Mycobacterium abscessus

Mycobacterium abscessus complex is a group of rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) species that are common soil and water contaminants. Although M. abscessus complex most commonly cause chronic lung infection and skin and soft tissue infection (SSTI), the complex can also cause infection in almost all human organs, mostly in patients with suppressed immune systems. ^[2]. Amongst NTM species responsible for disease, infection caused by M. abscesses complex are more difficult to treat due to antimicrobial drug resistance ^[3].

M. abscessus grown in starch-based medium on a petri dish. Colonies appear as light yellow streaks.

Still images of mycobacterium abscessus growing in culture over a period of 60 hours. Courtesy of Dr. Y. Av-Gay at Division of Infectious Diseases at University of British Columbia, Vancouver, Canada.

Description

M. abscessus cells are gram-positive, nonmotile, acid-fast rods of about 1.0 - 2.5 µm long by 0.5 µm wide. They may form colonies on Löwenstein-Jensen media that appear smooth or rough, white or greyish and nonphotochromogenic.

Physiology

M. abscessus shows growth at 28 °C and 37 °C after 7 days but not at 43 °C. It may grow on MacConkey agar at 28 °C and even 37 °C. It shows tolerance to saline media (5% NaCl) as well as 500 mg/l hydroxylamine (Ogawa egg medium) and 0.2% picrate (Sauton agar medium). Strains of the species have been shown to degrade the antibiotic p-aminosalicylate. M. abscessus has also been shown to produce arylsulfatase but not of nitrate reductase and Tween 80 hydrolase. It shows a negative result for the iron uptake test and no utilisation of fructose, glucose, oxalate or citrate as sole carbon sources.

Differential characteristics

M. abscessus and M. chelonae can be distinguished from M. fortuitum or M. peregrinum by their failure to reduce nitrate and to take up iron. Tolerance to 5% NaCl in Löwenstein-Jensen media, tolerance to 0.2% picrate in Sauton agar, and non-utilisation of citrate as a sole carbon source are characteristics that distinguish M. abscessus from M. chelonae. M. abscessus and M. chelonae sequevar I share an identical sequence in the 54-510 region of 16S rRNA, though both species can be differentiated by their hsp65, ITS or rpoB gene sequences.

Genetics

A draft genome sequence of M. abscessus subsp. bolletii BD^T was completed in 2012.^[4] More than 25 different strains of this subspecies, including pathogenic isolates, have had their genomes sequenced.^[5]

Pathogenesis

M. abscessus may cause chronic lung disease, especially in vulnerable hosts with underlying lung disease such as cystic fibrosis, bronchiectasis, and prior tuberculosis. "M. abscessus" can also cause post-traumatic wound infections and skin infections in immunodeficient patients.

Clinical symptoms vary in scope and intensity but commonly include chronic cough, often with purulent sputum. Hemoptysis may also be present. Systemic symptoms include malaise, fatigue, and weight loss in advance disease ^[6].

The diagnosis of M. abscessus pulmonary infection requires the presence of symptoms, radiologic abnormalities, and microbiologic cultures.

It can be associated with persistent culture-negative skin infections on otherwise healthy individuals. Culture-negative refers to an inability to produce a colony on typical agar plates. These persistent cutaneous infections have been seen at acupuncture sites.^[2]

It can be associated with middle ear infections (otitis media).^[7]

Treatment

The management of M. abscessus infections is a challenge due to antibiotic-resistance stains commonly observed in patients and toxicity and cost associated with combinations of multiple drugs. Treatment guidelines for NTM issued by the American Thoracic Society recommends a multi-drug regimen that includes Clarithromycin (Biaxin) or Axithromycin (Zithromax), Rifampin (Rifadin) or Rifabutin (Mycobutin) and Ethambutol (Myambutol), and Streptomycin or Amikacin (Amikin). Click here for a summary of available medications and their side effects.

Unfortunately, drug-resistance commonly leads to failure of conventional therapeutic drugs. This has led FDA to identify M. abscessus infections as a Disease Area to be the focus of FDA in 2016/2017, with special attention to high-risk patients with underlying lung disease such as cystic fibrosis (link here).

A few promising investigational new drugs are currently in Clinical trials for the treatment of NTM lung disease:

1. AIT Therapeutics (AIT) is recruiting patients diagnosed with M. abscessus NTM lung infection for treatment with inhaled nitric oxide (NO) gas (Link to clinicaltrials.gov). NO is naturally produced by the body’s immune system against invading bacterial and viral pathogens. The pharmacology and toxicity of inhaled NO in humans is well defines and its application has been approved by the FDA mainly as a vasodilator in pulmonary hypertension (reviewed here). Nitric oxide has also been shown to be effective against most antibiotic resistant bacterial strains ^[8].

2. Insmed Incorporated is recruiting patients diagnosed with NTM lung infection that is caused by Mycobacterium avium complex (MAC) to enroll in the “CONVERT” study. The CONVERT study is evaluating the efficacy of a novel delivery method for Amikacin (Liposomal Amikacin for inhalation) (link to clinicaltrials.gov).

Type strain

ATCC 19977 = CCUG 20993 = CIP 104536 = DSM 44196 = JCM 13569 = NCTC 13031

Etymology

From the Latin ab- (“away”) + cedere (“to go”), an abscess is named for the notion that humors leave the body through pus. Mycobacterium abscessus was first isolated from gluteal abscesses in a 62-year-old patient who had injured her knee as a child and had a disseminated infection 48 years later. The species M. bolletii, named after the late microbiologist and taxonomist Claude Bollet, was described in 2006. In current taxonomy, M. bolletii and M. massiliense (named for Massilia, the ancient Greek and Roman name for Marseille, where the organism was isolated) have been incorporated into M. abscessus subsp. bolletii.^[9]

References

This article incorporates public domain text from the CDC as cited

External links

• Type strain of Mycobacterium abscessus at BacDive - the Bacterial Diversity Metadatabase
• A guide for patients and clinicians - AIT Therapeutics