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Aims Methods Results Conclusions The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs.A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020.Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016–1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145–2.913), existing liver disease (OR = 2.464, 95% CI: 1.822–3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681–16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs.Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre‐existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity. [ABSTRACT FROM AUTHOR]

Aims: To explore the potential value of serum glutamate dehydrogenase (GLDH), ferrochelatase (FECH), heme oxygenase‐1 (HO‐1) and glutathione‐S‐transferase‐α (GST‐α) as diagnostic biomarkers for liver injury caused by antituberculosis drugs. Methods: We established a rat model of isoniazide‐induced liver injury and recruited 122 hospitalized tuberculosis patients taking antituberculosis drugs. We detected the concentration of GLDH, FECH, HO‐1 and GST‐α by enzyme‐linked immunosorbent assay. GraphPad Prism8 and SPSS 26.0 were used for statistical analysis. Results: In the rat model, serum GLDH concentration gradually increased during isoniazid (INH) administration, while serum FECH, HO‐1 and GST‐α concentrations significantly increased after INH administration was stopped. The receiver operating characteristic curve showed that the areas under the curve (AUCs) of serum GLDH and FECH for the diagnosis of anti‐tuberculosis (TB) drug‐induced liver injury (anti‐TB‐DILI) were 0.7692 (95% confidence interval [CI] 0.5442‐0.9943) and 0.7284 (95% CI 0.4863‐0.9705) and the diagnostic accuracies were 81.25% and 78.79%, respectively. In clinical research, the AUCs of GLDH and FECH were 0.9124 (95% CI 0.8380‐0.9867) and 0.6634 (95% CI 0.5391‐0.7877), and the optimal thresholds were 10.40 mIU/mL and 1.304 ng/mL, respectively. The diagnostic accuracy, specificity and positive predictive value (PPV) of GLDH were 82.61%, 79.38% and 47.22%. We performed a joint diagnostic test for GLDH and FECH. The diagnostic accuracy (90.43%), specificity (91.75%) and PPV (65.21%) of serial tests were better than for GLDH and FECH alone. Conclusions: GLDH in the diagnosis of liver injury induced by anti‐TB drugs has high sensitivity, but low specificity and low PPV. The combination of GLDH and FECH could significantly improve the specificity, PPV and diagnostic accuracy, and reduce the false‐positive rate of anti‐TB‐DILI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oral anti-tuberculosis drugs have serious systemic side effects after removal of bone and joint tuberculosis lesions. It is imperative to seek a sustained-release drug system that can not only save drug dosage, but also increase local drug concentration in lesions and reduce systemic blood drug concentration. OBJECTIVE: To observe the sustained-release properties of polymethyl methacrylate bone cement loaded with antituberculosis drugs pyrazinamide, capreomycin, moxifloxacin, and amikacin in PBS artificial simulated body fluid. METHODS: Polymethyl methacrylate bone cement Palacos R powder was mixed with antituberculosis drugs pyrazinamide, capreomycin, moxifloxacin, and amikacin in the proportion of 40 g:1.5 g and 40 g:2.5 g, respectively. The 20 mL of liquid monomer were added to prepare 8 groups of anti-tuberculosis drugloaded bone cement standard specimens, with 5 samples in each group. In the control group, 40 g bone cement powder and 20 mL liquid monomer were mixed in the same way to prepare 5 standard bone cement samples without drugs. The drug was soaked in PBS and placed in 37 ℃ constant temperature water bath oscillator. The extract was taken at set time points. The drug concentration of each group was determined by high performance liquid chromatography. RESULTS AND CONCLUSION: (1) The time of the lowest drug release concentration in PBS artificial simulated body fluid of pyrazinamide 1.5 g group, pyrazinamide 2.5 g group, capreomycin 1.5 g group, capreomycin 2.5 g group, moxifloxacin 1.5 g group, moxifloxacin 2.5 g group, amikacin 1.5 g group and amikacin 2.5 g group was 45, 60, 150, 150, 120, 120, 60 and 90 days, respectively. Among these groups, the capreomycin 1.5 g group, capreomycin 2.5 g group, moxifloxacin 1.5 g group, moxifloxacin 2.5 g group, and amikacin 2.5 g group had a longer drug release period, while the control group had no drug release. (2) It is concluded that polymethyl methacrylate bone cement loaded with capreomycin (1.5 g and 2.5 g), moxifloxacin (1.5 g and 2.5 g), and amikacin (2.5 g) has a long release cycle and good release performance. BACKGROUND: Oral anti-tuberculosis drugs have serious systemic side effects after removal of bone and joint tuberculosis lesions. It is imperative to seek a sustained-release drug system that can not only save drug dosage, but also increase local drug concentration in lesions and reduce systemic blood drug concentration. OBJECTIVE: To observe the sustained-release properties of polymethyl methacrylate bone cement loaded with antituberculosis drugs pyrazinamide, capreomycin, moxifloxacin, and amikacin in PBS artificial simulated body fluid. METHODS: Polymethyl methacrylate bone cement Palacos R powder was mixed with antituberculosis drugs pyrazinamide, capreomycin, moxifloxacin, and amikacin in the proportion of 40 g:1.5 g and 40 g:2.5 g, respectively. The 20 mL of liquid monomer were added to prepare 8 groups of anti-tuberculosis drugloaded bone cement standard specimens, with 5 samples in each group. In the control group, 40 g bone cement powder and 20 mL liquid monomer were mixed in the same way to prepare 5 standard bone cement samples without drugs. The drug was soaked in PBS and placed in 37 ℃ constant temperature water bath oscillator. The extract was taken at set time points. The drug concentration of each group was determined by high performance liquid chromatography. RESULTS AND CONCLUSION: (1) The time of the lowest drug release concentration in PBS artificial simulated body fluid of pyrazinamide 1.5 g group, pyrazinamide 2.5 g group, capreomycin 1.5 g group, capreomycin 2.5 g group, moxifloxacin 1.5 g group, moxifloxacin 2.5 g group, amikacin 1.5 g group and amikacin 2.5 g group was 45, 60, 150, 150, 120, 120, 60 and 90 days, respectively. Among these groups, the capreomycin 1.5 g group, capreomycin 2.5 g group, moxifloxacin 1.5 g group, moxifloxacin 2.5 g group, and amikacin 2.5 g group had a longer drug release period, while the control group had no drug release. (2) It is concluded that polymethyl methacrylate bone cement loaded with capreomycin (1.5 g and 2.5 g), moxifloxacin (1.5 g and 2.5 g), and amikacin (2.5 g) has a long release cycle and good release performance. [ABSTRACT FROM AUTHOR]

