OBJECTIVE: Mycobacterium abscessus complex (MABC) commonly causes lung disease (LD) and has a high treatment failure rate of around 50%. In this study, our objective is to investigate specific CT patterns for predicting treatment prognosis and monitoring treatment response, thus providing valuable insights for clinical physicians in the management of MABC-LD treatment.
METHODS: We retrospectively assessed 34 patients with MABC-LD treated between January 2015 and December 2020. CT scores for bronchiectasis, cellular bronchiolitis, consolidation, cavities, and nodules were measured at initiation and after treatment. The ability of the CT scores to predict treatment outcomes was analyzed in logistic regression analyses.
RESULTS: The CT scoring system had excellent inter-reader agreement (all intraclass correlation coefficients, > 0.82). The treatment failure (TF) group (17/34; 50%) had higher cavitation diameter (p = 0.049) and extension (p = 0.041) at initial CT and higher cavitation diameter (p = 0.049) and extension (p =0 .045), consolidation (p = 0.022), and total (p = 0.013) scores at follow-up CT than the treatment success (TS) group. The changes of total score and consolidation score (p = 0.049 and 0.024, respectively) increased in the TF group more than the TS group between the initial and follow-up CT. Multivariable logistic regression analysis showed initial cavitation extension, follow-up consolidation extension, and change in consolidation extension (adjusted odds ratio: 2.512, 2.495, and 9.094, respectively, per 1-point increase; all p < 0.05) were significant predictors of treatment failure.
CONCLUSIONS: A high pre-treatment cavitation extension score and an increase in the consolidation extension score during treatment on CT could be alarm signs of treatment failure requiring tailor the treatment of MABC-LD carefully.

OBJECTIVE: This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections.
METHODS: We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran\'s Q and the I2 statistic. All analyses were performed using CMA V3.0.
RESULTS: A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively.
CONCLUSIONS: This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.

OBJECTIVE: To investigate the spatial heterogeneity of nontuberculous mycobacterial pulmonary disease (NTM-PD) in Shanghai.
METHODS: A population-based retrospective study was conducted using presumptive pulmonary tuberculosis surveillance data of Shanghai between 2010 and 2019. The study described the spatial distribution of NTM-PD notification rates, employing hierarchical Bayesian mapping for high-risk areas and the Getis-Ord Gi* statistic to identify hot spots and explore associated factors.
RESULTS: Of 1652 NTM-PD cases, the most common species was Mycobacterium kansasii complex (MKC) (41.9%), followed by Mycobacterium avium complex (MAC) (27.1%) and Mycobacterium abscessus complex (MABC) (16.2%). MKC-PD patients were generally younger males with a higher incidence of pulmonary cavities, while MAC-PD patients were more often farmers or had a history of tuberculosis treatment. MKC-PD hot spots were primarily located in the areas alongside the Huangpu River, while MAC-PD hot spots were mainly in the western agricultural areas. Patients with MKC-PD and MAC-PD exhibited a higher risk of spatial clustering compared to those with MABC-PD.
CONCLUSIONS: Different types of NTM-PD exhibit distinct patterns of spatial clustering and are associated with various factors. These findings underscore the importance of environmental and host factors in the epidemic of NTM-PD.

