Objective To evaluate the diagnostic value of all diagnostic tests detecting the ethambutol resistance in Mycobacterium tuberculosis. Methods PubMed, EMbase, Chinese Biomedical Database (CBM), Chinese Scientific Journals Full-Text Database (CSJD), and Chinese Journal Full-text Database (CJFD) were searched, and QUADAS items were used to evaluate the quality of included studies. Meta-disc software was used to handle data from included studies. Such index as sensitivity, specificity, and SROC were applied to assess the diagnostic value of individual diagnostic test. Results Nine studies were included. The results of meta-analyses showed that compared with proportion method, the summary sensitivity, summary specificity, positive likelihood ratio, negative likelihood ratio, and SROC area under curve of a nitrate reductase assay were 92%, 99%, 30.50, 0.13, and 0.975 2, respectively, while compared with BACTEC 460 TB, the above mentioned indexes of BACTEC MGIT 960 System were 92%, 99%, 6.27, 0.11, and 0.9, respectively. Bacteriophage biological amplification method revealed relative good analysis effectiveness on MB/BacT. Conclusion According to the results, it is recommended that nitrate reductase assay can replace proportion method as screening test of ethambutol resistance in Mycobacterium tuberculosis, and BACTEC MGIT 960 System can replace BACTEC 460 as final diagnostic test of ethambutol resistance in Mycobacterium tuberculosis.
Objective To assess the rationale for including rifampicin150/isoniazid75/ethambuto/275mg fixed dose, combination oral tablets/3-FDC R150H75E275/ in the WHO Model List of Essential Medicines (WHO EML) for treatment of category II tuberculosis (TB II) and to provide evidence for the updating of national guidelines. Methods We searched Chinese Biomedical Database (CBM, 1978 to 2006), The Cochrane Library, Issue 4, 2006, the Database of Abstracts of Reviews of Effects (1994 to 2006, the Centre for Reviews and Dissemination website), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), BIOSIS Previews (1997 to 2006), websites for grey literature and the references of studies. We applied inclusion and exclusion criteria in assessing the studies we found and eligible studies were graded following an assessment of their quality. Results Thirty-six randomized controlled trials, 4 controlled clinical trials, 11 descriptive studies and 5 WHO/national guidelines were included. Rifampicin (R), isoniazid (H) and ethambutol (E) were used in the ccontinuation phase (CP) of TB II in guidelines of WHO and high tuberculosis (TB) burden countries, but the course of treatment and dosage regimens varied. R, H and E were also widely used in conditions of pulmonary tuberculosis (PTB), extrapulmonary tuberculosis (EPTB) and pulmonary diseases caused by nontuberculous mycobacteria (NTM).Conclusions It is recommended that FDC RHE be included in WHO EML for the treatment of TB II.The suggested dosage ratio of RHE is 1:1:2, which needs to be adjusted based on more solid clinical evidence. High quality clinical studies and systematic reviews on the effectiveness, safety, economics and applicability of WHO and national guidelines and their outcomes in high TB burden countries are needed to guide their updating, promote rational resource allocation and improve cost effectiveness. Alternative drugs or drug combinations with good profile of effectiveness, safety, economics, and applicability for the prevention and treatment of drug-resistant tuberculosis are also needed to be developed.
ObjectiveTo observe the clinical features and visual prognostic factors of ethambutol-induced optic neuropathy (EON).MethodsA cohort study. Twenty-four inpatients (46 eyes) identified as EON in Neuro-Ophthalmology Department of Chinese PLA General Hospital from January 2014 to December 2017 were enrolled, including 14 males (26 eyes) and 10 females (20 eyes) with a ratio of 1.4/1 male/female. The average age was 42.79±15.12 years and the average weight was 62.46±12.31 kg. The average time duration between oral administration of ethambutol and occurrence of EON was 9.94±16.49 months. The average time of ethambutol duration was 7.06±11.68 months, with an average accumulative dose of 156.7±1 779.0 g and the average daily dose of 15.07±8.95 mg/(kg·d). All patients were tested with visual acuity, fundus photos, colour vision, OCT, visual field, VEP, orbital MRI and the gene of OPA1 and mitochondrial deoxyribonucleic acid (mtDNA). All the patients accepted drug withdrawal immediately after diagnosis, and were given the treatment of systemic nerve nutrition and improvement of microcirculation for 2 weeks. The time of follow-up was more than 12 months. According to whether the visual acuity (VA) in any of eyes was over than 0.1 at the last follow-up, all the patients were divided into two groups: the bad VA group (VA less than or equal to 0.1) and the better VA group (VA over than 0.1) group. The χ2 test and Fisher's exact probabilistic method test were used to compare the counting data between groups, and the Wlincox rank sum test was used to compare the measurement data. Multiple factors of VA outcome between the patients with bad or better va were analyzed by logistic regression.ResultsThirty eyes (65.2%) had VA less than or equal to 0.1 and 5 eyes (10.9%) had VA over than 0.5 at EON onset. The VA of the rest 11 eyes (23.9%) was higher than 0.1 and lower than 0.5. At the last follow-up, 20 eyes (43.5%) had VA less than or equal to 0.1 and 9 eyes (19.6%) had VA over than 0.5, the VA of the rest 17 eyes (36.9%) was higher than 0.1 and lower than 0.5. Fundus examination revealed 7 eyes (15.3%) with optic disc edema. OCT revealed significant loss of the retinal nerve fiber layer (RNFL) in the affected eyes, mainly in the temporal RNFL of the optic disc. All patients had dyschromasia, mainly in distinguishing the color of red and green. The types of visual field defect was as following: central dark spot (52.2%), diffuse visual acuity decreased (30.4%), temporal hemianopsia (17.4%). Orbital MRI revealed that 12/24 (50.0%) patients had T2 lesions with T1 enhancement in 6/24 patients (25.0%). Genetic test showed that 4 patients (16.7%) had gene mutation. Among them, there were 2 patients with OPA1 mutation, 1 with mtDNA 14340 point mutation and 1 with the mtDNA 11778 point mutation. Thirteen patients showed better VA outcomes (over than 0.1) while 11 showed bad VA outcomes after discontinuation of ethambutol. Between the better VA group and the bad VA group, there were statistically significant differences in the daily dose of ethambutol and gene mutation (P=0.031, 0.023). The daily dose was related to visual prognosis of EON while only the daily dose of more than 18 mg/(kg·d) may lead to bad VA outcomes according to the logistic analysis (95% CI 0.007-0.736, OR=0.069, P=0.027).ConclusionsEON may have OPA1 and mtDNA mutation with more bilateral eyes involved and less optic edema, which about 43.5% of the patients showed irreversible visual impact. The daily dose of ethambutol is related to the vision recovery.