Management Of Drug-resistant TB Research Articles

Novel Approaches for the Treatment of Drug-Resistant Tuberculosis

Pharmacognosy Research,2023,15,2,235-241.DOI:10.5530/pres.15.2.025Published:February 2023Type:Review ArticleAuthors:Sonam Pushkar, Vibhav Varshney, Pushpendra Pushkar, and Harish Kumar Sagar Author(s) affiliations:Sonam Pushkar1,*, Vibhav Varshney2, Pushpendra Pushkar3, Harish Kumar Sagar4 1Department of Pharmacy, GSVM Medical College, Kanpur, Uttar Pradesh, INDIA. 2Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, INDIA. 3Department of Pharmacology, GSVM Medical College, Kanpur, Uttar Pradesh, INDIA. 4ICMR National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, Uttar Pradesh, INDIA. Abstract:Tuberculosis (TB) is a leading infectious disease that caused the deaths of a total of 1.5 million people in 2020 and is one of the top causes of death globally. India is a country with the highest TB burden, and it may affect all age groups. It is caused by the Mycobacterium tuberculosis bacteria, an intracellular pathogen, and its multidrug and extensively drug-resistant strains, which continue to emerge and spread, resulting in the deadliest infectious disease. After a gap of more than 40 years, the FDA approvals over the past decade of three second-line anti-TB drugs, bedaquiline, delamanid, and pretomanid, have been major forward steps in the management of drug-resistant-TB (DR-TB). Many medicinal plants such as Zanthoxylum leprieurii, Lantana camara, and Cryptolepis sanguinolenta have extensive therapeutic potential and represent a prospective option to fight against DR-TB. Some novel compounds are in the early clinical trial phases such as DprE1 inhibitors TBA-7371 and BTZ-043, and many others that are showing promising futures. This review describes DR-TB and its current chemotherapy guidelines including novel and repurposed drugs that are included in the anti-TB regimens, medicinal plants that have therapeutic potential for the development of drug-hit candidates, drugs that are currently in clinical development, host-directed therapy, and new drug delivery systems to better understand the novel therapeutic approaches that are currently being studied for the efficacious and safe management of DR-TB, a worldwide health problem. Keywords:Drug-resistant tuberculosis, immunomodulators., Medicinal plants, Nanotubes, NitroimidazolesView:PDF (189.22 KB)

High rate of successful treatment outcomes among childhood rifampicin/multidrug-resistant tuberculosis in Pakistan: a multicentre retrospective observational analysis

BackgroundThere was a complete lack of information about the treatment outcomes of rifampicin/multidrug resistant (RR/MDR) childhood TB patients (age ≤ 14 years) from Pakistan, an MDR-TB 5th high burden country. Therefore, this study evaluated the socio-demographic characteristics, drug resistance pattern, treatment outcomes and factors associated with unsuccessful outcomes among childhood RR/MDR-TB patients in Pakistan.MethodsThis was a multicentre retrospective record review of all microbiologically confirmed childhood RR/MDR-TB patients (age ≤ 14 years) enrolled for treatment at seven units of programmatic management of drug-resistant TB (PMDT) in Pakistan. The baseline and follow-up information of enrolled participants from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. World Health Organization (WHO) defined criterion was used for deciding treatment outcomes. The outcomes of “cured” and “treatment completed” were collectively grouped as successful, whereas “death”, “treatment failure” and “lost to follow-up” were grouped together as unsuccessful outcomes. Multivariable binary logistic regression analysis was used to find factors associated with unsuccessful outcomes. A p-value < 0.05 reflected statistically significant findings.ResultsA total of 213 children RR/MDR-TB (84 RR and 129 MDR-TB) were included in the study. Majority of them were females (74%), belonged to the age group 10–14 years (82.2%) and suffered from pulmonary TB (85.9%). A notable proportion (37.1%) of patients had no history of previous TB treatment. Patients were resistant to a median of two drugs (interquartile range: 1–4) and 23% were resistant to any second line anti-TB drug. A total of 174 (81.7%) patients achieved successful treatment outcomes with 144 (67.6%) patients being cured and 30 (14.1%) declared treatment completed. Among the 39 (18.3%) patients with unsuccessful outcomes, 35 (16.4%) died and 4 (1.9%) experienced treatment failure. In multivariable analysis, the use of ethambutol had statistically significant negative association with unsuccessful outcomes (odds ratio = 0.36, p-value = 0.02).ConclusionsIn this study, the WHO target of successful treatment outcomes (≥ 75%) among childhood RR/MDR-TB patients was achieved. The notable proportion of patients with no history of previous TB treatment (37.1%) and the disproportionately high number of female patients (74%) respectively stress for infection control measures and provision of early and high quality care for female drug susceptible TB patients.

