[Determination of in vitro synergy by a checkerboard method when 3 core antimicrobial agents of the retreatment new scheme combined against MDR-MTB and XDR-MTB].
OBJECTIVE
In order to detect the in vitro synergistic effect of 4 drugs-pasiniazid (PA), moxifloxacin, rifabutin and rifapentini on multidrug-resistant mycobacterium tuberculosis (MDR-MTB) and extensively drug-resistant mycobacterium tuberculosis(XDR-MTB), which were core drugs of"The program of retreatment research of tuberculosis".


METHODS
The checkerboard method was used to detect the minimum inhibitory concentration (MIC) of antituberculosis drug combination schemes (moxifloxacin-PA, moxifloxacin-PA-rifabutin and moxifloxacin-PA-rifapentini) to 40 strains of clinical drug resistant MTB(20 strains of MDR-MTB and 20 XDR-MTB) and the standard strain H37Rv, by calculating the fractional inhibitory concentration index of joint action in vitro to judge the combined effect, with fractional inhibitory concentration index(FICI)≤0.5 and FICI≤0.75 as the basis of 2 drugs and 3 drugs showing synergy.


RESULTS
The FICI of moxifloxacin-PA scheme for DR-MTB was 0.125 to 1.000, only 5 strains with a FICI ≤0.5, showing synergistic effect. The FICI of moxifloxacin-Pa-rifabutin scheme with 20 strains of MDR-MTB ranged from 0.310 to 1.260, 10 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifabutin scheme with 20 strains of XDR-MTB ranged from 0.215 to 1.250, 11 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifapentini scheme with 20 strains of MDR-MTB ranged from 0.150 to 0.780, 19 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifapentini scheme with 20 strains of XDR-MTB ranged from 0.200 to 1.280, 16 strains with a FICI≤0.75, showing synergistic effect.


CONCLUSIONS
The synergistic effect of moxifloxacin-PA scheme was poor, but showing better synergy when further combined with rifabutin or rifapentini. Rifabutin showed better effect than rifapentini, but the synergistic effect of moxifloxacin-PA-rifabutin combination scheme was poor than that of moxifloxacin-PA-rifapentini combination scheme.
Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Medical School, Tongji University, Shanghai 200433, China.
L L
LL
Zhang
H
H
Yang
H P
HP
Xiao
J M
JM
Lu
W
W
Sha
Q
Q
Zhang
D000636:Aminosalicylic Acids / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D024841:Fluoroquinolones / Q000627:therapeutic use; D007538:Isoniazid / Q000031:analogs & derivatives / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D019233:Retreatment; D017828:Rifabutin / Q000627:therapeutic use; D012293:Rifampin / Q000031:analogs & derivatives / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000636:Aminosalicylic Acids; D000904:Antibiotics, Antitubercular; D024841:Fluoroquinolones; D017828:Rifabutin; C008767:pasiniazide; D000077266:Moxifloxacin; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine