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Chest Jan 2022Mycobacterium abscessus is the second most common nontuberculous mycobacterial lung disease pathogen and comprises three subspecies: abscessus, massiliense, and... (Review)
Review
Mycobacterium abscessus is the second most common nontuberculous mycobacterial lung disease pathogen and comprises three subspecies: abscessus, massiliense, and bolletii. Subspecies identification is critical for disease management, as subspecies abscessus and bolletii have an inducible macrolide resistance gene [erm(41)] that results in clinical macrolide resistance. In contrast, subspecies massiliense does not have an active erm(41) gene and is therefore susceptible in vitro and clinically to macrolide-containing regimens. M abscessus is also vulnerable to acquired mutational macrolide resistance. Macrolide resistance has such a profoundly negative impact on M abscessus treatment response that preserving macrolide susceptibility with adequate companion drugs for macrolides is among the highest treatment priorities. After the macrolides, amikacin is regarded as the next most important drug for M abscessus treatment, although data validating that assertion are lacking. The considerations for preventing acquired macrolide resistance also apply to amikacin. Recent guidelines suggest that treatment should be guided by in vitro susceptibilities but, aside from macrolides and amikacin, no other antibiotics have a validated minimum inhibitory concentration for M abscessus. Currently, phase therapy (intensive and continuation) is recommended for M abscessus. This approach is successful with macrolide-susceptible M abscessus but not with macrolide-resistant M abscessus, in which even more aggressive therapy is not predictably successful. Newer drugs have become available, with encouraging in vitro activity against M abscessus, but in vivo validation of their superiority to current agents is not yet available. In the absence of unequivocally effective regimens, we offer suggestions for managing this treatment-refractory organism.
Topics: Amikacin; Anti-Bacterial Agents; Disease Management; Drug Resistance, Bacterial; Humans; Macrolides; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Tuberculosis, Pulmonary
PubMed: 34314673
DOI: 10.1016/j.chest.2021.07.035 -
Nature Reviews. Microbiology Jul 2020Infections caused by non-tuberculous mycobacteria (NTM) are increasing globally and are notoriously difficult to treat due to intrinsic resistance of these bacteria to... (Review)
Review
Infections caused by non-tuberculous mycobacteria (NTM) are increasing globally and are notoriously difficult to treat due to intrinsic resistance of these bacteria to many common antibiotics. NTM are diverse and ubiquitous in the environment, with only a few species causing serious and often opportunistic infections in humans, including Mycobacterium abscessus. This rapidly growing mycobacterium is one of the most commonly identified NTM species responsible for severe respiratory, skin and mucosal infections in humans. It is often regarded as one of the most antibiotic-resistant mycobacteria, leaving us with few therapeutic options. In this Review, we cover the proposed infection process of M. abscessus, its virulence factors and host interactions and highlight the commonalities and differences of M. abscessus with other NTM species. Finally, we discuss drug resistance mechanisms and future therapeutic options. Taken together, this knowledge is essential to further our understanding of this overlooked and neglected global threat.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 32086501
DOI: 10.1038/s41579-020-0331-1 -
Frontiers in Cellular and Infection... 2021(MABC is one of the most clinically relevant species among nontuberculous mycobacteria. MABC's prevalence has increased over the last two decades. Although these... (Review)
Review
(MABC is one of the most clinically relevant species among nontuberculous mycobacteria. MABC's prevalence has increased over the last two decades. Although these changes can be explained by improvements in microbiological and molecular techniques for identifying species and subspecies, a higher prevalence of chronic lung diseases may contribute to higher rates of MABC. High rates of antimicrobial resistance are seen in MABC, and patients experience multiple relapses with low cure rates. This review aims to integrate existing knowledge about MABC epidemiology, microbiological identification and familiarize readers with molecular mechanisms of resistance and therapeutic options for pulmonary infections with MABC.
Topics: Anti-Bacterial Agents; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Nontuberculous Mycobacteria
PubMed: 33981630
DOI: 10.3389/fcimb.2021.659997 -
Cell May 2022Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung...
Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.
Topics: Anti-Bacterial Agents; Bacteriophages; Cystic Fibrosis; Humans; Lung; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 35568033
DOI: 10.1016/j.cell.2022.04.024 -
Trends in Microbiology Oct 2021
Topics: Anti-Bacterial Agents; Bacterial Proteins; Cell Membrane; Cystic Fibrosis; Drug Resistance, Bacterial; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 34312062
DOI: 10.1016/j.tim.2021.06.006 -
Critical Reviews in Microbiology Aug 2023is a nontuberculous mycobacterium, associated with broncho-pulmonary infections in individuals suffering from cystic fibrosis, bronchiectasis, and pulmonary diseases.... (Review)
Review
is a nontuberculous mycobacterium, associated with broncho-pulmonary infections in individuals suffering from cystic fibrosis, bronchiectasis, and pulmonary diseases. The risk factors for transmission include biofilms, contaminated water resources, fomites, and infected individuals. is extensively resistant to antibiotics. To date, there is no vaccine and combination antibiotic therapy is followed. However, drug toxicities, low cure rates, and high cost of treatment make it imperfect. Over the last 20 years, bioinformatic studies on have advanced our understanding of the pathogen. This review integrates knowledge from the analysis of genomes, microbiomes, genomic variations, phylogeny, proteome, transcriptome, secretome, antibiotic resistance, and vaccine design to further our understanding. The utility of genome-based studies in comprehending disease progression, surveillance, tracing transmission routes, and epidemiological outbreaks on a global scale has been highlighted. Furthermore, this review underlined the importance of using computational methodologies for pinpointing factors responsible for pathogen survival and resistance. We reiterate the significance of interdisciplinary research to fight In a nutshell, the outcome of computational studies can go a long way in creating novel therapeutic avenues to control mediated pulmonary infections.
