Efficacy and safety of linezolid in the treatment of extensively drug-resistant tuberculosis.

Linezolid is a new antibiotic with activity against Mycobacterium tuberculosis in vitro and in vivo. This study aims to evaluate the efficacy and safety of linezolid in the treatment of extensively drug-resistant tuberculosis (XDR-TB). We used a linezolid-containing regimen in the treatment of 14 XDR-TB patients. Two years of individualized chemotherapy regimens were adopted on the basis of the patients'medication history and the results of drug susceptibility testing. The patients received 600 mg of linezolid twice a day for the first 1-2 months, followed by once a day thereafter. Eleven patients (78.6%) showed significant improvement in clinical symptoms. Chest computed tomography revealed that 10 patients (71.4%) showed cavity closure. Smear conversion and culture conversion were achieved in all 14 patients (100%) with an average of 64 and 63 days, respectively. The exact proportions of serious and minor adverse events determined by linezolid were 21.4% (3/14) and 64.3% (9/14), respectively. These data show that linezolid-containing chemotherapy for the treatment of XDR-TB may significantly improve clinical symptoms, promote lesion absorption and cavity closure, and accelerate sputum conversion. Further, adverse reactions can be tolerated and resolved with suitable intervention.

[Study on the correlation between polymorphisms of genes with susceptibility to tuberculosis and drug-resistant tuberculosis in Chinese Han population].

OBJECTIVE: To investigate the distribution of polymorphisms of SLC11A1 gene, VDR gene, MBL gene and IFNG gene with susceptibility to tuberculosis (TB) in Chinese Han population suffering from drug-sensitive TB and drug-resistant TB so as to identify the correlation between gene polymorphisms and the development of drug-resistant TB. METHODS: Single nucleotide polymorphisms (SNP) of VDR gene, SLC11A1 gene, MBL gene, IFNG gene were typed and analyzed by pyrosequencing, Real-time Probe and SNaPshot among 229 patients with drug-sensitive TB and 230 patients with drug-resistant TB. RESULTS: The polymorphic foci of VDR gene from the drug-sensitive TB group and the drug-resistant TB group showed no significant difference (P > 0.05). The genotype of INT4 site and allelic frequency of SLC11A1 gene for drug-sensitive TB group were significantly different from those for drug-resistant TB group (P = 0.031, 0.046). If recessive inheritance was assumed, the genotypes of INT4 site from the two groups were significantly different (OR = 5.756, 95%CI: 1.261 - 26.269, P = 0.011). Considering the relationship between OR values under various combination, our findings confirmed that the genetic mode of INT4 site was in accordance with recessive inheritance. The genotypes of Q/P site and allelic frequencies of MBL gene from drug-sensitive and drug-resistant groups were significantly different (P = 0.029, 0.033). The difference still existed under the hypothesis of recessive inheritance (OR = 9.290, 95%CI: 1.167 - 73.949, P = 0.011). The polymorphic foci of IFNG gene from the two groups showed no significant difference. CONCLUSION: INT4 sites on SLC11A1 gene and Q/P site on MBL gene were probably associated with the development of drug-resistant TB in Chinese Han population. Further study on this issue would be helpful in locating the population at high risk of drug-resistant TB and exploring the effective intervention to decrease the incidence of this disease.

[The changes and the significance of cellular immune function in peripheral blood of patients with multidrug-resistant and extensively drug-resistant pulmonary tuberculosis].

OBJECTIVE: To explore the expressions and the significance of CD(3)(+)CD(16)(+)CD(56)(+) NKT cells, CD(3)(-)CD(16)(+)CD(56)(+) NK cells and T lymphocyte subsets in peripheral blood of patients with multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) pulmonary tuberculosis. METHODS: The data of 316 patients with pulmonary tuberculosis hospitalized in Shanghai Pulmonary Hospital from January 2008 to June 2009 were retrospectively analyzed, of whom 119 were newly diagnosed, and 197 were retreated patients. There were 204 males and 112 females, aged from 17 - 88 years, mean (44 ± 16) years. According to the results of drug-resistance, these patients were divided into a MDR group, an XDR group and a sensitive group. There were 146 patients in the MDR group, with 102 males and 44 females, aged from 19 - 84 years, mean (42 ± 16) years. There were 77 patients in the XDR group, with 42 males and 35 females, aged from 18 - 88 years, mean (50 ± 16) years. There were 93 patients in the susceptible group, with 60 males and 33 females, aged from 17 - 83 years, mean (43 ± 19) years. According to the distribution of cavitation in lung fields, these patients were also divided into 1 - 2 lung field affected group (n = 132), 3 - 4 lung field affected group (n = 49) and 5 - 6 lung field affected group (n = 9). The frequencies of NKT cells, NK cells and T cells from whole blood were tested by flow cytometry. Rank test (SAS software) was used for statistic analyses. RESULTS: The expression rate of NKT cells and NK cells was the highest in the XDR group [11% (6% - 16%) and 7% (4% - 12%)], as compared to the MDR group [8% (5% - 14%) and 6% (4% - 11%)], and the susceptible group [7% (4% - 11%) and 5% (3% - 9%)], the difference being statistically significant (H = 6.478 - 8.369, P < 0.05). The expression rate of the NKT (14 ± 9)% and NK cells (11 ± 7)% in males of the XDR group was significantly higher than that in females [NKT (9 ± 5)% and NK cell (6 ± 4)%], while CD(4) (38 ± 10)% and CD(4)/CD(8) (1.9 ± 1.3) were significantly lower than those of the females [CD(4) (44 ± 10)% and CD(4)/CD(8)(2.2 ± 0.7)], the difference being statistically significant (z = -2.91 - -2.79, P < 0.05, P < 0.01). The expression rate of CD(4) (42 ± 9)% was the highest, but CD(8) (22 ± 8)% was the lowest in the 1 - 2 lung field group. While in the 5 - 6 lung field group, the expression rate of CD(4) (36 ± 11)% was the lowest, CD(8) (28 ± 12)% was the highest, and CD(4)/CD(8) (1.5 ± 0.8) was the lowest, the difference being statistically significant (H = 8.404 - 16.175, P < 0.01). CONCLUSIONS: With the increasing level of drug resistance, the expression rate of NKT cells and NK cells increased, while the expression of T cell subsets did not change. The value of CD(4) and CD(4)/CD(8) in peripheral blood decreased, but CD(8) increased as the extent of cavitation increased in these patients. The impairment of cellular immune function in XDR-TB was more prominent in male patients.

