Table 3.

Recent reports of NTM in vivo pharmacotherapy^a

Pharmacotherapeutic/citation	Study design and methods	Notable outcomes	Conclusion
BDQ
Philley et al. [23], 2015	Case series of off-label use of BDQ for treatment failure in lung disease caused by MAC or Mabs in 10 adult patients treated with best-available concurrent NTM therapy Included patients needed access to BDQ and ≥ 12-mo treatment failure for MAC and ≥ 6 mo for Mabs Oral BDQ 400 mg 1 time/d for 2 wk then 200 mg 3 times/wk (600 mg/wk)	After 6 mo of therapy, microbiologic response rate was 60%, with 50% ≥ 1 negative culture result Common adverse effects were nausea (60%), arthralgias (40%), anorexia, subjective fever (30%) No abnormal ECG findings were observed	Potential clinical and microbiologic activity of BDQ for advanced MAC or Mabs lung disease Needs confirmation by larger studies
CLO
Jarand et al. [24], 2016	Retrospective review of clinical and microbiologic outcomes for MAC-LD in those receiving CLO and/or RIF with macrolide and ethambutol Adult patients with MAC-LD who were treated and monitored for ≥ 6 mo after treatment were included (n = 170)	Majority (84%) were treated with CLO and (13%) with RIF Most patients (95%) had conversion from positive to negative sputum culture results in mean (SD) 4.5 (4.2) mo More patients treated with CLO had conversion to negative culture results vs. patients treated with RIF (100% vs. 71%, P < 0.001) Microbiologic relapse occurred in 52 of 107 patients (49%)	Initial outcomes and retreatment rates were at least as good in patients treated with CLO-containing regimens as in patients receiving RIF-containing regimens CLO should be considered as an alternative drug for MAC-LD
Yang et al. [25], 2017	Evaluated clinical efficacy of CLO-containing regimen for Mabs-LD via retrospective review Patients with Mabs-LD who were treated with CLO-containing regimens for initial or refractory disease were included (n = 42)	Treatment response rate was 81% according to symptoms and 31% according to radiographic findings Sputum culture conversion was achieved in 10 (24%) patients after CLO-containing antibiotic treatment Substantial decreases in positive semiquantitative sputum culture results for acid-fast bacilli in both the initial and salvage groups during treatment	CLO-containing regimens may improve treatment outcomes in patients with Mabs-LD, and a prospective evaluation is warranted
Martiniano et al. [26], 2017	Observational cohort study assessed CLO in 112 pediatric and adult patients with and without CF and pulmonary or extrapulmonary Mabs, MAC, or various NTM infections as part of a multidrug regimen	Median (range) CLO duration was 383 (3–2419) days Sixteen patients (14%) stopped CLO because of ADRs after a median (95% CI) of 101 (63–119) days Half of patients with pulmonary disease had sputum culture conversion within 12 mo	CLO was safe, reasonably tolerated, and active for NTM infection in pediatric and adult patients with and without CF CLO should be considered as an alternative drug for NTM disease
LZD
Parize et al. [27], 2016	Report the efficacy and tolerability of LZD with CLR for M. chelonae infection in patients who were immunocompromised	All patients had rapid clinical efficacy without relapse after a median follow-up duration of 2.25 y ADRs were frequent, including thrombocytopenia, myalgia, and mitochondrial toxicity All ADRs were reversible after discontinuing LZD	LZD/CLR combination was suggested as an initial therapy for M. chelonae skin infections in patients who are immunocompromised
Winthrop et al. [28], 2015	Retrospective cohort study of LZD tolerability in 102 patients with NTM infections at 6 NTM treatment centers in North America	Median (range) LZD therapy duration after initial drug start was 21.4 (1–201) wk Most (79%) were administered 600 mg (1 time/d); 12%, 300 mg (1 time/d); 5%, 600 mg (2 times/d) ADRs occurred in 46 (45%) patients, including peripheral neuropathy (n = 24, 24%), GI intolerance (n = 9, 9%), anemia (n = 8, 8%), and thrombocytopenia (n = 6, 6%)	LZD can be used for long durations in multidrug NTM treatment ADRs necessitating drug discontinuation were common, occurring in > 40% of patients regardless of concomitant vitamin B6 use
OMC
Pearson et al. [29], 2020	Case series of 4 patients treated with OMC with multidrug therapy for Mabs infection	NTM syndromes were cutaneous disease (n = 2), pulmonary disease (n = 1), osteomyelitis, and bacteremia (n = 1) Median (range) duration of OMC treatment was 166 (104–227) d Clinical cure was achieved in 3 of 4 patients, with 1 patient improving with ongoing treatment A patient discontinued OMC after 6 mo because of nausea	OMC is a novel oral option for the treatment of Mabs Further data are required to determine its definitive role
Morrisette et al. [30], 2021	Case series of 12 patients treated with OMC with multidrug therapy for Mabs infection	Majority were pulmonary infections (n = 7/12, 58%) Median (IQR) OMC treatment duration was 6.2 (4.2–11.0) mo Clinical success occurred in 9 of 12 (75%) patients. Three patients had a possible ADR	Prospective studies and larger postmarket reports are needed for OMC as NTM therapy
Duah and Beshay [31], 2022	Case series of 3 patients administered OMC as part of a first-line treatment for Mabs pulmonary infection	All 3 patients had reported clinical improvement One patient had a possible ADR (nausea/vomiting)	Findings support future study of OMC as a potential oral first-line option for Mabs pulmonary disease
TDZ
Poon et al. [32], 2021	Single-center retrospective cohort study of adult solid-organ transplant recipients receiving LZD or TDZ for NTM infection	During 7 wk, LZD and TZD did not differ for platelet counts, ANC, or hemoglobin, but ANC was significantly decreased for both LZD and TZD (P = 0.04) Approximately 20% of patients in each arm discontinued LZD or TZD because of an ADR Seven of 12 (58%) and 2 of 3 (67%) patients were cured or clinically cured	No significant safety benefit of TZD vs. LZD TZD and LZD had potential benefit for symptomatic and microbiologic improvement for NTM infections in solid-organ transplant recipients

ADR adverse drug reaction, ANC absolute neutrophil count, BDQ bedaquiline, CF cystic fibrosis, CLO clofazimine, CLR clarithromycin, ECG electrocardiograph, GI gastrointestinal, LD lung disease, LZD linezolid, Mabs Mycobacterium abscessus, MAC Mycobacterium avium complex, NTM nontuberculous mycobacteria, OMC omadacycline, RIF rifampin, TZD tedizolid

^aAll reports published in 2015 or later