We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii.
KEYWORDS: nontuberculous mycobacteria, Mycobacterium avium complex, Mycobacterium abscessus, Mycobacterium kansasii, rifamycins, rifabutin
ABSTRACT
We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii. Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.
INTRODUCTION
The prevalence of nontuberculous mycobacteria-pulmonary disease (NTM-PD) is increasing (1, 2). Among NTM species, Mycobacterium avium complex (MAC), which is mainly composed of M. avium and M. intracellulare, is the most common pathogen, and Mycobacterium abscessus (MABS), predominantly composed of M. abscessus subsp. abscessus (here termed M. abscessus) and M. abscessus subsp. massiliense (here termed M. massiliense), is the second most common pathogen in many countries (3–5). M. kansasii also causes chronic PD (6).
For MAC- or M. kansasii-PD, guidelines recommend a macrolide-based multidrug therapy including rifampin (3). However, there are no accurate data on which of the rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, is the most effective. The guidelines for MABS-PD recommend multidrug therapy, including macrolide and intravenous amikacin as key drugs (3). However, as MABS-PD is highly drug resistant, there are only a few effective oral drugs. Therefore, treatment outcomes of NTM-PD are unsatisfactory (7–9). Recently, oral agents, such as rifamycin derivatives, particularly rifabutin, were reported to have in vitro low MIC and synergistic effects with other drugs against NTM species (10–14). However, limited data are available from studies using various clinical strains or strains resistant to key antibiotics. Therefore, we evaluated the in vitro activity of rifamycin derivatives against clinical NTM isolates, including macrolide- and amikacin-resistant isolates.
We evaluated 311 clinical isolates of five major pathogenic NTM from 311 nonduplicated patients with treatment-naive NTM-PD (Table 1). Additionally, 57 macrolide-resistant and 44 aminoglycoside-resistant NTM isolates, which were confirmed by mutation analyses to be related to macrolide or aminoglycoside resistance, were included in the analysis (15–19). All data included in this study were obtained from an Institutional Review Board-approved observational cohort at Samsung Medical Center, South Korea (ClinicalTrials.gov registration no. NCT00970801). In vitro drug susceptibility testing was performed by measuring the MIC using the broth microdilution method according to guidelines from the Clinical and Laboratory Standards Institute (20). M. peregrinum ATCC 700686, M. abscessus ATCC 19977, M. avium ATCC 700898, and M. kansasii ATCC 12478 were used as controls.
TABLE 1.
MIC ranges and MIC50 and MIC90 values of four rifamycin derivatives for 311 clinical NTM isolates
| NTM species (no.) | Antibiotic | No. (%) of isolates with MIC (μg/ml) of: |
MIC range (μg/ml) | MIC50 (μg/ml) | MIC90 (μg/ml) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ≤0.062 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | 8 | 16 | 32 | 64 | >64 | |||||
