Meningitis posquirúrgica por Acinetobacter baumannii multirresistente. Actividad sinérgica in vivo de la asociación sulbactam/avibactam / Post-surgical meningitis due to multiresistant Acinetobacter baumannii. In vivo synergistic activity of the sulbactam/avibactam association

Acinetobacter baumannii (AB) es un bacilo gram negativo, no fermentador,con frecuencia oportunista, ubicuo en el medio ambiente, con capacidad para sobrevivir en condiciones medioambientales adversas promoviendo su persistencia y diseminación en diferentes áreas de un hospital. Ha sido relacionado con múltiples brotes de infecciones asociadas al cuidado de la salud como neumonía, bacteriemias, contaminación de heridas quirúrgicas o infecciones del tracto urinario, especialmente entre pacientes con comorbilidades graves, como aquellos que motivan el ingreso a unidades de cuidados intensivos (UCI). Las cepas más problemáticas son aquellas resistentes a los carbapenémicos, resistencia causada por enzimas de la clase de las oxacilinasas (bla OXA) cromosómicas o plasmídicas y más recientemente bla NDM-1. La aparición de estas cepas deja escasos antimicrobianos activos (colistin, minociclina, tigeciclina; amikacina) que son limitados en su eficacia y su uso se asocia con toxicidad. A esto se agrega, como en la paciente que se describe, que desarrolló una meningitis posquirúrgica, la limitada capacidad de difusión en el sistema nervioso central (SNC) de estas últimas opciones. Una de las alternativas terapéuticas, es buscar asociaciones como sulbactam/avibactam que mostraron una adecuada actividad sinérgica y bactericida en asilamientos resistentes a ampicilina/sulbactam en base a una significativa reducción de la CIM que permite administrar dosis habituales, con mejor tolerancia y lograr concentraciones terapéuticas en SNC. Se presenta una paciente que desarrolló una meningitis posquirúrgica debida a una cepa de AB multirresistente.

Acinetobacter baumannii (AB) is a non-fermenting gram-negative bacillus, largely opportunistic, ubiquitous in the environment, with the ability to survive in adverse environmental conditions, promoting its persistence and dissemination in different areas of the hospital. It has been implicated in many outbreaks of healthcare-associated infections such as pneumonia, bacteremia, surgical wounds contamination, or urinary tract infections, especially among patients with previous severe illnesses such as those requiring admission to intensive care units (ICU). The most problematic strains are those resistant to carbapenems, resistance caused by chromosomal or plasmid oxacillinase class (bla OXA), and more recently bla NDM-1. The appearance of these strains leaves few active antimicrobials (Colistin, Minocycline, Tigecycline; Amikacin) that are limited in their efficacy and toxic. To this we must add, as is the case of our patient who presented post-surgical meningitis, the limited diffusion capacity in the central nervous system (CNS) of these last options. One of the therapeutic alternatives is to search for synergistic associations such as sulbactam/avibactam that showed rapid synergistic and bactericidal activity in isolates resistant to ampicillin/sulbactam due to a significant reduction in its MIC, which allows us to administer usual, better tolerated doses that reach therapeutic concentrations in CNS. Here, we present a patient who developed a post-surgical meningitis due to multiresistant AB

The first successful cochlear implant in Latin America after severe aminoglycoside-induced ototoxicity in a Peruvian patient cured of extensively drug-resistant tuberculosis

Introduction: Multidrug-resistant tuberculosis is a significant public health problem for which drugs are used with many adverse effects. Among the devastating consequences of these diseases, there is a wide variation in the incidence of ototoxicity and hearing loss in patients with multidrug-resistant and extremely resistant tuberculosis. Cochlear implants may be indicated in patients with unilateral/severe bilateral hearing loss with no benefit from conventional hearing aids, but their use in patients with tuberculosis is rare. Case report: We present the first case of a right unilateral cochlear implant performed on a 34-year-old Peruvian patient who presented profound sensorineural hearing loss of cochlear origin. Conclusion: Cochlear implant surgery is an essential milestone in the treatment of patients with auditory sequelae of tuberculosis treatment. Close monitoring of possible complications of tuberculosis treatment should be strengthened in countries with a high incidence of multidrug-resistant and extremely resistant tuberculosis.

