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Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus , have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drug-sensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first- and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely successful. In general, the treatment duration is much longer for NTM diseases, compared to TB, and resection surgery of affected organ(s) is part of treatment for patients with NTM diseases that do not respond to the antibiotics treatment. Here, we discuss the epidemiology, diagnosis, and treatment modalities available for TB and NTM diseases of humans.

Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent than Mycobacterium tuberculosis, however, these organisms can cause diseases in both immunocompromised and immunocompetent hosts. As compared to tuberculosis, person-to-person transmission does not occur except with M. abscessus NTM species among cystic fibrosis patients. Lung is the most commonly involved organ, and the NTM-pulmonary disease (NTM-PD) occurs frequently in patients with pre-existing lung disease. NTM may also present as localized disease involving extrapulmonary sites such as lymph nodes, skin and soft tissues and rarely bones. Disseminated NTM disease is rare and occurs in individuals with congenital or acquired immune defects such as HIV/AIDS. Rapid molecular tests are now available for confirmation of NTM diagnosis at species and subspecies level. Drug susceptibility testing (DST) is not routinely done except in non-responsive disease due to slowly growing mycobacteria ( M. avium complex, M. kansasii) or infection due to rapidly growing mycobacteria, especially M. abscessus. While the decision to treat the patients with NTM-PD is made carefully, the treatment is given for 12 months after sputum culture conversion. Additional measures include pulmonary rehabilitation and correction of malnutrition. Treatment response in NTM-PD is variable and depends on isolated NTM species and severity of the underlying PD. Surgery is reserved for patients with localized disease with good pulmonary functions. Future research should focus on the development and validation of non-culture-based rapid diagnostic tests for early diagnosis and discovery of newer drugs with greater efficacy and lesser toxicity than the available ones.

Abstract Rationale Patients with idiopathic bronchiectasis are predominantly female and have an asthenic body morphotype and frequent nontuberculous mycobacterial respiratory infections. They also demonstrate phenotypic features (scoliosis, pectus deformity, mitral valve prolapse) that are commonly seen in individuals with heritable connective tissue disorders. Objectives To determine whether lumbar dural sac size is increased in patients with idiopathic bronchiectasis as compared with control subjects, and to assess whether dural sac size is correlated with phenotypic characteristics seen in individuals with heritable connective tissue disorders. Methods Two readers blinded to diagnosis measured anterior–posterior and transverse dural sac diameter using L1–L5 magnetic resonance images of 71 patients with idiopathic bronchiectasis, 72 control subjects without lung disease, 29 patients with cystic fibrosis, and 24 patients with Marfan syndrome. We compared groups by pairwise analysis of means, using Tukey’s method to adjust for multiple comparisons. Dural sac diameter association with phenotypic and clinical features was also tested. Measurements and Main Results: The L1–L5 (average) anterior–posterior dural sac diameter of the idiopathic bronchiectasis group was larger than those of the control group (P < 0.001) and the cystic fibrosis group (P = 0.002). There was a strong correlation between increased dural sac size and the presence of pulmonary nontuberculous mycobacterial infection (P = 0.007) and long fingers (P = 0.003). A trend toward larger dural sac diameter was seen in those with scoliosis (P = 0.130) and those with a family history of idiopathic bronchiectasis (P = 0.149). Conclusions Individuals with idiopathic bronchiectasis have an enlarged dural sac diameter, which is associated with pulmonary nontuberculous mycobacterial infection, long fingers, and family history of idiopathic bronchiectasis. These findings support our hypothesis that “idiopathic” bronchiectasis development reflects complex genetic variation in heritable connective tissue and associated transforming growth factor-β–related pathway genes.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered ‘good’ agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition.

We report a case of Mycobacterium riyadhense pulmonary disease in a patient who relocated from Saudi Arabia to Japan. Epidemiologic data and whole-genome analyses of the isolated strains suggested that the infection might have been acquired in Saudi Arabia and persisted, rather than a recent local acquisition in Japan.

Background. Nontuberculous mycobacteria (NTM) commonly colonize municipal water supplies and cause healthcare-associated outbreaks. We investigated a biphasic outbreak of Mycobacterium abscessus at a tertiary care hospital. Methods. Case patients had recent hospital exposure and laboratory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015. We conducted a multidisciplinary epidemiologic, field, and laboratory investigation. Results. The incidence rate of M. abscessus increased from 0.7 cases per 10 000 patient-days during the baseline period (January 2013–July 2013) to 3.0 cases per 10 000 patient-days during phase 1 of the outbreak (August 2013–May 2014) (incidence rate ratio, 4.6 [95% confidence interval, 2.3–8.8]; P < .001). Thirty-six of 71 (51%) phase 1 cases were lung transplant patients with positive respiratory cultures. We eliminated tap water exposure to the aerodigestive tract among high-risk patients, and the incidence rate decreased to baseline. Twelve of 24 (50%) phase 2 (December 2014–June 2015) cases occurred in cardiac surgery patients with invasive infections. Phase 2 resolved after we implemented an intensified disinfection protocol and used sterile water for heater-cooler units of cardiopulmonary bypass machines. Molecular fingerprinting of clinical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at a new hospital addition. We made several water engineering interventions to improve water flow and increase disinfectant levels. Conclusions. We investigated and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water. Healthcare facilities with endemic NTM should consider similar tap water avoidance and engineering strategies to decrease risk of NTM infection.

