Line Antitubercular Drugs Research Articles

Pattern of rapidly growing mycobacteria (RGM) species isolated from clinical samples: A 10-year retrospective study in a tertiary care hospital of Bangladesh

PurposeInfections caused by rapidly growing mycobacteria (RGM) are increasing worldwide. The study was conducted in a microbiological laboratory of Bangladesh to determine the pattern of detection of RGM from clinical samples. MethodsAll laboratory culture records of RGM from 2012 to 2022 were collected retrospectively and analyzed. ResultsA total 62 RGM infected patients with surgical site infection (74.1 %), injection site and skin abscess (9.7 %), septicaemia (4.8 %) and UTI (1.6 %) were identified. The annual isolation frequency of RGM increased 4.8 %–29.1 % in between year 2012 and 2022. RGM infected patients (14.5 %) were mistakenly treated with first line anti tubercular drug before correct microbiological diagnosis (median, IQR; 3, 2–5 months). Out of 23 RGM isolates, 86.9 % were M. abscessus and rest 13.1 % were M. fortuitum. Most of them (≥95 %) were sensitive to amikacin, linezolid, clarithromycin where as 27.1 % to imipenem and ciprofloxacin, 40 % to cefoxitin, 35.3 % and 1.7 % to doxycycline and co-trimoxazole respectively. ConclusionMisdiagnosis or delay in diagnosis and erroneous treatment with first line anti tubercular drug may cause prolong morbidity and therapeutic failure to patients with RGM infection. So, early and appropriate diagnosis is crucial for successful outcome.

Structural Studies on Mycobacterial NudC Reveal a Class of Zinc Independent NADH Pyrophosphatase

Non-tuberculous mycobacteria (NTM) have emerged as an increasing threat to public health, due to the extreme antibiotic resistance. NADH pyrophosphatase (NudC) was proposed involving in mycobacterial resistance to the first line anti-tubercular drug isoniazid (INH) or its analog ethionamide (ETH), by hydrolyzing their NAD modified active forms (NAD-INH and NAD-ETH). In this study, we performed enzymatic and structural studies on NudC from M. abscessus (NudCMab), which is highly resistant to isoniazid and emerging as the most worrisome NTM. We determined the crystal structures of NudCMab in apo form, substrate NAD-bound form and product AMP-bound form. We observed the mode for the Nudix motif of NudCMab capturing the pyrophosphate group of NAD mediated by three divalent cation ions, which provides details for understanding the mechanism on NudC hydrolyzing NAD(H) or NAD-capped substrate. Interestingly, our structures revealed a novel subclass NudC from mycobacteria characterized by a unique arginine residue on the conserved QPWPFPxS motif, as well as a unique tower domain that replaces a well-defined zinc-binding motif in E.coli NudC and catalytic domain of mammalian Nudt12. Thus, our structural studies on NudCMab not only present a class of zinc independent NADH pyrophosphatase in mycobacteria, but also may facilitate the design of NudC inhibitors for the treatment of mycobacteria infections in combination with INH or ETH.

Ethambutol induced subacute cutaneous lupus erythematosus in an elderly female with co-morbidities

Papulosquamous lesions in an elderly female with multiple co-morbidities often pose diagnostic challenge. We present an interesting case of anti-tubercular treatment (ATT) induced sub-acute cutaneous lupus erythematosus. The patient presented with papulosquamous lesions in generalised distribution, which showed interface dermatitis on histopathology. The serology for anti-nuclear antibodies, anti-Ro and anti-La was positive. The rash resolved spontaneously after stopping all the suspected drugs. Oral provocation was performed with first line anti-tubercular drugs and ethambutol was found to be the culprit drug, which was later confirmed by reappearance of skin rash by inadvertent ingestion of one dose of ethambutol by the patient.

Estimation of First Line Anti-Tubercular Drugs resistance and their genetic analysis by Geno Type MTBDRplus assay from an Intermediate Reference Laboratory in Eastern Uttar Pradesh, India

Estimation of First Line Anti-Tubercular Drugs resistance and their genetic analysis by Geno Type MTBDRplus assay from an Intermediate Reference Laboratory in Eastern Uttar Pradesh, India

A study on the mycobacterial burden and phenotypic drug resistance pattern with reference to the GeneXpert Cycle Threshold values in pulmonary tuberculosis

