Line Anti-tuberculosis Drugs Research Articles

Drug resistance pattern, prevalence and risk factors for resistance to second line anti-tuberculosis drugs in Balochistan, Pakistan

Background. Pakistan is high burden drug resistant tuberculosis (DR-TB) country. For devising a treatment regimen and optimizing empirical drug therapy, the local epidemiology and drug resistance patterns are needed to be considered. Objectives. To evaluate the drug resistance pattern, prevalence and risk factors for resistance to second line anti-tuberculosis drugs (SLD) among DR-TB patients in Balochistan, Pakistan. Design and setting. This cross-sectional study was carried out at the Fatimah Jinnah Chest and General Hospital in Quetta's programmatic management unit of the DR-TB (PMDT). Methods. This study included all DR-TB patients, regardless of their age, TB location, or medication resistance pattern. The sociodemographic, microbiological, and clinical data of the patients were gathered using a standard data collecting form. SPSS 20 was used to analyze the data. A statistically significant p-value was defined as less than 0.05. Results. A total of 354 patients were included in the final analysis. Among them majority were females (61.7%), belonged to the age group 19-30 years (36.7%), were previously treated for TB (95.8%) at public sector hospital (42.7%) and did not suffer from any other comorbidity(88.7%). The study participants were resistant to a median of three anti-TB drugs (range 1-8). The most common type of DR-TB was multi DR-TB (77.1%), followed by mono DR-TB (18.1%), extensive DR-TB(3.1%) and poly-DR (1.7%). A total of 147 (41.5%) patients were resistant to any second line anti-TB drug (SLD). Among SLD, the resistance was high for fluoroquinolones (38.4%), followed by ethionamide (4.8%) and injectable SLD(4.2%). Upon multivariate binary logistic regression analysis previous treatment of cat-II regimen had statistical significant association with resistance to any SLD (OR=5.273, 95%CI=1.098-25.316). Conclusion. It is concerning to see such a high level of SLD resistance, especially to fluoroquinolones. More stringent regulations are advised to regulate the non-prescription sale and indiscriminate use of fluoroquinolones, as well as testing for drug resistance in cat-I failures instead of placing patients on cat-II therapy.

First-Line Antituberculosis Drug Challenge Reactions in Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome in an HIV Endemic Setting

BackgroundIn high HIV prevalence settings, first line anti-tuberculosis drug (FLTD)-associated DRESS poses therapeutic challenges. Sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimises re-initiation of non-offending drugs. However, SADC-associated reaction complexities limit its utility. ObjectiveWe aimed to describe characteristics of FLTD-associated DRESS patients, their treatment-limiting SADC reactions and related outcomes. MethodsPatients hospitalized with FLTD-associated DRESS from 2013–2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible. ResultsSADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred, 34/47(72%) in 29/41(71%) patients, were treatment-limiting and 12/41(29%) reinitiated FLTDs uneventfully. Fifteen single and eight multiple drug-reactors were identified. Rifampicin, in 13/23(57%) reactors was the commonest individual offender. Ethambutol was most frequently involved in multiple drug-reactors. Median(IQR) time to a detectable reaction was 24(12-120) hours, 6/34(18%) being immediate (<6hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%) and facial oedema (18%), singly or in combination were commonest features. Three reactions, one epidermal necrolysis and two liver derangements, were CTCAE grade 4 (life-threatening) events. No predictors of multiple drug-reactivity were identified, but multiple reactors were hospitalised significantly longer, 125(100-134) versus 60(45-80) days. ConclusionsSADC optimises FLTD reinitiation. However, timing, clinical presentation and severity of SADC-associated reactions following FLTD-associated DRESS is markedly heterogenous. Additionally, multiple drug-reactors are a complex group requiring longer hospitalisation, and without routine biomarkers to differentiate true multiple drug hypersensitivity from non-specific flare-ups and guide long-term drug avoidance strategies.