Erythroderma or exfoliative dermatitis is a cutaneous disease characterized by erythema and scaling affecting more than 90% of body surface area. This can be resulted from malignancy, drug eruption, idiopathic and underlying disease like psoriasis, atopic dermatitis and seborrhoic dermatitis. Patients with HIV/AIDS are prone to drug eruption. A 50 year old man presented to our outpatient clinic with exfoliative scaly skin all over his body after consuming anti-TB therapy. He was diagnosed with lung tuberculosis (TB), human immunodeficiency virus (HIV) infection stage 3. Histopathological examination revealed mild acanthosis and spongiosis in the epidermis, dropping melanin, lymphocyte, histiocyte and perivascular polymorphonuclear (PMN) leukocytes in the dermis. We treated this patient by discontinuing his anti-TB drug, the suspected causative drug, hydrating with intravenous fluid, placing him in warm room and covering him with thin blanket. He was treated with methylprednisolone IV 62.5 mg/24 hours for 5 days, cetirizine tablet 10 mg once daily, topical vaselin applicative twice per day, gentamicin ointments applied on the erosive area twice daily and extra egg white diet 1700 kcal. Our patient's condition improved after discontinuing anti-TB drugs and receiving systemic corticosteroid as well as topical emollient. Erythroderma due to the first line antitubercular drug is uncommon. It can lead to a serious potentially life threatening problem. Therefore early recognition, early diagnosis and early treatment determine the outcome. [ABSTRACT FROM AUTHOR]