Background. Mycobacterium abscessus and Mycobacterium massiliense are grouped as the Mycobacterium abscessus complex. The aim of this study was to elucidate the differences between M. abscessus and M. massiliense lung diseases in terms of progression rate, treatment outcome, and the predictors thereof. Methods. Between 1 January 2006 and 30 June 2015, 56 patients and patients were diagnosed with M. abscessus and M. massiliense lung diseases, respectively. The time to progression requiring treatment and treatment outcomes were compared between the 2 groups of patients, and predictors of progression and sustained culture conversion with treatment were analyzed. In addition, mediation analysis was performed to evaluate the effect of susceptibility to clarithromycin on treatment outcomes. Results. During follow-up, 21 of 56 patients with M. abscessus lung diseases and 21 of 54 patients with M. massiliense lung diseases progressed, requiring treatment. No difference was detected in the time to progression between the 2 patient groups. Lower body mass index, bilateral lung involvement, and fibrocavitary-type disease were identified as predictors of disease progression. Among the patients who began treatment, infection with M. massiliense rather than M. abscessus and the use of azithromycin rather than clarithromycin were associated with sustained culture conversion. The difference in treatment outcomes was partly mediated by the organism's susceptibility to clarithromycin. Conclusions. Progression rates were similar but treatment outcomes differed significantly between patients with lung disease caused by M. abscessus and M. massiliense. This difference in treatment outcomes was partly explained by the susceptibility of these organisms to clarithromycin.

Non-tuberculous mycobacteria (NTM) include more than 160 ubiquitous, environmental, acid-fast-staining bacterial species, some of which may cause disease in humans. Chronic pulmonary infection is the most common clinical manifestation. Although patients suffering from chronic lung diseases are particularly susceptible to NTM pulmonary disease, many affected patients have no apparent risk factors. Host and pathogen factors leading to NTM pulmonary disease are not well understood and preventive therapies are lacking. NTM isolation and pulmonary disease are reported to rise in frequency in Europe as well as in other parts of the world. Differentiation between contamination, infection, and disease remains challenging. Treatment of NTM pulmonary disease is arduous, lengthy, and costly. Correlations between results of in vitro antibiotic susceptibility testing and clinical treatment outcomes are only evident for the Mycobacterium avium complex, M. kansasii, and some rapidly growing mycobacteria. We describe the epidemiology of NTM pulmonary disease as well as emerging NTM pathogens and their geographical distribution in non-cystic fibrosis patients in Europe. We also review recent innovations for the diagnosis of NTM pulmonary disease, summarize treatment recommendations, and identify future research priorities to improve the management of patients affected by NTM pulmonary disease.

We describe the epidemiology, diagnosis, and management of nontuberculous mycobacterial lymphadenitis cases detailed in a 28-year (1996-2023) multicenter cohort from Spain. The case numbers remained stable during the initial prospective phase (2013-2020), but a sharp decline was observed during 2021-2022. Disease onset occurred during spring or June in 45.9% of cases. Mycobacterium avium complex (43.1%) and M. lentiflavum (39.9%) were the most common species detected. M. lentiflavum affected mostly younger children from central Spain. The most common treatment strategy was complete surgical resection with (n = 80) or without (n = 88) antimicrobial drug treatment, followed by antimicrobial drugs alone (n = 76). Facial palsy developed in 10.4% of surgical cases. Adverse events because of antimicrobial drugs were uncommon. New fistula formation during follow-up occurred more in children managed with observation alone than in those treated with antimicrobial drugs alone (relative risk 2.7 [95% CI 1.3-5.3]; p = 0.014).

Mycobacterium nebraskense infection is rarely encountered; only 7 human cases have been reported worldwide since the initial report of 5 cases in Nebraska, USA, in 2004. We report 9 patients from Connecticut and 2 from Oregon, USA, who had M. nebraskense isolated from respiratory secretions; 7 patients met the American Thoracic Society/Infectious Diseases Society of America criteria for nontuberculous mycobacterial pulmonary disease. In 4 cases, the organism was isolated 1 time and caused brief or no symptoms. Most cases in Connecticut were reported after 2017. Antimicrobial drug susceptibility testing of 6 isolates showed clarithromycin susceptibility. In 2 cases, infection was refractory to treatment. The 9 Connecticut patients lived in 8 different towns; thus, a common water supply did not explain the high frequency of M. nebraskense isolation. M. nebraskense is a clinically significant cause of nontuberculous mycobacterial pulmonary disease in Connecticut; continued surveillance will be needed to determine its frequency and optimum treatment.