Isoniazid And Rifampicin Research Articles

Prevalence and Distribution of Multidrug-Resistant Mutations in Mycobacterium tuberculosis in Tanzania

Background: Molecular identification of mutations resulting in multidrug-resistant tuberculosis (MDR-TB) is an important approach for improving understanding of MDR-TB epidemiology and planning for appropriate interventions. We aimed to estimate the prevalence and distribution of mutations causing MDR-TB as well as determine the gene distribution among patients previously treated for TB. Methods: This was a cross-sectional, hospital-based study conducted from April 2017 to October 2018 at Kibong’oto Infectious Diseases Hospital (KIDH). KIDH is the national MDR-TB referral hospital. Participants were patients presumptively diagnosed with MDR-TB and referred to KIDH from district and regional hospitals across Tanzania. Sputum samples were collected and analysed using the Xpert MTB/RIF assay, direct sputum smear fluorescence microscopy, culture on Lowenstein-Jensen medium, and line probe assay using the GenoType MTBDRplus VER 2.0 system. Demographic information and mutation frequencies were reported as counts and percentages and analysed using descriptive statistics. Results: A total of 208 (69.3%) participants had rpoB gene mutations conferring resistance to only rifampicin; 92 (30.7%) had rpoB, katG, and inhA mutations conferring resistance to rifampicin and isoniazid; 78 (26%) had rpoB and katG mutations conferring resistance to rifampicin and isoniazid; and 14 (4.7%) had rpoB and inhA mutations conferring resistance to rifampicin and isoniazid. Conclusion: The mutation prevalences identified in this study indicate the most frequent mutations were the S531L mutation of the rpoB gene, the S315T1 mutation of the katG gene, and the S315T mutation in the promoter region of the inhA gene. To control the emergence and spread of MDR-TB, drug sensitivity testing must be carried for GeneXpert-confirmed TB patients prior to initiating second-line anti-TB regimens.

Tuberculosis Epidemiology, Pathogenesis, Drugs and Drug Resistance Development: A Review

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis and classified as pulmonary and extrapulmonary based on their site of infection. Antituberculosis drugs developed since the 1940s and as their discovery resistance also developed against them. World health organization recognized tuberculosis as emergency public health in 1993. Acquired and primary drug resistances are the common pathways for the development of anti-tuberculosis drug resistance. Acquired drug resistance is the result of inappropriate treatment, poor quality of the drugs and inadequate drug intake and primary drug resistance is due to exposure to the drug-resistant anti-tuberculosis. Types of anti-tuberculosis drug-resistant are multidrug-resistant tuberculosis is the result of resistance to isoniazid and rifampicin, extensively drug-resistant tuberculosis a consequence of resistance to isoniazid, rifampicin, fluoroquinolones and one of the second-line injectable drugs and totally drug-resistant tuberculosis is a resistance to all first and second-line anti-tuberculosis drugs. Anti-tuberculosis drugs primarily actions are on protein synthesis, mycolic acid synthesis, DNA synthesis, folic acid synthesis, and ATP synthase. These drugs could produce bacteriostatic or bactericidal effects on the mycobacteria. The main resistance mechanism to the anti-tuberculosis drug is the mutation of the target gene accountable for the action of anti-tuberculosis drugs. This resistance to the antituberculosis drug produces a devastating effect on public health. Therefore, further study should be conducted in the areas of finding a new target for the development of new anti-tuberculosis drugs.

Diagnosis and treatment of tuberculosis peritonitis in patients with maintenance hemodialysis

Objective To investigate the clinical characteristics and treatment strategies of patients with maintenance hemodialysis and tuberculous peritonitis. Methods The clinical data of maintenance hemodialysis 12 patients combined with tuberculous peritonitis were analyzed retrospectively. Results The pathogenesis of maintenance hemodialysis combined with tuberculous peritonitis was concealed, and history of tuberculosis in 4 cases (33%), 10 cases of peripheral blood lymphocyte count 2.5 g/dL, peritoneal effusion ADA>30 U/L in 9 cases (75%), all cases of peritoneal effusion LDH>90 U/L. All 12 patients received two (isoniazid and rifampicin) or triple (isoniazid, rifampicin and ethambutol) anti-tuberculosis treatment, daily single medication for 9 months. Ten patients were discharged with a better health condition. Conclusions Active anti-tuberculosis in the treatment of maintenance hemodialysis patients with tuberculous peritonitis can achieve better results. Key words: Renal Dialysis; Peritonitis, Tuberculous