Izoniazidom navodené poškodenie pečene sprevádzané ikterom

Summary: Isoniazid belongs to the first line antituberculosis drugs and can be used for the treatment of both active and latent tuberculosis infections. It is a part of combined regimens, for the preventive treatment of tuberculosis isoniazid can be used in monotherapy as well. Even though elevations in serum aminotransferases levels during isoniazid therapy are seen frequently, the development of symptomatic hepatitis is rare, according to specialised literature. This article describes a case of a patient who developed drug-induced liver injury accompanied by jaundice during the isoniazid preventive treatment of tuberculosis. It also provides a summary of the currently known risk factors, pathogenesis, and incidence of hepatotoxicity observed throughout therapy with this antituberculosis drug. We also illustrate the process of diagnosing drug--induced liver injury in clinical practice settings with the utilisation of the updated RUCAM score. Key words: jaundice – isoniazid – drug-induced liver injury – tuberculosis preventative therapy – updated RUCAM score.

Evaluation of Drug Susceptibility Testing of Mycobacterium tuberculosis Isolates Against First Line Antituberculosis Drugs With a New Agar Medium

Tüberküloz (TB), dünya genelinde enfeksiyon kaynaklı hastalıklar arasında ölümün önde gelen nedenlerinden biri olan bulaşıcı bir hastalıktır. TB’nin epidemiyolojik dağılımına göre, yüksek oranda TB basili ile enfekte hastaların bulunduğu ülkelerin büyük bir bölümü orta ve düşük gelirli ülkelerdir. Bu nedenle çalışmada düşük gelirli ülkelerde ve laboratuvarlarda TB ve çok ilaca dirençli ( TB izolatlarının ilaç duyarlılık testleri için kolayca kullanılabilecek yeni bir besiyeri olan AYC.2.2 agar besiyerinin klinik izolatlarla etkinliğinin değerlendirilmesi amaçlanmıştır. Çalışmada Mycobacterium tuberculosis ATCC 27294 (H37Rv, tüm ilaçlara duyarlı), ATCC 35822 (izoniazid dirençli), ATCC 35838 (rifampisin dirençli), ATCC 35820 (streptomisin dirençli) ve ATCC 35837 (etambutol dirençli) referans suşlar ve 34 klinik izolat test edilmiştir. Çalışmadaki tüm anti TB ilaçlar ve izolatlar için kullanılan referans yöntem ve AYC.2.2 agar kullanılarak yapılan agar proporsiyon metodu arasında duyarlılık, özgüllük, pozitif prediktif değer (PPD), negatif prediktif değer (NPD) ve uyum hesaplanmıştır. İzoniazid ve rifampisin için tüm değerler %100 bulunmuştur. Etambutol için duyarlılık %100, özgüllük %88.23, PPD %89.47, NPD %100, uyum %94 olarak hesaplanmıştır. Streptomisin için duyarlılık %100, özgüllük %77.77, PPD %80, NPD %100, uyum %88 bulunmuştur. M. tuberculosis ATCC suşları klinik izolatların değerlendirilmesine dahil edilmemiş ve bunlardaki uyum %100 bulunmuştur. Elde edilen sonuçlara göre, sıvı otomatize sistemlere oranla üreme süresi dezavantaj olmasına rağmen, AYC.2.2. agar duyarlılık sonuçlarının belirlenmesinde otomatik sistemler kadar etkili bir şekilde kullanılabilmiştir. Maliyetinin düşük olması ve hazırlanmasının kolay olması en büyük avantajlarındandır. Ancak, rutin kullanıma geçmeden önce çok merkezli çalışmalara ihtiyaç vardır.

Whole genome sequencing reveals candidate genes involving in PAS resistance in M. Tuberculosis isolated from patients in Thailand.

Para-amino salicylic acid (PAS) was first reported by Lehmann in 1946 and used for tuberculosis treatment. However, due to its adverse effects, it is now used only as a second line anti-tuberculosis drug for treatment of multidrug resistant or extensively drug resistant M. tuberculosis. The structure of PAS is similar to para-amino benzoic acid (pABA), an intermediate metabolite in the folate synthesis pathway. The study has identified mutations in genes in folate pathway and their intergenic regions for their possibilities in responsible for PAS resistance. Genomic DNA from 120 PAS-resistant and 49 PAS-sensitive M. tuberculosis isolated from tuberculosis patients in Thailand were studied by whole genome sequencing. Twelve genes in the folate synthesis pathway were investigated for variants associated with PAS resistance. Fifty-one SNVs were found in nine genes and their intergenic regions (pabC, pabB, folC, ribD, thyX, dfrA, thyA, folK, folP). Functional correlation test confirmed mutations in RibD, ThyX, and ThyA are responsible for PAS resistance. Detection of mutation in thyA, folC, intergenic regions of thyX, ribD, and double deletion of thyA dfrA are proposed for determination of PAS resistant M. tuberculosis.

