Management Of Resistant Tuberculosis Research Articles

Role of second-line injectable antituberculosis drugs in the treatment of MDR/XDR tuberculosis

Second-line injectable antituberculosis drugs (aminoglycosides and capreomycin) are the main drugs used in the management of resistant tuberculosis. Their preserved efficacy in the case of multi-drug-resistant bacillus is counterbalanced by frequent adverse events. Adverse events are linked to the drugs themselves and to the recommended 8-month period of parenteral administration. In numerous countries facing a high incidence of multi-drug-resistant tuberculosis, treatment is administered by intramuscular injection. This procedure is painful and restrictive, and therefore treatment adherence is limited. This study reports the follow-up of 11 patients diagnosed with multi-drug- and extensively-resistant tuberculosis and treated with parenteral amikacin, and discusses the role of amikacin in the treatment of resistant tuberculosis.

Detection of KatG/inhA Mutation to Guide Isoniazid and Ethionamide Use for Drug-resistant Tuberculosis

BackgroundBoth Mozambique and Brazil are countries with a high burden of tuberculosis. Isoniazid (INH) is one of the cornerstones of tuberculosis treatment and, depending on the mutated gene (katG or inhA), the organism may be susceptible to high doses of INH (inhA mutation) or to ethionamide (-Eth-KatG mutation).MethodsTo analyze isoniazid genotypic resistance profile in Mycobacterium tuberculosis to guide decision making about management of resistant tuberculosis. Descriptive study of 311 M. tuberculosis isolated from Ribeirão Preto, Brazil (2011–2014) and 155 isolates from Beira, Mozambique (2014–2015). Drug resistance patterns and the specific genes mutations were determined using Genotype MTBDRplus (Hain Lifescience GmbH, Germany).ResultsMutations in katG gene were detected in 13/22 (59%) of Brazilian and in 32/38 (84.2%) of Mozambican isolates. Unique inhA mutations were observed in 8/22 (36%) isolates in Brazil and 4/38 (10.5%) in Mozambique. Both katG and inhA mutations where detected in 1/22 (5%) and 2/38(5.2%), respectively. katG mutations were more frequent among INH previously treated patients.ConclusionThere is a geographical variation of INH mutations and the new molecular tests can be used to guide and accelerate decision making towards the use of ETH or high doses of INH based on detected mutations.Disclosures All authors: No reported disclosures.

A study on the cooperation between centers for disease control and special tuberculosis hospitals for treatment and management of multi-drug resistant tuberculosis

To improve the effectiveness of case detection and treatment of multi-drug resistant tuberculosis (MDR-TB) by implementing a mechanism of cooperation between hospitals and centers for disease control (CDC). Since 1 March 2010, a new mechanism of cooperation between hospitals and CDCs had been established in 5 cities including Daqing, Quzhou, Puyang, Tianjin and Wanzhou in China. Data of MDR-TB case-detection, treatment and economic burdens before the intervention (January 1, 2006-June 30, 2009) and after the intervention (March 1, 2010-February 29, 2012) were collected. Then all data were analyzed by statistical method. After the intervention, samples from 68.4% (5 287/7 733) of smear-positive TB patients in the study regions underwent TB drug-resistant testing, and the number of the detected MDR-TB cases were 9.8 times that prior to the intervention. 93.1% (108/116) of the patients incorporated into the treatment of MDR-TB received the standardized initial chemotherapy program, and the number was 7 times that before the intervention. The referral rates after hospital discharge raised from 0% before the intervention to 92.8% after (90/97) the intervention; and 85.7% (83/97) of the patients received treatment and management by CDC. When the 6-month injection ended, MDR-TB patients still under treatment after the intervention were 84.5% (82/97), and those whose sputum culture became negative were 56.7% (55/97). The proportion of patients with self-paid and with catastrophic expenditures after the intervention were reduced to 18.0% (1 678/9 324) and 44.7% (17/38) respectively, as compared to 75.4% (7 659/10 158) and 76.7% (23/30) respectively before the intervention. To establish a well-performed Hospital-CDC cooperation mechanism could promote the performance of MDR-TB case detection and treatment.

In-vitro activity of ofloxacin against Mycobacterium tuberculosis and its clinical efficacy in multiply resistant pulmonary tuberculosis

The in-vitro susceptibilities to ofloxacin of 159 clinical sputum isolates of Mycobacterium tuberculosis, comprising 95 isolates sensitive to all drugs, 31 isolates resistant to streptomycin or isoniazid or both, 27 isolates resistant to streptomycin, isoniazid and rifampicin and six isolates resistant to rifampicin (and in three cases to other drugs) were determined. Favourable MICs of ofloxacin (0.63-1.25 mg/l) were demonstrated for 147 isolates (92%). Twenty-two patients with resistant strains (including one patient with rifampicin intolerance) were studied: ten were given 300 mg ofloxacin and ten were given 800 mg ofloxacin, once daily in both cases, together with second-line accompanying drugs, for nine months to one year. Two received 800 mg of ofloxacin once daily alone for similar periods. In the 300 mg-ofloxacin group and the 800 mg-ofloxacin group, five and eight patients, respectively, achieved culture conversion; the rest failed. In the former group, the peak serum ofloxacin concentrations were 3.71-8.08 mg/l and the mean sputum/serum ratio was 0.85. In the latter group, the corresponding values were 10-18.7 mg/l, and 0.76, respectively. All patients tolerated the drugs well. Analysing only patients with accompanying drugs, those on ofloxacin 800 mg once daily had more rapid sputum culture conversion than those on ofloxacin 300 mg once daily (Mann-Whitney Wilcoxon Rank Sum Test: P less than 0.05), indicating more rapid bacteriolysis and implying the definite efficacy of ofloxacin when used together with second-line accompanying drugs in the management of resistant tuberculosis.