ABSTRACT Macozinone (MCZ; PBTZ169) is a first-in-class antituberculosis clinical-stage benzothiazinone-based drug candidate. Although its efficacy and safety have been strongly proven in several preclinical and clinical studies, the physicochemical and pharmacokinetic properties specific to MCZ required further optimization. Accordingly, this study aimed to evaluate the pharmacokinetics of MCZ administered as extended-release (ER) tablets F2 and F6 compared to immediate-release (IR) dispersible tablets for oral suspension. Oral absorption of MCZ from ER tablets was significantly different from that of IR tablets after a single oral dose in Beagle dogs in both fasted and fed states. In addition, food directly affects the bioavailability of MCZ from ER tablets but does not affect it from IR tablets. The high values of relative bioavailability of the prolonged-release tablets F2 and F6 compared to the IR tablets may indicate an indirect confirmation of their gastroretentive properties. Taken together, pharmacokinetic parameters have demonstrated that these MCZ oral formulations not just enhance drug bioavailability but may also improve regimen adherence by reducing MCZ dose frequency and reducing the development of drug resistance. IMPORTANCE Macozinone (MCZ) is the newest first-in-class clinical-stage benzothiazinone-based drug candidate for the treatment of tuberculosis. Yet, the extremely low oral bioavailability of MCZ, a major problem in clinical trials, needed to be addressed, and we are pleased to present our attempts to solve this issue. We report that extended-release tablets of MCZ significantly increased key pharmacokinetic parameters in the preclinical setting. We suggest that these MCZ oral formulations not just enhance drug bioavailability but may also improve regimen adherence by reducing MCZ dose frequency and reducing the development of drug resistance.

The study was conducted to examine the protective potential of ethanol seed extract (ESEt) of Avena fatua (wild oats) against antituberculosis drug (ATD)-induced hepatotoxicity in rats. Four groups of rats (n=6) were used. Of which, three groups were given ATD (Rimstar 900mg/15kg) and divided them into hepatotoxic control (distilled water 1mL/kg), positive control (silymarin 200mg/kg) and test group (ESEt 800mg/kg). The fourth was the normal control group treated only with distilled water (1mL/kg). All treatments were orally administered in their respective groups for 26 days. On the 27thday, rats were decapitated. Body and liver weights were measured whereas serum and liver samples were collected for biochemical and histopathological assessments. The rats treated with silymarin and ESEt showed a significant decrease (p<0.05, 0.01& 0.0001) in liver enzymes including alanine & aspartate transaminases, gamma glutamyltranspeptidase and alkaline phosphatase. ESEt also improved total bilirubin (particularly indirect bilirubin), total protein, albumin and low density lipoprotein cholesterol levels in test group. The hepatoprotective ability of extract was also evident by histological study of liver tissues of the test group that showed normal architecture as compared to liver of ATD treated hepatotoxic control group displayed heterogeneous hepatocytes, inflamed central vein, fatty deposits, enlarged sinusoid, Kupffer's cells infiltration, hypertrophy and fibrosis. In conclusion, ESEt of A.fatua is hepatoprotective in nature which may be due to the presence of total phenols and flavonoids already reported from the seeds of this plant. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In this study, we aimed to investigate antituberculosis drug susceptibility of the Mycobacterium tuberculosis complex isolates, between 2014 and 2017 retrospectively. METHODS: The specimens from patientswith a pre-diagnosis of tuberculosis were stained with Ehrlich-Ziehl-Neelsen method and evaluated microscopically. After then, specimens were inoculated onto Löwenstein-Jensen medium and BACTEC MGIT 960 (Becton Dickinson, USA) automated culture system. If bacterial growth was detected, Mycobacterium tuberculosis complex typing was done and antituberculosis drug susceptibilities for streptomycin, isoniazid, rifampicin and ethambutol were tested at BACTEC MGIT 960 (Becton Dickinson, USA). RESULTS: Totally 78 Mycobacterium tuberculosis complex isolates were enrolled in the study. A single strain for each patient was taken to the study. Resistance rates of isoniazid, streptomycin and ethambutol were determined as 1.2%, 8.9% and 1.2%, respectively and no resistance to rifampicin was detected. 82% of the isolates were susceptible to all drugs and the highest resistance among antimycobacterial drugs was determined for streptomycin. DISCUSSION AND CONCLUSION: The single drug resistance that determined in our study was lower than 2017 tuberculosis report however it is known that there might have been differences between the regions.