Effects of benzothiazinone and ethambutol on the integrity of the corynebacterial cell envelope

The mycomembrane (MM) is a mycolic acid layer covering the surface of Mycobacteria and related species. This group includes important pathogens such as Mycobacterium tuberculosis, Corynebacterium diphtheriae, but also the biotechnologically important strain Corynebacterium glutamicum. Biosynthesis of the MM is an attractive target for antibiotic intervention. The first line anti-tuberculosis drug ethambutol (EMB) and the new drug candidate, benzothiazinone 043 (BTZ) interfere with the synthesis of the arabinogalactan (AG), which is a structural scaffold for covalently attached mycolic acids that form the inner leaflet of the MM. We previously showed that C. glutamicum cells treated with a sublethal concentration of EMB lose the integrity of the MM. In this study we examined the effects of BTZ on the cell envelope. Our work shows that BTZ efficiently blocks the apical growth machinery, however effects in combinatorial treatment with β-lactam antibiotics are only additive, not synergistic. Transmission electron microscopy (TEM) analysis revealed a distinct middle layer in the septum of control cells considered to be the inner leaflet of the MM covalently attached to the AG. This layer was not detectable in the septa of BTZ or EMB treated cells. In addition, we observed that EMB treated cells have a thicker and less electron dense peptidoglycan (PG). While EMB and BTZ both effectively block elongation growth, BTZ also strongly reduces septal cell wall synthesis, slowing down growth effectively. This renders BTZ treated cells likely more tolerant to antibiotics that act on growing bacteria.

Standardization and validation of a novel UPLC-MS/MS method to quantify first line anti-tuberculosis drugs in plasma and dried blood spots

Tuberculosis (TB) is a high-burden infectious disease with high prevalence and mortality rates. The first-line anti-TB drugs include isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB). At present, the standard method of blood sampling for therapeutic drug monitoring (TDM) analysis is venipuncture. Dried blood spots (DBS) are a minimally invasive method for collecting small quantities of whole blood from fingertips. The aim of the current study was to develop an ultrahigh-performance liquid chromatography technique coupled to tandem mass spectrometry (UPLC-MS/MS) for simultaneous quantification of the first-line anti-TB drugs in human plasma and DBS as a sampling alternative. The separation and detection conditions were optimized to quantify INH, RMP, PZA, and EMB in both matrices in an ACQUITY UPLC H Class system coupled to a XEVO TQD detector. Chromatographic separation was performed through an Acquity HSS T3 column (2.1 × 100 mm, 1.8 μm) with 0.1% formic acid in water and acetonitrile as the mobile phase. The total run time was 7 min for both methods, with retention time in plasma of 0.85, 1.22, 3.16, and 4.04 min and 0.74, 0.87, 0.97, and 4.16 min for EMB, INH, PZA, and RMP in DBS, respectively. The bioanalytical methods developed were proved selective, linear, precise, and accurate (inter- and intra-assay); the matrix effect was demonstrated to be within the established limits. Short- and long-term stability, freeze–thaw cycles for plasma, and short-term stability for DBS were established. A total of 15 patients with 46 ± 17 (mean ± SD) years old were included, and anti-TB drug concentrations were quantified on plasma and DBS as proof of concept. Based on RMP and INH plasma concentrations (Cp), and Bayesian estimation of individual pharmacokinetic parameters, a dose adjustment was necessary for 93% of patients. The slopes of the correlation lines between plasma and DBS concentrations of RMP, EMB, INH, and PZA were 0.5321, 0.8125, 0.5680, and 0.6791, respectively. Finally, significant correlations (p < 0.05) were observed between DBS and plasma concentrations for RMP (r2 = 0.6961), EMB (r2 = 0.4369), INH (r2 = 0.8675) and PZA (r2 = 0.7363). A simple, fast, and reliable UPLC-MS/MS method was developed to quantify first-line anti-TB drugs in plasma and DBS, which provides an easy sampling and storage to be applied as a new strategy for TDM in patients with TB.

