associated lung disease, it becomes imperative to
understand how to adequately diagnose and treat this disease. This paper will review the current recommendations on
diagnosis, treatment and overall management of patients with non-tuberculous mycobacterial lung disease.

Signs and Symptoms

The symptoms of NTM-PD are varied and non-specific.6 The most common symptoms include a persistent cough,
fatigue, unintended weight loss, dyspnea, hemoptysis, increased mucus production, and night sweats.6,7 Chronic NTM
pulmonary infection affects 94% of patients and can cause progressive damage to the lungs and over time can impair
lung function.7

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 Pathak et al Dovepress

There are two main radiographic presentations for NTM-PD which are detected using high resolution CT imaging
(HRCT). The less severe form is referred to as nodular bronchiectasis and the more severe form causes cavitary lung
disease.3 Nodular bronchiectasis is seen in at least 50% of patients with MAC-PD.8 In this condition, the airways become
damaged and subsequently dilate and become scarred (Figure 1). This results in the loss of the ability to effectively clear
mucus, which then accumulates within the airways and serves as a nidus for NTM growth as well as for growth of other
respiratory pathogens.8 Nodules and bronchiectasis are most frequently encountered in the right middle lobe and lingula.9
Nodular bronchiectasis predominantly affects thin, older women of Caucasian or Asian descent, over half of which have
no prior history of smoking or underlying lung disease.7 Additional clinical characteristics associated with increased
susceptibility to NTM-PD include scoliosis, pectus excavatum, mitral valve prolapse, and mutations in the CFTR gene.10
Cavitary lung disease occurs as a result of progressive scarring or fibrosis of the lung which results in the formation of
cavities (Figure 2). These generally occur within the upper lobes of the lung.11 This condition can cause ongoing fibrosis
of the lung and respiratory failure over time. Individuals predominantly affected are prior smokers with underlying
COPD or structural lung disease. In addition, individuals with higher disease burden or with M. abscessus lung infection
are also more likely to have the cavitary form of NTM infection.11
While pulmonary manifestations of NTM remain the most encountered, these infections can also involve the skin,
bones, and lymph nodes.7 Disseminated infections rarely occur but are a risk in individuals who are
immunocompromised.7

Figure 1 (A and B) Nodular bronchiectatic changes in an 80-year-old woman with MAC pulmonary infection.

Figure 2 Cavitary bronchiectatic changes in a 65-year-old woman with MAC pulmonary infection.

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Table 1 Clinical, Radiographic, and Microbiologic Criteria for the Diagnosis of NTM
Clinical Symptoms Compatible Radiographic Findings Microbiologic Criteria
With NTM Infection Compatible With NTM Infection Confirming NTM Infection

● Cough ● Multiple nodules ● Two separate sputum cultures

● Fatigue ● Multifocal bronchiectasis positive for NTM
● Weight loss ● Nodules and bronchiectasis (usually ● One bronchoscopic culture
● Dyspnea within the RML or lingula) positive for NTM
● Hemoptysis ● Cavities ● Lung biopsy showing
● Fevers ● Alveolar infiltrates granulomatous inflammation or
● Night sweats positive AFB stain and positive
NTM culture

Diagnosis
A diagnosis of NTM-PD requires characteristic symptoms in addition to clinical evaluation with laboratory testing. The
American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) have published joint guidelines,
most recently updated in 2020, which outline the diagnostic criteria for NTM-PD. As per these guidelines, the affected
individuals must meet a combination of clinical, radiographic, and microbiologic criteria to establish a formal diagnosis
of NTM, as outlined in Table 1.12
While chest x-rays can be used to examine the lung, high resolution CT imaging is able to give sharper and more
detailed images of the lungs and is preferable for evaluation of NTM-PD.
The diagnosis of NTM-PD requires microbiologic confirmation from a laboratory with the capability to perform
accurate identification of NTM species and in vitro drug susceptibility testing. NTM infections have been classified into
rapidly growing and slowly growing mycobacteria.12 Rapidly growing mycobacteria usually grow in culture within
a week and include: M. abscessus, M. chelonae, and M. fortuitum. M. abscessus has three subspecies which include M.
abscessus abscessus, M. abscessus massiliense, and M. abscessus bolletii. It is important to distinguish between the
subspecies of M. abscessus as certain subspecies carry mutational resistance genes, which then affect treatment options.
Slowly growing mycobacteria include the most common species, MAC, as well as M. kansasii. On liquid media, these
take 10–14 days to grow; however, on solid media, can take up to 2–6 weeks to grow. M. kansasii is pathogenic and often
presents as upper lobe predominant cavitary disease.12
Positive cultures for NTM must be interpreted cautiously as these organisms can be present without causing overt
lung infection. Additionally, given their ubiquitous presence in the environment, they can sometimes contaminate
laboratory specimens.