[The correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of tuberculosis in 459 Han patients].

OBJECTIVE: To study the correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of tuberculosis in Han population. METHODS: Four hundred and fifty-nine tuberculosis inpatients of Han population in Shanghai Pulmonary Hospital from Jan 2007 to Dec 2008 were recruited. The clinical characteristics of tuberculosis (gender, fever, extent of lesions, cavity formation, hemoptysis, initial treatment and retreatment) were observed. The polymorphisms of VDR gene (variants in FokI and TaqI), NRAMP1 gene (variants in INT4, D543N and 3 UTR), MBL gene (variants in HL, YX and QP) and IFNG gene (variants in 874AT) were genotyped by a variety of SNP genotyping techniques. The correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of the disease was analyzed by ANOVAs. RESULTS: The frequency of CC, CT and TT variants of FokI in VDR gene in cases with fever were 54.7% (29/53), 13.2% (7/53) and 32.1% (17/53), respectively, compared to 40.6% (52/128), 30.5% (39/128) and 28.9% (37/128) in cases without fever, the difference being significant (χ² = 6.183, P < 0.05). In patients with CT variants, 15.2% (7/46) had fever, while in patients with non-CT variants, 34.1% (46/135) had fever (χ² = 5.891, P < 0.05), suggesting that patients with CT variants were less likely to have fever. The frequencies of TT + TC and CC variants of QP in the MBL gene in initial treatment cases were 28.3% (60/212) and 71.7% (152/212), respectively, compared to 19.1% (41/215) and 80.9% (174/215) in retreatment cases, the difference being significant (χ² = 5.038, P < 0.05). No significant correlation was observed between the other variants and the clinical characteristics of tuberculosis (χ² = 0.001 - 2.732, P > 0.05). CONCLUSIONS: The polymorphisms of FokI in VDR gene was associated with fever among the clinical characteristics of tuberculosis, and patients with CT variants might be protected from fever. The polymorphisms of QP in MBL gene might be associated with recurrence of tuberculosis.

[Clinical, pathological and radiological characteristics of 83 cases of pleural tuberculoma].

OBJECTIVE: To investigate the clinical, pathological and radiological characteristics of pleural tuberculoma, so as to improve the understanding of this disease. METHODS: We retrospectively analyzed the clinical, laboratory, pathological and radiological data of 83 cases of pleural tuberculoma diagnosed by pathology and(or) bacteriology in Shanghai Pulmonary Hospital Affiliated to Tongji University. RESULTS: In the recruited 83 cases, there were 50 males and 33 females, aged from 7 to 85 years old, with a mean age of 37.8 years. Cough, fever and chest pain were common symptoms, but no significant symptoms were seen in 25 patients (31.3%). Some patients had positive physical signs, such as dullness to percussion and low breath sound. Pulmonary tuberculosis was also present in 36 patients (43.3%) with pleural tuberculoma. A history of tuberculous pleurisy was elicited in 80 patients, among whom 45 (56.3%) received delayed antituberculous treatment and 42 (52.5%) received nonstandard treatment. Forty-eight cases (60.0%) did not receive corticosteroids. Fifty-nine cases underwent CT-guided percutaneous biopsy, while 24 underwent thoracoscopic surgery, and tuberculosis was pathologically confirmed in 62 (74.7%). Pathological profiles included granuloma, coagulation or caseation necrosis, lymphocyte infiltration, epithelioid cells, inflammatory cells, histiocytes and scar tissue. Fifteen (18.1%) specimens from percutaneous biopsy were anti-fast smear positive, while Mycobacterium tuberculosis was obtained by culture in 21 (25.3%) cases. Chest X-ray showed that solitary lesions were seen in 68 cases, multiple foci in 15. The lesions of 46 cases (55.4%) occupied the lower right lobes. Round-like shadows were the most common signs, which were present in 63 cases (75.9%). CT examination demonstrated homogeneous density in 20, heterogeneous density in 40, calcification in 9, central attenuation in 34, and peripheral intensification in 28 cases. CONCLUSIONS: Pleural tuberculoma is an important sequelae of tuberculous pleurisy. Understanding its clinical, pathological and radiological characteristics is helpful for the differential diagnosis of pleural and lung diseases.