The Incidence and Epidemiology of Tuberculosis in Sistan Region: an Update to Past Researches

Introduction: Tuberculosis (TB) is a chronic disease which spreads through respiration and develops lesions in lung or other organs. The most usual kind of TB is pulmonary TB. The highest incidence rate of TB is in the eastern neighbors of Iran rendering high TB incidence in Sistan and Baluchistan province of Iran. The current research was conducted to investigate the epidemiology of TB in the north of the province, the Sistan region. Methods: In this survey, data of all suspected and established TB cases in the Zabol city was collected from their profiles in health care centers during 2010-2013. The trend of the disease, and its prevalence based on residency and gender were assessed. Results: In this period of time, a total of 1800 TB cases were detected. Of these, 485 (27%) were from urban areas and 1315 (73%) were from rural areas. The trend of TB identification increased with a slope of nearly 46.4. In this research, the most resistance to drug was related to Isoniazid and Rifampin and the least resistance was to ethambutol and streptomycin. Conclusion: Dust storms in this area because of successive droughts and other living conditions can make the region susceptible to TB disease. Therefore, people in this area, especially in rural regions, should be given sufficient education to be protected against this infection.

RAPID DETECTION OF MULTI DRUG RESISTANCE AMONG MULTI DRUG RESISTANT TUBERCULOSIS SUSPECTS USING LINE PROBE ASSAY

ABSTRACTObjective: GenoType MTBDRplus line probe assay (LPA) is developed for performing drug susceptibility testing (DST) for Rifampicin (RIF) andisoniazid in sputum specimens from smear-positive pulmonary tuberculosis (TB) patients and revised national TB control Programme (RNTCP)has endorsed LPA for the diagnosis of multi drug resistant TB (MDR-TB). This study was conducted to assess the potential utility of LPA for MDR-TBpatient management.Methods: MDR-TB suspects under RNTCP PMDT criteria C referred from different districts in Delhi state were included in the study January 2013 toDecember 2014. Sputum specimens found acid-fast bacilli positive by fluorescent microscopy were processed for LPA.Results: Out of 3062 specimens, 2055 (67.1%) MDR-TB suspects were read as positive and specimens from 1007 (32.9%) suspects were read asnegative in sputum smear microscopy. Out of 2019 specimens valid LPA results, 1427 were found to be pan-sensitive, 280 were MDR-TB, 40 were RIFmonoresistant, 183 were Isoniazid (INH) monoresistant, and 89 specimens were found negative for Mycobacterium tuberculosis.Conclusion: Routine use of LPA can substantially reduce the time to diagnosis of RIF and/or INH-resistant TB and can hence potentially enable earliercommencement of appropriate drug therapy and thereby facilitate prevention of further transmission of drug resistant strains.Keywords: Multi drug resistant tuberculosis, Line probe assay, Rifampicin, Isoniazid.

Antibiotic Susceptibility in Biofilms of Mycobacterium smegmatis

In the present article we observed the quantification and morphological, ultrastructural features of biofilms of fast growing clinical isolates M. smegmatis in presence of first line antibacterial drug streptomycin, isoniazid rifampicin, ethambutol and pyrazinamide. Biofilm of M. smegmatis was found to be unaffected at concentration of drugs that inhibited growth of planktonic bacilli .Thus, the biofilm growth modus appears to be a strategy for replicating bacilli to evade the trap of antibacterials. Planktonic and biofilm cells had similar intrinsic antibiotic susceptibility. Electron microscopy revealed that control (no drug) biofilms consisted primarily of bacterial clusters and fibrillar elements. The extracellular polymeric substance (EPS) material was less abundant in antibiotic-treated than in control biofilms beacause in the presence of high antibiotic concentrations at MIC level. The study is explored that the effect of drug on biofilm is time dependent means if the drugs were added at initial phase of biofilm, significant inhibitory effect were observed.Int J Appl Sci Biotechnol, Vol 3(4): 635-641

SILA-421 activity in vitro against rifampicin-susceptible and rifampicin-resistant Mycobacterium tuberculosis, and in vivo in a murine tuberculosis model

