Curative effect of capreomycin in adjuvant treatment of multidrug-resistant pulmonary tuberculosis and its effect on quality of life and immune function / 中国热带医学

@#Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx（Lfx）-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx（Lfx）-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions　Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.

Clinical Observation of Levofloxacin and Capreomycin Combined with Chemotherapy Regimen in the Treat-ment of Multi-drug Resistant Tuberculosis / 中国药房

OBJECTIVE:To observe the efficacy and safety of levofloxacin and capreomycin combined with chemotherapy regi-men in the treatment of multi-drug resistant tuberculosis(MDR-TB). METHODS:84 MDR-TB patients were randomly divided in-to observation group (42 cases) and control group (42 cases). Observation group received 0.75 g Capreomycin sulfate for injec-tion,addint into 100 ml 0.9% Sodium chloride injection,intravenous infusion,once a day+0.4 g Levofloxacin hydrochloride tab-let,orally,once a day+0.2 g Protionamide tablet,orally,3 times a day+0.3 g Pasiniazid tablet,orally,3 times a day+0.5 g Pyra-zinamide tablet,orally,4 times a day. Control group received 0.4 g Amikacin sulfate injection,adding into 100 ml 0.9% Sodium chloride injection,once a day,intravenous infusion+0.3 g Ofloxacin tablet,orally,twice a day+Protionamide tablet (the same dose with observation group)+Pasiniazid tablet (the same dose with observation group)+Pyrazinamide tablet (the same dose with observation group). All patient were given 0.1 g Glucuronolactone tablet,orally,3 times a day. The treatment course for both group was 12 months. Sputum negative conversion rate,negative conversion time,symptom improvement time,lesion absorption and lung cavity closing,and cell immune indexes (CD4+CD25+/CD4+,CD4+CD25+CD127low/CD4+),IL-17 level before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The sputum negative conversion rate,ab-sorption rate,lung cavity closing and narrowing cases in research group after 3,6,9,12,18 months treatment were significantly higher than control group,sputum negative conversion time,symptom improvement time in observation group were significantly lower than control group,the differences were statistically significant(P0.05). After treatment,CD4+CD25+/CD4+,CD4+CD25+CD127low/CD4+ in 2 groups were significantly lower than before,and observation group was lower than control group,IL-17 level was significantly higher than before,and observation group was higher than control group,the differences were statistically significant (P0.05). CON-CLUSIONS:Levofloxacin and capreomycin combined with chemotherapy in the treatment of MDR-TB,it can reduce T regulatory cells,increase IL-17 level,do not increase the incidence of adverse reactions.

Outcomes and Use of Therapeutic Drug Monitoring in Multidrug-Resistant Tuberculosis Patients Treated in Virginia, 2009-2014 / 결핵및호흡기질환

BACKGROUND: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. METHODS: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak (Cmax), were compared to expected ranges. RESULTS: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean C2hr, 16.6+/-10.2 microg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C2hr, 3.2+/-1.5 microg/mL; 1 [20%] below); capreomycin in five (mean C2hr, 21.5+/-14.0 microg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr, 65.0+/-29.1 microg/mL; all within or above); linezolid in three (mean C2hr, 11.4+/-4.1 microg/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3+/-3.7 microg/mL; 1 [50%] below); ethionamide in one (C2hr, 1.49 microg/mL, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. CONCLUSION: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

Study on Preparation and Pharmaceutical Character of Capreomycin Sulfate Liposomes by Three Kinds of Methods / 中国药房

OBJECTIVE:To prepare and characterize capreomycin sulfate liposomes(CSL).METHODS:Capreomycin sulfate was entrapped into liposomes using active loading that pH gradient methods,ammonium sulfate gradient methods and sodium acetate gradient methods respectively followed by lyophilization technique.The liposome was characterized by entrapment efficiency,particle size,? potential and the stability.RESULTS:The entrapment efficiency of CSL pre-and post-lyophilization prepared by three methods were 65.7% and 65.2 %,20.1% and 18.6%,34.6% and 32.4%,with particle size of 136 and 145 nm,144 and 153 nm,142 and 159 nm,? potential of —20.2 and —19.5 mV,—24.4 and —22.9 mV,—18.7 and —17.8 mV respectively.No obvious changes were found in all the indexes in the stability test.CONCLUSIONS:The pH gradient technique is suitable for preparing CSL in 3 kinds of methods.

Observation on Therapeutic Effect of Combined Use of Capreomycin in Treating 268 Patients with Multiple-drug-resistant Tuberculosis / 中国药房

OBJECTIVE:To observe the therapeutic effect of combined use of capreomycin in treating multiple-drug-resistant tuberculosis.METHODS:After 268 patients with multiple-drug-resistant tuberculosis had underwent intensive treatment with levofloxacin,pyrazinamide,pasiniazid,protioamide and capreomycin for 3 months,they underwent another 9 months of strengthened treatment with levofloxacin,pasiniazid,and rotioamide.RESULTS:The negative rate determined in sputum test for tuberculosis bacteria was up to 78.36%,and the closing rate of the cavity was up to 37.76%.CONCLUSION:The therapeutic effect for treatment of multiple-drug-resistant tuberculosis can be improved by carrying out the principle of whole range direct monitoring of chemotherapy and using capreomycin in combination with other drugs to increase the sensitivity to mycobacterium tuberculosis.