scholarly journals Recent advances in nontuberculous mycobacterial lung infections

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1710 ◽  
Author(s):  
David Horne ◽  
Shawn Skerrett
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Natural History ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Leprae ◽  
Mycobacterium Abscessus ◽  
Recent Developments ◽  
Lung Infections ◽  
Ntm Lung Disease

Nontuberculous mycobacteria (NTM) are members of the Mycobacterium genus other than Mycobacterium tuberculosis complex and Mycobacterium leprae. NTM are widely distributed in the environment and are increasingly recognized as causes of chronic lung disease that can be challenging to treat. In this brief review, we consider recent developments in the ecology, epidemiology, natural history, and treatment of NTM lung disease with a focus on Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex.

scholarly journals Immunological Markers of Lung Disease Due to Non-Tuberculous Mycobacteria

2010 ◽  
Vol 29 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Andrew Lim ◽  
Caris Allison ◽  
Dino Bee Aik Tan ◽  
Ben Oliver ◽  
Patricia Price ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Disease ◽  
Plasma Levels ◽  
Nontuberculous Mycobacteria ◽  
T Cell Subsets ◽  
Adult Offspring ◽  
Immunological Markers ◽  
Successful Control ◽  
Ntm Lung Disease ◽  
Inflammatory Molecules

Lung disease due to nontuberculous mycobacteria (NTM) is a poorly understood condition that is difficult to treat. Treatment remains problematic as few tools are available to help clinicians monitor disease progression or predict treatment outcome. In this study, plasma levels of several inflammatory molecules and the frequency of circulating T cell subsets were measured in patients with NTM lung disease and known treatment status, and compared with their adult offspring and with unrelated healthy controls. Plasma levels of the chemokine CXCL10 and IL18 were assessed for associations with treatment efficacy. CXCL10 was higher in patients than adult offspring (p < 0.001) and unrelated controls (p< 0.001). Plasma CXCL10 was also lower in patients who responded well to therapy or who controlled their infection without requiring therapy, when compared to patients who did not respond to therapy (p= 0.03). Frequencies of activated (HLADR+) CD4+T cells were higher in patients than adult offspring (p< 0.001) and unrelated controls (p< 0.05), with the highest frequencies in individuals who had completed at least 6 months of treatment. Frequencies of activated (CD38+) CD8+T cells in most treatment responders were similar to unrelated controls. Low plasma levels of CXCL10 may reflect successful control of NTM lung disease with or without therapy. Compared with responders, patients who responded poorly to treatment generally had higher plasma levels of CXCL10 and IL18, and higher frequencies of activated CD8+T cells.

scholarly journals A Mycobacterium tuberculosis NBTI DNA gyrase inhibitor is active against Mycobacterium abscessus

2021 ◽  
Author(s):  
Uday S. Ganapathy ◽  
Rubén González del Río ◽  
Mónica Cacho-Izquierdo ◽  
Fátima Ortega ◽  
Joël Lelièvre ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Low Frequency ◽  
Dna Gyrase ◽  
Resistant Mutant ◽  
Mycobacterium Abscessus ◽  
Mutant Selection ◽  
Intrinsic Drug Resistance ◽  
Lung Infections ◽  
Gyrase Inhibitors

Fluoroquinolones – the only clinically used DNA gyrase inhibitors – are effective against tuberculosis (TB) but are in limited clinical use for non-tuberculous mycobacteria (NTM) lung infections due to intrinsic drug resistance. We sought to test alternative DNA gyrase inhibitors for anti-NTM activity. Mycobacterium tuberculosis Gyrase Inhibitors (MGIs), a subclass of Novel Bacterial Topoisomerase Inhibitors (NBTIs), were recently shown to be active against the tubercle bacillus. Here, we show that the MGI EC/11716 not only has potent anti-tubercular activity but is active against M. abscessus and M. avium in vitro . Focusing on M. abscessus , which causes the most difficult to cure NTM disease, we show that EC/11716 is bactericidal, active against drug-tolerant biofilms, and efficacious in a murine model of M. abscessus lung infection. Based on resistant mutant selection experiments, we report a low frequency of resistance to EC/11716 and confirm DNA gyrase as its target. Our findings demonstrate the potential of NBTIs as anti- M. abscessus and possibly broad spectrum anti-mycobacterial agents.