Introduction and aim. Tuberculosis (TB) remains a significant global health challenge. Early and accurate diagnosis is crucial to prevent further transmission. The present study aimed to correlate cycle threshold values with smear microscopy and culture positivity, and determine cut-off cycle threshold values for levels of smear grade and culture positivity. Material and methods. Forty presumptive cases of pulmonary TB were included and subjected to Ziehl- Neelsen stain, culture on Lowenstein Jensen media, CBNAAT and drug susceptibility testing for first line anti-tubercular drugs. Results. Our study predicts 3+, 2+, and 1+ sputum smear grade at a cut-off of Ct value ≤ 16.74, ≤19.68, and ≤ 22.32 respectively. A strong positive correlation was found between time to culture positivity and Ct value. A cut-off of Ct value ≤22.32 predicts culture positivity with a sensitivity of 92%, and a specificity of 67%. None of the isolates showed rifampicin resistance by 1% proportion method. Conclusion. Understanding the appropriate utilization of CBNAAT Ct values and their correlation with smear microscopy grade, culture, and drug susceptibility testing can assist clinicians in early identification and prompt initiation of appropriate treatment. This knowledge can contribute to the prevention of drug resistance, reduced transmission, and a decreased disease burden associated with TB.

Lineage classification and antitubercular drug resistance surveillance of Mycobacterium tuberculosis by whole-genome sequencing in Southern India.

Studies mapping genetic heterogeneity of clinical isolates of M. tuberculosis for determining their strain lineage and drug resistance by whole-genome sequencing are limited in high tuberculosis burden settings. We carried out whole-genome sequencing of 242 M. tuberculosis isolates from drug-sensitive and drug-resistant tuberculosis patients, identified and collected as part of the TB Portals Program, to have a comprehensive insight into the genetic diversity of M. tuberculosis in Southern India. We report several genetic variations in M. tuberculosis that may confer resistance to antitubercular drugs. Further wide-scale efforts are required to fully characterize M. tuberculosis genetic diversity at a population level in high tuberculosis burden settings for providing precise tuberculosis treatment.

A Review Study on Safety and Efficacy on Second Line Anti Tubercular Drugs

Due to intestinal dysbiosis brought on by second-line anti-tubercular medication therapy, the patient's resistance to MTB appears to have decreased. This is likely due to an impact on immune cell proliferation and autophagic processes. therefore adversely influencing the patients' treatment results. The objectives of review articles are the safety and efficacy on the second line anti tubercular drugs. The results of these review article in the year 2015 to 2020. The conversation of these review article is the safety and efficacy of second line anti tubercular drugs . The discussion of these study about the safety and efficacy on second line anti tubercular drugs . 2016 levofloxacin is a not more safe and less effective because result insufficient control to the tuberculosis patient it adverse events is underactive thyroid. 2020 Ethionamide is a safe and effective for the TB patients. The conclusion of these review study and efficacy of the second line anti tubercular drugs. The ofloxacin are the most effective and safe when compared to the other second line anti tubercular drugs. In second line anti tubercular drugs the levofloxacin is having the less efficacy when compared to other second line anti tubercular drugs because it is having the adverse effect of the hypothyroidism. For the treatment of tuberculosis the drugs used are the levofloxacin, kanamycin, etc and these are most commonly used for the prevention of the disease.

Cubosome Lipid Nanocarriers As a Drug Delivery Vehicle for Intracellular Mycobacterium tuberculosis Infections

Mycobacterium tuberculosis (MTB) causes the infectious disease tuberculosis (TB), responsible for more deaths than any other single infectious disease in history. Intracellular MTB are slow growing and difficult to target with traditional antitubercular drugs, leading to the emergence of multidrug resistance in TB infection, which is a major global public health issue. Recent advances in innovative lipid nanotechnologies for drug delivery have demonstrated promising outcomes for chronic infectious diseases but have not yet been tested as potential delivery systems for intracellular infections such as TB. The current study evaluates the potential of monoolein (MO)-based cationic cubosomes for the encapsulation and delivery of the first line antitubercular drug rifampicin (RIF) against an MTB-H37Ra in vitro culture model. In particular, we show that the use of cationic cubosomes as delivery vehicles reduced the minimum inhibitory concentration (MIC) of RIF by 2-fold against actively replicating MTB-H37Ra (compared to that of the free drug) and also shortened the lifecycle duration of axenic MTB-H37Ra from 5 to 3 days. The cubosome-mediated delivery was also found to be effective against intracellular MTB-H37Ra within THP-1 human macrophages, with a 2.8 log reduction in viability of the bacilli after 6 days incubation at the MIC. The killing time was also reduced from 8 to 6 days without distressing the host macrophages. Mechanistic studies on the uptake of RIF-loaded cationic cubosomes using total internal reflection fluorescence microscopy (TIRFM) demonstrated the capacity of these lipid particles to effectively target intracellular bacteria. Overall, these results demonstrate that cationic cubosomes are a potent delivery system for the antitubercular drug RIF for therapeutic management of TB.