Introducción: La tuberculosis multidrogorresistente es un importante problema de salud pública para el que se utilizan fármacos con múltiples efectos adversos. Entre las devastadoras consecuencias de estas enfermedades, existe una amplia variación en la incidencia de ototoxicidad y pérdida auditiva en pacientes con tuberculosis multirresistente y extremadamente resistente. Los implantes cocleares pueden estar indicados en pacientes con pérdida auditiva unilateral/bilateral severa sin beneficio de los audífonos convencionales, pero su uso en pacientes con tuberculosis es raro. Reporte de un caso: Presentamos el primer caso de implante coclear unilateral derecho realizado a un paciente peruano de 34 años que presentaba hipoacusia neurosensorial profunda de origen coclear. Conclusión: La cirugía de implante coclear es un hito fundamental en el tratamiento de los pacientes con secuelas auditivas del tratamiento de la tuberculosis. Se debe fortalecer la vigilancia estrecha de las posibles complicaciones del tratamiento de la tuberculosis en los países con una alta incidencia de tuberculosis multirresistente y extremadamente resistente.

Early detection of Pre-XDR TB with line probe assay in a high TB burden country

Background - Worldwide, tuberculosis (TB) is one of the top 10 causes of death. Drug resistant tuberculosis has lately become a major public health problem that threatens progress made in Tuberculosis (TB) care and control worldwide. The aim of this study was to determine the prevalence of Pre-extensive drug resistant TB among MDR TB in North Central of Nigeria. Methods - This study was conducted from October, 2018 to August, 2019 with 150 samples. In Nigeria, guidelines for DR-TB as recommended by WHO is followed. All the samples from the patients who gave their consent were transported to a zonal reference TB laboratory (ZRL). Results - Mean age was 38.6 ± 13.4 years with peak age at 35-44. Out of these 103 samples processed with LPA, 101(98%) were rifampicin resistant and 2 were rifampicin sensitive, 99(96%) were INH resistant and 4 (4%) were INH sensitive, 5(5%) were fluoroquinolone resistant, 98(95%) were fluoroquinolone sensitive, 12 (12%) were Aminoglycoside + Capreomycin resistant, 91(83%) were Aminoglycoside + Capreomycin sensitive. Conclusion - Multidrug resistant TB and its severe forms (Pre-extensive & extensively drug resistant TB) can be detected early with rapid tool- Line Probe Assay rapid and prevented timely by early initiation on treatment.

Multidrug resistant clinical strains isolated from tracheal aspirates of patients in Dhaka, Bangladesh

Background: Antimicrobial resistance poses a major threat in the treatment of respiratory disease especially in developing countries like Bangladesh. Multidrug-resistant (MDR) bacteria along with extremely drug resistant (XDR) bacteria have emerged as major clinical and therapeutic dilemma in the treatment of tracheal infections here. Thus, the aim of this study is to assess multidrug resistance among clinical strains isolated from tracheal aspirates of patients in Dhaka, Bangladesh.Methods: Total 200 clinical isolates from tracheal aspirates were identified and their antibiotic susceptibility profiles were evaluated by using the VITEK 2 system following the Clinical and Laboratory Standards Institute guidelines. Patient information on diagnosis, sex, age was obtained from hospital data.Results: Of 200 clinical isolates obtained, Pseudomonas aeruginosa was the most frequent pathogens (30.5%) followed by Acinetobacter baumannii (29%), Klebsiella pneumoniae (22.5%), Streptococcus pneumoniae (7.5%), Escherichia coli (5%), Staphylococcus aureus (2%), Proteus spp (1.5%), Enterobacter spp (1%), Citrobacter spp (0.5%), Providencia spp (0.5%). Of 20 different antibiotics tested, highest number of isolates (86%) showed resistance to third generation cephalosporin cefixime, however least number of isolates showed resistance to polymixin antibiotics- colistin (12.5%) and polymixin B (6%). Tracheal infection was found to be more prevalent in males rather than in females although this difference was not statistically significant. The prevalence of infections was highest among the patients of age-group (old adults) ≥60 years (61.5%). Of 200 clinical isolates, 43 (21.5%) were XDR and 125 (62.5%) were MDR bacteria. Of 200 clinical isolates, the synthesis of extended spectrum β-lactamases (ESBL) and carbepenemase were detected in 59 (29.5%) and 98 (49%) strains respectively.Conclusions: Tracheal infections caused by β-lactamase producing MDR and XDR pathogens among patients are high in Dhaka, Bangladesh. Therefore, there is an urgent need for constant surveillance and interventions in Bangladesh in order to prevent further spreading of those resistant organisms.