scholarly journals Fluorescent Reporter DS6A Mycobacteriophages Reveal Unique Variations in Infectibility and Phage Production in Mycobacteria

2016 ◽  
Vol 198 (23) ◽  
pp. 3220-3232 ◽  
Author(s):  
Oren Mayer ◽  
Paras Jain ◽  
Torin R. Weisbrod ◽  
Daniel Biro ◽  
Libby Ho ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Striking Difference ◽  
Mycobacterial Species ◽  
Fluorescent Reporter ◽  
Content Type ◽  
Specific Phage ◽  
Phage Production ◽  
Specific Restriction

ABSTRACTMycobacteriophage DS6A is unique among the more than 8,000 isolated mycobacteriophages due to its ability to form plaques exclusively on mycobacteria belonging to theMycobacterium tuberculosiscomplex (MTBC). Speculation surrounding this specificity has led to unsupported assertions in published studies and patents that nontuberculous mycobacteria (NTM) are wholly resistant to DS6A infection. In this study, we identified two independent nonessential regions in the DS6A genome and replaced them with an mVenus-expressing plasmid to generate fluorescent reporter phages Φ2GFP12 and Φ2GFP13. We show that even though DS6A is able to form plaques only on MTBC bacteria, infection of various NTM results in mVenus expression in transduced cells. The efficiency of DS6A in delivering DNA varied between NTM species. Additionally, we saw a striking difference in the efficiency of DNA delivery between the closely related members of theMycobacterium abscessuscomplex,M. abscessusandMycobacterium massiliense. We also demonstrated that TM4 and DS6A, two phages that do not form plaques onM. massiliense, differ in their ability to deliver DNA, suggesting that there is a phage-specific restriction between mycobacterial species. Phylogenetic analysis reveals that the DS6A genome has a characteristically mosaic structure but provided few insights into the basis for the specificity for MTBC hosts. This study demonstrates that the inability of the MTBC-specific phage DS6A to form plaques on NTM is more complex than previously thought. Moreover, the DS6A-derived fluorophages provide important new tools for the study of mycobacterial biology.IMPORTANCEThe coevolution of bacteria and their infecting phages involves a constant arms race for bacteria to prevent phage infection and phage to overcome these preventions. Although a diverse array of phage defense systems is well characterized in bacteria, very few phage restriction systems are known in mycobacteria. The DS6A mycobacteriophage is unique in the mycobacterial world in that it forms plaques only on members of theMycobacterium tuberculosiscomplex. However, the novel DS6A reporter phages developed in this work demonstrate that DS6A can infect nontuberculous mycobacteria at various efficiencies. By comparing the abilities of DS6A and another phage, TM4, to infect and form plaques on various mycobacterial species, we can begin to discern new phage restriction systems employed within the genus.

scholarly journals Toll-Like Receptor 2 Polymorphisms and Nontuberculous Mycobacterial Lung Diseases

2006 ◽  
Vol 13 (7) ◽  
pp. 818-819 ◽  
Author(s):  
Yon Ju Ryu ◽  
Eun Joo Kim ◽  
Won-Jung Koh ◽  
Hojoong Kim ◽  
O Jung Kwon ◽  
...  
Keyword(s):  
Lung Disease ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Nontuberculous Mycobacteria ◽  
Host Susceptibility ◽  
Korean Population ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
Ntm Lung Disease

ABSTRACT To investigate the occurrence of the Toll-like receptor 2 (TLR2) polymorphisms in patients with pulmonary disease caused by nontuberculous mycobacteria (NTM), TLR2 Arg677Trp and Arg753Gln polymorphisms were examined. TLR2 polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in the Korean population.

Validation of the Nontuberculous Mycobacteria (NTM) Module in NTM Lung Disease

2018 ◽  
Author(s):  
Chinmay Deshpande ◽  
Alexandra Quittner ◽  
Engels Chou ◽  
Ruchit Shah ◽  
Srimoyee Bose ◽  
...  
Keyword(s):  
Lung Disease ◽  
Nontuberculous Mycobacteria ◽  
Ntm Lung Disease

scholarly journals Nontuberculous Mycobacterial Lung Diseases Caused by Mixed Infection with Mycobacterium avium Complex and Mycobacterium abscessus Complex