Due to the emergence of multidrug-resistant and extensively drug-resistant tuberculosis (TB), there is an urgent need for new TB drugs or for compounds that improve the efficacy of currently used drugs. In this study, time–kill kinetics of SILA-421 as a single drug and in combination with isoniazid (INH), rifampicin (RIF), moxifloxacin (MXF) or amikacin (AMK) against Mycobacterium tuberculosis were assessed. Therapeutic efficacy in vivo in a mouse TB model was also studied. Further in vitro analysis was performed with a RIF-susceptible and RIF-resistant strains of M. tuberculosis. When used as a single drug, SILA-421 in vitro showed concentration-dependent and time-dependent bactericidal activity. SILA-421 also enhanced the activity of INH and RIF, resulting in synergy in the case of INH. Emergence of INH resistance following exposure to INH can be prevented by the addition SILA-421. SILA-421 had no additional value in combination with MXF or AMK. Furthermore, SILA-421 enhanced the activity of RIF towards a RIF-resistant strain and resulted in complete elimination of RIF-resistant mycobacteria. Unfortunately, in mice with TB induced by a Beijing genotype strain, addition of SILA-421 to an isoniazid–rifampicin–pyrazinamide regimen for 13 weeks did not result in enhanced therapeutic efficacy.

Hepatoprotective activity of methanolic extract of Mussaenda philippica (stems) against anti-tubercular drugs induced hepatotoxicity

The present study was designed to evaluate the hepatoprotective effect of methanolic extract of Mussaenda philippica against isoniazid and rifampicin induced hepatotoxicity in experimental rats. Six groups of six rat were selected for the study. Methanolic extract of Mussaendaphilippica at a dose of 100, 200 and 400 mg/kg as well as silymarin (50 mg/kg) were administered orally once daily for 14 d in isoniazid and rifampicin group. The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase, and bilirubin were estimated along with total protein. Histopathological analysis was carried out to assess injury to the liver. The altered biochemical parameters were significantly reverting back by the methanolic extract treatment. Histopathology also supported the biochemical variation. From this study it has been concluded that the methanolic extract of Mussaendaphilippica shows significant hepatoprotective activity.

Treatment of latent tuberculosis infection: a network meta-analysis.

Effective treatment of latent tuberculosis infection (LTBI) is an important component of TB elimination programs. Promising new regimens that may be more effective are being introduced. Because few regimens can be directly compared, network meta-analyses, which allow indirect comparisons to be made, strengthen conclusions. To determine the most efficacious regimen for preventing active TB with the lowest likelihood of adverse events to inform LTBI treatment policies. PubMed, EMBASE, and Web of Science up to 29 January 2014; clinical trial registries; and conference abstracts. Randomized, controlled trials that evaluated LTBI treatment in humans and recorded at least 1 of 2 prespecified end points (preventing active TB or hepatotoxicity), without language or date restrictions. Data from eligible studies were independently extracted by 2 investigators according to a standard protocol. Of the 1516 articles identified, 53 studies met the inclusion criteria. Data on 15 regimens were available; of 105 possible comparisons, 42 (40%) were compared directly. Compared with placebo, isoniazid for 6 months (odds ratio [OR], 0.64 [95% credible interval {CrI}, 0.48 to 0.83]) or 12 months or longer (OR, 0.52 [CrI, 0.41 to 0.66]), rifampicin for 3 to 4 months (OR, 0.41 [CrI, 0.18 to 0.86]), and rifampicin-isoniazid regimens for 3 to 4 months (OR, 0.52 [CrI, 0.34 to 0.79]) were efficacious within the network. The risk of bias was unclear for many studies across various domains. Evidence was sparse for some comparisons, particularly hepatotoxicity. Comparison of different LTBI treatment regimens showed that various therapies containing rifamycins for 3 months or more were efficacious at preventing active TB, potentially more so than isoniazid alone. Regimens containing rifamycins may be effective alternatives to isoniazid monotherapy. None.

Tuberculosis in dialysis patients: a nine-year retrospective analysis

Diagnosis of tuberculosis (TB) among dialysis patients may be difficult because of increased frequency of extra-pulmonary presentations, atypical clinical manifestations, and non-specific symptoms. This study aimed to investigate the spectrum of clinical presentations and outcome in dialysis patients during a nine-year period. A total of 651 patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) for at least three months in our unit between 2001 and 2010 were studied. Dialysis and follow-up were performed in our tertiary care center located in the eastern region of Turkey. Diagnosis of TB was established by combining clinical, radiological, biochemical, microbiological, and histological findings. Choice of anti-TB drug used, the results of therapy, and patient outcome were noted. Out of 651 dialysis patients studied, 322 (49.4%) were on PD and the remainder on HD (50.6%). Twenty-six (4%) of the 651 dialysis patients were diagnosed with TB (15 PD, 11 HD), 5 of whom were diagnosed by microbiological assessment, 9 by pathological assessment, and 12 by clinical and radiological findings. Mean age at diagnosis was 41.5 ± 16.5 years and the female/male ratio was 1.18. Three patients had a history of pulmonary TB. Extra-pulmonary involvement was observed in 17 (65.4%) patients. All patients were treated with rifampicin isoniazid, ethambutol, pyrazinamide and pyridoxine. Four patients died during the study. TB occurred in dialysis patients and extra-pulmonary TB was more commonly identified than pulmonary TB. Tuberculous lymphadenitis was the most frequent form of extra-pulmonary TB in our cohort.

Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

Intravesical Bacilli Calmette-Guérin (BCG) immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain) immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin), he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS) prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP) Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin) and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

Evaluation of DNA microarray for detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis isolates

Objective To evaluate the performance of DNA microarray for rapid detection resistance to rifampin and isoniazid in Mycobacterium tuberculosis clinical isolates and identify suitable target sites for molecular genetic test. Methods Twenty-four clinical Mycobacterium tuberculosis isolates were collected retrospectively from Shenzhen Center for Chronic Disease Control in 2009 and 127 isolates from project on anti-tuberculosis drug resistance surveillance in Shenzhen during 2007 to 2009.Drug susceptibility to rifampin and isoniazid of the stains were determined by DNA microarray, and results were compared to that obtained with reference proportion method drug susceptibility testing for sensitivity, specificity and accuracy.The consistency of microarray and phenotypic susceptibility testing was evaluated by Kappa test.Genetic mutations in rpoB, katG, inhA，regulatory region of inhA, and regulatory region of ahpC were investigated by DNA sequencing to assess proper loci for rapid molecular diagnosis. Results Compared against results of proportion method, the sensitivity, specificity and accuracy of the DNA microarray assay for rifampin resistance were 94.4%, 97.5% and 96.0% respectively, and for isoniazid resistance were 79.1%, 100% and 86.8% respectively.Mutations in resistance-determining region of rpoB were observed in 97.2%（70/72） of the isolates resistant to rifampin, which contributed in the 531, 526, 516, 511 and 533 codon region.Mutations in katG315 codon, inhA-15, and ahpC regulatory region were found in 70.3%（64/91）, 11.0%（10/91） and 9.9%（9/90） of the isolates resistant to isoniazid, respectively.Mutations of ahpC promoter region consists of ahpC-9 (4 strains), ahpC-10 (2 strains), ahpC-6 (2 strains), ahpC-12 (1 strain), and ahpC-32 (1 strain). Conclusions DNA microarray provided a rapid method for the detection of drug-resistant Mycobacterium tuberculosis isolates, and demonstrated good performance except less sensitive for isoniazid resistance.The mutations in ahpC regulatory region might be good target loci for detection of isoniazid-resistant Mycobacterium tuberculosis, so screening the region may significantly improve the sensitivity for molecular genetic tests.（Chin J Lab Med,2012,35:1125-1129） Key words: Mycobacterium tuberculosis; Drug resistance; bacterial; Rifampin; Isoniazid; Oligonucleotide array sequence analysis

Bilateral Bacilli Calmette–Guérin-induced lupus vulgaris

Abstract A 9-month-old female child was brought with a history of asymptomatic lesions on the upper arms, at the site of Bacilli Calmette–Guerin (BCG) injections. The lesions were painless but slowly progressive. On examination, there were two erythematous plaques on either arm, with central atrophy and a scaly border. The diascopy test was positive. Mantoux test was positive, while histopathology showed tuberculoid granulomas. Culture was negative. A diagnosis of BCG-induced lupus vulgaris was made and the patient was started on two drug regimens of rifampicin and isoniazid with good response.