A Study on Adverse Drug Reaction Profile of 2nd Line Drugs in Multi Drug Resistant (MDR) and Extensively Drug Resistant (XDR) Tuberculosis Cases Registered under DR-TB Centre in a Tertiary Care Hospital

The emergence of drug resistant mycobacterium has become a significant public health problem creating an obstacle to effective tuberculosis (TB) control. Freedom from TB is possible with timely, regular, complete treatment, with assurance, prevention and management of side effects of antitubercular drugs. Present study was conducted to evaluate common and rare adverse drug reactions (ADR) of CAT IV and CAT V to analyse demographic, radiological and bacteriological profile and treatment outcome in MDR & XDR patients. We wanted to evaluate the common and rare adverse drug reactions of intensive phase treatment of Multi Drug Resistant Tuberculosis (MDR) and Extensively Drug Resistant Tuberculosis (XDR) as per WHO-UMC Causality Assessment Scale.METHODS76 patients of MDR and XDR Tuberculosis were admitted in DR-TB (Drug Resistant TB) centre, Burdwan Medical College and Hospital and the adverse drug reaction profile of 2nd line drugs were analysed during the intensive phase from April 2016 to September 2017 after fulfilling the inclusion and exclusion criteria. Treatment was given as per the guidelines of Revised National TB Control Program PMDT (Programmatic Management of Drug-Resistant TB).RESULTSAdverse drug reactions on GI system were nausea 73 patients (96.10%), vomiting 70 (92.10%), acidity 41 (53.9%), and sulphurous belching and hepatitis 1 (1.31%) each. Peripheral neuropathy, hearing deficit, myopathy, skin rashes, hepatitis, nephrotoxicity, cardiac toxicity and convulsion were also observed. In psychosis, 3 (3.95%) had depression and made suicidal attempt. 1 each (1.31%) in hallucination and paranoia. 5 patients (6.58%) had blurring of vision, 2 patients (3.95%) had redness of eyes and one (1.31%) had eye irritation. Reactions were common in first 60 days of the regimen and in patients with BMI ≤18.CONCLUSIONSVigilant monitoring is required for these patients during the initial period and sputum smear and culture conversion is very well correlated with clinical and radiological improvement.

Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil

BACKGROUND Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the number of new cases of multidrug resistant TB (MDR-TB), pre extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB) has increased considerably worldwide. OBJECTIVES Herein, using 156 M. tuberculosis isolates from 106 patients previously classified as MDR or pre-XDR or XDR isolates, we investigated the genetic mutation profiles associated with phenotypic resistances in patients with MDR-TB, pre-XDR-TB and XDR-TB, treatment outcomes and resistance evolution. METHODS Molecular analyses were performed by partial sequencing of the rpoB, katG, gyrA, gyrB, rrs genes and analysis of the fabG-inhA promoter region. Clinical, epidemiologic and demographic data were obtained from the TB Notification database system of São Paulo (TB-WEB) and the Information System for Special Tuberculosis Treatments (SITE-TB). FINDINGS Drug resistance was attributed to previously known mutations and a novel Asp449Val mutation in gyrB was observed in four isolates from the same patient. Ten patients had more than one isolate evaluated and eight of these patients displayed resistance progression. MAIN CONCLUSIONS The present study is the first to report the frequency of mutations related to second-line drug resistance in MDR-TB, pre-XDR-TB and XDR-TB isolates. The results could lead to the improvement of available technologies for the rapid detection of drug resistant TB.