Treatment
The management of NTM pulmonary disease (NTM-PD) is complex and warrants a multimodal approach that includes
antimicrobial therapy in carefully selected patients, mucus clearance techniques, implementation of environmental and
lifestyle modifications to limit exposure to NTM, maintenance of a healthy body weight, and minimizing gastroesopha­
geal reflux.12,13 First, we will discuss antibiotic therapy, as this is the mainstay of treatment for NTM-PD. Later, we will
discuss adjunctive therapies and ways in which to reduce environmental exposure to NTM.
When discussing treatment of NTM-PD, it is important to note that not all patients will require therapeutic
intervention. When making the decision on whether to treat a patient with NTM-PD, multiple considerations must be
made. These include microbiologic, radiographic, and clinical findings. A discussion between the clinician and patient is
necessary as treatment regimens may be difficult to tolerate due to adverse effects and require patients to adhere to
a lengthy duration of therapy, highlighting the importance of assessing a patient’s symptom burden and disease severity
and weighing this against potential risks of treatment.
As mentioned above, NTM-PD may manifest radiographically as nodular bronchiectatic or fibrocavitary disease. The
latter form of disease has been associated with more rapid progression and increased disease severity, so treatment is

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generally recommended for this cohort. This is in contrast to patients with nodular bronchiectatic disease, as these
patients tend to have variable clinical presentations so the decision to treat is often made on a case-by-case basis. Factors
that may lead a clinician to recommend therapy include severe symptomatology, progressive radiographic changes, or
a high burden of organisms as indicated by smear positivity.12 The latter has been demonstrated in studies to be an
independent predictor of radiographic progression.14,15 Conversely, an elderly patient with multiple comorbidities and
relatively mild disease may not benefit from treatment. If the decision has been made to observe a patient rather than treat
with antibiotics, the patient must be regularly assessed for disease progression and, if this occurs, initiation of therapy
should be reconsidered.7 Predictors of disease progression include low body mass index (specifically, a lower visceral fat
ratio), the presence of pulmonary cavitation (felt to be related to higher bacterial burden in the cavity), serum albumin
<3.5 g/dL (reflective of severe inflammation) and forced vital capacity (FVC) <80% predicted.16

Treatment Regimens and Antimicrobial Susceptibility Testing

Antibiotics are the mainstay of treatment for NTM-PD. Treatment regimens vary depending on which species of NTM is
isolated (more specifically, slowly growing versus rapidly growing species), severity of disease, as well as in vivo
antibiotic susceptibility testing. Recommendations for treatment have been outlined in a recently updated clinical practice
guideline published by the American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) in
2020.12 Treatment will be subdivided below based on the most common species that cause NTM-PD. It should be
mentioned that there have been no large-scale clinical trials that have tested these treatment regimens, with the exception
of a recently published trial investigating inhaled liposomal amikacin suspension, which will be discussed in more detail
below. Current recommendations are based on small series of patients and expert opinion. Table 2 summarizes dosing
guidelines for drug use in the management of NTM-PD. This was modified from the ATS/IDSA 2020 clinical practice
guideline. Please note that some medications require dosage adjustment for hepatic or renal impairment and this is not
reflected in Table 2.

Table 2 Dosing Guidelines for Antimicrobials Used More Commonly in the Treatment of NTM-PD
Drug Dosing

Daily Three Times Weekly

Azithromycin 250mg 500mg

Clarithromycin 500mg twice daily 500mg twice per day

Clofazimine 100mg N/A

Ethambutol 15mg/kg 25mg/kg

Isoniazid 5mg/kg up to max 300mg N/A

Linezolid 600mg N/A

Rifabutin 150–300mg (150mg if given with 300mg

clarithromycin)

Rifampin 10mg/kg (450 or 600mg) 600mg

Amikacin* 10–15mg/kg 15–25mg/kg

Streptomycin* 10–15mg/kg 15–25mg/kg

Amikacin liposome inhalation 590mg N/A

suspension**

Amikacin*** 250–500mg per day N/A

Notes: *Parenteral, dosages adjusted based on drug level monitoring. **Inhalational. ***Inhalation of parenteral formulation.