| M. avium (63) | Rifampin | 2 (3.2) | 2 (3.2) | 6 (9.5) | 16 (25.4) | 8 (12.7) | 7 (11.1) | 2 (3.2) | 3 (4.8) | 11 (17.4) | 6 (9.5) | 0.25–>64 | 4 | 64 | ||
| Rifapentine | 3 (4.8) | 4 (6.3) | 22 (34.9) | 9 (14.3) | 6 (9.5) | 6 (9.5) | 5 (7.9) | 4 (6.3) | 1 (1.6) | 3 (4.8) | 0.125–>64 | 1 | 16 | |||
| Rifaximin | 1 (1.6) | 2 (3.2) | 2 (3.2) | 15 (24) | 19 (30.2) | 10 (15.9) | 4 (6.3) | 6 (9.5) | 1 (1.6) | 3 (4.8) | 0.125–>64 | 2 | 16 | |||
| Rifabutin | 33 (52.4) | 7 (11.1) | 4 (6.3) | 5 (7.9) | 9 (14.3) | 1 (1.6) | 1 (1.6) | 3 (3.2) | ≤0.062–64 | ≤0.062 | 0.25 | |||||
| M. intracellulare (58) | Rifampin | 1 (1.7) | 1 (1.7) | 1 (1.7) | 11 (19) | 41 (70.7) | 3 (5.2) | 0.25–>64 | 64 | 64 | ||||||
| Rifapentine | 1 (1.7) | 5 (8.6) | 19 (32.8) | 19 (32.8) | 9 (15.5) | 2 (3.4) | 1 (1.7) | 2 (3.4) | ≤0.062–>64 | 8 | 16 | |||||
| Rifaximin | 1 (1.7) | 2 (3.4) | 12 (20.7) | 41 (70.7) | 2 (3.4) | 8–>64 | 64 | 64 | ||||||||
| Rifabutin | 1 (1.7) | 2 (3.4) | 8 (12.7) | 26 (44.8) | 16 (28.4) | 2 (3.4) | 1 (1.7) | 2 (3.4) | ≤0.062–16 | 0.5 | 1 | |||||
| M. kansasii (58) | Rifampin | 6 (10.3) | 32 (55.2) | 9 (15.5) | 3 (5.2) | 3 (5.2) | 1 (1.7) | 2 (3.4) | 2 (3.4) | 0.5–>64 | 1 | 8 | ||||
| Rifapentine | 14 (24.1) | 30 (51.7) | 5 (8.6) | 4 (6.9) | 2 (3.4) | 1 (1.7) | 2 (3.4) | 0.125–>64 | 0.25 | 1 | ||||||
| Rifaximin | 13 (22.4) | 26 (44.8) | 10 (17.2) | 3 (5.2) | 1 (1.7) | 1 (1.7) | 2 (3.4) | 2 (3.4) | 0.25–>64 | 0.5 | 4 | |||||
| Rifabutin | 51 (87.9) | 1 (1.7) | 3 (5.2) | 1 (1.7) | 1 (1.7) | 1 (1.7) | ≤0.062–64 | ≤0.062 | ≤0.062 | |||||||
| M. abscessus (65) | Rifampin | 1 (1.5) | 64 (98.5) | 64–>64 | >64 | >64 | ||||||||||
| Rifapentine | 1 (1.5) | 3 (4.6) | 61 (93.8) | 32–>64 | >64 | >64 | ||||||||||
| Rifaximin | 1 (1.5) | 2 (3.1) | 18 (27.7) | 44 (67.7) | 4–>64 | >64 | >64 | |||||||||
| Rifabutin | 1 (1.5) | 3 (4.6) | 8 (12.3) | 25 (38.5) | 26 (40) | 2 (3.1) | 0.25–32 | 8 | 16 | |||||||
| M. massiliense (67) | Rifampin | 1 (1.5) | 1 (1.5) | 1 (1.5) | 17 (25.4) | 47 (70.1) | 0.125–>64 | >64 | >64 | |||||||
| Rifapentine | 1 (1.5) | 3 (4.5) | 4 (6) | 5 (7.5) | 33 (49.3) | 21 (31.3) | 1–>64 | 64 | >64 | |||||||
| Rifaximin | 4 (6) | 5 (7.5) | 6 (9) | 19 (28.4) | 31 (46.3) | 2 (3) | 2–>64 | 32 | 64 | |||||||
| Rifabutin | 1 (1.5) | 3 (4.5) | 2 (3) | 16 (23.9) | 24 (35.8) | 12 (17.9) | 9 (13.4) | ≤0.062–16 | 4 | 16 | ||||||
Table 1 shows MIC levels of rifamycin derivatives for the 311 clinical NTM isolates. In MAC, the MIC50 (≤0.062 to 0.5 μg/ml) and MIC90 (0.25 to 1 μg/ml) values of rifabutin were 16 to 256 times lower than those of other rifamycins. In M. kansasii, the MIC50 (≤0.062 μg/ml) and MIC90 (≤0.062 μg/ml) values of rifabutin were lowest among the rifamycin derivatives. However, unlike MAC and M. kansasii, MABS showed relatively higher MIC50 (32 to >64 μg/ml) and MIC90 (>64 μg/ml) values for rifampin, rifapentine, or rifaximin. Nevertheless, the MIC50 (4 to 8 μg/ml) and MIC90 (16 μg/ml) values of rifabutin for MABS remained the lowest.