Incidence rate and time to serious adverse events among rifampicin resistant tuberculosis patients in Georgia treated with new and repurposed anti-tuberculosis drugs, 2016-2018

Considering the complexity of second-line anti-tuberculosis (TB) treatment regimens, the management of drug-resistant TB (DR-TB) in Georgia remains a major challenge. Since the introduction of new and repurposed anti-TB medications, the implementation of active TB Drug Safety Monitoring (aDSM) was a critical program component to help establish safety and manage all treatment related Serious Adverse Events (SAEs). In our study, we aimed to describe the occurrence, characteristics and timing of SAE among patients with Rifampicin Resistant and Multi-Drug Resistant TB (RR/MDR-TB) receiving new and/or repurposed anti-TB medications (bedaquiline, delamanid, linezolid, clofazimine, imipenem) during the period of 2016–2018 in Georgia and identify predictors of SAE. The data were obtained from the medical charts, electronic database and standardized aDSM reports During 2016–2018 period in total 970 people with RR/MDR-TB were notified in Georgia and 388 of them received new and/or repurposed TB drugs as part of their treatment regimen and all were included into the study. The results showed a total of 73 SAEs registered among 49 (12.6%) patients receiving new and/or repurposed drugs. The overall SAE incidence rate per 100 person-months was 1.16. The severity of the majority of the SAEs (46.6%) was grade III and 21.9% were grade IV. The most common SAE reported was hepatotoxicity, with an incidence of 0.26 per 100 person-month (n=16, 21.9%) followed by cardiotoxicity with an incidence of 0.16 per 100 person-month (n=10, 13.7%). Median time to SAE occurrence was 183 days (IQR 84 – 334) after treatment initiation. Resistance profile was the only predictor associated with occurrence of a SAEs. There was increased hazard of SAEs among patients with XDR-TB (adjusted HR=2.18, 95% CI: 1.12–4.23). Our findings on SAEs among patients treated with new or repurposed anti-TB drugs are echoing the findings available in the literature. They highlight the need for close monitoring of patients and underlines the importance of the aDSM during the whole treatment. Safety profile of the medications and combinations used are yet to be established and larger datasets comprised of patients receiving same treatment regimens need to be utilized.

The operational issues in the management of drug-resistant TB

The operational issues in the management of drug-resistant TB

Mechanistic analysis of A46V, H57Y, and D129N in pyrazinamidase associated with pyrazinamide resistance.

Pyrazinamide (PZA) is a component of first-line drugs, active against latent Mycobacterium tuberculosis (MTB) isolates. The prodrug is activated into the active form, pyrazinoic acid (POA) via pncA gene-encoded pyrazinamidase (PZase). Mutations in pncA have been reported, most commonly responsible for PZA-resistance in more than 70% of the resistant cases. In our previous study, we detected many mutations in PZase among PZA-resistance MTB isolates including A46V, H71Y, and D129N. The current study was aimed to investigate the molecular mechanism of PZA-resistance behind mutants (MTs) A46V, H71Y, and D129N in comparison with the wild type (WT) through molecular dynamic (MD) simulation. MTB positive samples were subjected to PZA drug susceptibility testing (DST) against critical concentration (100ug/ml). The resistant samples were subjected to pncA sequencing. Thirty-six various mutations have been observed in the coding region of pncA of PZA-resistant isolates (GenBank accession No. MH461111) including A46V, H71Y, and D129N. The post-simulation analysis revealed a significant variation in MTs structural dynamics as compared to the WT. Root means square deviations (RMSD) and Root means square fluctuation (RMSF) has been found in variation between WT and MTs. Folding effect and pocket volume were altered in MTs when compared with WT. Geometric matching supports the effect of mutation A46V, H71Y, and D129N on PZase structure that may have an insight effect on PZase dynamics, making them vulnerable to convert pro-PZA into active form, POA. In conclusion, the current analyses will provide useful information behind PZA-resistance for better management of drug-resistant TB.

Burden of baseline resistance of Mycobacterium tuberculosis to fluoroquinolones and second-line injectables in central India.