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Susceptibility-based treatment is preferred over empiric antibiotic therapy. In patients with MAC and M. abscessus,
susceptibility testing should be performed for macrolides and amikacin.12 Acquired macrolide resistance occurs due
a 23S rRNA gene mutation and acquired resistance to amikacin is due to a mutation in the 16S rRNA gene.12 Specific to
M. abscessus is the need for at least a 14-day incubation period to evaluate for potential inducible resistance to
macrolides via the erythromycin resistance methylase (erm(41)) gene.12 More on this will be discussed below. In patients
with M. kansasii, susceptibility testing should be done for rifampicin and clarithromycin and, if resistance to rifampicin is
encountered, susceptibility testing for other antibiotics such as amikacin and linezolid is recommended.13 There is
insufficient data to confirm the benefit of susceptibility testing for other antibiotics used in the treatment of NTM-PD, but
it is often used to guide therapy in macrolide-resistant organisms.

Treatment of MAC
ATS/IDSA guidelines suggest a three-drug regimen consisting of a macrolide, ethambutol, and a rifamycin to treat MAC-
PD.12 Retrospective studies have reported sputum conversion rates of 75–86% with macrolide-containing regimens.17,18
Macrolide susceptibility has been consistently shown to be a predictor of treatment success; thus, macrolides are the
foundation of MAC-PD therapy, specifically clarithromycin and azithromycin. Further proof of the superiority of
macrolides in the treatment of MAC-PD is the reduced rate of conversion of sputum cultures to negative and increased
mortality when macrolides are dropped from treatment regimens.19 No head-to-head studies have been performed
comparing clarithromycin and azithromycin; however, azithromycin is preferred due to its improved tolerability, less
drug–drug interactions, and equal efficacy.18,20 Ethambutol is important as a companion drug for preventing macrolide
resistance from emerging.12 The role of rifamycin is less clear but is thought to further reduce the development of
macrolide resistance.
Two randomized controlled trials have evaluated the efficacy of two-drug compared to three-drug regimens. A more
recent study published in 2014 evaluated the combination of clarithromycin and ethambutol with or without rifampicin
(taken daily for 12 months) in the treatment of MAC-PD and found improved rates of sputum culture conversion in those
treated with two-drug regimens (55% vs 40.6% in intention-to-treat analysis).21 The study has been criticized due to its
unblinded nature as well as small sample size (59 patients) with loss of patients during the study, resulting in the study
being underpowered to detect a between-group difference in rates of macrolide resistance. Serum clarithromycin
concentrations are lowered by the rifampicin-mediated induction of CYP3A4. In this study, the dose of clarithromycin
used was below that recommended by the ATS/IDSA, thus the addition of rifampicin may have led to ineffective serum
levels of clarithromycin, potentially influencing the results. According to the ATS/IDSA NTM guidelines, the currently
available literature is insufficient to determine the risk of acquired macrolide resistance with a two-drug rather than
a three-drug regimen, reiterating the recommendation for three-drug treatment regimens.12 Macrolide monotherapy is
strongly advised against, due to the increased risk of developing macrolide resistance.22,23
Intermittent dosing of therapy (ie, three times weekly) is recommended for patients with non-severe nodular
bronchiectatic disease.12 Three times weekly therapy in this patient population has been shown to be as effective as
daily therapy with regard to symptomatic and radiographic improvement as well as sputum conversion rates, although no
randomized controlled trials have been done to specifically evaluate this.12,18 Importantly, intermittent therapy has not
been shown to increase the rates of macrolide resistance.12,15 Escalation to daily therapy is advised in those patients who
fail to respond to intermittent dosing (ie, those who fail to convert sputum cultures to negative), as this has been shown to
achieve success in an additional 30% of patients.24
For patients with severe nodular bronchiectatic or fibrocavitary MAC-PD, daily triple-drug therapy is recommended
over three times weekly therapy.12 The addition of a parenteral aminoglycoside is suggested for patients with extensive
cavitary disease, those who progress despite daily three-drug therapy, and those with macrolide-resistant MAC-PD.12 The
recommended dosing interval is intramuscular streptomycin or intravenous amikacin 10–15mg/kg three times a week for
at least 2–3 months, although the dosing of amikacin in studies has varied and often requires dosage adjustment based on
patient tolerability.12,25,26 Lower doses at 5–8mg/kg may be considered in those older than age 50, with weight <50kg, or
in those receiving >3 months of parenteral therapy.13 Although not studied in any randomized controlled trials, experts