Side Effects of TB Therapy and Recent Therapeutic Approaches for Tuberculosis Management

Tuberculosis or TB caused by the micro-organism Mycobacterium tuberculosis is a highly contagious and the second most fatal disease after AIDS. It is estimated that it will soon surpass the deaths caused by HIV.BCG is the only vaccine available to prevent TB, however it is not effective in case of adult pulmonary TB which is actually the most common type of TB. The currently used treatment regimen in most developing countries is a single tablet with fixed dose combination of four drugs- Isoniazid (INH), Rifampicin, Ethambutol and Pyrazinamide which are 1st line anti-tubercular drugs. This combination reduces the risk of development of multi-drug resistant (MDR) Mycobacterium. But this drug combination is known to have various severe side-effects, which if not taken into consideration might lead to fatal reactions. MDR-TB treatment involves the use of 2nd line drugs which are less potent and more toxic compared to 1st line drugs. Increasing number of MDR strains of mycobacterium and failure of these conventional regimens to treat them is a huge challenge. Also, these side-effects associated with anti-TB drugs are a major reason for patient non-compliance and non-adherence to the treatment. Treatment discontinuation leads to increased risk of mortality and morbidity due to TB. Thus, it is very important to develop new therapeutic approaches towards the treatment of this disease which provide a better cure without relapse, lesser side-effects and prevents formation of drug resistant strains. The article reviews the various side-effects associated with the Anti-Tubercular drugs that are currently used and discusses certain newer, nanoparticle-basedapproaches to overcome the shortcomings of the current conventional therapy.

Cycloserine Induced Psychosis, Insomnia and Suicidal Attempts in a Young Female Patient with Pre-Extensively Drug Resistant Tuberculosis

The World Health Organization classifies cycloserine as a group four second line anti tubercular drug for the treatment of drug resistant tuberculosis. Neuropsychiatric adverse drug reactions associated with cycloserine need more attention as they may compromise treatment success. Here, we report a case of cycloserine induced psychosis, insomnia and suicidal attempts in a young female patient with pre-extensively drug resistant tuberculosis (pre-XDR-TB). A 20-year-old female patient was prescribed longer oral XDR-TB regimen (high dose of moxifloxacin, cycloserine, linezolid, clofazimine, bedaquiline and pyridoxine). After fifteen days of treatment, patient developed changes in behaviour with frequent episodes of spontaneous and excessive laughing or crying. She also developed insomnia, started to hear voices and made two attempts of suicide. Following this, cycloserine was discontinued. Clonazepam and clomipramine were prescribed to her. Patient gradually recovered over a period of one month. Extreme caution with regular and close monitoring should be exercised while administering cycloserine because psychiatric adverse drug reactions could be associated with increased risk of poor drug adherence in drug resistant tuberculosis.

Missed phenotypic drug resistance in pediatric tuberculosis: A cause of concern in a resource-limited setting

BackgroundMulti-drug resistance (MDR) in pediatric tuberculosis (TB) is a growing global threat. Unavailability of conventional or molecular drug susceptibility test (DST) in resource-limited settings often impede the determination of the extent of first line anti-tubercular drugs deployed in national programs. Materials and methodPulmonary and extra pulmonary specimens were collected from clinically suspected pediatric TB cases, who were microbiologically confirmed. Resistance to first-line anti-TB was detected by 1% proportion method. KatG315 and inhA-15 genes were amplified by PCR and detection of mutations were done by sequencing. Genotypic resistance for rifampicin was detected by Xpert MTB/RIF assay (Cepheid Inc., Sunnyvale, California). ResultsFifty-one cases of pediatric tuberculosis were confirmed microbiologically. Resistance to isoniazid, streptomycin, rifampicin and ethambutol were 5 (14%), 4 (11%), 2 (5.5%) and 2 (5.5%) respectively by 1% proportion method. Genotypic Rifampicin and isoniazid resistance was found in 2 (5.5%) and 7 (14%) samples respectively. ConclusionExisting genotypic methods, detect targeted mutations conferring rifampicin resistance, however isoniazid (INH) resistance often go undetected. Since the resistance to pivotal anti-TB drugs are often encoded by multiple genes which may not be targeted by widely available molecular tests, discrepancies in molecular and culture-based DST reports should be interpreted with caution.