Mycobacterium tuberculosis (Mtb) caused an estimated 10 million cases of tuberculosis and 1.2 million deaths in 2019 globally. The increasing emergence of multidrug-resistant and extensively drug-resistant Mtb is becoming a public health threat worldwide and makes the identification of anti-Mtb drug targets urgent. Elongation factor G (EF-G) is involved in tRNA translocation on ribosomes during protein translation. Therefore, EF-G is a major focus of structural analysis and a valuable drug target of antibiotics. However, the crystal structure of Mtb EF-G1 is not yet available, and this has limited the design of inhibitors. Here, we report the crystal structure of Mtb EF-G1 in complex with GDP. The unique crystal form of the Mtb EF-G1-GDP complex provides an excellent platform for fragment-based screening using a crystallographic approach. Our findings provide a structure-based explanation for GDP recognition, and facilitate the identification of EF-G1 inhibitors with potential interest in the context of drug discovery.

Antituberculosis (anti‐TB) drug‐induced hepatotoxicity may be related to the excessive reactive oxygen species induced by hepatotoxic metabolites. Antioxidant activity involves the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway. The BTB domain and CNC homologue 1 (Bach1) may compete with Nrf2 for binding to transcriptional enhancers. Elimination of Bach1‐mediated transcriptional repression depends on nuclear exporter exportin 1 (Xpo1). Thus, Xpo1 may indirectly affect antioxidant activity. The present study aimed to examine the role of tag single‐nucleotide polymorphisms in XPO1 in Chinese anti‐TB treatment patients. A 1:2 matched case‐control study was conducted using 314 anti‐TB drug‐induced hepatotoxicity cases and 628 controls. After correcting for weight and hepatoprotectant use, conditional logistic regression analysis showed that patients carrying the AA genotype of rs4430924 in XPO1 were at higher risk of anti‐TB drug‐induced hepatotoxicity than those carrying the GG genotype based on the subgroup of probable cases (adjusted OR, 1.938; 95%CI, 1.035‐3.628; P =.039), and marginally significant differences were also found under the recessive model (P =.048) and the additive model (P =.047). Based on this 1:2 matched case‐control study, the AA genotype of rs4430924 in XPO1 may be associated with higher risk of anti‐TB drug‐induced hepatotoxicity in Chinese anti‐TB treatment patients. Further studies in larger and more varied populations are required to validate this relationship. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI).Methods: Cases of M. tuberculosis PJI documented in 7 referral French centers were retrospectively reviewed. Data were collected from medical files on a standardized questionnaire. We performed a literature review using the keywords 'prosthetic joint', and 'tuberculosis'.Results: During years 1997-2016, 13 patients (8 males, 5 females, median age 79 years [range, 60-86]) had documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to diagnosis was 9 years [0.4-20]. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months [6-32]). Nine patients underwent surgery: debridement (n = 4), resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. Seventeen additional cases of documented M. tuberculosis PJI have been reported, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement, 86% (19/22) with revision arthroplasty, and 81% (17/21) with resection (NS).Conclusions: M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment. [ABSTRACT FROM AUTHOR]