The current situation and treatment of childhood tuberculosis

We performed a retrospective analysis of 394 patients who were treated for active tuberculosis (TB) at our hospital from 1976 to 1997. The diagnosis criteria for establishing TB were history of direct contact with TB patients, tuberculin skin test reactivity, positive bacteriology and radiographic findings compatible with TB. There were 192 males and 202 females (age range 1 month to 18 years of age, mean 6.3 years of age). Fifty-four percent of the cases were under 5 years of age. Primary pulmonary TB was presented in 200, post primary pulmonary TB in 97, pleural effusion in 53, endbronchial TB in 4, TB meningitis (TBM) in 28, miliary TB in 28 and other extra-pulmonary TB in 31. A history of contact with the patients was obtained in 72.8% of cases. Two hundred and thirty (58.4%) had received BCG, 134 (34%) no BCG, 30 (7.6%) were unclear. Especially, under 5 years of age, only 29 (13.6%) had received BCG. TBM is not disappeared in Japan and there were 28 cases with TBM. Fifteen patients out of them recovered completely, 8 patients recovered with severe neurological sequelae which included mental retardation, motor weakness, seizures and hydrocephalus and 5 patients died. Twenty-six had no BCG. Particularly in 1990s, we had experienced 4 dead TBM cases, 1 multi-drug resistant (MDR) TBM case and 1 TBM case due to nosocomial infection. Children with TBM should received 12-month regimen using initial daily treatment with isoniazid, rifampin, pyrazinamide, and streptmycin, followed by isoniazid and rifampin administered daily. Pulmonary TB in children is successfully treated with 6-month standard chemotherapy using isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin daily for 4 months. In order to promote TB control and eliminate childhood TB, especially in infants, the following is necessary; 1) early detection and treatment of adult TB patients, source of infection, 2) prompt and appropriate contact examination and chemoprophylaxis, 3) BCG vaccination during early infancy, 4) protection from MDR TB are most important in Japan.

Anti-tuberculosis drug resistance in Japan and in the world

In 1994, the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD) launched a global project on anti-tuberculosis drug resistance surveillance. The results from the first 4 years (1994-1997) and the second 4 years (1996-1999) of the projects were reported in 1998 and 2000, respectively. These surveillance results showed that resistance to anti-tuberculosis drugs is a global problem. The reports also showed that there were several hot spots around the world where prevalence of multidrug resistant tuberculosis (MDR-TB, defined as resistance to at least isoniazid and rifampin) was particularly high and could possibly threaten control programs. The Tuberculosis Research Committee of Japan (Ryoken) has conducted nationwide surveys for drug resistant tuberculosis at 2- or 5-yearly intervals since 1957. The 1997 survey showed that among patients with no prior treatment, resistance to any of the four drugs was found in 10.3%, and the prevalence of primary MDR was 0.8%. The prevalence of drug resistance in the previously treated cases was 42.4% for any of the four drugs and 19.7% for MDR, indicating a high prevalence rate compared with those reported in the global project. Compared with the previous survey in 1992, the current survey shows increased prevalence of drug resistance in both new and re-treatment cases. No significant differences in resistance rates by sex, age group, nationality, district, and/or accompanying diseases were observed in any of the new or re-treatment cases. Other factors associated with the high prevalence in re-treatment cases remain to be determined. A total of 78 hospitals in various districts of Japan participated the cooperative study. Each collaborating laboratory sent all the isolated mycobacterial cultures to the Research Institute of Tuberculosis (RIT). In the local laboratories, the absolute concentration method using 1% Ogawa egg slant, its modified methods using a 48-well plate and a 16-well plate, combination of above 2 or 3 methods, and other method were used for drugsusceptibility testing, and the proportion method using 1% Ogawa egg slant was used in the RIT. The results in the local laboratories were compared with those in the RIT. There was no significant difference in the concordance rates according to the test drugs among methods for drug susceptibility testing used in the local laboratories. Relatively lower concordance rates were seen in the laboratories using the Microtiter method related to high overestimation rates, compared with those in the laboratories using the standard method and Well-pack method. However, relatively lower concordance rates (less than 90%) were seen in the laboratories using any of the three methods, indicating that there are variations among facilities.

Standardization of laboratory tests for tuberculosis and their proficiency testing