ATT associated DRESS syndrome in a patient of multidrug resistant tuberculosis diagnosed on lymph node FNAC

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare type of idiosyncratic drug reaction. It is usually associated with antiepileptic drugs. It can also be associated with first line anti-tubercular drugs (ATDs), antibiotics, herbal medicines and many other drugs. We report a case of DRESS syndrome presented with erythematous lesions all over the body following the intake of second line ATDs for multi drug resistant tuberculosis. FNAC was done from the enlarged inguinal lymph node which revealed the presence of atypical lymphocytes. Clinical and other supportive features confirmed the diagnosis of DRESS syndrome.

Elucidating the function of hypothetical PE_PGRS45 protein of Mycobacterium tuberculosis as an oxido-reductase: a potential target for drug repurposing for the treatment of tuberculosis

Mycobacterium tuberculosis (Mtb) encodes a total of 67 PE_PGRS proteins and definite functions of many of them are still unknown. This study reports PE_PGRS45 (Rv2615c) protein from Mtb as NADPH dependent oxido-reductase having substrate specificity for fatty acyl Coenzyme A. Computational studies predicted PE_PGRS45 to be an integral membrane protein of Mtb. Expression of PE_PGRS45 in non-pathogenic Mycobacterium smegmatis, which does not possess PE_PGRS genes, confirmed its membrane localization. This protein was observed to have NADPH binding motif. Experimental validation confirmed its NADPH dependent oxido-reductase activity (Km value = 34.85 ± 9.478 μM, Vmax = 96.77 ± 7.184 nmol/min/mg of protein). Therefore, its potential to be targeted by first line anti-tubercular drug Isoniazid (INH) was investigated. INH was predicted to bind within the active site of PE_PGRS45 protein and experiments validated its inhibitory effect on the oxido-reductase activity of PE_PGRS45 with IC50/Ki values of 5.66 μM. Mtb is resistant to first line drugs including INH. Therefore, to address the problem of drug resistant TB, docking and Molecular Dynamics (MD) simulation studies between PE_PGRS45 and three drugs (Entacapone, Tolcapone and Verapamil) which are being used in Parkinson’s and hypertension treatment were performed. PE_PGRS45 bound the three drugs with similar or better affinity in comparison to INH. Additionally, INH and these drugs bound within the same active site of PE_PGRS45. This study discovered Mtb’s PE_PGRS45 protein to have an oxido-reductase activity and could be targeted by drugs that can be repurposed for TB treatment. Furthermore, in-vitro and in-vivo validation will aid in drug-resistant TB treatment. HIGHLIGHTS In-silico and in-vitro studies of hypothetical protein PE_PGRS45 (Rv2615c) of Mycobacterium tuberculosis (Mtb) reveals it to be an integral membrane protein PE_PGRS45 protein has substrate specificity for fatty acyl Coenzyme A (fatty acyl CoA) and possess NADPH dependent oxido-reductase activity Docking and simulation studies revealed that first line anti-tubercular drug Isoniazid (INH) and other drugs with anti-TB property have strong affinity for PE_PGRS45 protein Oxido-reductase activity of PE_PGRS45 protein is inhibited by INH PE_PGRS45 protein could be targeted by drugs that can be repurposed for TB treatment Communicated by Ramaswamy H. Sarma

A Case Report of Drug Resistant Tuberculosis Involving Brain

We report a 21 year old male resident of Tasgaon, Maharashtra who was diagnosed with drug resistant tuberculosis affecting his lungs and brain, resistant to first line antitubercular drug Rifampicin. Initially he was diagnosed as a case of extrapulmonary tuberculosis, left sided tubercular pleural effusion. Later during course of treatment he developed central nervous system tuberculosis confirmed on magnetic resonance imaging brain contrast study and Cerebrospinal fluid study. Cerebrospinal fluid catridge based nucleic acid amplification test showed Rifampicin resistance. He was started on Modified longer oral Multidrug/extensively drug resistant tuberculosis regimen according to Programmatic management of drug resistant tuberculosis in India, 2021 guidelines. Keywords: Tuberculosis, Extra pulmonary, Programmatic management of drug resistance, Oral regimen, Central nervous system tuberculosis

ISOLATION IDENTIFICATION AND PATTERNS OF ANTI-TUBERCULOSIS DRUG RESISTANCE FROM TERTIARY CARE HOSPITAL UDAIPUR (RAJASTHAN)