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Sun Hye Shin ◽  
Byung Woo Jhun ◽  
Su-Young Kim ◽  
Junsu Choe ◽  
Kyeongman Jeon ◽  
...  
Keyword(s):  
Lung Disease ◽  
Treatment Outcomes ◽  
Mycobacterium Avium ◽  
Mixed Infection ◽  
Mycobacterium Abscessus ◽  
Limited Data ◽  
Content Type ◽  
Nontuberculous Mycobacterial Lung Disease ◽  
Conversion Rates ◽  
Ntm Lung Disease

ABSTRACT Mycobacterium avium complex (MAC) and M. abscessus complex (MABC) comprise the two most important human pathogen groups causing nontuberculous mycobacterial lung disease (NTM-LD). However, there are limited data regarding NTM-LD caused by mixed NTM infections. This study aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-LD caused by mixed infection with these two major NTM pathogen groups. Seventy-one consecutive patients who had been diagnosed with NTM-LD caused by mixed infection with MAC (M. avium or M. intracellulare) and MABC (M. abscessus or M. massiliense) between January 2010 and December 2015 were identified. Nearly all patients (96%) had the nodular bronchiectatic form of NTM-LD. Mixed infection with MAC and M. massiliense (n = 47, 66%) was more common than mixed infection with MAC and M. abscessus (n = 24, 34%), and among the 43 (61%) patients who were treated for NTM-LD for more than 12 months, sputum culture conversion rates were significantly lower in patients infected with MAC and M. abscessus (25% [3/12]) than in patients infected with MAC and M. massiliense (61% [19/31, P = 0.033]). Additionally, M. massiliense and M. abscessus showed marked differences in clarithromycin susceptibility (90% versus 6%, P < 0.001). Of the 23 patients who successfully completed treatment, 11 (48%) redeveloped NTM lung disease, with mycobacterial genotyping results indicating that the majority of cases were due to reinfection. Precise identification of etiologic NTM organisms could help predict treatment outcomes in patients with NTM-LD due to mixed infections.

scholarly journals Acetic Acid, the Active Component of Vinegar, Is an Effective Tuberculocidal Disinfectant

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Claudia Cortesia ◽  
Catherine Vilchèze ◽  
Audrey Bernut ◽  
Whendy Contreras ◽  
Keyla Gómez ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Mycobacterium Tuberculosis ◽  
Nontuberculous Mycobacteria ◽  
Acetic Acid Solution ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Resistant Bacteria ◽  
Content Type ◽  
Poor Countries ◽  
Immunosuppressed Patients

ABSTRACT Effective and economical mycobactericidal disinfectants are needed to kill both Mycobacterium tuberculosis and non-M. tuberculosis mycobacteria. We found that acetic acid (vinegar) efficiently kills M. tuberculosis after 30 min of exposure to a 6% acetic acid solution. The activity is not due to pH alone, and propionic acid also appears to be bactericidal. M. bolletii and M. massiliense nontuberculous mycobacteria were more resistant, although a 30-min exposure to 10% acetic acid resulted in at least a 6-log10 reduction of viable bacteria. Acetic acid (vinegar) is an effective mycobactericidal disinfectant that should also be active against most other bacteria. These findings are consistent with and extend the results of studies performed in the early and mid-20th century on the disinfectant capacity of organic acids. IMPORTANCE Mycobacteria are best known for causing tuberculosis and leprosy, but infections with nontuberculous mycobacteria are an increasing problem after surgical or cosmetic procedures or in the lungs of cystic fibrosis and immunosuppressed patients. Killing mycobacteria is important because Mycobacterium tuberculosis strains can be multidrug resistant and therefore potentially fatal biohazards, and environmental mycobacteria must be thoroughly eliminated from surgical implements and respiratory equipment. Currently used mycobactericidal disinfectants can be toxic, unstable, and expensive. We fortuitously found that acetic acid kills mycobacteria and then showed that it is an effective mycobactericidal agent, even against the very resistant, clinically important Mycobacterium abscessus complex. Vinegar has been used for thousands of years as a common disinfectant, and if it can kill mycobacteria, the most disinfectant-resistant bacteria, it may prove to be a broadly effective, economical biocide with potential usefulness in health care settings and laboratories, especially in resource-poor countries.

scholarly journals In VitroSynergy between Clofazimine and Amikacin in Treatment of Nontuberculous Mycobacterial Disease