Explanations of proper collection procedures are imperative for accurate laboratory analysis. The quality of specimens collected and the proper transport of those specimens to the laboratory are critical to successful isolation of etiological agents. Most mycobacteria grow at a relatively slow rate. Therefore, the acid-fast smear plays an important role in the early diagnosis of mycobacterial infection. There are several methods of determining the acid-fast nature of an organism. In the carbolfuchsin procedures (Ziehl-Neelsen, Kinyoun), acid-fast organisms appear red, and in the fluorochrome procedures (auramine O, auramine-rhodamine, acridine orange), the acid-fast organisms fluoresce yellow to orange. Fluorochrome-stained slides may be directly restained with any of the carbolfuchsin staining procedures. This may be done to confirm a positive fluorochrome slide and to study organism morphology. In the last 10 years, there were many advances in the culture examinations of mycobacteria. The newly developed Mycobacteria Growth Indicator Tube (MGIT), BacT/Alert, ESP Myco, MB Redox and KRD "Nichi B", biphasic Septi-Chek AFB and Myco-Acid, and radiometric BACTEC 460TB systems based on liquid media, proved to be significantly better than the egg-based solid media for the isolation of mycobacteria from clinical specimens. In addition to liquid-based medium, agar (Middlebrook 7H10 or 7H11)- or egg (Ogawa or Löwenstein-Jensen)-based media should be used in the primary isolation of mycobacteria. To identify mycobacteria, conventional biochemical tests are traditionally used. Key test can be used to identify species, or further preliminary grouping may be used. Other approaches to identifying some species of mycobacteria are available. They include niacin accumulation, p-nitrobenzoic acid and p-nitro-alpha-acetylamino-beta-hydroxypropiophenone tests for discrimination of the Mycobacterium tuberculosis complex from mycobacteria other than M. tuberculosis (MOTT); DNA probe methods for identification or confirmation of the M. tuberculosis complex, M. avium complex, M. kansasii, and M. gordonae; DNA-DNA hybridization method for identification of 22 Mycobacterium species; and gas-liquid chromatography or high performance liquid chromatography analyses for recognizing the patterns of the mycobacterial cell wall fatty acids or mycolic acids. The advantages of the last four methods are that they are capable of providing definitive identification within 2 to 5 h after adequate growth. Capilia TB is the newly developed immunochromatographic assay for rapid discrimination between the M. tuberculosis complex and MOTT bacilli. The kit can be easily used for rapid identification of the M. tuberculosis complex in combination with the culture systems based on liquid media. In addition, Capilia TB could correctly detect the M. tuberculosis complex from mixed cultures with the M. tuberculosis complex and MOTT bacilli. The WHO/IUATLD supranational reference laboratory (SRL) network was created in 1994, to ascertain the accuracy of the susceptibility test methods used in different laboratories across the world, and to allow comparability of the surveillance data gathered in countries participating in the Global Project on Anti-tuberculosis Drug Resistance Surveillance. Today, the network has evolved and 23 SRLs actively participate. Results of five rounds of proficiency testing in the SRL network suggest that performance of the network has improved substantially through the years. This progress has been particularly evident for streptomycin and ethambutol sensitivity, which was very low in the first rounds of proficiency testing. In 1998 sensitivity for these two drugs was higher than 95%. For isoniazid and rifampin, sensitivity has been consistently high since the beginning of the Global Project. This indeed reflects the enhanced efforts made by the SRLs to improve their individual performance.

Desensitization therapy for antituberculous drugs

We retrospectively evaluated the effectiveness of desensitization therapy for antituberculous drugs (Rifampicin and Isoniazid) in 28 cases (29 episodes) with adverse reactions to these drugs. Desensitization therapy for RFP was performed in 23 cases (24 episodes) with administration of a first dose of 1-150 mg and a final dose of 300-450 mg for 1-29 days. The success rate of this therapy was 79% (19 of 24 episodes). Desensitization therapy for INH was performed in 12 cases with administration of a first dose of 2.5-100 mg and a final dose of 200-400 mg for 3-25 days. The success rate of this therapy was 83% (10 of 12 cases). Based on a comparative study of cases between successful and unsuccessful desensitization to RFP and INH it was concluded that there were no significant differences with regard to allergic history, adverse effects and their periods of appearance, the first dose and final dose of administration and the interval of administration, starting periods of the desensitization therapy and the periods of appearance of adverse effects due to this therapy. We evaluated desensitization therapy for two antituberculous drugs (RFP and INH) for tuberculous patients for whom the use of such drugs was restricted because of adverse effects, and we found it is a useful treatment, showing a high rate of success (80%).

Leukopenia due to anti-tuberculous chemotherapy including rifampicin and isoniazid

Leukopenia due to anti-tuberculous chemotherapy including rifampicin and isoniazid

A Four-Drug Fixed-Dose Combination Regimen for TB

Because it improves adherence without reducing effectiveness, the fixed-dose combination (FDC) of isoniazid and rifampin is widely used for the final 4 months of treatment of pulmonary tuberculosis (TB). Some studies have suggested that FDCs might also be safe and effective during the initial 2-month intensive phase …

Updated Guidelines for the Programmatic Management of Drug-Resistant TB

Target Population: Public health professionals involved in the prevention and control of drug-resistant tuberculosis (TB) Sponsoring Organization: WHO Type: Evidence-based consensus guidelines using a grading system Key Points: This document updates and expands guidelines for diagnosing and treating multidrug-resistant TB (MDR-TB — i.e., infection with Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin) that were first released in 2006 and were updated on …