Emergence of drug-resistance to antituberculosis agents is a global challenge that requires development of novel drugs, active against resistant Mycobacterium tuberculosis strains. One of the tasks of drug development is to determine the mechanism of resistance of the pathogen to the drug candidate. The mycobacterial MmpS5-MmpL5 efflux system can provide resistance to a wide range of antibiotics, including bedaquiline, clofazimine, thiacetazones, azoles, and imidazo[1,2-b][1,2,4,5]tetrazines. We were able to construct a recombinant M. smegmatis Δmmp5 strain, which carries a deletion within the mmpS5-mmpL5 operon and is hypersensitive to imidazo[1,2-b][1,2,4,5]tetrazines. Comparing the sensitivity of M. smegmatis mc2 155 and M. smegmatis Δmmp5 to candidate antimycobacterials can be used as a test system for determining the possible role of the MmpS5-MmpL5 efflux system in developing drug resistance at early screening stages. [ABSTRACT FROM AUTHOR]

Résumé Il est primordial de maintenir une recherche active dans le domaine de l’infectiologie compte tenu des phénomènes de résistance et de la grande variabilité des germes, particulièrement de certains types de virus. Les thérapeutiques anti-infectieuses doivent être savamment orchestrées et contrôlées afin de maîtriser la propagation des infections dans le monde. Summary It is essential to continue active research in the field of infectious diseases, given resistance phenomena and the high variability of germs, particularly of certain types of virus. Anti-infective therapies must be carefully managed and controlled in order to curb the spread of infections in the world. [ABSTRACT FROM AUTHOR]

An HPLC-MS/MS method for quantitative determination of the new antituberculosis drug PBTZ169 in blood serum, urine, and feces using perindopril as an internal standard was developed and validated. The method was selective, specific, accurate, and precise. Calibration curves were linear in the ranges 2 - 2,000, 5 - 3,000, and 100 - 10,000 ng/mL for blood serum, urine, and feces, respectively, with correlation coefficients >0.99. The detection limits of PBTZ169 were 1, 2.5, and 50 ng/mL for serum, urine, and feces, respectively. The limits of quantitation were 2 ng/mL in serum; 5, urine; and 100, feces. [ABSTRACT FROM AUTHOR]

• Compound 1A was synthetized and analyzed by spectroscopic (FT-IR, FT-Raman and NMR) techniques and DFT computations. • The molecular interactions were investigated by FMOs, RDG, ELF, MEP and Hirshfeld surface analyses. • In vitro and vivo activity experiments were evaluated to confirm its anti-tuberculosis activity. • Drug-likeness analysis was conducted for compound 1A. Herein, a novel Mtb LeuRS inhibitor compound 1A was synthesized and crystallized. And compound 1A was found to be active targeting Mtb LeuRS with IC 50 values =21.37 ± 0.2 μM and against Mtb H37Ra with MIC values =18.85 ± 0.2 μM. Therefore, compound 1A was selected to conduct deeply research on molecular structure information and interaction with Mtb LeuRS. Firstly, quantum chemical calculation was used to predict spectral properties of the compound 1A , such as, structure optimization, IR, Raman, 1HNMR and 13CNMR. What's more, Hirshfeld surface analysis was used to explain multiple interactions of compound 1A , and 2D fingerprint was used to quantify intermolecular interactions accurately. Molecular electrostatic potential (MEP), reduced density gradient (RDG) and Electron localization function (ELF) were used to describe the relevant sites that can form electrostatic interaction. FMOs were used to determine chemical stability of compound 1A. At last, molecular docking were conducted to elaborate the interactions between Mtb LeuRS and compound 1A , and ADMET prediction indicates compound 1A has perfect druggability and pharmacokinetic properties. [Display omitted] [ABSTRACT FROM AUTHOR]