Drug-resistant TB is a serious public health problem in India. Pre-existing resistance to fluoroquinolones (FQs) and second-line injectable drugs (SLIDs) in strains of Mycobacterium tuberculosis (MTB) resistant to rifampicin (RIF) and/or isoniazid (INH) contributes to treatment failures and consequent transmission of drug-resistant TB. A baseline assessment of resistance of MTB to FQs and SLIDs may help guide policies to further improve management of drug-resistant TB in India. This study aims to determine the prevalence of resistance to FQs and SLIDs among MTB strains having RIF and/or INH resistance in central India. A total of 1032 smear positive sputum samples were subjected to line probe assay (GenoType MTBDRsl version 2) to test for resistance to FQs and SLIDs, according to the integrated diagnostic algorithm of the revised national TB control programme. Of 1032 samples, 92 (8.91%) were not interpretable and hence excluded, 295 (31.38%) were resistant to FQs alone, 13 (1.38%) were resistant to SLIDs alone, 15 (1.59%) were resistant to both FQs as well as SLIDs and 617 (65.63%) were sensitive to both FQs and SLIDs. The most common mutations in gyrA and gyrB genes were observed at codons D94G and E540V, respectively. Mutations at codon A1401G in rrs genes and in the C-14T region of eis genes were most frequently observed. High levels of FQ resistance points towards indiscriminate use of this class of drugs. Regulation for judicial use of FQs is an urgent requirement.

Pyrazinamide resistance and mutations in pncA among isolates of Mycobacterium tuberculosis from Khyber Pakhtunkhwa, Pakistan

BackgroundPyrazinamide (PZA) is an important component of first-line drugs because of its distinctive capability to kill subpopulations of persistent Mycobacterium tuberculosis (MTB). The prodrug (PZA) is converted to its active form, pyrazinoic acid (POA) by MTB pncA-encoded pyrazinamidase (PZase). Mutation in pncA is the most common and primary cause of PZA resistance. The aim of the present study was to explore the molecular characterization of PZA resistance in a Pashtun-dominated region of Khyber Pakhtunkhwa, Pakistan.MethodsWe performed drug susceptibility testing (DST) on 753 culture-positive isolates collected from the Provincial Tuberculosis Control Program Khyber Pakhtunkhwa using the BACTEC MGIT 960 PZA method. In addition, the pncA gene was sequenced in PZA-resistant isolates, and PZA susceptibility testing results were used to determine the sensitivity and specificity of pncA gene mutations.ResultsA total of 69 isolates were PZA resistant (14.8%). Mutations were investigated in 69 resistant, 26 susceptible and one H37Rv isolates by sequencing. Thirty-six different mutations were identified in PZA-resistant isolates, with fifteen mutations, including 194_203delCCTCGTCGTG and 317_318delTC, that have not been reported in TBDRM and GMTV Databases and previous studies. Mutations Lys96Thr and Ser179Gly were found in the maximum number of isolates (n = 4 each). We did not detect mutations in sensitive isolates, except for the synonymous mutation 195C > T (Ser65Ser). The sensitivity and specificity of the pncA sequencing method were 79.31% (95% CI, 69.29 to 87.25%) and 86.67% (95% CI, 69.28 to 96.24%).ConclusionMutations in the pncA gene in circulating isolates of geographically distinct regions, especially in high-burden countries, should be investigated for better control and management of drug-resistant TB. Molecular methods for the investigation of PZA resistance are better than DST.

Pre-treatment loss to follow-up among patients with rifampicin-resistant tuberculosis in Baluchistan, Pakistan, 2012-17: a retrospective cohort study

Background: Patients with rifampicin-resistant TB (RR-TB) pretreatment loss to follow-up continue to be a global health challenge. Although the accuracy of diagnosis significantly increased with the implementation of Xpert MTB/RIF assay, which is a rapid molecular based test and more sensitive than conventional microscopy which detects MTB even present in small limit of 136 MTB/ml of sputum, but still data suggest a wide treatment initiation gap among diagnosed. This study was done to assess the proportion of patients with RR-TB pretreatment lost to follow-up and the socio-demographic factors associated with this in Balochistan, Pakistan. Methods: This was a retrospective cohort study based on review of the routinely managed program records. The data included all patients with RR-TB detected at Fatima Jinnah Chest &amp; General Hospital Quetta and District Head Quarter Hospital Loralai, Xpert sites and enrolled at programmatic management of drug resistant TB (PMDT) sites during 2012-2017. Data collected was double-entered, validated and analyzed using EpiData. Results: Of the 396 patients with RR-TB detected during 2012-17, 78 (19.8%) underwent pre-treatment lost to follow-up. The mean age of those detected with RR-TB was 37 years (SD ±16.98); 189 (48%) were of age group 15-34, while 60% were female. Among 84 individuals referred out to other facilities, only 6 started treatment. Almost half of the ‘pretreatment lost to follow-up’ patients were from age group 15-34, while 43 were from within the Quetta and Loralai districts. Conclusions: The high proportion of patients with RR-TB that were pre-treatment lost to follow-up in Balochistan needs immediate strategies to establish linkages between Xpert and PMDT sites for the timely management of patients to prevent the spread of RR-TB infection.

Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007-2011): Evidence leading to policy enhancement.

BackgroundGlobally, India has the world’s highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP.ObjectiveTo evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment.MethodsThis is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics.ResultsIn the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92–125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202–381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and continuation phase (CP); cavitary disease; prior treatment episodes characterized by re-treatment regimen taken twice, longer duration and more episodes of treatment; any weight loss during treatment; males and additional resistance to first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment success, half of the success (54.8%) seen in Ofloxacin sensitive patients. Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55) significantly doubled and quadrupled the chances for culture conversion respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also significantly reduced the odds of unfavorable treatment outcomes (p value ≤0.05) in multinomial logistic regression model.ConclusionIndia’s initial MDR-TB patients’ cohort treated under the RNTCP experienced poor treatment outcomes. To address the factors associated with poor treatment outcomes revealed in our study, a systematic multi-pronged approach would be needed. A series of policies and interventions have been developed to address these factors to improve DR-TB treatment outcomes and are being scaled-up in India.

Occurrence of adverse events in patient receiving community-based therapy for multidrug-resistant tuberculosis in Pakistan.

Pakistan ranks 4th among 22 multidrug resistant tuberculosis (MDR-TB) high burden countries. The increasing rate of MDR-TB in Pakistan underscores the importance of effective treatment programs of drug-resistant TB. Clinical management of MDR-TB requires prolonged multidrug regimens that often cause adverse events (AEs). This retrospective case series study include all patients who were enrolled for MDR-TB treatment during January 2014 till April 2015 at Programmatic Management of Drug Resistant TB (PMDT) unit at tertiary care hospital, Lady Reading Hospital (LRH) Peshawar Pakistan. In this study we sought to ascertain the occurrence of treatment related adverse events and factors associated with these events. Here we also examined the frequency of and reasons for changing drug regimens. We further sought to determine whether the occurrence of adverse events negatively impacts the treatment outcome and management of adverse effects without requiring the discontinuation of MDR-TB therapy. At the time of analysis final outcomes of all 200 enrolled patients exist. Among these 52.5% were females and (81.5%) were aged ≤ 44 years. Among study cases 155 (77.2%) experienced at least one adverse event during treatment. The most commonly reported events were psychiatric issues (70%) whereas the less common was skin rashes (7.5%). A change in drug dose due to adverse events occurred in 16.5% cases, while 13.5% cases had at least one drug discontinued temporarily. Younger age and lung cavities at baseline were positive association with occurrence of adverse events. Association was also found between adverse events and treatment outcomes (OR 0.480, 0.236-0.978, p= 0.041). Adverse events were prevalent among MDR-TB patients treated at PMDT-LRH Peshawar. All patients who were younger aged and cavitory lungs should be closely monitored for occurrence of adverse events.

Challenges and Opportunities for Programmatic Management of Drug Resistant TB in India

Challenges and Opportunities for Programmatic Management of Drug Resistant TB in India

Challenges and Opportunities for Programmatic Management of Drug Resistant TB in India

Challenges and Opportunities for Programmatic Management of Drug Resistant TB in India

Resistance Patterns among Multidrug-Resistant Tuberculosis Patients: A Multi-Center Study from Pakistan