One hundred and eighteen sputum specimens suspected of Mycobacterium abscessus infection were collected. Species level identification of M. abscessus was performed by rpoB sequencing. Clonality analysis was done by multilocus sequence typing (MLST) for M. abscessus. Antibiotic susceptibility testing was performed for clarithromycin, amikacin, ciprofloxacin and moxifloxacin. Altogether 128 isolates were obtained and were subjected to rpoB gene sequencing for definite identification. Among them 59 were identified as M. abscessus, and these included 22 (37.28%) isolates of M. abscessus subsp. abscessus, 22 (37.28%) isolates of M. abscessus subsp. massiliense, and 15 (25.42%) isolates of M. abscessus subsp. bolletii. All 59 M. abscessus complex isolates were analyzed by MLST in this study. Certain sequence types (STs) were identified among the 59 isolates and were specific for each subspecies. Two STs (ST40 and ST33) were specific to M. abscessus subsp. abscessus, one ST (ST20) was specific to M. abscessus subsp. bolletii, and one ST (ST15) was specific to M. abscessus subsp. massiliense. In antibiotic resistance, clarithromycin susceptibility testing of 22 M. abscessus subsp. abscessus strains detected 15 (68.18%) resistant strains, while among 22 M. abscessus subsp. massiliense strains 5 (22.72%) exhibited resistance, and among 15 M. abscessus subsp. bolletii 8 (53.33%) were resistant. Our study revealed a significant level of antibiotic resistance in isolates of the M. abscessus complex.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are a group of bacteria that cause rare lung infections and are increasingly recognized as causative agents of opportunistic and device-associated infections in humans. In Gabon, there is a lack of data on NTM species identification and drug susceptibility. The aim of this study was to identify the frequency of NTM species and their genotypic susceptibility pattern to commonly used antibiotics for NTM infections in Gabon.
METHODS: A cross-sectional study was conducted at the CERMEL TB laboratory from January 2020 to December 2022, NTM subspecies identification and drug susceptibility testing to macrolides and aminoglycosides were performed using the genotype NTM-DR kit.
RESULTS: The study found that out of 524 culture-positive specimens, 146 (28%) were NTM, with the predominant group being Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABC). All MAC isolates were fully susceptible to macrolides and aminoglycosides, while five MABC isolates carried mutations indicative of reduced susceptibility to macrolide and aminoglycoside drugs.
CONCLUSIONS: These findings suggest that clinicians may use macrolides and aminoglycosides to manage NTM infections caused by MAC, but further investigation is required to determine MABC drug susceptibility.

Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance.
Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease?
In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance.
Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%).
In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy.
ClinicalTrials.gov; No.: NCT03038178; URL: www.
gov.

Mycobacterium abscessus (MABS) is the most pathogenic and drug-resistant rapidly growing mycobacteria. However, studies on MABS epidemiology, especially those focusing on subspecies level, are scarce. We aimed to determine MABS subspecies distribution and its correlation with phenotypic and genotypic antibiotic profiles. A retrospective multicenter study of 96 clinical MABS isolates in Madrid between 2016 to 2021 was conducted. Identification at the subspecies level and resistance to macrolides and aminoglycosides were performed by the GenoType NTM-DR assay. The MICs of 11 antimicrobials tested against MABS isolates were determined using the broth microdilution method (RAPMYCOI Sensititer titration plates). Clinical isolates included 50 (52.1%) MABS subsp. abscessus; 33 (34.4%) MABS subsp. massiliense; and 13 (13.5%) MABS subsp. bolletii. The lowest resistance rates corresponded to amikacin (2.1%), linezolid (6.3%), cefoxitin (7.3%), and imipenem (14.6%), and the highest to doxycycline (100.0%), ciprofloxacin (89.6%), moxifloxacin (82.3%), cotrimoxazole (82.3%), tobramycin (81.3%), and clarithromycin (50.0% at day 14 of incubation). Regarding tigecycline, although there are no susceptibility breakpoints, all strains but one showed MICs ≤ 1 μg/mL. Four isolates harbored mutations at positions 2058/9 of the rrl gene, one strain harbored a mutation at position 1408 of the rrl gene, and 18/50 harbored the T28C substitution at erm(41) gene. Agreement of the GenoType results with clarithromycin and amikacin susceptibility testing was 99.0% (95/96). The rate of MABS isolates showed an upward trend during the study period, being M. abscessus subsp. abscessus the most frequently isolated subspecies. Amikacin, cefoxitin, linezolid, and imipenem showed great in vitro activity. The GenoType NTM-DR assay provides a reliable and complementary tool to broth microdilution for drug resistance detection. IMPORTANCE Infections caused by Mycobacterium abscessus (MABS) are increasingly being reported worldwide. Identifying MABS subspecies and assessing their phenotypic resistance profiles are crucial for optimal management and better patient outcomes. M. abscessus subspecies differ in erm(41) gene functionality, which is a critical determinant of macrolide resistance. Additionally, resistance profiles of MABS and the subspecies distribution can vary geographically, highlighting the importance of understanding local epidemiology and resistance patterns. This study provides valuable insights into the epidemiology and resistance patterns of MABS and its subspecies in Madrid. Elevated resistance rates were observed for several recommended antimicrobials, emphasizing the need for cautious drug use. Furthermore, we assessed the GenoType NTM-DR assay, which examines principal mutations in macrolides and aminoglycosides resistance-related genes. We observed a high level of agreement between the GenoType NTM-DR assay and the microdilution method, indicating its usefulness as an initial tool for early initiation of appropriate therapy.