Table 2 shows the MIC levels of rifamycin derivatives for macrolide (n = 57)- and aminoglycoside (n = 44)-resistant NTM. Similarly, rifabutin showed the lowest MIC50 (≤0.062 to 8 μg/ml) and MIC90 (0.5 to 16 μg/ml) values against macrolide- and aminoglycoside-resistant NTM isolates, including MAC, M. abscessus, and M. massiliense.
TABLE 2.
MIC ranges and MIC50 and MIC90 values of four rifamycin antibiotics for 57 macrolide-resistant and 44 aminoglycoside-resistant clinical NTM isolates
| NTM species (no.) | Antibiotic | No. (%) of isolates with MIC (μg/ml) of: |
MIC range (μg/ml) | MIC50 (μg/ml) | MIC90 (μg/ml) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ≤0.062 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | 8 | 16 | 32 | 64 | >64 | |||||
| Macrolide resistant | ||||||||||||||||
| M. avium (10) | Rifampin | 1 (10) | 1 (10) | 1 (10) | 1 (10) | 2 (20) | 4 (40) | ≤0.062–>64 | 64 | >64 | ||||||
| Rifapentine | 1 (10) | 1 (10) | 1 (10) | 1 (10) | 3 (30) | 1 (10) | 2 (20) | ≤0.062–>64 | 8 | >64 | ||||||
| Rifaximin | 1 (10) | 1 (10) | 3 (30) | 1 (10) | 2 (20) | 2 (20) | ≤0.062–>64 | 4 | >64 | |||||||
| Rifabutin | 1 (10) | 3 (30) | 2 (20) | 3 (30) | 1 (10) | ≤0.062–2 | 0.5 | 2 | ||||||||
| M. intracellulare (17) | Rifampin | 2 (11.8) | 1 (5.9) | 1 (5.9) | 3 (17.6) | 10 (58.8) | ≤0.062–64 | 64 | 64 | |||||||
| Rifapentine | 1 (5.9) | 1 (5.9) | 1 (5.9) | 2 (11.8) | 8 (47.1) | 3 (17.6) | 1 (5.9) | ≤0.062–64 | 8 | 16 | ||||||
| Rifaximin | 1 (5.9) | 2 (11.8) | 1 (5.9) | 4 (23.5) | 9 (52.9) | ≤0.062–64 | 64 | 64 | ||||||||
| Rifabutin | 3 (17.6) | 2 (11.8) | 2 (11.8) | 9 (52.9) | 1 (5.9) | ≤0.062–16 | 2 | 2 | ||||||||
| M. abscessus (13) | Rifampin | 1 (7.7) | 1 (7.7) | 11 (84.6) | 32–>64 | >64 | >64 | |||||||||
| Rifapentine | 2 (15.4) | 2 (15.4) | 9 (69.2) | 32–>64 | >64 | >64 | ||||||||||
| Rifaximin | 3 (23) | 3 (23) | 3 (23) | 4 (30.8) | 16–>64 | 64 | >64 | |||||||||
| Rifabutin | 5 (38.5) | 3 (23) | 4 (30.8) | 1 (9) | 2–16 | 4 | 8 | |||||||||
| M. massiliense (17) | Rifampin | 3 | 2 (11.8) | 12 (70.6) | 32–>64 | >64 | >64 | |||||||||
| Rifapentine | 2 (11.8) | 4 (23.5) | 11 (64.7) | 16–>64 | >64 | >64 | ||||||||||
| Rifaximin | 2 (11.8) | 3 (17.6) | 1 (5.9) | 4 (23.5) | 2 (11.8) | 5 (29.4) | 4–>64 | 32 | >64 | |||||||
| Rifabutin | 1 (5.9) | 1 (5.9) | 7 (41.8) | 2 (11.8) | 4 (23.5) | 2 (11.8) | 0.5–16 | 2 | 16 | |||||||
| Aminoglycoside resistant | ||||||||||||||||
| M. avium (12) | Rifampin | 1 (8.3) | 5 (41.7) | 1 (8.3) | 1 (8.3) | 1 (8.3) | 3 (25) | 1–64 | 2 | 64 | ||||||
| Rifapentine | 7 (58.3) | 1 (8.3) | 1 (8.3) | 1 (8.3) | 2 (16.7) | 0.5–8 | 0.5 | 8 | ||||||||
| Rifaximin | 2 (16.7) | 3 (25) | 2 (16.7) | 2 (16.7) | 1 (8.3) | 2 (16.7) | 0.25–16 | 1 | 16 | |||||||
| Rifabutin | 7 (58.3) | 1 (8.3) | 1 (8.3) | 3 (25) | ≤0.062–0.5 | ≤0.062 | 0.5 | |||||||||