To Study the Culture Conversion and XDR Suspect of Cat-IV Patients in DOTS Plus Site, S. N. Medical College, Agra

BACKGROUND - Multi-drug resistant tuberculosis (MDR-TB) is an increasing health problem in India. Globally,3.5% of new TB cases and 18% of previously treated cases had MDR/RR-TB.(GLOBAL TUBERCULOSIS REPORT 2018). As per the India TB Report 2018 the estimated incidence of  MDRTB/RR in India was approximately 1,47,000.Outcome of MDR patient put on MDR regime is poor due to high cost, long duration of treatment, and various side effect of second line ATT. MATERIAL & METHOD - Study comprised patients who were diagnosed MDR by culture and DST method from RNTCP accredited lab and initiated CAT–IV treatment in D.R.TB Centre, Department of Tuberculosis & Chest Diseases, S. N. Medical College, Agra. Detailed history and pre clinical evaluation as per guideline were done and at the end of 3rd ,4th,5th  and 6th month sputum  were send for AFB staining and culture. RESULT – Out of 109 MDR patient put on CAT-IV, culture conversion at 3rd month occur in 52(47.70%)  patients, at 4th month in 58 patients (53.21%), and in 5th month 66 patients (60.55%). Out of 109 MDR TB patients 12 patients (11.01%) were found suspected XDR. CONCLUSION – MDR TB is major health problem worldwide. Due to less efficacy and more side effect of second line ATT, longer duration of treatment, MDR TB is difficult to treat even with free supply of ATT through DOTS PLUS. Close attention is needed for early diagnosis  of MDR TB , and adequate clinically monitoring of during treatment is essential.

High Burden of Antibiotic Resistant Bacteria Isolated from Tracheal Culture in a Tertiary Care Institute

Introduction: Multidrug resistant bacteria is causing a veryserious problem in the proper treatment and management ofsick patients in ICU’s. Study aimed to find out antimicrobialsusceptibility pattern of bacterial isolates from trachealculture.Material and methods: This study was carried over a periodof 6 months from July to December 2017 in the departmentof microbiology. Total of 470 tracheal aspirates were studied.Each specimen was streaked on 5% sheep blood agar andMacConkey agar. After isolation and identification, sensitivityof selected organisms against different antibiotics was studiedResults: Out of 470 tracheal aspirates, 328 samples showedsingle bacterial growth, 76 were sterile; contaminants weregrown in 58 samples and in remaining 8 samples yeast weregrown. The incidence of positivity in our study was 83.8%,with gram negative bacteria outnumbering the gram positiveones. Of the 328 samples which showed bacterial growth,Acinetobacter spp 159(40.3) was the most common organismfollowed by Klebsiella pneumoniae 72(18.2), Pseudomonasspp 46(11.6), Escherichia coli 27(6.8), Staphylococcus aureus13(3.2), Klebsiella oxytoca 5(1.26), Enterococcus spp 3(0.76),Proteus spp, Citrobacter spp, Providencia stuartii 1(0.25)each. Also XDR (extensively drug resistant) bacteria wereisolated at a high frequency (67%) with Acinetobacter spp.being the most common 128(56.6)) followed by Klebsiellaspp. 39(17.2) Pseudomonas spp. 38(16.8), and E.coli 12(5.3).Conclusion: Gram negative were main organisms responsiblefor lower respiratory tract infections in hospitalized patientsand the majority of the isolates belong to XDR and MDRcategory.

Study of Resistance Pattern in Mucoid and Non Mucoid Isolates of Pseudomonas aeruginosa from Lower Respiratory Tract Specimens in a Tertiary Care Centre of Western U.P.

