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Background. Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. Methods. Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. Results. Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. Conclusions. Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. Clinical Trials Registration. NCT00970801.

Background. An urgent UK investigation was launched to assess risk of invasive Mycobacterium chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and The Netherlands. Methods. Parallel investigations were pursued: (1) identification of cardiopulmonary bypass–associated M. chimaera infection through national laboratory and hospital admissions data linkage; (2) cohort study to assess patient risk; (3) microbiological and aerobiological investigations of heater-coolers in situ and under controlled laboratory conditions; and (4) whole-genome sequencing of clinical and environmental isolates. Results. Eighteen probable cases of cardiopulmonary bypass–associated M. chimaera infection were identified; all except one occurred in adults. Patients had undergone valve replacement in 11 hospitals between 2007 and 2015, a median of 19 months prior to onset (range, 3 months to 5 years). Risk to patients increased after 2010 from <0.2 to 1.65 per 10000 person-years in 2013, a 9-fold rise for infections within 2 years of surgery (rate ratio, 9.08 [95% CI, 1.81–87.76]). Endocarditis was the most common presentation (n = 11). To date, 9 patients have died. Investigations identified aerosol release through breaches in heater-cooler tanks. Mycobacterium chimaera and other pathogens were recovered from water and air samples. Phylogenetic analysis found close clustering of strains from probable cases. Conclusions. We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.

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.

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. Invasive Mycobacterium chimaera infections were diagnosed in 2012 in 2 heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak and to implement preventive measures. Methods. We collected water samples from operating theaters, intensive care units, and wards, including air samples from operating theaters. Mycobacterium chimaera strains were characterized by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. Results. We identified 6 male patients aged between 49 and 64 years with prosthetic valve endocarditis or vascular graft infection due to M. chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. Mycobacterium chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. chimaera strains from heater-cooler unit water circuits and air samples, and strains in 2 patient clusters. Conclusions. The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery.

Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with >5 floodings per year versus no flooding (rate ratio 1.38, 95% CI 1.26-1.52). Higher risk for NTM infection was associated with older age, rurality, and more flooding. Clinicians and public health professionals should be aware of increased risk for NTM infections, especially in similar environments.

Nontuberculous mycobacteria (NTM) are emerging as notable causative agents of opportunistic infections. To examine clinical significance, species distribution, and temporal trends of NTM in Denmark, we performed a nationwide register-based study of all unique persons with NTM isolated in the country during 1991-2022. We categorized patients as having definite disease, possible disease, or isolation by using a previously validated method. The incidence of pulmonary NTM increased throughout the study period, in contrast to earlier findings. Mycobacterium malmoense, M. kansasii, M. szulgai, and M. avium complex were the most clinically significant species based on microbiologic findings; M. avium dominated in incidence. This study shows the need for surveillance for an emerging infection that is not notifiable in most countries, provides evidence to support clinical decision-making, and highlights the importance of not considering NTM as a single entity.

Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens via autophagic machinery. Nontuberculous mycobacteria (NTMs) are ubiquitous microbes, have become increasingly prevalent, and are emerging as clinically important strains due to drug-resistant issues. Compared to Mycobacterium tuberculosis (Mtb), the causal pathogen for human tuberculosis, the roles of autophagy remain largely uncharacterized in the context of a variety of NTM infections. Compelling evidence suggests that host autophagy activation plays an essential role in the enhancement of antimicrobial immune responses and controlling pathological inflammation against various NTM infections. As similar to Mtb, it is believed that NTM bacteria evolve multiple strategies to manipulate and hijack host autophagy pathways. Despite this, we are just beginning to understand the molecular mechanisms underlying the crosstalk between pathogen and the host autophagy system in a battle with NTM bacteria. In this review, we will explore the function of autophagy, which is involved in shaping host–pathogen interaction and disease outcomes during NTM infections. These efforts will lead to the development of autophagy-based host-directed therapeutics against NTM infection.

Nontuberculous mycobacteria (NTM) infection is considered one of the most severe waterborne diseases. NTMs are widespread in fish pond water, which may serve as a significant exposure pathway for NTM infections, raising substantial concerns for public health. Consequently, the purpose of this study was to investigate the presence of NTM and determine their drug resistance in 120 fish pond waters (FPW). Totally, 120 water samples were gathered from FPW. After being filtered through a 0.45 μm membrane, the samples were decontaminated with 0.005% cetylpyridinium chloride and subsequently cultured on two Lowenstein-Jensen media. The cultures were incubated at 25 °C and 37 °C for a period of 8 weeks. The identification of different NTM species was conducted using molecular tests targeting the hsp65 , rpoB , and 16 S rDNA genes. The identification of NTM isolates included several species: M. marinum , M. chelonae , M. fortuitum , M. mucogenicum , M. lentiflavum , M. abscessus , M. gordonae , M. porcinum , M. kansasii , M. conceptionense , M. simiae , M. phocaicum , M. xenopi , and M. neoaurum . The NTM counts across the 110 water samples ranged from 10 to over 1,000 CFU/1,000 mL, with a median of 400 CFU/1000 mL. Furthermore, we documented two cases of skin infections attributed to M. marinum and M. chelonae , with the source of infection traced back to NTM-contaminated FPW. In conclusions, the study revealed that a significant proportion of FPWs were contaminated with NTM, presenting a potential health risk to humans. This study highlights the critical importance of implementing rigorous water quality control measures in fish breeding ponds, with a particular focus on ensuring the absence of NTM.