Objective: Resistance against Mycobacterium tuberculosis (MTB) is important in the sense that it has an implication in the control of tuberculosis. The terms used to describe resistance to antituberculosis drugs are resistance among new cases (or primary resistance) and resistance among previously treated patients. The resistance among previously treated patients may be due to faulty treatment like prescription of inadequate treatment regimens, interrupted availability or poor quality of drugs, or incomplete treatment adherence while subsequent transmission of these resistant organisms to others will lead to development of disease which is resistant from the beginning called primary resistance. Pakistan is ranked eighth in terms of global estimated burden of tuberculosis cases. Multi-Drug Resistant (MDR) tuberculosis among new cases and MDR among previously treated patients is 3.2% and 35% respectively. Material and methods: - AFB smear examination and grading: - AFB smear examination was carried out by direct microscopy using the Ziehl Neelsen (ZN) method. Sputum smear result was examined and interpreted according to the AFB grading. AFB culture and drug susceptibility test: - Culture examinations were done on all diagnostic specimens of AFB smear positivity. Sputum specimens from each patient were processed with sodium hydroxide (NaOH) method-Modied Petroff 's procedure and cultured on Lowenstein-Jensen (LJ) slopes.10 All inoculated LJ drug and control media were incubated at 37ºC. All cultures were examined 48-72 hours after inoculation to detect gross contaminants. Thereafter, cultures were examined weekly, up to eight weeks on a specied day of the week. Typical colonies of M. tuberculosis were rough, crumbly, waxy, non-pigmented (buff coloured) and slow-growers, i.e., only appeared two to three weeks after inoculation. The colony was conrmed by ZN staining. Detection time for MOTT was 25 days. M. tuberculosis positive strains were culture negative when they grew on p-nitro benzoate (PNB) containing medium. Only a few colonies of non-tuberculosis Mycobacteria (NTM – often pigmented, with smooth morphology or PNB positive) were grown as visible colonies on PNB containing medium. Anti-TB drug susceptibility testing: - anti-susceptibility testing perform on pre-formed LJ media with antitubercular drugs Tuberculosis First Line Kit (Total 7 slants) Containing ve antitubercular agent (Isoniazid, Streptomycin, Ethambutol, Rifampicin and Pyrazinamide) 2 controls without any antimicrobial agent. Results: out of 119 samples antitubercular testing against rst line antitubercular drugs such as Pyrazinamide were shows 12 (10.08%) sample were resistance which accounts maximum resistance among rst line antitubercular another rst line antitubercular drugs shows resistance as follows Streptomycin (9.24%), Ethambutol (8.40%), Isoniazid (7.56%), Rifampicin (6.72%), drugs out of 119 samples in which 107 samples were susceptible to the Pyrazinamide drug in in-vitro antitubercular susceptibility testing. Antitubercular resistance against second line antitubercular drugs were shows as follows out of 119 samples antitubercular testing Ethionamide were shows 9 (8.18%) sample were resistance which accounts maximum resistance among second line antitubercular another second line antitubercular drugs shows resistance as follows Clarithromycin (6.72%), Ciprooxacin (5.88%), D- Cycloserine (5.88%), Amikacin (5.04%), Kanamycin (4.20%), P- aminosalicylic acid ( 4.20%) and Rifabutin (3.36%) drugs out of 119 samples in which 107 samples were susceptible to the Pyrazinamide drug in in-vitro antitubercular susceptibility testing. MDR-TB emerged in patients who were resistant to Rifampicin and Isoniazide was 6 in number during this study.

STEVENS-JOHNSON SYNDROME (SJS) AND TOXIC EPIDERMAL NECROLYSIS (TEN) ASSOCIATED WITH ANTI-TUBERCULAR DRUGS: A CASE REPORT

Introduction: Steven-Johnson syndrome (SJS) is an acute reaction that typically involves the skin and mucous membranes which are characterized by damage and flaking of the skin, accompanied by pain, and can cause death. Toxic epidermal necrolysis (TEN) is a rare, life-threatening skin reaction usually caused by medication,which is characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and mucous membranes, resulting in exfoliation and possible sepsis and/or death.SJS and TEN are some of the rare side-effects from Drugs used in Anti-Tubercular Treatment.we report here a caseofSJS and TEN, due to side effects of 1st line Anti-Tubercular Drugs. Case description: A 50-year-old man presented at emergency room with chief complaints ofmultiple blisters on the trunk and erosions on the mouth and genitals for the past 4 days.He also had shortness of breath for the past 10 days, fever and cough for the past 3 days. He was apparently normal 11days back.Symptoms started appearing after initiation of Anti-Tubercular Treatment. Conclusion: As soon as the diagnosis of Anti-Tubercular Drugs induced SJS and TEN was confirmed, Patient was taken offfrom ATD and administeredwith intravenous systemic steroids as immunosuppressive therapy, antifungals, and antibiotics. After 10 days of treatment, lesions healed and started desquamating.