Introduction: Respiratory tract infections are a majorcause of ambulatory visits to the family practitioners.However, increase in antibiotic resistant strains of bacteriahas complicated the use of empiric therapy of this commonhuman disease. Among the Gram negative bacilli which arethe commonest pathogen of LRTI, Pseudomonas aeruginosais the most challenging, because of its high rate of resistanceto antimicrobial agent. Objectives: To obtain a comprehensiveinsight into the different resistant types: Multi drug resistant,Extensively drug resistant, Carbapenem Resistant, and MBLproducing Pseudomonas aeruginosa isolated from lowerrespiratory tract specimens and antibiotic susceptibilitydifferences between its mucoid and non mucoid colony typesbased on colony morphology.Material and Methods: A total of 926 lower respiratorytract samples consisting of sputum,pleural fluid,endotrachealaspirates,Bronchoalveolar lavage from patients of all ageand sex , suggestive of LRTI were included . FollowingDirect Gram staining and culture, the organisms wereisolated and Pseudomonas aeruginosa among them wereidentified by standard biochemical tests. The different typesof colony morphologies of Pseudomonas aeruginosa and theantimicrobial susceptibility differences amongst the differentcolony types were statistically analysed.Results: A total 175 (18.8%) Pseudomonas were isolatedfrom different Lower respiratory specimen Out of these, only103 Pseudomonas aeruginosa were found to be clinicallysignificant with 84.5% non mucoid and 11.4% mucoid colonytypes. The mucoid colony types showed high resistanceto Cefepime (35%), followed by Ceftazidime (20%) andAmikacin (15%).Conclusion: The high rate of MDR and XDR Pseudomonasaeruginosa also resistant to Carbapenems from this regionreveals a frightening scenario.As molecular methods are notavailable in majority of resource constrained laboratories ofIndia, the phenotypic methods should be regularly performedto detect the various beta-lactamases, besides strict infectioncontrol practices.

Analysis on drug resistance characteristics and risk factors for extensively drug resistant tuberculosis patients / 中华疾病控制杂志

@# Objective To analyze the drug resistance profile and risk factors for extensively drug resistant tuberculosis (XDR-TB) patients. Methods XDR-TB cases were identified by sixteen anti-TB drug susceptibility kits among inpatients with a diagnosis of laboratory-confirmed mycobacterium tuberculosis. Single-factor and Logistic analysis were used to analyze the risk factors for drug resistant of the first and second-line anti-TB drugs in XDR-TB patients. Results Resistant rate of rifampin, isoniazid and rifampicin were 100%, Resistant rate of streptomycin, rifampicin and dean, b sulfur isoniazid, levofloxacin and capreomycin were from 90% to 100%, resistant rate of kanamycin and amino salicylic acid were from 70% to 80%, resistant rate of amikacin from 60% to 70%, resistant rate of sulfur isoniazid was from 50% to 60%, resistant rate of ethambutol and moxifloxacin were from 40% to 50%, resistant rate of clarithromycin was from 10% to 20%, resistant rate of clofazimine 5.2%. 92.1% of XDR-TB patients were resistant to more than 10 anti-TB drugs, and the least of the patients were resistant to 6 anti-TB drugs.Logistic regression analysis showed the risk factors for XDR-TB first-and second-line anti-tb drugs included age ［20-40 year (OR=6.318, 95% CI:1.204-33.15, P=0.029;40-60 year (OR=4.772, 95% CI:0.973-23.392, P=0.054); 60 year (OR=41.366, 95% CI:2.909-588.265, P=0.006)］and anti-TB treatment history was retreatment(OR=28.013, 95% CI:3.357-233.766, P=0.002). Conclusions XDR-TB patients have serious drug resistance, but there were some drug treatable drug resistance types, and the risk factors mainly come from age and anti-TB treatment history.

A study on pre-XDR & XDR tuberculosis & their prevalent genotypes in clinical isolates of Mycobacterium tuberculosis in north India.