2012 ◽  
Vol 56 (12) ◽  
pp. 6324-6327 ◽  
Author(s):  
Jakko van Ingen ◽  
Sarah E. Totten ◽  
Niels K. Helstrom ◽  
Leonid B. Heifets ◽  
Martin J. Boeree ◽  
...  
Keyword(s):  
Lung Disease ◽  
Nontuberculous Mycobacteria ◽  
Synergistic Activity ◽  
Mycobacterial Disease ◽  
Content Type ◽  
Susceptibility Tests ◽  
Ntm Lung Disease ◽  
Intracellular Targets ◽  
Mycobacterium Simiae

ABSTRACTDisease caused by nontuberculous mycobacteria (NTM) is increasing in frequency. The outcome of treatment for NTM lung disease is poor, particularly lung disease caused byMycobacterium simiaeandM. abscessus. Exploring synergy between active available drugs is a sensible way forward given the lack of new active drugs. We tested for synergy between amikacin and clofazimine, using standardized methods, in 564 consecutive clinical isolates identified as 21 species of rapidly growing mycobacteria, 16 clinicalM. aviumcomplex isolates, and 10M. simiaeisolates. Clofazimine and amikacin are each activein vitroagainst NTM; 97% (n= 548) of the rapid growers revealed MICs of clofazimine of ≤1 μg/ml, and 93% (n= 524) proved susceptible to amikacin. The combination showed significant synergistic activity in 56 of 68 (82%) eligibleM. abscessusisolates, 4 of 5M. chelonaeisolates, and 1M. fortuitumand 1M. cosmeticumisolate, with 4- to 8-fold decreases in MICs to both drugs. Significant synergy could also be demonstrated against allM. aviumcomplex andM. simiaeisolates, with fractional inhibitory concentrations of <0.5. Clofazimine and amikacin show significant synergistic activity against both rapidly and slowly growing nontuberculous mycobacteria. The safety and tolerability of adding clofazimine to amikacin-containing regimens should be tested in clinical trials, and the results of susceptibility tests for these two compounds and their combination merit clinical validation. Synergy between clofazimine and other antibiotics with intracellular targets should be explored.

scholarly journals Sensitivity of Fluorochrome Microscopy for Detection of Mycobacterium tuberculosis versus Nontuberculous Mycobacteria

1998 ◽  
Vol 36 (4) ◽  
pp. 1046-1049 ◽  
Author(s):  
Paul W. Wright ◽  
Richard J. Wallace ◽  
Nathan W. Wright ◽  
Barbara A. Brown ◽  
David E. Griffith
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nontuberculous Mycobacteria ◽  
Fluorescent Microscopy ◽  
Common Species ◽  
Rapidly Growing Mycobacteria ◽  
Clinical Criteria ◽  
Cavitary Disease ◽  
Low Incidence ◽  
Ntm Lung Disease ◽  
Respiratory Specimens

The results for 6,532 consecutive mycobacterial respiratory specimens collected from 1,040 patients from 1993 to 1995 in a Texas hospital were studied to determine the sensitivity of fluorescence microscopy for detection of Mycobacterium tuberculosisand nontuberculous mycobacteria (NTM). Smears were positive for acid-fast bacilli (AFB) in 63% (677 of 1,082) of specimens growingM. tuberculosis and 56% (638 of 1,148) of specimens growing the four most common species of NTM. Smear positivity by species was 58% (446 of 776) for M. avium complex, 51% (154 of 300) for rapidly growing mycobacteria (98% were M. abscessus), 78% (29 of 37) for M. kansasii, and 26% (9 of 35) for M. gordonae. Definite or probable disease by clinical criteria was present in 79% of patients withM. avium complex, 93% of patients with rapidly growing mycobacteria, 100% of patients with M. kansasii, and 0% of patients with M. gordonae. Patients with M. avium complex had a low incidence of AIDS (7%), and approximately 50% of non-AIDS patients had upper-lobe cavitary disease and 50% had nodular bronchiectasis. Only 23 of 6,532 (0.35%) of AFB smears were positive with a negative culture excluding patients on therapy for established mycobacterial disease. These studies suggest that NTM are as likely as M. tuberculosis to be detected by fluorescent microscopy in specimens from patients from areas endemic for NTM lung disease and at low risk for AIDS.

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