| Tuberculosis (TB) remains a serious problem of public health worldwide and in China. China has the world's second largest TB epidemic with more than 4.5 million cases of TB, and 130,000 death of TB every year. Furthermore, almost half of population was already infected with Mycobacterium tuberculosis (M.TB) in China. The emergence of drug resistant TB, especially multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB), pose a substantial threat to TB control programs, and become an urgent issue to be solved.In this study, we performed a retrospective study including all drug-resistance TB in Shanghai from Jan 2009 to Dec 2009 to determine the current situation of second-line drug resistance of M.TB and risk factors of second-line drug resistant TB. Meanwhile, based on the epidemiologic study, molecular biology techniques was used to investigate the relationship between the Beijing genotype strains and second-line drugs resistance. In addition, to investigate the prevalence of Ofloxacin resistance among the TB patients in shanghai during 15 months of 2009 to 2010.(1) Resistance to second-line drugs in drug resistance TB patients in Shanghai, China.A total of 4380 pulmonary TB patients were diagnosed at the TB hospitals and clinics in Shanghai during Jan 2009 and Dec 2009, of whom 2170 (48.8%) were culture positive. Among those cases,1908 were infected with M. tuberculosis isolates. With the DST to INH, RIF, EMB and SM,410 (21.5%) cases with resistance to at least one of first-line anti-TB drugs were included in this study and further DST of SLDs was performed. Among the 410 cases, the overall resistance rate to SLDs was 28.3%. The rate of drug resistance was ofloxacin (15.6%), kanamycin (8.8%), para-aminosalicylic acid (7.8%), capreomycin (6.3%), amikacin (5.1%) and prothionamide (2.0%). The rates of resistance to any SLDs were 53.0%(53/100),27.8%(25/65) and 17.3%(38/220) in MDR-TB, poly-drug resistance and monoresistance. Compare to poly-drug resistance and mono-drug resistance, the MDR-TB patients have significant high rate of resistance to more than three SLDs and 9.0% of MDR-TB patient were XDR-TB.Furthermore, we estimated the associated factors with resistance to SLDs. We found that patients with MDR-TB (OR=4.335,95% CI:2.463-7.629, p＜0.001) and previous TB treatment (OR=1.717,95% CI:1.013-2.910, p=0.045) were more likely to be resistance to SLDs. These results suggest that in Shanghai the high prevalence of resistance to SLDs in TB patients, Especially MDR-TB patient more easily resistant to SLDs, MDR-TB and previous TB treatment are the risk factors for SLDs resistance. The patient should taken more easily accepted by way of supervision and to strengthen supervision management efforts to prevent further spread of drug resistance. (2) Association between second-line drug resistance and beijing family strains in patients with pulmonary tuberculosis in Shanghai, China.Beijing family tuberculosis shared the majority of their IS6110 DNA-containing restriction fragments, and also, the DNA polymorphism associated with other repetitive DNA elements, like the polymorphic GC-rich sequence and the direct repeat, was very limited. Deletion of the RD105 region PCR was applied to investigate the Beijing family tuberculosis and its association with the second-line drug resistant in this study. Of the 410 M. tuberculosis strains with first-line drug-resistance,321(78.3%) were identified as Beijing family strain. The rate of second-line drug resistance was 30.1%(97/321) in beijing family strains, which was higher than in non-beijing family strains (OR=1.595,95% CI:0.890-2.961, p=0.1002). The rates of Ofloxacin resistance, para-aminosalicylic acid resistance and prothionamide resistance were 19%,9.0% and 1.9% in Beijing family strains, respectively. The percentages of resistance to there of the injectable drugs kanamycin, capreomycin and amikacin were 7.5%,7.8% and 5.3%, respectively. Although the Beijing family strain was significantly associated with Ofloxacin resistance (OR=3.589,95% CI:1.012-12.723, p=0.048) and kanamycin resistance (OR=0.348,95% CI:0.152-0.797, p=0.013), no significant association was found between the overall rate of second-line drug resistance and beijing family strain in this study.(3) Ofloxacin Resistance in Patients with pulmonary tuberculosis in Shanghai, China.Fluoroquinolones is one of the important classis of second-line drugs in the treatment of tuberculosis. In recent two decades, these drugs are widely used in clinical treatment of other bacterial infections, which triggered widespread resistance. However, the prevalence of fluoroquinolones resistance in TB patients in shanghai was unclear. We aim to investigate the prevalence of Ofloxacin resistance in pulmonary tuberculosis in Shanghai, and the association factors with ofloxacin resistance. In total,598 tuberculosis isolates were collected from the clinical trials, including the TB mono-resistance to INH 58, SM 167, RFP9, EMB6, MDR-TB 111, poly-drug resistance 96, and 151 isolates with pan-susceptible to first-line drugs were selected as control group. Among the 447 drug-resistant isolates,72 (16.1%) were found to resistant to Ofloxacin, and the resistantance rate among multiple drug-resistant (MDR) isolates was 39.6% (44/111). Ofloxacin resistance was also found in 4 (2.6%) of the 151 drug sensitive isolates. Logistic analysis showed that first-line drug-resistance (MDR/pan-susceptibility:OR=19.512, 95% CI:6.408-59.408, p＜0.001), (polyresistance/pan-susceptibility:OR=5.624,95% CI: 1.745-18.123, p=0.004); previous treatment history (previously treated cases/new cases: OR=2.277,95% CI:1.273-4.071, p=0.006), origin (local resident/urban migrant:OR=2.058,95% CI:1.113-3.740, p=0.018) were significantly associated with Ofloxacin resistance. Furthermore, DNA sequencing of gyrA was performed for the 76 ofloxacin resistance strains. Resistance mutations in the gyrA genes were detected in 62 of 76 (81.6%) isolates with phenotypic Ofloxacin-resistance. The resistance level to Ofloxacin was low among TB patients who were first line drug-susceptible. However, Ofloxacin resistance in MDR-TB patients was high. Ofloxacin resistance in MDR-patients was high. MDR-TB, poly-drug resistance, previously treated cases and local resident are risk factors for Ofloxacin resistance. Therefore, it is necessary to strengthen the early diagnosis of TB and treatment of TB patients.
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