Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis

Waters, Valerie; Ratjen, Félix

doi:10.1002/14651858.cd010004.pub4

Cited by 9 publications

(3 citation statements)

References 55 publications

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“…These infections are caused by diverse NTM species, each with unique characteristics and susceptibilities to antimicrobial agents. Consequently, the first-line drugs, such as macrolides (e.g., azithromycin and clarithromycin), ethambutol, and rifamycins (e.g., rifampin and rifabutin), form the backbone of treatment due to their effectiveness against a broad spectrum of NTM species [ 49 ].…”

Section: Reviewmentioning

confidence: 99%

Unveiling the Clinical Diversity in Nontuberculous Mycobacteria (NTM) Infections: A Comprehensive Review

Bhanushali,

Jadhav,

Ghewade

et al. 2023

Cureus

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Once considered rare, nontuberculous mycobacterial (NTM) infections have garnered increasing attention in recent years. This comprehensive review provides insights into the epidemiology, clinical diversity, diagnostic methods, treatment strategies, prevention, and emerging research trends in NTM infections. Key findings reveal the global prevalence of NTM infections, their diverse clinical presentations affecting respiratory and extra-pulmonary systems, and the diagnostic challenges addressed by advances in microbiological, radiological, and immunological methods. Treatment complexities, especially drug resistance and patient adherence, are discussed, along with the vulnerability of special populations. The importance of early detection and management is underscored. Prospects in NTM research, including genomics, diagnostics, drug development, and multidisciplinary approaches, promise to enhance our understanding and treatment of these infections. This review encapsulates the multifaceted nature of NTM infections, offering a valuable resource for clinicians, researchers, and public health professionals.

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Section: Reviewmentioning

confidence: 99%

Unveiling the Clinical Diversity in Nontuberculous Mycobacteria (NTM) Infections: A Comprehensive Review

Bhanushali,

Jadhav,

Ghewade

et al. 2023

Cureus

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“…NTM infections in CF patients, particularly of M. abscessus , are associated with an increased morbidity and mortality, and a rapid lung function decline [237]. Moreover, the treatment is particularly challenging due to an intrinsic resistance to several antibiotics, including those commonly used in CF infections [238].…”

Section: Emerging Cf Pathogensmentioning

confidence: 99%

Quorum Sensing as Antivirulence Target in Cystic Fibrosis Pathogens

Scoffone

Trespidi

Chiarelli

et al. 2019

IJMS

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder which leads to the secretion of a viscous mucus layer on the respiratory epithelium that facilitates colonization by various bacterial pathogens. The problem of drug resistance has been reported for all the species able to colonize the lung of CF patients, so alternative treatments are urgently needed. In this context, a valid approach is to investigate new natural and synthetic molecules for their ability to counteract alternative pathways, such as virulence regulating quorum sensing (QS). In this review we describe the pathogens most commonly associated with CF lung infections: Staphylococcus aureus, Pseudomonas aeruginosa, species of the Burkholderia cepacia complex and the emerging pathogens Stenotrophomonas maltophilia, Haemophilus influenzae and non-tuberculous Mycobacteria. For each bacterium, the QS system(s) and the molecules targeting the different components of this pathway are described. The amount of investigations published in the last five years clearly indicate the interest and the expectations on antivirulence therapy as an alternative to classical antibiotics.

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“…However, the lack of activity of many anti-tubercular drugs against M. abscessus , including the front-line TB drugs rifampicin (Rif) and isoniazid (Inh) ( Abraham, 2007 ; Otchere et al, 2017 ), has limited the success of this approach. In other studies, incremental improvements of existing drugs by scaffold modification or formulation as multidrug cocktails have yielded a few new M. abscessus active compound series ( Nessar et al, 2012 ; Benwill and Wallace, 2014 ; Baranyai et al, 2015 ; Kang and Koh, 2016 ; Waters and Ratjen, 2016 ). There is often a notable lack of correlation between potent in vitro inhibition of M. abscessus and in vivo efficacy, revealing an ignorance of the in vivo physiology of M. abscessus .…”

Section: Introductionmentioning

confidence: 99%

Reporter-Based Assays for High-Throughput Drug Screening against Mycobacterium abscessus

et al. 2017

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Mycobacterium abscessus is a non-tuberculous mycobacterium that causes pulmonary and non-pulmonary infections. M. abscessus is resistant to many chemotherapeutic agents and the current treatment options show poor clinical outcomes. Thus, there is a dire need to find new antimicrobials effective at killing M. abscessus. Screening drug libraries to identify potential antimicrobials has been impeded by the lack of validated HTS assays for M. abscessus. In this study, we developed two 384-well high-throughput screening assays using fluorescent and bioluminescent reporter strains of M. abscessus for drug discovery. Optimization of inoculum size, incubation time and the volume-per-well based on Z-factor and signal intensity yielded two complementary, robust tools for M. abscessus drug discovery with Z-factor > 0.8. The MIC of known drugs, amikacin and clarithromycin, as determined by bioluminescence was in agreement with the published MIC values. A proof-of-concept screen of 2,093 natural product-inspired compounds was conducted using the 384-well bioluminescent assay to identify novel scaffolds active against M. abscessus. Five active “hit” compounds identified in this pilot screen were confirmed and characterized by a CFU assay and MIC determination. Overall, we developed and validated a 384-well screen that offers simple, sensitive and fast screening of compounds for activity against this emerging pathogen. To our knowledge, this is the first reporter–based high-throughput screening study aimed at M. abscessus drug discovery.

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Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis

Abstract: Waters V, Ratjen F. Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis.

Cited by 9 publications

References 55 publications

Unveiling the Clinical Diversity in Nontuberculous Mycobacteria (NTM) Infections: A Comprehensive Review

Unveiling the Clinical Diversity in Nontuberculous Mycobacteria (NTM) Infections: A Comprehensive Review

Quorum Sensing as Antivirulence Target in Cystic Fibrosis Pathogens

Reporter-Based Assays for High-Throughput Drug Screening against Mycobacterium abscessus

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