A systematic review of tetracyclines for nontuberculous mycobacteria: focus on rapidly growing mycobacteria.

BACKGROUND

The incidence and prevalence of disease caused by nontuberculous mycobacteria (NTM) are increasing globally, yet treatment regimens remain complex and often ineffective. Newer tetracyclines have shown promise as a potent therapeutic. In this systematic review, we assessed the evidence for the use of tetracyclines for the treatment of NTM disease, complemented by a narrative review of nonclinical data.

METHODS

Medline (PubMed) and Web of Science were searched from inception to February 2024 for clinical studies that assessed the safety, tolerability or efficacy of tetracyclines for NTM disease. Search results were screened against pre-defined inclusion and exclusion criteria. Nonclinical data were identified using a targeted literature search and are presented in a narrative synthesis.

RESULTS

A total of 89 citations were included, comprising 43 clinical studies (six prospective observational studies, 18 retrospective studies and 19 case series) and 46 nonclinical studies. Nonclinical studies demonstrated potent in vitro activity for tigecycline, omadacycline and eravacycline, particularly against rapidly growing mycobacteria (RGM). No randomised controlled trials (RCTs) were identified. Most clinical experience was for RGM (largely Mycobacterium abscessus) and supported the use of newer tetracyclines. Evidence for the treatment of slowly growing mycobacteria, particularly Mycobacterium avium complex, was more limited.

CONCLUSIONS

There remains a significant unmet need for effective, well-tolerated therapies for the treatment of NTM, especially those that improve quality of life. Although tetracyclines have not been evaluated in RCTs, clinical evidence suggests that tetracyclines may contribute to the efficacy of combination regimens used to treat NTM disease and further RCTs are warranted.