Mycobacterium abscessus, an Emerging and Worrisome Pathogen among Cystic Fibrosis Patients

Degiacomi, Giulia; Sammartino, José Camilla; Chiarelli, Laurent R.; Riabova, Olga; Makarov, Vadim; Pasca, Maria Rosalia

doi:10.3390/ijms20235868

Cited by 113 publications

(99 citation statements)

References 123 publications

(263 reference statements)

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“…Available data suggest that TB inactive compounds may retain activity against NTM species, encouraging a broader perspective on potential candidates for treating NTM infections. In testing NTM species, different morphotypes should be assessed because of the potential for varied susceptibility to antimicrobials [ 26 , 98 ].…”

Section: Discussionmentioning

confidence: 99%

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

Sethiya

Sowards

Jackson

et al. 2020

IJMS

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Outside of Mycobacterium tuberculosis and Mycobacterium leprae, nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.

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Section: Discussionmentioning

confidence: 99%

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

Sethiya

Sowards

Jackson

et al. 2020

IJMS

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“…Lastly, the novel formulation of liposomal amikacin for inhalation (LAI) that reduced toxicity and improved effectiveness for M. abscessus also completed clinical phase II in 2019. However, as yet, no study results have been posted on ( ) for all these clinical trials [ 16 , 17 ]. To make matters worse, there are not many active new drug candidates in clinical phase I studies, even at the discovery level.…”

Section: Discussionmentioning

confidence: 99%

Etamycin as a Novel Mycobacterium abscessus Inhibitor

Hanh

Kim

Park

et al. 2020

IJMS

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The increase in drug-resistant Mycobacterium abscessus, which has become resistant to existing standard-of-care agents, is a major concern, and new antibacterial agents are strongly needed. In this study, we introduced etamycin that showed an excellent activity against M. abscessus. We found that etamycin significantly inhibited the growth of M. abscessus wild-type strain, three subspecies, and clinical isolates in vitro and inhibited the growth of M. abscessus that resides in macrophages without cytotoxicity. Furthermore, the in vivo efficacy of etamycin in the zebrafish (Danio rerio) infection model was greater than that of clarithromycin, which is recommended as the core agent for treating M. abscessus infections. Thus, we concluded that etamycin is a potential anti-M. abscessus candidate for further development as a clinical drug candidate.

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“…However, recent evidence suggests person-to-person transfer among patients with cystic fibrosis. 11,12 Historically, NTM strains are isolated from natural sources such as water supplies and soil. 2,10 NTM strains are found in constructed sources such as bathroom showers and household water heaters where temperature settings are insufficient to kill the organism, thus leading to aerosolization of the organism that makes it capable of infiltrating alveoli.…”

Section: Mechanism Of Infection and Epidemiologymentioning

confidence: 99%

<p>The Use of Amikacin Liposome Inhalation Suspension (Arikayce) in the Treatment of Refractory Nontuberculous Mycobacterial Lung Disease in Adults</p>

Khan¹,

Chaudary²

2020

DDDT

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Nontuberculous mycobacteria (NTM) can cause and perpetuate chronic inflammation and lung infection. Despite having the diagnostic criteria, as defined by the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA), clinicians find it challenging to diagnose and treat NTM-induced lung disease. Inhaled antibiotics are suitable for patients with lung infection caused by Pseudomonas aeruginosa and other organisms, but until recently, their utility in NTM-induced infection was not established. The most common NTM pathogens identified are the slow-growing Mycobacterium avium complex (MAC) and the rapid-growing M. abscessus complex (MABSC), both of which include several subspecies. Other less commonly isolated species include M. kansasii, M. simiae, and M. fortuitum. NTM strains are frequently more resistant than what is found in bacterial sputum cultures. Until recently, there was no approved inhaled antibiotic therapy for patients who were culture positive for pulmonary NTM infection. Of late, inhaled amikacin has been under investigation for the treatment of NTM-induced pulmonary infection. The FDA approved Arikayce (amikacin liposome inhalation suspension or ALIS) based on results from the ongoing Phase 3 CONVERT trial. In this study, the use of Arikayce met its primary endpoint of sputum culture conversion by the sixth month of treatment. The addition of Arikayce to guidelinebased therapy led to negative sputum cultures for NTM by month 6 in 29% of patients compared to 8.9% of patients treated with guideline-based therapy alone. The effectiveness of Arikayce holds promise. However, due to limited data on Arikayce's safety, it is currently useful only for a specific population, particularly patients with refractory NTM-induced lung disease. Future trials must verify the target group and endorse the clinical benefits of Arikayce.

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Mycobacterium abscessus, an Emerging and Worrisome Pathogen among Cystic Fibrosis Patients

Cited by 113 publications

References 123 publications

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

Etamycin as a Novel Mycobacterium abscessus Inhibitor

<p>The Use of Amikacin Liposome Inhalation Suspension (Arikayce) in the Treatment of Refractory Nontuberculous Mycobacterial Lung Disease in Adults</p>

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