The role of invasive methods in errors in the differential diagnosis of tuberculosis of the lungs and pleura: clinical examples

BACKGROUND. Differential diagnosis between non-specific diseases of the lungs and pleura and tuberculosis (TB) of these organs is an urgent problem. According to a number of authors, the frequency of false diagnosis of TB is 34-40 %. Difficulties in the differential diagnosis of pulmonary TB (pleura) and non-specific diseases of the lungs and pleura arise in most cases with exudative and caseous inflammation of the lung tissue. The use of various types of surgical interventions, both diagnostic and therapeutic, provides a greater range of conducting various laboratory tests, especially when this issue may be related to the differential diagnosis of TB. Thus, during surgical intervention, it is possible to obtain biopsy material, which can be sent for pathological, molecular genetic and bacteriological research.&#x0D; MATERIALS AND METHODS. Two clinical cases are presented, in which, due to suspicion of specific inflammation in the lungs and pleura, we used all the above-mentioned methods of laboratory diagnosis of resection biopsy material during surgical interventions.&#x0D; CONCLUSIONS. This approach provides objective morphological and biological detection of Mycobacterium tuberculosis, and also makes it possible to determine the sensitivity to 1st and 2nd line antituberculosis drugs, which ultimately helps to establish the correct diagnosis and prescribe an effective treatment scheme.

Effect of Aloe Vera Extract and Second Line Anti-Tuberculosis Drugs on Mycobacterium Tuberculosis Strain-H37Rv

The present study was undertaken to examine the direct effect of second line anti-tuberculosis drugs Ethionamide (ETH), Para amino salicylic acid (PAS), Aloe vera on Mycobacterium tuberculosis (MTB) strain H37Rv ATCC No- 27294. It is found that Aloe vera does not interfere with single or in the combination of both ETH and PAS showing the bioenhancer activity. In vitro study of Aloe vera observed that the extract inhibited the growth of H37Rv strains. The present results will pave new avenues to find a new medicine that possesses Aloe vera alone or in combination with drugs to combat H37Rv strains controlling tuberculosis.

2,4-Disubstituted pyridine derivatives are effective against intracellular and biofilm-forming tubercle bacilli.

It was recently reported that 4-substituted picolinohydrazonamides carrying hydrophilic cyclic amines, such as morpholine and pyrrolidine, at the end of their thiosemicarbazide chain have potent antimycobacterial activity in vitro at concentrations below 1μg/ml. Here, two selected compounds, 2,4-disubstituted pyridine derivatives 11 and 15, revealed significant bactericidal activity against Mycobacterium tuberculosis localized intracellularly within human macrophages, as well as against biofilm-forming tubercle bacilli. Mutants were selected that were resistant to the investigated compounds at an efficiency similar to that identified in the presence of the first line antituberculosis drug rifampicin. The resistant mutants were viable in the presence of the tested compounds exclusively on solid media. Genome-wide sequencing of the mutants selected in the presence of compound 11 revealed the accumulation of nonsynonymous mutations in the mmpR5 gene encoding a transcriptional repressor of the MmpS5-MmpL5 efflux pump, whose upregulation has been associated with bedaquiline resistance. The depletion of MmpR5 in wild-type M. tuberculosis using CRISPR-Cas9 technology increased the resistance of this strain to compound 11. Mass spectrometry-based proteomics (LC-MS/MS) of wild-type tubercle bacilli growing in subinhibitory concentrations of compounds 11 or 15 revealed 15 overproduced proteins not detectable in the control cells, including virulence-related proteins.

Determinants of stock-outs of first line anti-tuberculosis drugs: the case of public health facilities of Addis Ababa city administration health bureau, Addis Ababa, Ethiopia