| M. intracellulare (17) | Rifampin | 1 (5.9) | 2 (11.8) | 5 (29.4) | 8 (47.1) | 1 (5.9) | 0.5–>64 | 32 | 64 | |||||||
| Rifapentine | 1 (5.9) | 1 (5.9) | 3 (17.6) | 5 (29.4) | 3 (17.6) | 3 (17.6) | 1 (5.9) | ≤0.062–32 | 4 | 16 | ||||||
| Rifaximin | 1 (5.9) | 1 (5.9) | 1 (5.9) | 4 (23.5) | 3 (17.6) | 5 (29.4) | 2 (11.8) | 0.25–>64 | 32 | >64 | ||||||
| Rifabutin | 2 (11.8) | 3 (17.6) | 6 (35.3) | 2 (11.8) | 1 (5.9) | 2 (11.8) | 1 (5.9) | ≤0.062–8 | 0.5 | 4 | ||||||
| M. abscessus (9) | Rifampin | 9 (100) | >64 | >64 | >64 | |||||||||||
| Rifapentine | 1 (11.1) | 8 (88.9) | 64–>64 | >64 | >64 | |||||||||||
| Rifaximin | 2 (22.2) | 7 | 32–64 | 64 | 64 | |||||||||||
| Rifabutin | 6 (66.7) | 2 (22.2) | 1 (11.1) | 4–16 | 4 | 16 | ||||||||||
| M. massiliense (6) | Rifampin | 6 (100) | >64 | >64 | >64 | |||||||||||
| Rifapentine | 3 (50) | 3 (50) | 64–>64 | >64 | >64 | |||||||||||
| Rifaximin | 5 (83.3) | 1 (16.6) | 64–>64 | >64 | >64 | |||||||||||
| Rifabutin | 1 (16.7) | 1 (16.7) | 2 (33.3) | 2 (33.3) | 2–16 | 8 | 16 | |||||||||
We examined the in vitro activity of rifamycin derivatives against major pathogenic NTM species, including macrolide- and aminoglycoside-resistant NTM. Among the various rifamycin antibiotics, rifabutin showed the greatest effect in vitro for major NTM species regardless of resistance to key antibiotics, such as macrolides or aminoglycosides. Our data suggest that rifabutin is a therapeutic option for NTM-PD, particularly drug-resistant disease.
Interestingly, we found that the MIC50 (1 to 2 μg/ml) and MIC90 (16 μg/ml) values of rifapentine and rifaximin in M. avium were lower than those of rifampin (4 and 64 μg/ml, respectively) and that the MIC50 (8 μg/ml) and MIC90 (16 μg/ml) values of rifapentine in M. intracellulare were lower than those of rifampin (64 and >64 μg/ml, respectively). However, in MABS, all rifamycin antibiotics except rifabutin had very high MIC50 (32 to >64 μg/ml) and MIC90 (64 to >64 μg/ml) values. These findings indicate that rifamycin antibiotics, except rifabutin, have different in vitro activities for each NTM species and that rifapentine or rifaximin is a treatment option for NTM-PD, particularly MAC.
NTM-PD caused by macrolide- and aminoglycoside-resistant strains is difficult to treat (21, 22). Several oral agents, such as bedaquiline, clofazimine, and linezolid, were recently reported to have low in vitro MICs against NTM and were suggested for use in maintenance therapy. However, data are limited, and drugs such as linezolid can have severe side effects. In these contexts, as rifabutin had lower MIC50 and MIC90 values for macrolide- and aminoglycoside-resistant NTM, our results suggest that rifabutin is appropriate as a treatment for both drug-susceptible and drug-resistant NTM-PD.