Background: The high burden of multi-drug resistance tuberculosis (MDR TB) is a matter of great concern. The increasing resistance to anti tuberculosis drugs has been the area of growing concern and are posing threats to TB control. The aim of this study was to evaluate the drug resistance patterns for the first line and second line anti-Tuberculosis drugs in multiple drug resistant tuberculosis (MDR-TB) patients. Method: The study was retrospective, observational, employing purposive, non-random sampling technique for data collection conducted at the TB Clinic- of the different healthcare centers in the provinces of Pakistan Sindh and Baluchistan from December 2010 to May 2016. All bacteriologically confirmed TB patients who were found to be Rifampin Resistant (RR) on Genotypic drug susceptibility testing (GXP), or detected to be drug resistant on phenotypic Universal drug susceptibility testing were enrolled into the study. Results: Out of total 3776 patients, 96.3% were resistant to Rifampicin and 94.7% were resistant to Isoniazid. 25.5% isolates were resistant to all five first line drugs. Resistances against Pyrazinamide and Ethambutol was 54.2% and 51.6% respectively. 36.3% patients were resistant to Fluoroquinolones (FQ), 9.7% were resistant to Ethionamide (Eto) and 4.1% were resistant to both FQ and Eto. 33.5% patients were MDR plus resistant to FQ. However, the resistance to both FQ plus Aminogycosides was quite low, 2.7%. Conclusion: The drug resistance rates are quiet high in MDR-TB for both first line and second line drugs. The standardized MDR TB regimen needs to be updated, based on the prevalence of drug resistance patterns in the community for the effective management of drug resistant TB.

Isolation unit for multidrug-resistant tuberculosis patients in a low endemic country, a step towards the World Health Organization End TB Strategy.

Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates. Management of drug-resistant TB is of particular importance. In this paper, we discuss the different models of care of multidrug-resistant TB (MDR-TB), the ethical considerations and the specific constraints present in high income countries. The management model chosen by the Belgian TB specialists in accordance with public health authorities as well as building of a specific MDR/XDR-TB isolation unit are also discussed.

Rifampicin resistance mutations in the 81bp RRDR of rpoB gene in Mycobacterium tuberculosis clinical isolates using Xpert MTB/RIF in Khyber Pakhtunkhwa, Pakistan: a retrospective study.

BackgroundMulti-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries. World Health Organization (WHO) recommends use of Xpert MTB/RIF assay to simultaneously detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance. The primary objective of this study was to determine the frequency of MDR-TB in patients suspected to have drug resistance in Khyber Pakhtunkhwa. The frequency of probes for various rpoB gene mutations using Xpert MTB/RIF assay within 81 bp RRDR (Rifampicin Resistance Determining Region) was the secondary objective.MethodsA total of 2391 specimens, received at Programmatic Management of Drug Resistant TB (PMDT) Unit, Lady Reading Hospital (LRH) Peshawar, Pakistan, between October 2011 and December 2014, were analyzed by Xpert MTB/RIF test. MTB positive with rifampicin resistance were further analyzed to first line anti-mycobacterial drug susceptibility testing (DST) using middle brook 7H10 medium. The data was analyzed using statistical software; SPSS version 18.ResultsOut of 2391 specimens, 1408 (59 %) were found positive for MTB and among them, 408 (29 %) showed rifampicin-resistance with four different rpoB gene mutations within 81 bp RRDR. The frequency of various probes among RIF-resistant isolates was observed as: probe E, in 314 out of 408 isolates; B, 44 out of 408; A, 5 out of 408; D, 34 out of 408; and probe C was observed among 6 out of 408 RIF-resistant isolates. The probe A&B and E&D mutation combination was found in only 1 isolate in each case, while B&D mutation combination was detected among 3 out of 408 RIF-resistant isolates.ConclusionsHence, it is concluded from our study on a selected population, 29 % of patients had MDR-TB. Probe E related mutations (also known as codon 531and 533) were the most common rpoB genetic mutation [314 (77 %)], acknowledged by Xpert MTB/RIF assay. Least mutation was detected within the sequence 511 (1.2 %).

Multidrug-resistant tuberculosis among different types of suspected cases: Study from New Delhi

There are limited data of multidrug-resistant tuberculosis (MDR-TB) diagnosed in various patient categories by implementing Programmatic Management of Drug Resistant TB (PMDT) using line probe assay (LPA) from our country. Samples from presumptive MDR-TB from five districts of New Delhi were subjected to LPA from 1st October 2011 to 31st December 2014. The MDR-TB diagnosed in 4th & 5th month follow-up positives were significantly higher than other categories of the patients. Only 3/232 (2.2%) RIF resistants were diagnosed among smear negative re-treatment cases. The data suggest interim cost–benefit analysis of the program especially among smear negatives retreatment cases.

Effects of introducing Xpert MTB/RIF test on multi-drug resistant tuberculosis diagnosis in KwaZulu-Natal South Africa.

