Omadacycline for management of Mycobacterium abscessus infections: a review of its effectiveness, place in therapy, and considerations for use

Abstract

The Mycobacteriumabscessus complex (MABC) is a group of acid-fast, rapidly dividing non-tuberculous mycobacteria (NTM) that include a number of clinically important subspecies, including M.abscessus,M.bolletii, and M.massiliense. These organisms are prevalent in the environment and are primarily associated with human pulmonary or skin and skin structure infections (SSSI) but may cause more deep-seeded disseminated infections and bacteremia in the immunocompromised. Importantly, these NTM are resistant to most first-line anti-tuberculous agents and, due to intrinsic or acquired resistance, exhibit exceedingly low, variable, and geographically distinct susceptibilities to commonly used antibacterial agents including older tetracyclines, macrolides, aminoglycosides, cephalosporins, carbapenems, and sulfamethoxazole-trimethoprim. Omadacycline is a novel third-generation member of the tetracycline family of antibacterials that has recently been demonstrated to have potent anti-NTM effects and clinical efficacy against MABC, including M.abscessus. The purpose of this review is to present a comprehensive and up-to-date assessment on the body of literature on the role of omadacycline for M.abscessus infections. Specifically, the in vitro and in vivo microbiology, mechanisms of action, mechanisms of resistance, clinical pharmacokinetics, clinical efficacy, adverse effects, dosage and administration, and place in therapy of omadacycline in management of M.abscessus infections will be detailed.

Emergence of Third Generation Tetracyclines: New Magic Bullets to Tackle Antibiotic Resistance in the Post-antibiotic Era

“…In vitro omadacycline has demonstrated bactericidal activity against Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis [44]. Mycobacterium abscessus complex (MABC)-non-tuberculous mycobacteria that include (M. abscessus, M. bolletii, and M. massiliense) which are the major cause of human pulmonary or skin and skin structure infections (SSSI) has acquired resistance to older tetracyclines but now sensitive to omadacycline [45][46][47]. The characteristics of omadacycline include broad-spectrum activity, and overcoming the two primary mechanisms of tetracycline resistance, efflux, and ribosome protection.…”

“…Moreover, omadacycline is also equally effective against Gram-negative pathogens, such as E. coli, K. pneumoniae, P. aeruginosa, E. cloacae, H. influenzae, H. parainfluenzae Citrobacter spp., and P. mirabilis. Further, its antibacterial spectrum is also extended to respective ESBL and carbapenem-resistant Enterobacteriaceae (CRE) phenotypes as well as ceftazidimeresistant strains [26,46]. It also exhibits potent in vitro activity against non-mycobacterial atypical organisms, including Mycoplasma pneumoniae and M. hominis, Legionella pneumophilia, and Chlamydia pneumoniae.…”