Background & objectives: Pre-extensively drug resistant (pre-XDR) and extensively drug resistant tuberculosis (XDR-TB) have been areas of growing concern, and are posing threat to global efforts of TB control. The present study was planned to study the presence of pre-XDR and XDR Mycobacterium tuberculosis and their genotypes in clinical isolates obtained from previously treated cases of pulmonary TB. Methods: A total of 219 isolates obtained from previously treated cases of pulmonary TB were subjected to first-line (streptomycin, isoniazid, rifampicin and ethambutol) and second-line (ofloxacin, kanamycin, capreomycin and amikacin) drug susceptibility testing on solid Lowenstein-Jensen medium by proportion method. Genotyping was done for pre-XDR and XDR-TB isolates using 12 loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR). Results: Multi-drug resistance was observed in 39.7 per cent (87/219) isolates. Pre-XDR and XDR M. tuberculosis isolates amongst 87 multi-drug resistant (MDR) TB isolates were 43 (49.4%) and 10 (11.4%), respectively. Two most dominant genotypes among pre-XDR and XDR M. tuberculosis isolates were Beijing and Delhi/CAS types. Interpretation & conclusions: Resistance to second-line anti-tubercular drugs should be routinely assessed in areas endemic for TB. Similar genotype patterns were seen in pre-XDR and XDR-TB isolates. Beijing and Delhi/CAS were predominant genotypes.

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011

INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. METHODS: Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. RESULTS: A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. CONCLUSION: This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

Drug resistance among extrapulmonary TB patients: Six years experience from a supranational reference laboratory.

Background & objectives: There is limited information available about the drug resistance patterns in extrapulmonary tuberculosis (EPTB), especially from high burden countries. This may be due to difficulty in obtaining extrapulmonary specimens and limited facilities for drug susceptibility testing. This study was undertaken to review and report the first and second-line anti-TB drug susceptibility patterns in extrapulmonary specimens received at the National Institute for Research in Tuberculosis (NIRT), Chennai, India, between 2005 and 2012. Methods: Extrapulmonary specimens received from referring hospitals were decontaminated and cultured using standard procedures. Drug susceptibility testing (DST) for Mycobacterium tuberculosis was done by absolute concentration or resistance ratio methods for the first and the second line anti-TB drugs. Results: Between 2005 and 2012, of the 1295 extrapulmonary specimens, 189 grew M. tuberculosis, 37 (19%) cases were multidrug resistant (MDR) while one was extensively drug resistant (XDR). Specimen-wise MDR prevalence was found to be: CSF-10 per cent, urine-6 per cent, fluids and aspirates-27 per cent, pus-23 per cent, lymph nodes-19 per cent. Resistance to isoniazid and ethionamide was found to be high (31 and 38%, respectively). Interpretation & conclusions: Drug resistance including MDR-TB was observed in a significant proportion of extrapulmonary specimens referred for DST. Access to culture and DST for extrapulmonary specimens should be expanded. Guidelines for MDR-TB management should have explicit sections on extra-pulmonary tuberculosis and training on laboratory techniques is urgently required.

Role of RNTCP in the management of MDR-TB.

