TABLE 3

Summary of repurposed and emerging treatments for nontuberculous mycobacterial pulmonary disease (NTM-PD)

	Evidence	References
Bedaquiline	6 months of bedaquiline treatment associated with one or more negative cultures among 50% of a cohort of 10 patients with NTM-PD	[79]
	Adding clofazimine to bedaquiline in vitro improves bacteriostatic effect of bedaquiline against M. abscessus (but promotes bedaquiline resistance); has modest effect on bactericidal effect of bedaquiline against M. avium (and slows emergence of bedaquiline resistance)	[82]
Tedizolid	Concentration-dependent activity in vitro against M. avium; enhanced when combined with ethambutol Weak bacteriostatic activity in vitro against MAB; enhanced when combined with amikacin	[85]
	Well-tolerated and efficacious in patient with pulmonary TB and liver transplant due to hepatic failure secondary to anti-TB medications	[87]
	No significant difference in safety profile between tedizolid and linezolid when used to treat NTM infections in solid-organ transplant recipients	[86]
	Probably contributed to anaemia in patient with pulmonary mycobacterial infection, and thrombocytopenia in patient with disseminated mycobacterial infection	[88]
Omadacycline	Potent activity against rapid-growing NTM in vitro; similar activity to tigecycline against MAB, M. chelonae and M. fortuitum	[89–91]
	Symptomatic improvement and radiographic stability at 1-month follow-up in a patient who had previously failed NTM-PD treatment following treatment with 4-week course of omadacycline plus amikacin and aztreonam	[92]
	Tolerated for >7 months in a patient with MAB-PD; lobectomy required 5 months into omadacycline treatment	[93]
	Associated with treatment success in five out of seven patients with MAB-PD; treatment failure in MAB-PD in one patient with fibrocavitary disease and one patient with nodular-bronchiectatic disease with dissemination	[94]
Eravacycline	In vitro activity against MAB; MIC₅₀ and MIC₉₀ two-fold lower than tigecycline and omadacycline	[96]
Dual β-lactams	Ceftazidime synergises with imipenem or ceftaroline against MAB in vitro	[97]
	Amoxicillin synergises with imipenem–relebactam against MAB in vitro	[98]
	Cefoxitin synergises with imipenem against MAB in vitro	[99]
	Ceftaroline synergises with imipenem against MAB in vitro	[100]
Inhaled antibiotics (other than ALIS)	Inhaled imipenem–cilastatin well-tolerated and resulted in lung function stability in two paediatric MAB-PD patients	[104]
	Inhaled high-dose tigecycline effective in a dose-dependent manner at reducing pulmonary bacterial load in a GM-CSF knockout model of MAB infection	[105]
	Clofazimine inhalation suspension achieved four-fold higher concentration in the lungs than oral clofazimine and was well-tolerated in a mouse model of NTM lung disease	[106]
IFN-γ	Inhaled IFN-γ improves NTM clearance in patients with IFN-γ deficiency	[107]
	Inhaled IFN-γ poor at promoting sputum culture conversion among those with cavitary disease	[108]
	Adjuvant intramuscular IFN-γ associated with higher treatment response rates relative to placebo and fewer disease-related deaths in MAC-PD	[109]
GM-CSF	Adjuvant inhaled GM-CSF associated with improved lung function and culture conversion in two patients with CF and MAB-PD	[112]
Inhaled NO	160 ppm inhaled NO for 21 days followed by 240 ppm for 8 days resulted in improvement in quality of life, lung function and 6MWD, but not MAB eradication	[114]
	Intermittent inhalations of 160 ppm NO associated with reductions in pulmonary MAB loads in two patients	[115]
	Intermittent inhaled NO treatment improved FEV₁ and 6MWD among nine patients with CF and MAB-PD, but culture conversion not achieved	[116]
Benzimidazoles	SPR719 and EJMCh-6 potent against various NTM species in vitro	[120, 121]
Engineered bacteriophage therapy	Clinical improvement in lung function, liver function and skin lesions in a patient with CF with disseminated drug-resistant MAB infection	[126]

ALIS: amikacin liposome inhalation suspension; IFN: interferon; GM-CSF: granulocyte–macrophage colony-stimulating factor; NO: nitric oxide; TB: tuberculosis; MAB: Mycobacterium abscessus; MIC_50/90: minimum inhibitory concentration required to inhibit the growth of 50%/90%; MAC: Mycobacterium avium complex; CF: cystic fibrosis; 6MWD: 6-min walk distance; FEV₁: forced expiratory volume in 1 s.