Analysis of Adverse Drug Reactions associated with Anti-tubercular drugs – A Retrospective Study

Background: Adverse Drug Reactions (ADR’s) to anti-TB drugs might contribute to the extension of treatment period, final termination, drug resistance and treatment failure as Anti-TB medications are the main stay treatment in Tuberculosis. These ADR’s may cause unintended interruption of treatment which may pose a challenge in TB management. Aim: This study aims to explore and observe adverse reactions of 1st line antitubercular drugs in DOTS treatment. Methodology: This is a analysis of ADRs of antitubercular drugs that were reported to ADR monitoring centre (AMC), SDSTRC and RGICD ,Bangalore either by spontaneous reporting or found by active surveillance methods. This study was for about 32 months. During this period all the ADRs caused by antitubercular drugs reported to the AMC were collected and classified based on WHO causality assessment. Later all those data were analyzed and results were generated Results: A total of 507 ADR’s were reported and out of which the majority of ADR’s were reported in adult population (45%). Based on gender, Male had a higher incidence of ADR (324, 63.9%). Based on WHO causality assessment scale, 69.4% of ADRs were ‘possible’ followed by 25.2% being ‘probable’ and 4.1% being ‘certain’. Conclusion: Monitoring of patients on Anti tubercular treatment with early identification and appropriate management of ADR becomes very essential. The timely and aggressive management of adverse effects of anti-tubercular drugs greatly facilitates patient adherence.

Disseminated Tuberculosis with Neurotuberculosis Presenting as Status Epilepticus: A Case Report

Disseminated Tuberculosis (TB) results when the infection spreads though lymphohaematogenous route involving multiple organ systems. Irrespective of the availability of diagnostic modalities and treatment, it is usually diagnosed late increasing the mortality. Though, it usually occurs in immunocompromised patients, yet, incidence of disseminated TB is rising in immunocompetent subjects. This case report describes a 48-year-old male who presented to the Emergency Department (ED) with status epilepticus. Investigations revealed neurotuberculosis along with generalised tubercular lymphadenopathy involving cervical, axillary, mediastinal and abdominal lymphnodes. Diagnosis was confirmed after Cerebrospinal Fluid (CSF) and lymphnode biopsy. He was started on first line antitubercular drugs and tapering dose of tab. Prednisolone over one month. He was discharged after two weeks of hospitalisation. At 15 days follow-up the patient was asymptomatic.

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.

An observational study of adverse drug reactions in hospitalized patients of drug resistance tuberculosis taking PMDT therapy in a tertiary care hospital

Background: Drug resistant tuberculosis is an important public health issue in India. The treatment regimen followed is Programmatic Management of Drug resistant Tuberculosis (PMDT) approach. Adverse drug reactions (ADRs) are a serious issue which increases the risk of defaulter rate if poorly managed. Thus study was undertaken to assess the ADRs caused by PMDT therapy in indoor patients of Department of Respiratory Medicine in a tertiary care hospital at Surat.Methods: The prospective and observational study was carried out for one year period. The causality was determined by World Health Organization (WHO) Uppasala Monitoring Centre (UMC) scale and severity was determined by Modified Hartwig and Siegel scale. Fisher exact test was applied for statistical analysis.Results: Among 24 drug resistant tuberculosis patients, 12 (50%) patients developed ADRs due to second line antitubercular drugs. Occurrence of ADRs was more among Category V (100%) as compared to Category IV (36.8%). Occurrence of ADRs was more among females (60%). The commonly involved systems are auditory system (33.3%). Majority of ADRs developed within 61-90 days (66.7%) of initiation of drug therapy. Highest percentage of ADRs causing drugs was pyrazinamide (27.8%). On evaluation of the causality of ADRs, majority were found to be possible (53.3%). The severity assessment showed that most of the patients ADRs were of moderate level (73.3%).Conclusions: PMDT therapy is complicated but early management and reporting of ADRs decreases default rate.