Background: MDR-TB is defined as resistance to isoniazid and rifampicin with or without resistance to other drugs. India is one of the countries with largest burden of MDR TB in the world. Second line Anti-tuberculous therapy is now available for patients with MDR-TB under the RNTCP Category IV. but there are many challenges for MDR-TB control in india. This study was done to analyses the RNTCP data for MDR-TB maintained at a TU, in the city of Ahmedabad, Gujarat, and to compare it with the data available in literature. This study also aimed to identify challenges faced while treating MDR-TB and to address the same. Material and methods: We had restropectively analyzed 353 patients referred to the TU from the respective Direct Microscopy Center (DMC) with suspicion of MDR-TB during a period of January 2014 to December 2014. Results: Of the 353 suspected MDR_TB patients referred to the TU, 48 patients (13.597%) were diagnosed to have MDR-TB. Of these 48 patients, 46 patients had pulmonary TB (95.833%) and 2 patients had extra-pulmonary MDR-TB (4.166%). Of the 48 patients, 08 (16.67%) patients were transferred to their respective TU and 40 patients (83.33%) were enrolled for Cat IV from our TU. Of the 40 patients enrolled at our TU, 30 patients (75%) were continuing Category IV at the end of 2014 (25 were on intensive phase and 05 were on continuation phase), 03 patients (7.5%) died during treatment, 01 patient (2.5%) defaulted treatment, 05 patients (12.5%) refused treatment and 01 patient had XDR-TB (2.5%). Of the 40 patients, 05 patients (12.5%) had ofloxacin resistance. NO patient had intolerance to any oral or injectable ATT. None of the diagnosed MDR-TB patients had HIV co-infection Conclusion: Drug resistance in tuberculosis is a “man-made problem”. Anti-TB chemotherapy must be given optimally by (i) ensuring adequate absorption of drugs, (ii) timely diagnosis and management of drug toxicities and (iii) treatment adherence. To ensure that all patients get adequate treatment and to have a close follow-up of defaulters and patients who refuse treatment; we need to strengthen our existing management information system and also incorporate private sectors into our system.

First Susceptibility Testing of <i>Mycobacterium tuberculosis</i> for Second-line Anti-tuberculosis Drugs in Ghana

We performed drug susceptibility testing on first- and second-line drugs in <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>) for the first time in Ghana to obtain preliminary data on drug-resistant tuberculosis. Of 21 isolates (4 new cases and 17 treated cases), 5 (23.8%) were multi-drug resistant tuberculosis (MDR-TB) and 19 (90.5%) were resistant to at least one drug, but no extensively drug-resistant TB (XDR-TB) was identified. Since the target patients were Category II, IV or smear positive at follow-up microscopy, it is understandable that there were many drug-resistant TB cases. Six isolates were resistant to one or two second-line drugs, but the second-line drugs were not approved in Ghana. It is considered that the bacilli were imported from abroad. Preventing the import of drug-resistant TB bacilli is probably one of best ways to control TB in Ghana.

Bedaquiline: a new weapon against MDR and XDR-TB.

Multidrug-resistant tuberculosis (MDR-TB) is a global public health problem. It requires treatment with combination therapy consisting of four to six drugs including combinations of bactericidal and bacteriostatic drugs, usually for a period of 2 years. There is alarming rise in MDR and XDR-TB all over the world and better treatment options are needed to control the global MDR-TB and XDR-TB epidemic. Drugs which can shorten the treatment duration and which are free from serious adverse effects are urgently needed. Bedaquiline (TMC-207) is a newly FDA approved anti-TB drug, having unique mechanism of action i.e. causes inhibition of the proton pump activity of the ATP synthase in M. tuberculosis and targets the energy metabolism. It is found to active within macrophages, and is a promising agent in shortening the duration of anti- TB treatment. It is metabolized by CYP3A4, so interactions with inducers and inhibitors of this enzyme are expected. It has shown promising results in preclinical and clinical studies and it seems to be a good option for MDR and XDR-TB. Adverse effects reported in various studies were of mild nature except nausea which was the most commonly associated. Few cases of prolongation of QT intervals were reported, so it demands careful monitoring and use of bedaquiline as a reserve drug for patients in whom conventional regimens are not effective. Currently it is approved as part of combination therapy in adults of ≥18 year with pulmonary MDR-TB. Long term studies are needed to explore its full safety profile.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): Lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of ‘new smear-positives’ diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

Extensively drug-resistant tuberculosis in India: A review.

