Objective To evaluate the resistance of multidrug-resistant Mycobacterium tuberculosis ( M. tb) strains to bedaquiline ( BDQ) and to analyze the relationships between their genotypes and BDQ-re-sistant phenotypes in order to provide a scientific basis for rational use of BDQ for the treatment of multidrug-resistant tuberculosis ( MDR-TB) in clinical practice. Methods A total of 387 clinical M. tb strains, inclu-ding 100 pan-susceptible strains and 287 strains isolated from patients with MDR ( MDR-TB strains) , were enrolled in this study. Of the 287 MDR-TB strains, 77 strains were collected in Chongqing in 2015 and the other strains were collected in a national drug-resistant tuberculosis survey conducted in China during 2007 to 2008. Minimum inhibitory concentrations (MIC) of BDQ against those strains were detected. Genotypes of those strains were analyzed by Spoligotyping. Differences in the resistant rates against BDQ between Beijing genotype and non-Beijng genotype MDR-TB strains were comparatively analyzed. Results MIC50 and MIC90 of BDQ against the 287 MDR-TB strains were 0. 03 μg/ml and 0. 25 μg/ml, respectively. Nineteen out of the 287 MDR-TB strains (6. 6%) were resistant to BDQ. Based on the Spoligotyping, 195 strains were clas-sified into Beijing genotype, and the other 92 strains belonged to non-Beijing genotype. Statistical analysis revealed that the BDQ-resistant rate in Being genotype strains (4. 6%, 9/195) was lower than that in non-Beijing genotype strains (10. 9%, 10/92, χ2=3. 955, P=0. 047). In addition, the MIC50 and MIC90 of BDQ against pan-susceptible strains were 0. 03 μg/ml and 0. 12 μg/ml, respectively. Sixty-three pan-sus-ceptible strains belonged to Beijing genotype and the other 37 strains belonged to non-Beijing genotype. None of the pan-susceptible strains was resistant to BDQ. Conclusion This study indicates that BDQ showed stronger in vitro antibacterial activity against the MDR-TB strains isolated in China. A correlation between non-Beijing genotype and BDQ resistance is observed in those MDR strains. MDR strains of Beijing genotype are more susceptible to BDQ than those of non-Beijing genotype.

Objective To report a case of disseminated cryptococcosis with cutaneous manifestations and osteomyelitis. Methods and Results A 33 year old female was admitted due to multiple nodules and ulcers on the upper arms, shoulders, buttocks and thighs for one year. The patient was pregnant when admitted, and gave birth to a premature baby during her illness. The nodules increased half a month after delivery, which was suspected to be hematogenously disseminated pulmonary tuberculosis and was given anti tuberculous therapy for three months but failed. Physical examination showed there were 39 nodules or ulcers on the face, gum, trunk, buttocks and extre mities. The bone structure of the left tibia and fibula destroyed and a sinus developed on the left fibula. Microbiologic examination showed that lots of spores were seen in the smear of pus and necrotic tissues, which produced yeast like colonies in culture with positive urease and caffeic acid test. Cryptococcus neoformans, serotype A was identified by API yeast reaction band and serology. Inoculation with mice and rats showed that their brains, lungs and livers were involved easily. Further identification as C.neoformans var.neoformans was obtained based on sequence analysis of ribosomal internal transcribed spacer region 2. The anti tuberculous therapy was stopped and anti fungal therapy was initiated at once. Intravenous and topical amphotericin B in combination with fluconazole were chosen in the initial therapy and itraconazole for maintenance. The nodules disappeared after 30 days and the last ulcer in the left tibia healed completely after 200 days. The anti fungal therapy was discontinued after 277 days and the patient was completely cured.