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Table 2 Treatment regimen and outcomes of MR-MAC-PD

From: Clinical characteristics and treatment outcomes of patients with macrolide-resistant Mycobacterium avium complex pulmonary disease: a systematic review and meta-analysis

StudyNTreatment regimen, n (%)FQ, n (%)AG, n (%)CFZ, n(%)Surgery, n (%)Treatment duration, months
Tanaka 1999 [13]6NANANANRNRNA
Griffith 2006 [5]51Surgery, prolonged (≥6 mo) AG: 14 (27)
Surgery, no prolonged AG: 2 (4)
No surgery, prolonged AG: 8 (16)
No surgery, no prolonged AG: 27 (53)
CIPX 4 (8)
GTFX 6 (12)
SM 24 (47)
AMK 11 (22)
4 (8)16 (31)NA*
Moon 2016 [6]34Macrolide 16 (47), EMB 25 (74),
RIF or RFB 34 (100)
MFX 17 (50)SM 13 (38)4 (12)2 (6)23.0
(16.8–45.3)
Morimoto 2016 [7]90CAM 55 (61), RFB 15 (17)
FQ 56 (62) for median 12 mo
AG 52 (58) for median 6 mo
STFX 44 (49)
MFX 11 (12)
LFX 8 (9)
AMKi 32 (36)
AMKn 7 (8)
KM 10 (11)
SM 4 (4)
NR11 (12)21
(10–37)
Kadota 2016 [8]33CAM 24 (73), AZM 2 (6),
Regimen without macrolide 7 (21)
FQ for median 5 mo
LFX 16 (48)
MFX 2 (6)
STFX 2 (6)
KM 9 (27)NR0 (0)10.4 ± 1.6
Yagi 2017 [14]9RIF + EMB + FQ + AMKn: 4 (44)
RIF (RFB) + FQ + AMKn: 2 (22)
EMB + FQ + AMKn: 1 (11)
RIF + EMB + AMKn: 1 (11)
CAM + EMB + AMKn: 1 (11)
STFX 6 (67)
MFX 1 (11)
AMKn 9 (100)0 (0)0 (0)(6–16)#
Aznar 2018 [15]8All patients received GBT, including a macrolide, ethambutol, and a rifamycin when possible. Four patients had adjuvant surgery.NANANA4 (50)> 12
Griffith 2018 [16]73Patients were randomly assigned in a 2:1 ratio to receive ALIS to GBT or GBT alone.NAALIS 51 (70)NANANA
Asakura 2019 [17]15GBT plus STFX 200 mg 14 (93)
GBT plus STFX 100 mg 1 (7)
STFX 15 (100)AMKi or AMKn
5 (33)
NR2 (13)≥12 mo: 13 (87%)
< 12 mo: 2 (13%)
StudyNSputum culture conversion definitionConversion, n (%)Mortality, n (%)Follow-up duration,
months
  
Tanaka 1999 [13]6Consecutive negative cultures during a 3-month period1 (17)NRNA  
Griffith 2006 [5]51A minimum of three consecutive negative cultures over a minimum time of three months13 (26)1-yr 13 (25)
2-yr 17 (33)
(16–84)
(18–54)
  
Moon 2016 [6]34Three consecutive negative cultures, 2- to 3-month intervals5 (15)§1-yr 3 (9)
3-yr 8 (24)
5-yr 16 (47)
39.3
(22.9–43.4)
  
Morimoto 2016 [7]90Three consecutive negative cultures10 (11)1-yr 8 (9)
2-yr 13 (15)
3-yr 15 (17)
5-yr 26 (29)
21
(10–37)
  
Kadota 2016 [8]33Two consecutive negative cultures. If the patient could not expectorate sputum, it was considered to have converted to negative12 (36)1-yr 2 (6)10.4 ± 1.6  
Yagi 2017 [14]9Three consecutive negative cultures after amikacin inhalation3 (33)NRNR  
Aznar 2018 [15]8Persistently negative cultures or when unable to provide sputum specimens for culture during at least 12 months3 (38)1-yr 0 (0)> 12  
Griffith 2018 [16]73Three consecutive monthly MAC-negative cultures by Month 68 (11)NR6**  
Asakura 2019 [17]15Three consecutive negative cultures. If the patients did not expectorate sputum, the status was recorded as negative.6 (40)NANA  
  1. Note: Data are presented as mean ± standard deviation or median (interquartile range) unless otherwise indicated
  2. *Duration of prolonged aminoglycoside therapy for 14 patients is 12.0 ± 4.1 (range 7–19) months
  3. †Range of follow-up duration for survived patients who remained culture-positive after resistance diagnosis
  4. ‡Range of follow-up duration for survived patients who were cured or culture converted after resistance diagnosis
  5. §Number of patients who achieved ‘favorable outcome,’ which was defined as sputum culture conversion within 12 months after initiation of treatment and maintenance of a negative culture for 12 months or longer on treatment
  6. #Range of AMKn duration except for one patient who discontinued within 1 month due to pneumothorax. Two of eight patients used AMKi at some interval
  7. ** The study reported primary results at 6 months of ongoing phase 3 CONVERT study
  8. Abbreviations: MR-MAC-PD macrolide-resistant M. avium complex pulmonary disease, CAM clarithromycin, AZM azithromycin, EMB ethambutol, RIF rifampicin, RFB rifabutin, CIPX ciprofloxacin, LFX levofloxacin, MFX moxifloxacin, STFX sitafloxacin, GTFX gatifloxacin, AMKn amikacin inhalation, AMKi amikacin injection, ALIS amikacin liposome inhalation suspension, SM streptomycin, KM kanamycin, CFZ clofazimine, GBT guideline-based therapy, NR not reported in the article, NA specific data for MR-MAC-PD patients are not available