Mycobacterial cell walls are less permeable than the outer membranes of other Gram-negative bacteria because of their higher lipid content (23, 24). The cell wall of M. chelonae, a mycobacterium classified as the same species as MABS until the early 1990s, was reported to be 10 to 20 times less permeable than M. tuberculosis, and, due to the structural specificity of this cell wall, MABS is considered resistant to rifamycins (25–27). In addition, MABS has intrinsic rifamycin resistance, whereby rifamycin is inactivated through metabolism by ADP-ribosyltransferase MABS_0591 (28–30).
Rifabutin is considered a new candidate antibiotic for MABS-PD (27). In a recent study of more than 2,700 U.S. Food and Drug Administration-approved drugs, rifabutin was effective against MABS, and recent data showed that rifabutin had synergistic effects with several antibiotics and no antagonism (10, 27). After the initial report that rifabutin was effective against MABS, several studies confirmed the MICs of rifabutin for clinical MABS isolates, and these MIC50 and MIC90 values were not significantly different from our result. Most recently, Chew et al. tested 218 M. abscessus isolates, including 146 respiratory isolates, and reported that the MIC50 and MIC90 of rifabutin were 16 and 32 μg/ml, respectively (12, 31). In addition, it was reported that rifabutin is effective for MABS in mice, zebrafish, and macrophage infection models (13, 14, 32). However, there are limited data on the in vitro activity of rifabutin using large sample sizes and various types of clinical NTM strains.
In summary, rifabutin showed effective in vitro activity against clinical NTM isolates regardless of macrolide or aminoglycoside resistance.
ACKNOWLEDGMENTS
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI20C0017), and was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2020R1I1A1A01066970 to D.H.K.).
We express our heartfelt gratitude and respect to Won-Jung Koh for giving us invaluable guidance and unfailing support from the very beginning of this research. Won-Jung Koh passed away in August 2019. We dedicate this work to his memory.
We have no conflicts of interest to declare.
REFERENCES
- 1.Prevots DR, Marras TK. 2015. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med 36:13–34. doi: 10.1016/j.ccm.2014.10.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lee H, Myung W, Koh WJ, Moon SM, Jhun BW. 2019. Epidemiology of nontuberculous mycobacterial infection, South Korea, 2007–2016. Emerg Infect Dis 25:569–572. doi: 10.3201/eid2503.181597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ, Andrejak C, Böttger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL. 2020. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clin Infect Dis 71:905–913. doi: 10.1093/cid/ciaa1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Floto RA, Olivier KN, Saiman L, Daley CL, Herrmann JL, Nick JA, Noone PG, Bilton D, Corris P, Gibson RL, Hempstead SE, Koetz K, Sabadosa KA, Sermet-Gaudelus I, Smyth AR, van Ingen J, Wallace RJ, Winthrop KL, Marshall BC, Haworth CS, US Cystic Fibrosis Foundation and European Cystic Fibrosis Society . 2016. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax 71(Suppl 1):i1–i22. doi: 10.1136/thoraxjnl-2015-207360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Tortoli E, Kohl TA, Brown-Elliott BA, Trovato A, Leão SC, Garcia MJ, Vasireddy S, Turenne CY, Griffith DE, Philley JV, Baldan R, Campana S, Cariani L, Colombo C, Taccetti G, Teri A, Niemann S, Wallace RJ, Jr, Cirillo DM. 2016. Emended description of Mycobacterium abscessus, Mycobacterium abscessus subsp. abscessus and Mycobacteriumabscessus subsp. bolletii and designation of Mycobacteriumabscessus subsp. massiliense comb. nov. Int J Syst Evol Microbiol 66:4471–4479. doi: 10.1099/ijsem.0.001376. [DOI] [PubMed] [Google Scholar]
- 6.Johnston JC, Chiang L, Elwood K. January 2017. Mycobacterium kansasii. Microbiol Spectr doi: 10.1128/microbiolspec.TNMI7-0011-2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Pasipanodya JG, Ogbonna D, Ferro BE, Magombedze G, Srivastava S, Deshpande D, Gumbo T. 2017. Systematic review and meta-analyses of the effect of chemotherapy on pulmonary Mycobacterium abscessus outcomes and disease recurrence. Antimicrob Agents Chemother 61:e01206. doi: 10.1128/AAC.01206-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kwak N, Dalcolmo MP, Daley CL, Eather G, Gayoso R, Hasegawa N, Jhun BW, Koh WJ, Namkoong H, Park J, Thomson R, van Ingen J, Zweijpfenning SMH, Yim JJ. 2019. Mycobacterium abscessus pulmonary disease: individual patient data meta-analysis. Eur Respir J 54:1801991. doi: 10.1183/13993003.01991-2018. [DOI] [PubMed] [Google Scholar]
- 9.Koh WJ, Jeon K, Lee NY, Kim BJ, Kook YH, Lee SH, Park YK, Kim CK, Shin SJ, Huitt GA, Daley CL, Kwon OJ. 2011. Clinical significance of differentiation of Mycobacterium massiliense from Mycobacterium abscessus. Am J Respir Crit Care Med 183:405–410. doi: 10.1164/rccm.201003-0395OC. [DOI] [PubMed] [Google Scholar]
- 10.Aziz DB, Low JL, Wu ML, Gengenbacher M, Teo JWP, Dartois V, Dick T. 2017. Rifabutin is active against Mycobacterium abscessus complex. Antimicrob Agents Chemother 61:e00155. doi: 10.1128/AAC.00155-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Pryjma M, Burian J, Thompson CJ. 2018. Rifabutin acts in synergy and is bactericidal with frontline Mycobacterium abscessus antibiotics clarithromycin and tigecycline, suggesting a potent treatment combination. Antimicrob Agents Chemother 62:e00283. doi: 10.1128/AAC.00283-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Cheng A, Tsai YT, Chang SY, Sun HY, Wu UI, Sheng WH, Chen YC, Chang SC. 2019. In vitro synergism of rifabutin with clarithromycin, imipenem, and tigecycline against the Mycobacterium abscessus complex. Antimicrob Agents Chemother 63:e02234. doi: 10.1128/AAC.02234-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Dick T, Shin SJ, Koh WJ, Dartois V, Gengenbacher M. 2019. Rifabutin is active against Mycobacterium abscessus in mice. Antimicrob Agents Chemother 64:e01943. doi: 10.1128/AAC.01943-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Johansen MD, Daher W, Roquet-Baneres F, Raynaud C, Alcaraz M, Maurer FP, Kremer L. 2020. Rifabutin is bactericidal against intracellular and extracellular forms of Mycobacterium abscessus. Antimicrob Agents Chemother 64:e00363-20. doi: 10.1128/AAC.00363-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Moon SM, Park HY, Kim SY, Jhun BW, Lee H, Jeon K, Kim DH, Huh HJ, Ki CS, Lee NY, Kim HK, Choi YS, Kim J, Lee SH, Kim CK, Shin SJ, Daley CL, Koh WJ. 2016. Clinical characteristics, treatment outcomes, and resistance mutations associated with macrolide-resistant Mycobacterium avium complex lung disease. Antimicrob Agents Chemother 60:6758–6765. doi: 10.1128/AAC.01240-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Choi H, Kim SY, Kim DH, Huh HJ, Ki CS, Lee NY, Lee SH, Shin S, Shin SJ, Daley CL, Koh WJ. 2017. Clinical characteristics and treatment outcomes of patients with acquired macrolide-resistant Mycobacterium abscessus lung disease. Antimicrob Agents Chemother 61:e01146. doi: 10.1128/AAC.01146-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Choi H, Kim SY, Lee H, Jhun BW, Park HY, Jeon K, Kim DH, Huh HJ, Ki CS, Lee NY, Lee SH, Shin SJ, Daley CL, Koh WJ. 2017. Clinical characteristics and treatment outcomes of patients with macrolide-resistant Mycobacterium massiliense lung disease. Antimicrob Agents Chemother 61:e02189. doi: 10.1128/AAC.02189-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Jhun BW, Yang B, Moon SM, Lee H, Park HY, Jeon K, Kwon OJ, Ahn J, Moon IJ, Shin SJ, Daley CL, Koh WJ. 2018. Amikacin inhalation as salvage therapy for refractory nontuberculous mycobacterial lung disease. Antimicrob Agents Chemother 62:e00011. doi: 10.1128/AAC.00011-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Huh HJ, Kim SY, Shim HJ, Kim DH, Yoo IY, Kang OK, Ki CS, Shin SY, Jhun BW, Shin SJ, Daley CL, Koh WJ, Lee NY. 2019. GenoType NTM-DR performance evaluation for identification of Mycobacterium avium complex and Mycobacterium abscessus and determination of clarithromycin and amikacin resistance. J Clin Microbiol 57:e00516. doi: 10.1128/JCM.00516-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.CLSI. 2011. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes; approved standard, 2nd ed. CLSI document no. M24-A2. Clinical Laboratory Standards Institute, Wayne, PA. [PubMed] [Google Scholar]
- 21.Nessar R, Cambau E, Reyrat JM, Murray A, Gicquel B. 2012. Mycobacterium abscessus: a new antibiotic nightmare. J Antimicrob Chemother 67:810–818. doi: 10.1093/jac/dkr578. [DOI] [PubMed] [Google Scholar]
- 22.Nessar R, Reyrat JM, Murray A, Gicquel B. 2011. Genetic analysis of new 16S rRNA mutations conferring aminoglycoside resistance in Mycobacterium abscessus. J Antimicrob Chemother 66:1719–1724. doi: 10.1093/jac/dkr209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Lambert PA. 2002. Cellular impermeability and uptake of biocides and antibiotics in gram-positive bacteria and mycobacteria. Symp Ser Soc Appl Microbiol 92:46S–54S. doi: 10.1046/j.1365-2672.92.5s1.7.x. [DOI] [PubMed] [Google Scholar]
- 24.Brennan PJ, Nikaido H. 1995. The envelope of mycobacteria. Annu Rev Biochem 64:29–63. doi: 10.1146/annurev.bi.64.070195.000333. [DOI] [PubMed] [Google Scholar]
- 25.Jarlier V, Nikaido H. 1994. Mycobacterial cell wall: structure and role in natural resistance to antibiotics. FEMS Microbiol Lett 123:11–18. doi: 10.1111/j.1574-6968.1994.tb07194.x. [DOI] [PubMed] [Google Scholar]
- 26.Brown-Elliott BA, Wallace RJ, Jr.. 2002. Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin Microbiol Rev 15:716–746. doi: 10.1128/cmr.15.4.716-746.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Ganapathy US, Dartois V, Dick T. 2019. Repositioning rifamycins for Mycobacterium abscessus lung disease. Expert Opin Drug Discov 14:867–878. doi: 10.1080/17460441.2019.1629414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Ripoll F, Pasek S, Schenowitz C, Dossat C, Barbe V, Rottman M, Macheras E, Heym B, Herrmann JL, Daffe M, Brosch R, Risler JL, Gaillard JL. 2009. Non mycobacterial virulence genes in the genome of the emerging pathogen Mycobacterium abscessus. PLoS One 4:e5660. doi: 10.1371/journal.pone.0005660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Baysarowich J, Koteva K, Hughes DW, Ejim L, Griffiths E, Zhang K, Junop M, Wright GD. 2008. Rifamycin antibiotic resistance by ADP-ribosylation: structure and diversity of Arr. Proc Natl Acad Sci U S A 105:4886–4891. doi: 10.1073/pnas.0711939105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Rominski A, Roditscheff A, Selchow P, Bottger EC, Sander P. 2017. Intrinsic rifamycin resistance of Mycobacterium abscessus is mediated by ADP-ribosyltransferase MAB_0591. J Antimicrob Chemother 72:376–384. doi: 10.1093/jac/dkw466. [DOI] [PubMed] [Google Scholar]
- 31.Chew KL, Octavia S, Go J, Ng S, Tang YE, Soh P, Yong J, Jureen R, Lin RTP, Yeoh SF, Teo J. 18 December 2020. In vitro susceptibility of Mycobacterium abscessus complex and feasibility of standardizing treatment regimens. J Antimicrob Chemother doi: 10.1093/jac/dkaa520. [DOI] [PubMed] [Google Scholar]
- 32.Le Run E, Arthur M, Mainardi JL. 2018. In vitro and intracellular activity of imipenem combined with rifabutin and avibactam against Mycobacterium abscessus. Antimicrob Agents Chemother 62:e01915. doi: 10.1128/AAC.00623-18. [DOI] [PMC free article] [PubMed] [Google Scholar]