BackgroundThe health sectors success has been determined by consistent and reasonably priced health commodities supply. Despite possible death from the disease, Tuberculosis (TB) can be prevented with early diagnosis and appropriate treatment for which enough, effective, and qualified medicines need to be available. However, studies revealed stock of anti-TB drugs in health facilities. Here we present the recent finding on determinants of stock out of Anti-TB drug at public health facilities of Addis Ababa.ObjectiveThis study aimed to identify determinants of stock outs of first line anti TB drugs at public health facilities under Addis Ababa City Administration Health Bureau.MethodMixed study design were employed. A total of 106 facilities were included in the sampling frame and data were collected from the study population such as drug store managers of health facilities providing TB treatment using semi structured questionnaire and through in-depth interview with Addis Ababa hubs of the Ethiopian Pharmaceuticals Supply Agency (EPSA), Addis Ababa City Administration Health Bureau and selected heads of pharmacy departments of health facilities from May 1–30, 2020 considering one year back retrospective data from March 20,2019 to March 20,2020. Structured record review of data from Logistics Management Information System (LMIS) tools having TB drugs was done using structured observation checklist. Data were entered, cleaned, and analyzed using SPSS Version 20. Both descriptive and multiple logistic regression analysis were performed.Result52(62.7%) of health facilities encountered stock out for at least one of these drugs during the past 1 year. Rifampicin 75 mg + Isoniazid 50 mg (RH 75/50 mg) were most stocked out first line anti-TB drug from 33(39.8%) of facilities with 17 mean stocks out days while Rifampicin 75 mg + Isoniazid 50 mg + Pyrazinamide 150 mg (RHZ 75/50/150 mg) were the least first line anti-TB drug stocked out from facilities with mean 5 days of stock out. Delayed supply of anti TB drug from EPSA, delivery of reduced quantity of anti TB drugs by EPSA and stocked out of anti TB Drugs at EPSA were significant determinate factors of stock out of first line anti-TB drug from facilities with 95%CI of 10.34(2.167–49.329), 11.452(2.183–60.079) and 5.646(1.240–25.707) respectively.ConclusionAbove median of health facilities encountered stock out of first line anti-TB drug in Addis Ababa. Delayed supply of anti TB drug from EPSA, delivery of reduced quantity of anti TB drugs by EPSA and stocked out of anti TB Drugs at EPSA were significant determinate factor of stocked out of first line anti-TB drug from facilities. EPSA and other responsible bodies shall work collaboratively to improve their service and ensure availability of adequate amount of Anti TB drug in health facilities.

Multi Drug Resistance: A Continuous Challenge by a Century Old Mycobacterium Tuberculosis

Background: Tuberculosis is a mycobacterial infection caused by mycobacterium tuberculous bacillus. Anti-tuberculous drugs are drugs used to treat tuberculosis which include first line anti-tuberculosis drugs used to treat tuberculosis initially when the infection is non-resistant these include Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol. Second line anti-tuberculosis drugs which are used to treat resistant tuberculosis or when first line drugs are contraindicated these include Ethionamide, Capreomycin, ciprofloxacin etc. Multidrug-resistant tuberculosis is tuberculosis not responding to 2 first line anti-tuberculosis drugs.&#x0D; Methods: This study was aimed at determining the frequency of MDR pattern in multidrug-resistant tuberculosis cases. The design was cross sectional and the study was conducted at Tuberculosis and chest diseases Center Mirpur Khas in 2017 over two years.&#x0D; Results: Total 458 MDR patients were evaluated 252(55%) females and 206(45%) were males. Isoniazid and Rifampicin were resistant in 97 (21.17%) cases while Isoniazid, Ethambutol and Rifampicin were found to be resistant in 40(8.73%) cases. The resistance for Isoniazid, Pyrazinamide and Rifampicin was observed in 50(10.92%) cases whereas 60(13.10%) patients were resistant to Isoniazid, Rifampicin and Streptomycin. Isoniazid, Ethambutol, Rifampicin and Streptomycin were resistant in 75(16.38%) cases. Isoniazid, Pyrazinamide, Rifampicin and Streptomycin resistance was seen in 40(8.73%) patients and 96(20.96%) of the cases shoed resistance to Isoniazid, Ethambutol, Pyrazinamide and Rifampicin.&#x0D; Conclusion: Multidrug-resistant tuberculosis is highly prevalent in the region.

Management of tuberculosis during pregnancy: first line anti-tuberculosis drug

Tuberculosis is a widespread, infectious disease caused by various strains of mycobacteria, commonly Mycobacterium tuberculosis. Tuberculosis not only responsible for an important proportion of the global burden of disease, but it is also an important contributor to maternal mortality, with the disease being among the three leading causes of death among women aged fifteen to forty five years. The main goals of tuberculosis treatment are to cure the patients, to prevent maternal and perinatal complications and to minimize the possibility of transmission of the bacillus to healthy individuals. First-line anti-tuberculosis treatment for medicine-sensitive tuberculosis can be highly effective; however, in absence of well-controlled studies in pregnant women, first-line tuberculosis medications have been listed as United States Food and Drug Administration pregnancy category C (ie, no adequate well-controlled human studies have been performed, but benefits may be acceptable despite potential risks) except ethambutol categorized as pregnancy category B. Rifampicin can be highly used by pregnant women; due to it is believed to be safe for pregnancy and no teratogenic effects has been observed. Neonates who born from mothers who have been taken rifampicin combination therapy may be developed an increased risk of haemorrhagic disorders in the new-born (postpartum hemorrhage); to avoid this postpartum hemorrhage supplemental vitamin K (10mg/day) should be given for the last four to eight weeks of pregnancy.

