Study on the antibacterial activity of carrimycin against Mycobacterium Kansasii in vitro and in vivo
Objective To evaluate the activity of carrimycin(CAM)against M.kansasii(MK)in vitro and in vivo and provide more options for clinical treatment in pulmonary disease due to MK.Methods The standard strain(ATCC12478)and 3 clinical isolates of MK were used in experiments.The microplate alamar blue assay(MABA)was used to determine the minimal inhibitory concentrations(MICs)of CAM,spiramycin(SPM),azithromycin(AZM)and rifampicin(RIF).The checkerboard assay was used to evaluate the interaction between CAM and 8 clinically used drugs including AZM and RIF.The antibacterial activity of CAM,AZM and SPM in J774A.1 cells was evaluated and the model of BALB/c mice infected with MK was established.CFU counting was used to determine the bacillary load of organs in the black control group,CAM treatment group,AZM treatment group,and SPM treatment group.HE staining was used to assess the degree of lung injury.Results The MIC values of CAM,SPM,AZM and RIF in MK standar strains(ATCC12478)and three clincal isolates were 4～8 mg/L,＞64 mg/L,4～8 mg/L and 0.125～0.25 mg/L,respectively.No antagonism between CAM and drugs used in this study were observed(fractional inhibitory concentration index,FICI＜4).CAM was partially synergized with isoniazid and rifampicin.The concentration of 2 mg/L CAM,SPM and AZM could reduce lgCFU from 0.3 to 0.4 in the macrophage infection model compared with the control group(P＜0.001).In the BALB/c mouse model infected with middle dosage MK,compared with the control group,continuous administration of 100 mg/kg CAM,AZM and SPM could reduce the bacillary load to 0.73,0.69 and 0.22 lgCFU(P＜0.001)in the lungs after 2 weeks of treatment and 0.74,1.02 and 0.41 lgCFU(P＜0.001)after 4 weeks of treatment,respectively.In the BALB/c mouse model infected with high-dose MK,continuous administration of 100 mg/kg CAM for 4 weeks could reduce the bacillary load 0.98 lgCFU(P＜0.001)in the lungs compared with the control group.CAM treatment could significantly reduce inflammatory cells compared with the control group(P=0.001).Conclusion CAM has potent activity against MK in vitro and in vivo.CAM not only reduced the bacillary load in organs,but also mitigated lung damage.Therefore,CAM deserves further clinical trials.
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