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recommend monitoring of serum drug concentrations for patients on amikacin or streptomycin who are at risk for
ototoxicity and nephrotoxicity.
Inhaled amikacin has also been recommended as add-on therapy for patients with MAC-PD who have failed to
convert sputum cultures to negative despite at least 6 months of guideline-directed treatment (refractory MAC-PD).12,27
A more recent prospective randomized controlled trial (CONVERT) published in 2018 investigated the safety and
efficacy of amikacin liposome inhalation suspension (ALIS) added to standard three-drug regimens in 336 patients with
refractory MAC-PD.27 The investigators found that 29% of patients treated with ALIS achieved culture conversion
compared to only 8.9% of patients on guideline-directed therapy alone.27 Patients treated with ALIS experienced more
primarily respiratory adverse events, including hoarseness, cough, dyspnea, and bronchospasm; however, serious adverse
events were comparable between groups, including respiratory infections and hemoptysis.27 Audiologic adverse effects
were similar between groups.27 Of note, most adverse effects were mild to moderate in severity and typically reported in
the first month of treatment with ALIS, with less incidence thereafter.27 Based on results of this study, ALIS was FDA
approved for difficult-to-treat MAC-PD at a dosage of 590mg daily.27

Treatment of M. abscessus
Mycobacterium abscessus is a unique species of NTM in that certain strains of M. abscessus not only develop mutational
macrolide resistance via the 23S rRNA gene but can also induce macrolide resistance in the presence of a macrolide, thus
macrolide susceptibility testing becomes very important when managing patients with M. abscessus, as briefly mentioned
above.19 Inducible or mutational resistance is conveyed through a functional erm(41) gene, which may be found in M.
abscessus subspecies M. abscessus and M. bolletii.12,19 The erm(41) gene is non-functional in subspecies M. massiliense,
which renders this subspecies susceptible to macrolides.12,19 Not surprisingly, subspecies without inducible macrolide
resistance were more likely to convert sputum cultures to negative and thus have improved treatment outcomes compared
to those with macrolide resistance, highlighting the importance of macrolide therapy in treatment of M. abscessus.12,35,36
A macrolide-containing three-drug regimen is preferred in patients without inducible or mutational macrolide
resistance.12 In strains with inducible resistance, a macrolide-containing regimen is still suggested for its immunomo­
dulatory effects alone but should not be considered an active drug in the treatment regimen, which should consist of at
least 3 additional drugs active against the subspecies in the initial phase of treatment and at least 2–3 active drugs in the
continuation phase of therapy, guided by in vitro susceptibility testing.12 Therapy is recommended to be given daily and
should be continued for >12 months, although the optimal treatment duration is not clear.12 A typical treatment regimen
includes induction therapy with ≥2 parenteral antibiotics (choices include amikacin, imipenem, tigecycline) for 6–8
weeks, followed by maintenance therapy with clofazimine and inhaled amikacin, with or without azithromycin.12

Treatment of M. Kansasii
Rifampicin-susceptible strains of M. kansasii pulmonary disease (PD) should be treated with rifampicin, ethambutol, and
either isoniazid or a macrolide.12 Unlike with MAC-PD, patients with M. kansasii PD should not be treated with
parenteral aminoglycosides, as the previously mentioned three-drug regimens have been shown to be highly effective in
achieving culture conversion and thus the risk of adverse effects with amikacin or streptomycin likely outweigh any
potential benefit.12 The ATS/IDSA panel do suggest that a parenteral aminoglycoside may be considered in patients with
M. kansasii PD only if a rifampicin cannot be used or in very severe disease.12

Second-Line Therapies
Macrolide resistance presents a challenge when treating patients with MAC-PD. As alluded to above, the development of
macrolide-resistant MAC-PD conveys poorer patient outcomes and increased mortality.23 In this patient group, the
addition of second-line drugs is usually necessary. Options include clofazimine, bedaquiline, and delamanid.
Two observational studies performed in the last decade have evaluated the safety, efficacy, and clinical and
microbiologic outcomes in patients treated with clofazimine, which is an oral bactericidal antimicrobial agent primarily
used in the treatment of leprosy and which has been shown to have excellent in vitro activity against MAC and other
species of NTM.13,28 Clofazimine has been shown to be safe and tolerable in the treatment of NTM-PD.29,30 Most