Signal detection of adverse drug reaction to first line anti tuberculosis drugs using the Indonesian pharmacovigilance database

Introduction: Pharmacovigilance is a key component to identify risks associated with drug use. The safety of antituberculosis drugs (ATDs) is a concern. Aim: To detect first-line ATD signals in the Indonesian pharmacovigilance database. Methods: A retrospective cohort with a sample report of ADRs obtained from the National Agency of Drug and Food Control (NADFC) from 2012 to May 2018. The validity was seen from the completeness of the data. The signals found were verified against registered product labels, books, and reports from other countries' databases. Results: ATD ADRs reported was 5.3%. The ATD that met the requirements as a signal was rash maculopapular (PRR 4.53; ROR 6.19; IC 0.74 and p=035) for Rifampicin-Isoniazid-Pyrazinamide-Ethambutol (RHZE) and rash (PRR 2.94; ROR 4.23; IC 1.41 and p=0.046) for RH. Conclusion: Safety signals detected in the Indonesian pharmacovigilance database between 2012 and May 2018 were rash maculopapular.

Structure-Activity Relationship of Anti-Mycobacterium abscessus Piperidine-4-carboxamides, a New Class of NBTI DNA Gyrase Inhibitors.

Mycobacterium abscessus causes difficult-to-cure pulmonary infections. The bacterium is resistant to most anti-infective agents, including first line antituberculosis (anti-TB) drugs. MMV688844 (844) is a piperidine-4-carboxamide (P4C) with bactericidal properties against M. abscessus. We recently identified DNA gyrase as the molecular target of 844. Here, we present in silico docking and genetic evidence suggesting that P4Cs display a similar binding mode to DNA gyrase as gepotidacin. Gepotidacin is a member of the Novel Bacterial Topoisomerase Inhibitors (NBTIs), a new class of nonfluoroquinolone DNA gyrase poisons. Thus, our work suggests that P4Cs present a novel structural subclass of NBTI. We describe structure-activity relationship studies of 844 leading to analogues showing increased antibacterial activity. Selected derivatives were tested for their inhibitory activity against recombinant M. abscessus DNA gyrase. Further optimization of the lead structures led to improved stability in mouse plasma and increased oral bioavailability.

Pattern of resistance to second line anti-tuberculosis drugs and associated risk factors among multidrug-resistant patients of pulmonary tuberculosis from Agra region of Uttar Pradesh, North India

Present study was aimed to determine the status of second-line anti-TB drug resistance and risk factorsfor extensively drug-resistance (XDR)-tuberculosis among multi-drug resistant (MDR)-tuberculosis patients from Agra region of Uttar Pradesh, North India.A total of 279 MDR-Mycobacterium tuberculosis isolates from pulmonary tuberculosis patients of Agra region of Uttar Pradesh were analyzed for the resistance to second-line anti-TB drugs (SLDs). The demographic, behavioral, clinical and social information was compared with the results of drug susceptibility testing and analyzed statistically. Out of 279 MDR-isolates, 195 (69.89%) isolates were found resistant to at least one of the SLDs. The rates of general resistance to each of the drugs were as follows: kanamycin (42.29%), amikacin (17.92%), levofloxacin (40.14%) and ofloxacin (51.97%). Among the MDR-TB isolates, 53.76, 43.01 and 26.88% isolates were resistant to fluoroquinolone, second line injectable drugs and XDR, respectively. Among the demographic/ clinical variables, occupation, gender and number of family members were associated with the development of XDR-TB in MDR-TB patients of Agra region of Uttar Pradesh(P value: &lt;0.05).Present study has provided baseline information about the risk factors associated with SLDs resistance and XDRamong MDR-TB patients which can be useful to strengthen the implementation of targeted interventions in order to minimize the cases of drug resistance tuberculosis in Uttar Pradesh, North India.