Background & objectives: Extensively drug resistant tuberculosis (XDR-TB) has become a new threat for the control of TB in many countries including India. Its prevalence is not known in India as there is no nation-wide surveillance. However, there have been some reports from various hospitals in the country. Methods: We have reviewed the studies/information available in the public domain and found data from 10 tertiary care centres in 9 cities in India. Results: A total of 598 isolates of XDR Mycobacterium tuberculosis have been reported in the studies included. However, the reliability of microbiological methods used in these studies was not checked and thus the XDR-TB data remained invalidated in reference laboratories. Interpretation & conclusions: Systematic surveillance and containment interventions are urgently needed.

Partial Extensively Drug Resistance (XDR) Tuberculosis in Children.

Emergence of resistance to two most potent first line anti-TB drugs i.e. isoniazid and rifampicin (multidrug resistant TB – MDR TB) is well known, but, the second line drugs used to treat MDR-TB are also showing resistance to the same strain of Mycobacteria (extensively drug resistance TB, XDR-TB). We report 3 children with partial XDR TB. Two responded to treatment while one was lost to follow-up.

Study of promoter and structural gene sequence of whiB7 in MDR and XDR forms of Mycobacterium tuberculosis / Estudio del promotor del ADN y la secuencia de genes estructurales de whiB7 en las formas MDR y XDR de Mycobacterium tuberculosis

Resistance phenomenon in M tuberculosis is mainly based on decreased permeability of the bacterial envelope and function of effluent pumps. The regulatory gene of the whiB7 transcription determines drug resistance in these bacteria. Increases in WhiB7 protein activity induce transcription of resistance genes leading to intrinsic multidrug resistance. The aim of this work was to evaluate the whiB7 gene sequence in susceptible, MDR and XDR clinical isolates of M tuberculosis in order to further design an inhibitor. Thirty-three clinical isolates of MTB identified as susceptible, MDR and XDR-TB were investigated by PCRfor sequencing of the entire promoter (429 bp), structural gene (279 bp) and the end of the upstream gene uvrD (265 bp). No differences were detected in the sequences of the structural gene in susceptible and MDR with XDR isolates and all of them terminated at TGA as stop codon. Examination of sequence profiles of the promoter part of whiB7 by several sets ofprimers proved that there were no differences between sequence ofsusceptible, MDR and XDR isolates by type strain (H37Rr). Furthermore, the structure of WhiB7 protein was studied in achieved sequences from clinical isolates. We found that the promoter and structural gene of whiB7 are highly conservative in clinical susceptible and resistant isolates. It is a key finding that would assist in the design ofan inhibitor for the WhiB7 protein in all clinical forms in further studies.

El fenómeno de resistencia en M tuberculosis se basa principalmente en la disminución de la permeabilidad de la envoltura bacterial y la función de las bombas efluentes. El gene regulador de la trascripción de whiB7 determina la resistencia al medicamento en estas bacterias. Los aumentos en la actividad de proteína de WhiB7 inducen la trascripción de genes de resistencia que llevan a la resistencia intrínseca de multimedicamentos. El objetivo de este trabajo fue evaluar la secuencia de genes de whiB7 en aislados clínicos susceptibles MDR y XDR de M tuberculosis para mejorar el diseño de un inhibidor. Treinta y tres aislados clínicos de MTB identificados como MDR y XDR-TB susceptibles, fueron investigados por PCR para la secuenciación del promotor entero (429 bp), el gene estructural (279 bp) y el extremo del uvrD gen arriba (265 bp). No se detectó diferencia alguna en las secuencias del gene estructural en aislados susceptibles, MDR y XDR, terminando todos ellos en TGA como codón de terminación. El examen de perfiles de la secuencia de la parte de promotor de whiB7 por varios conjuntos de iniciadores (primers), demostró que no había ninguna diferencia entre la secuencia de aislados susceptibles MDR y XDR por tipo de cepa (H37Rv). Además, la estructura de la proteína de WhiB7 se estudió en secuencias logradas de aislados clínicos. Se encontró que el promotor y el gene estructural whiB7 son muy conservadores en aislados clínicos susceptibles y resistentes. Se trata de un hallazgo clave que ayudaría a designar un inhibidor para la proteína WhiB7 en todas las formas de este patógeno en estudios ulteriores.