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commonly, patients report skin discoloration while taking the medication, although this typically does not lead to drug
discontinuation.29 One particular study evaluating outcomes found that 95% of patients treated with a clofazimine-
containing regimen converted from positive to negative sputum cultures in a mean of 4.5 ± 4.2 months.31
Bedaquiline is a diarylquinolone used to treat multidrug-resistant tuberculosis (MDR-TB) and has shown promise as
salvage therapy for MAC and M. abscessus in small case series.32,33 In patients treated with bedaquiline, rifabutin rather
than rifampin should be used if a rifamycin is needed, because both bedaquiline and rifampin are metabolized by
cytochrome P-450.13
Much like bedaquiline, delamanid is a novel drug used in the treatment of MDR-TB and has demonstrated in vitro
activity against certain strains of NTM but in vivo activity has not been tested.34 There have not been any clinical trials
published to date regarding the use of either drug in treatment of NTM-PD.
In patients with rifampicin-resistant M. kansasii disease or are unable to tolerate one of the first-line drugs, second-
line treatment includes the addition of a fluoroquinolone.12 Recommendations for intermittent versus daily dosing are
similar for M. kansasii PD as with MAC-PD.12

Role of Surgery
Surgical resection by a surgeon experienced in mycobacterial lung disease may be considered in patients with localized
disease, such as focal bronchiectasis or cavitary disease, and in patients with refractory severe symptoms (ie, hemoptysis)
who fail to respond to medical management.12,37,38 Previous studies evaluating surgical outcomes after adjunctive
surgery have found variable rates of sputum culture conversion and post-operative complications, ranging from 57–
100% and 0–46%, respectively.12,37 Improved outcomes have been achieved in patients with negative sputum cultures
pre-operatively and in patients who undergo a partial lung resection rather than a pneumonectomy.12,37 However, the
optimal surgical candidate and timing of surgical invention has not been clearly defined and the long-term outcomes of
patients undergoing adjunctive surgery are not yet known.

Treatment Duration, Therapeutic Goals, and Surveillance

Once initiated, the recommended duration of treatment for NTM-PD is at least 12 months after sputum cultures convert
from positive for infection to negative (referred to as culture conversion); however, the optimal duration of therapy is not
known.12,16 The goal of treatment includes both clinical and radiologic improvement and achievement of negative
sputum cultures whilst limiting treatment-associated adverse effects. Sputum cultures should be monitored at regular
intervals. Close monitoring of patients while on treatment for NTM-PD is very important in order to identify treatment
failures and medication side effects early. As alluded to above, patients may have difficulty adhering to therapy so it is
prudent to ask about a patient’s adherence to all prescribed medications at regular intervals. It is important to assess for
adverse effects of treatment in patients with NTM. Some of the most common side effects include adverse gastro­
intestinal, audiologic (hearing loss, tinnitus), and hepatotoxic effects, thus it is important to monitor patients clinically
and with regular audiologic examinations as well as routine bloodwork, including liver function testing.12 Medications
such as macrolides and clofazimine may prolong the QT interval, so a baseline EKG should be obtained and repeated at
regular intervals.12 Ethambutol may cause changes to visual acuity and/or color vision, so patients taking this medication
should be referred for routine ophthalmologic examination.12 Patients should also be counseled to monitor for peripheral
neuropathy from ethambutol. Rifampin can cause cytopenias and hepatotoxicity so regular bloodwork to monitor liver
function tests and complete blood counts should be performed. Patients on clofazimine should be made aware of the
potential for skin tanning and dryness.12 Streptomycins may cause nephrotoxicity and/or derangements in electrolytes, so
serum creatinine and metabolic profiles should be monitored in these patients.12

Adjunctive Therapies
Effective mucus clearance using a multimodal approach is an important part of the management of NTM-PD. This can be
achieved through the use of non-pharmacologic methods such as aerobic exercise, manual chest percussion, postural
drainage maneuvers, chest wall oscillation vests, and positive expiratory pressure devices or through inhaled medications,

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such as beta agonists followed by nebulized hypertonic saline or N-acetyl cysteine. Oral mucolytics such as guaifenesin
are also useful in some patients.