Adverse drug reactions to first line anti-tuberculosis drugs in newly diagnosed tuberculosis patients

Tuberculosis (TB) continues to be an important public health problem throughout much of the world. Drug treatment is the only effective treatment method, but adverse drug events (ADEs) and adverse drug reactions (ADRs) can affect medical adherence. As the number of drug resistant TB patients and the number of anti-TB drugs have increased, it is necessary to explore the risk factors for ADEs/ADRs to reduce their occurrence. Here we reported three different cases of ADRs due to first line anti-tubercular drugs.

Clinical, laboratory and radiological associations with extending of the intensive phase of treatment in patients with first diagnosed infiltrative pulmonary tuberculosis

Despite the availability of medical services, timely detection of pulmonary tuberculosis, before the appearance of destructive changes, is often difficult. The management of patients with an infiltrative form in a hospital setting does not always guarantee the same positive effect and sometimes requires prolongation of therapy. The effectiveness of therapy can be associated with various factors and is of interest to study. The aim of this work was to study the effectiveness of standard therapy in patients with first diagnosed infiltrative pulmonary tuberculosis, clinical laboratory and radiological associations with prolongation of the intensive phase of treatment. Materials and methods. The study involved 109 men from 18 to 53 years old with first diagnosed infiltrative pulmonary tuberculosis with preserved MBT sensitivity to 1-st line anti-tuberculosis drugs. Patients were examined before and after 60 doses of the intensive phase of treatment, after which two groups were formed. Group 1 included patients with pronounced positive clinical and radiological dynamics, who entered the continuation phase of therapy. Group 2 included patients with insufficient clinical and radiological dynamics, for whom the intensive phase of treatment was extended to 90 doses. Results. Weak dynamics in patients who needed prolongation of treatment was associated with the characteristics of the initial data of patients in this group compared with similar indicators in Group 1. These were a reliably higher frequency of symptoms of intoxication and coughing, a reliably greater number of patients excreting mycobacterium tuberculosis in large quantities in sputum, with reliably high blood concentrations of haptoglobin and ceruloplasmin levels. Conclusions. Patients requiring prolongation of the intensive phase of treatment are characterized by an initially higher prevalence of infiltrative changes in the lungs, a small number of lung lesions limited to 2 segments, the presence of destructive changes in 100 % of cases, and a significant increase in the factors of the systemic inflammatory response

Distribution patterns of drug resistance Mycobacterium tuberculosis among HIV negative and positive tuberculosis patients in Western Kenya

Distribution patterns of drug resistance Mycobacterium tuberculosis among HIV negative and positive tuberculosis patients in Western Kenya

Testing Susceptibility of &lt;i&gt;M. tuberculosis&lt;/i&gt; to Second Line Anti-Tuberculosis Drugs Using the XDR Test in Clinical Trials and International Professional Testing Cycles

The objective of the study: to evaluate the commercial XDR test for susceptibility testing of M. tuberculosis to second line anti-tuberculosis drugs in clinical trials and as part of annual professional testing cycles coordinated by the World Health Organization (WHO).Subjects and Methods. Cultures of M. tuberculosis (n = 90) freshly isolated on egg media from clinical samples collected in tuberculosis patients were tested using the Bactec MGIT 960 system and the XDR test under identical conditions. Well-studied strains of M. tuberculosis (n = 216) obtained from the WHO supranational laboratories were repeatedly cultured on Middlebrook 7H10 medium before the study. The drug susceptibility of the cultures was assessed using the XDR test by the nitrate reductase method.Results. A high concurrence (96.7-100%) of the results was shown when testing susceptibility of 90 M. tuberculosis isolates to kanamycin, amikacin, capreomycin and ofloxacin using the XDR test and the Bactec MGIT 960 system with comparable test periods. The use of the XDR test for drug susceptibility testing of 216 M. tuberculosis strains in eleven annual professional testing cycles coordinated by the WHO supranational laboratories provided the results consistent with the consensus one for kanamycin, capreomycin, ofloxacin and amikacin in 98.6, 99.4, 99.4, and 99.0% of cases, respectively. For moxifloxacin and levofloxacin additionally incorporated to the XDR test, completely identical results were obtained.