BackgroundAn algorithm instituted following Xpert MTB/RIF (Xpert) introduction in South Africa advocates for treating all Xpert rifampicin resistant patients as MDR-TB cases while awaiting confirmation by phenotypic or genotypic drug susceptibility testing. This study evaluates how the Xpert has influenced the diagnosis and management of drug resistant TB in the highest burdened district of KwaZulu-Natal Province.MethodsData was retrospectively collected from all patients with rifampicin resistance on Xpert performed between March 2011 and April 2012. Xpert results were compared with those of phenotypic and/genotypic drug susceptibility testing. Patients’ records were used to determine the time to treatment initiation.ResultsOut of 637 patients tested by Xpert, 50% had confirmatory results, of which a third were sent on the same day as Xpert test. The rate of rifampicin discordance and monoresistance was 8.8% and 13.4% respectively and there was no difference between phenotypic and genotypic confirmation. Among those who had been initiated on treatment, 28%, 40%, 21% and 8% of patients commenced within 2 weeks, 1 month, 2 months and 3 months of Xpert testing respectively, while the remaining 3% were observed without treatment.ConclusionThis study emphasizes the importance of complying with the algorithm in confirming all Xpert rif resistant cases so as to ensure proper management of these patients. Despite the rapidity of the Xpert results, only about 70% of patients had been initiated treatment at one month. Therefore there is a definite need to improve the health systems in order to improve on these delays.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-442) contains supplementary material, which is available to authorized users.

Exploring the role of drug resistant tuberculosis center in the programmatic management: An Indian perspective

Global tuberculosis control report – 2012 has revealed that 3.7% of new cases and 20% of retreated cases are estimated to have multi-drug resistant (MDR) TB worldwide. Specific strategies have been implemented under the Programmatic Management of Drug Resistant TB in India (PMDT) to address the MDR-TB problem. Considering the long duration of treatment, PMDT recommends that treatment of drug resistant forms of TB should be decentralized. However, to supervise and guide the health care providers in the complex medical needs, an expert resource center called as Drug-resistant TB (DR-TB) center has been proposed. A DR-TB center plays a crucial role at different levels in the management of drug resistant forms of TB such as pre-treatment evaluation; initiation of treatment; maintenance of hospital wards & airborne infection control measures; management of severe adverse drug reactions; modification in the choice of drugs based on the drug sensitivity test results; and as a clinical expert resource for guidance to the program managers and the health care providers. To conclude, DR-TB center plays a defining role in the overall integrated model of care in RNTCP-PMDT services.

Diagnosis and management of TB in children: an update

In recent years, several notable modifications have occurred in the management of TB infection and disease in children. First, we review new data related to infection, including alternative regimens for the treatment of latent TB, management of drug-resistant infection and preventive therapy in the context of HIV infection. Next, we summarize updated WHO guidelines for the treatment of TB in children, explore issues specific to the management of disease in HIV-infected children, and retreatment of TB, and review pediatric recommendations for the management of drug-resistant TB. Finally, we conclude with a discussion of adjunctive therapy and new drugs in development.

Assessment of trends of ofloxacin resistance in Mycobacterium tuberculosis

Purpose: Ofloxacin (OFX) is one of the potent fluoroquinolone (FQ) recommended to treat MDR-TB. Over a decade, the preexposure of this drug for the treatment of other bacterial infections has resulted in acquisition of FQ resistance among Mycobacterium tuberculosis strains. Considering this possibility, a study was undertaken in a tertiary care center in the capital city (India) to assess the drug resistance trends of OFX among susceptible and multidrug resistant (MDR) strains of M. tuberculosis. Materials and Methods: A total of 102 M. tuberculosis isolates (47 susceptible to fi rst-line drugs and 55 MDR isolates) were screened for susceptibility testing of OFX with a critical concentration of 2 μg/ml by Lowenstein Jensen (LJ) proportion method. Results: The results showed 40 (85.1%) isolates among 47 susceptible isolates and 34 (61.8%) isolates among 55 MDR isolates, were found to be susceptible to OFX. Fisher’s exact test showed significant P-value (0.0136) demonstrating 1.377 fold (95% confidence interval) increased risk to become resistant to OFX than susceptible isolates. These finding shows decreased OFX susceptibility is not only limited to MDR isolates but also increasingly seen in susceptible strains as a result of drug abuse. Conclusions: Our finding were not alarming, but highlights the general risk of acquiring resistance to OFX, jeopardizing the potential for these drugs to be used as second-line anti-TB agents in the management of drug-resistant TB and creating incurable TB strains.