Prevention
The recurrence rate of NTM-PD has been reported to be as high as 30–50%.18 A study published in 2015 evaluated risk
factors for recurrence after successful treatment of NTM-PD and found increased rates of recurrence in patients with
the nodular bronchiectatic form of NTM-PD compared to those with fibrocavitary disease.39 In this study and others,
the majority of recurrences have been attributed to re-infection with a new genotype rather than recurrent infection with
the same isolate.18,39 Lessening exposure to NTM may reduce the risk of initial infection and recurrence after
treatment.
Since most reinfections come from repeated environmental exposures, an effort should be made by susceptible
patients to reduce environmental exposures to NTM, which include house dust,40,41 garden soils,42,43 and water sources
such as showerheads,44,45 sink faucets,46–48 underground water pipes,49–51 indoor swimming pools,52 hot tubs,53
continuous positive airway pressure machines,54 and humidifiers.55 There have been no studies proving that limiting
environmental exposure to NTM will reduce disease burden, but it appears to be prudent to try to reduce exposures
through some of the following household and lifestyle modifications.

Household Plumbing
Granular activated charcoal filters should not be used on faucets and showerheads as NTM can accumulate on their
surface, and they do not filter out mycobacteria. Instead, specialized 0.2 micrometer filters can be used, which do filter
out NTM, but also can become clogged and need to be changed frequently. NTM have been isolated in high numbers
from refrigerator taps and ice machines, and avoiding these should be considered in individuals at risk for NTM
infection. Showerheads and shower aerosols have also been found to harbor high concentrations of NTM, and are likely
the predominant mode of exposure of individuals to NTM in the environment.45,46,56–58 NTM adhere more to the biofilm
of plastic showerheads than metal, and these can be cleaned manually on a regular basis, and then disinfected by
immersing in undiluted bleach for 30 minutes or inserting into boiling water. Showerheads with larger diameter holes
likely produced less aerosol-containing NTM than those that produce a mist with smaller particles. Finally, patients
should be instructed to minimize the amount of time spent in the shower and to ventilate the bathroom as much as
possible.
Hot water heaters are likely serving as incubators for NTM within the home environment. They should be drained on
a regular basis, as the sediment which accumulates at the bottom of the tank contains the highest concentration of NTM.
In addition, the hot water heater temperature should be kept at 120°F, as tanks kept at this temperature were shown to
have less NTM growth than those kept at or below 110° F.59

Changes in Individual Behaviors and Habits

Tabletop humidifiers as well as humidifiers attached to central heating units have been shown to harbor NTM and should
be avoided.58 Continuous positive airway pressure machine humidifiers should be filled with either sterile water or
previously boiled water which has then cooled to room temperature.54 Hot tubs and steam rooms should be avoided, and
patients should consider avoiding the use of indoor pools,52,53 as this has been associated with NTM infection in
individuals with cystic fibrosis,60 with the air above the pool containing more NTM than the pool water itself.61
Individuals who garden should be counseled to moisten potting soil prior to using it in order to decrease the generation
of dust aerosols, and to consider wearing an N95 mask while gardening, as NTM have been found in natural and
commercial soil and peat and their aerosols, with concentrations as high as one million organisms per gram.40,42,62
Caution should also be used with exposure to household and vacuum cleaner dust which have been shown to contain
NTM.40,41

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Association with Gastroesophageal Reflux Disease

It has been hypothesized that MAC organisms may be ingested through drinking water and subsequently aspirated into
the respiratory tract in the setting of reflux, particularly silent nocturnal reflux.63 Such reflux and aspiration may also
result in local damage to the airways which then may predispose individuals to MAC-PD after environmental aerosol
exposure. In order to try to mitigate the possible contribution of reflux to MAC-PD, drinking water can be sterilized by
10 minutes of boiling and measures to try to prevent gastroesophageal reflux can be employed, such as not eating
immediately prior to lying down, avoiding foods that aggravate reflux and sleeping with the head of bed elevated above
30 degrees.64,65 Finally, since patients with a lower body mass index have an increased susceptibility to NTM infection,
trying to avoid weight loss is an essential aspect of the management of NTM infection.66

Conclusion
The diagnosis and management of MAC-PD requires a comprehensive understanding of the genetic and environmental
risk factors that predispose individuals to infections and progressive lung disease. Furthermore, a multimodal approach to
treatment including antimicrobial therapy, mucous clearance regimens, attenuation of reflux, and minimizing environ­
mental exposures is crucial to achieving long-term control of disease.

Disclosure
The authors report no conflicts of interest in this work.

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