Table 1.

Characteristics of used antibiotics in NTM infections based on action and resistance mechanisms.

	Antibiotic	Action mechanism	Resistance mechanism	Highest activity against	Lowest activity against
Suppression of cell wall synthesis	Ethambutol	Suppression of arabinogalactan biosynthesis	Mutation in embCAB and inhibition of mycobacterial arabinosyl transferase translation	Rapid growers of NTM MAC1 M. kansasii	M. kansasii M. avium M. smegmatis
	Beta-lactams (imipenem)	Suppression of enzymatic activity of PBPs2 and peptidoglycan synthesis	Enhance cell wall permeability, the affinity of PBP, and the activity of β-lactamases	Rapid growers of NTM	M. fortuitum M. chelonae M. smegmatis M. abscessus M. avium
	Isoniazid	Suppression of mycolic acid synthesis	Lack of catalase-peroxidase KatG and isoniazid efflux pump	M. kansasii M. xenopi	Most species of NTM
	Vancomycin	Suppression of mature peptidoglycan assembly	Enhance cell wall permeability	Most species of NTM	Most species of NTM
	Delamanid	Suppression of keto- and methoxy-mycolic acid synthesis	Not determined for NTM species	MDR-TB3 M. intracellulare M. avium	M. kansasii
Suppression of DNA synthesis	Fluoroquinolones	Suppression of topoisomerase IV and DNA gyrase	Mutations in gyrA and gyrB genes LfrA efflux pump The main mechanism is not clear	Macrolide-resistant MAC M. abscessus	MAC M. abscessus M. smegmatis M. vanbaalenii
	Sulfamethoxazole	Suppression of microbial folate metabolism and nucleic acid synthesis	Activity of reductase	Most species of NTM	M. avium M. smegmatis
	SPR719 and SPR720	Suppression of ATPase activity gyrase and topoisomerase IV	Not determined for NTM species	M. tuberculosis MAC M. abscessus M. kansasii	Not determined for NTM species
Suppression of protein synthesis	Macrolides (clarithromycin and azithromycin)	Suppression of peptide chain elongation by binding to the exited peptide from ribosome	Activity of ribosomal methyltransferase (erm) Mutation in 23SrRNA	Most species of NTM	M. bolletii M. goodie M. kansasii M. chelonae M. abscessus M. wolinskyi M. boenickei M. fortuitum M. porcinum M. smegmatis M. massiliense M. houstonense M. mageritense M. neworleansense
	Oxazolidinones (linezolid, tedizolid, and LCB01-0371)	Binding to the 23SrRNA and suppression of protein synthesis	Mutation in rplC and 23SrRNA	Most species of NTM (linezolid for MAC and M. abscessus)	M. tuberculosis Not determined for NTM species
	Aminoglycosides	Irreversible binding to the 30S ribosomal subunit and suppression of translation process	Mutation in 16SrRNA (rpsL) Activity of phosphotransferases and acetyltransferase	Most species of NTM	MAC M. chelonae M. massiliense M. abscessus M. fortuitum M. avium
	Tetracyclines	Reversibly bind to the 30S ribosomal subunit and suppression of binding of tRNA and mRNA-ribosome complex	Activity of ribosome protection proteins (otrA and tetM) Activity of efflux pumps (Tet, Otr, and Tap)	Most species of NTM	Most species of NTM
	Tigecycline	Binding to 30S ribosomal subunit and suppression of acyltRNA binding	Tet(X) enzyme	M. abscessus M. chelonae	Not determined for NTM species
	Rifampin	Suppression of DNA-dependent RNA polymerase of bacteria	Mutation in rpoB Expression of arr	MAC M. kansasii	MAC M. kansasii M. ulcerans M. smegmatis M. abscessus
Suppression of respiratory chain	Bedaquiline	Suppression of atpE gene, a mycobacterial ATP synthase, and lack of ATP production	Mutations in atpE, mmpT5, and pepQ	MDR-TB MAC M. leprae M. avium M. abscessus M. massiliense	M. avium M. kansasii M. abscessus M. fortuitum M. flavescens M. massiliense M. intracellulare
	Clofazimine	Suppression of bacterial proliferation by blocking the intracellular redox cycling	Mutation in mmpR5 and pepQ	Most species of NTM	M. tuberculosis M. abscessus M. intracellulare

¹ M. avium complex; ²penicillin-binding proteins; ³multidrug-resistant tuberculosis.