Topics: Humans; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Cystic Fibrosis; Anti-Bacterial Agents
PubMed: 35696783
DOI: 10.1080/1040841X.2022.2082268 -
Science (New York, N.Y.) Apr 2021Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as , have evolved to cause transmissible human infection. By analyzing the...
Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as , have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones.
Topics: Communicable Diseases, Emerging; Datasets as Topic; Epigenesis, Genetic; Evolution, Molecular; Gene Transfer, Horizontal; Genetic Fitness; Genome, Bacterial; Humans; Lung; Mutation; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Pneumonia, Bacterial; Virulence
PubMed: 33926925
DOI: 10.1126/science.abb8699 -
Nature Medicine May 2019A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung...
A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.
Topics: Adolescent; Cystic Fibrosis; Drug Resistance, Bacterial; Female; Genetic Engineering; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Phage Therapy
PubMed: 31068712
DOI: 10.1038/s41591-019-0437-z -
PLoS Pathogens May 2023Mycobacterium abscessus is a nontuberculosis mycobacterium (NTM) that has shown an exponential rise in its ability to cause disease. Due to its ubiquitous presence in... (Review)
Review
Mycobacterium abscessus is a nontuberculosis mycobacterium (NTM) that has shown an exponential rise in its ability to cause disease. Due to its ubiquitous presence in the environment, M. abscessus is widely implicated in secondary exacerbations of many nosocomial infections and genetic respiratory disorders, such as cystic fibrosis (CF). Contrary to other rapidly growing NTMs, the cell envelope of M. abscessus harbors several prominent features and undergoes modifications that are responsible for its pathogenesis. Compositional changes of the mycobacterial outer membrane (MOM) significantly decrease the presence of glycopeptidolipids (GPLs) and enable the transition from a colonizing, smooth morphotype into a virulent, rough morphotype. The GPLs are transported to the MOM by the Mycobacterial membrane proteins Large (MmpL), which further act as drug efflux pumps and confer antibiotic resistance. Lastly, M. abscessus possesses 2 type VII secretion systems (T7SS): ESX-3 and ESX-4, both of which have recently been implicated in host-pathogen interactions and virulence. This review summarizes the current knowledge of M. abscessus pathogenesis and highlights the clinically relevant association between the structure and functions of its cell envelope.
Topics: Humans; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Mycobacterium; Virulence
PubMed: 37200238
DOI: 10.1371/journal.ppat.1011318 -
Clinical Microbiology and Infection :... Jun 2024Nontuberculous mycobacteria (NTM) are highly abundant in soil, dust, and water sources, making human-pathogen contact frequent and recurrent. NTM represents over 200... (Review)
Review
BACKGROUND
Nontuberculous mycobacteria (NTM) are highly abundant in soil, dust, and water sources, making human-pathogen contact frequent and recurrent. NTM represents over 200 species/subspecies; some are considered strict or opportunistic pathogens. Mycobacterium abscessus, often regarded as one of the most antibiotic-resistant mycobacteria, is the second most frequent NTM pulmonary disease pathogen.
OBJECTIVES
To describe the epidemiology of M. abscessus through a literature review focusing on clinical aspects.
SOURCES
We conducted searches on PubMed and Web of Knowledge for articles published from 2010 to the present using the keywords 'Mycobacterium abscessus', 'Nontuberculous mycobacteria', and 'epidemiology'. Our search prioritized original reports on the occurrence of NTM and M. abscessus infection/disease.
CONTENT
Advanced molecular and genetic diagnostic techniques have refined the M. abscessus complex (MABC) microbiological classification over the last few decades. MABC can adhere to surfaces and form a biofilm. This characteristic and its resistance to common disinfectants allow these microorganisms to persist in the water distribution systems, becoming a constant reservoir. The frequency and manifestation of NTM species vary geographically because of environmental conditions and population susceptibility differences. MABC lung disease, the most frequent site of NTM infection in humans, is often seen in patients with underlying lung diseases such as bronchiectasis, whereas MABC disseminated disease is related to immunosuppression. Skin and soft tissue infections are associated with surgical or injection procedures. Epidemiological evidence suggests an overall increase in MABC infection and disease in the last decade.
IMPLICATIONS
Establishing the burden of this disease is challenging because of varying measures of incidence and prevalence, referral bias, and differences in medical practices and reporting. Furthermore, environmental and structural determinants, infection routes, and MABC pulmonary disease mechanisms require additional investigation. This review contributes to a better understanding of the epidemiology of MABC, which could inform clinical practice and future research.
Topics: Humans; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous
PubMed: 37778416
DOI: 10.1016/j.cmi.2023.08.035