BACKGROUND: The prevalence of nontuberculous mycobacteria (NTM) infections is rising in people with cystic fibrosis (pwCF). NTM infection, especially infection with Mycobacterium abscessus complex (MABC), is commonly associated with severe lung deterioration. The current treatment modalities, including multiple intravenous antibiotics, frequently fail to achieve airway eradication. Although treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to modulate the lung microbiome, data regarding its role in eradicating NTM in pwCF is lacking. Our aim was to evaluate the impact of ETI on the rate of NTM eradication in pwCF.
METHODS: This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment.
RESULTS: Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05).
CONCLUSIONS: For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM.

Mycobacterium abscessus is a non-tuberculous mycobacterium (NTM) able to cause invasive pulmonary infections, named NTM pulmonary disease. The therapeutic approaches are limited, and infections are difficult to treat due to antibiotic resistance conferred by an impermeable cell wall, drug efflux pumps, or drug-modifying enzymes. The development of new therapeutics, intended as antimicrobials or drug limiting immunopathology, is urgently necessary. In this context, the preclinical murine models of M. abscessus represent a useful tool to validate and translate in vitro-proofed concepts. These in vivo models are essential for developing new targets and drugs, ameliorating our knowledge in combinatorial regimens of current existing antibiotic treatments, and repurposing existing drugs for new therapeutic options against M. abscessus infection. Thus, this review aims at providing an overview of the current state of the art of preclinical murine models to study M. abscessus lung infection and its exploitation for new therapeutic approaches. This review discusses the murine models available focusing on the different bacterial challenges (aerosol, intranasal, intratracheal, and intravenous administrations), murine genetic background, and additional bacterial related factors. Then, we discuss the successful preclinical models for M. abscessus respiratory infection exploited to study the efficacy and safety of new antimicrobials or to determine the best dosage and route of administration of existing drugs. Finally, we present the current murine models exploited to develop new therapeutic approaches to modulate the host immune response and limit immunopathological damage during M. abscessus lung disease. In conclusion, our review article provides an overview of current and available murine models to characterize acute or chronic infections and to study the outcome of new therapeutic strategies against M. abscessus lung infection.

Nontuberculous mycobacteria (NTM) are emerging pathogens increasingly implicated in healthcare facility-associated (HCFA) infections and outbreaks. We analyzed the performance of statistical process control (SPC) methods in detecting HCFA NTM outbreaks.
We retrospectively analyzed 3 NTM outbreaks that occurred from 2013 to 2016 at a tertiary care hospital. The outbreaks consisted of pulmonary Mycobacterium abscessus complex (MABC) acquisition, cardiac surgery-associated extrapulmonary MABC infection, and a bronchoscopy-associated pseudo-outbreak of Mycobacterium avium complex (MAC). We analyzed monthly case rates of unique patients who had positive respiratory cultures for MABC, non-respiratory cultures for MABC, and bronchoalveolar lavage cultures for MAC, respectively. For each outbreak, we used these rates to construct a pilot moving average (MA) SPC chart with a rolling baseline window. We also explored the performance of numerous alternative control charts, including exponentially weighted MA, Shewhart, and cumulative sum charts.
The pilot MA chart detected each outbreak within 2 months of outbreak onset, preceding actual outbreak detection by an average of 6 months. Over a combined 117 months of pre-outbreak and post-outbreak surveillance, no false-positive SPC signals occurred (specificity, 100%). Prospective use of this chart for NTM surveillance could have prevented an estimated 108 cases of NTM. Six high-performing alternative charts detected all outbreaks during the month of onset, with specificities ranging from 85.7% to 94.9%.
SPC methods have potential to substantially improve HCFA NTM surveillance, promoting early outbreak detection and prevention of NTM infections. Additional study is needed to determine the best application of SPC for prospective HCFA NTM surveillance in other settings.