Adverse drug reaction and resistance to antituberculosis drugs remain the causes of tuberculosis therapeutic failure. This research aimed to find the combination effect of standard antituberculosis drugs with Hibiscus sabdariffa L., Kaempferia galanga L., and Piper crocatum N.E. Br against multi-drug resistant (MDR) Mycobacterium tuberculosis isolates. Two MDR strains (i.e., isoniazid/ethambutol resistant and rifampicin/streptomycin resistant) of M. tuberculosis were inoculated in Löwenstein-Jensen medium containing a combination of standard antituberculosis drugs and ethanolic extracts of H. sabdariffa calyces, K. galanga rhizomes, and P. crocatum leaves using various concentration combinations of drug and extract. The colony numbers were observed for 8 weeks. The effect of the combination was analyzed using the proportion method which was calculated by the mean percentage of inhibition reduction in a number of colonies on drug-extract containing medium compared to extract-free control medium. The results showed that all three plant extracts achieved good combination effects with rifampicin against the rifampicin/streptomycin resistant strain. Antagonistic effects were, however, observed with streptomycin, ethambutol and isoniazid, therefore calling for caution when using these plants in combination with antituberculosis treatment. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) in elderly is a worldwide problem. Objective: To evaluate differences in clinical, radiological, laboratory features, adverse antituberculosis drug reactions and TB-related mortality in elderly and young pulmonary TB patients. Results: The study included analysis of the medical history, chest radiographic and laboratory findings in 124 elderly and 124 young pulmonary TB patients, with mean age of 60.5 ± 9.1 and 31.6 ± 10.8 years, respectively (p

Introdução: Atendendo às características do Mycobacterium tuberculosis (MT), o tratamento da tuberculose (TB) é feito com uma associação de vários fármacos, por um período de tempo alargado (≥ a 6 meses), cada um com potencial para provocar reacções adversas (RA). Estas podem acompanhar-se de significativa morbilidade e comprometer o tratamento da TB. Objectivos: Determinar a incidência, a gravidade e os factores de risco das principais RA induzidas pelos antibacilares, em doentes internados com TB em tratamento. Material e métodos: Análise retrospectiva dos registos clínicos dos doentes internados no Serviço de Pneumologia III do Hospital de Pulido Valente com tuberculose activa, medicados com antibacilares, durante o período de Abril de 1999 a Julho de 2007. Foram registadas as RA que resultaram em modificação ou descontinuação do tratamento ou que foram a causa de internamento. As características demográficas e os dados clínicos dos doentes foram usados como variáveis independentes. A relação entre variáveis independentes e a frequência e gravidade das RA foi feita através de uma análise multivariada, utilizando um modelo de regressão logística. Os dados foram analisados pelo teste t de Student, one-way ANOVA e regressão logística. A aplicação utilizada para a análise estatística foi o programa SPSS (Statistical Package for the Social Sciences), versão 15.0. Resultados: Dos 1400 doentes internados e tratados por TB activa entre 1999 e 2007, 175 doentes (12,5%), 118 homens e 57 mulheres, apresentaram pelo menos uma RA induzida pelos antibacilares, num total de 192 eventos. A hepatotoxicidade foi a RA mais prevalente (83/47,4%), seguindo-se a reacção cutânea (55/31,4%) e a intolerância gastrintestinal (24/13,7%). Em 76 doentes (43,4%) as RA causaram o prolongamento do internamento. Constatou-se que a demora média do grupo de doentes com RA foi de 58,4 dias. Esta demora média apresentou diferenças estatisticamente significativas (p< 0,001) em relação à demora média dos doentes sem RA, que foi de 26 dias. Os fármacos mais implicados foram a isoniazida (62,2%) e a rifampicina (51,9%). Dos 134 casos em que foi possível caracterizar a gravidade das RA, em 106 casos (79%) houve necessidade de suspensão do fármaco. A relação causal fármaco-RA foi definitiva em 23 casos (17%). Dos 13 doentes (9,6%) que faleceram, em 6 (4,4%) a RA esteve directamente implicada na causa de morte. A ocorrência de qualquer RA foi associada ao alcoolismo (risco relativo [RR] de 3,0; 95% de intervalo confiança [IC], 1,1-7,9) e aos níveis de CD4 < 350 células/ mm3 ([RR] de 2,6 ; [IC], 1,4-5). No modelo preditivo, as reacções hepáticas foram associadas à ocorrência de hepatites virais B e/ou C ([RR] de 2,5; [IC], 1,2-5,1) e aos níveis de CD4 < 350 células/mm3 ([RR] de 5,5; [IC], 1,6-18,6). Conclusões: Os antibacilares estão associados a um número significativo de RA que podem condicionar grande morbilidade, prolongamento do internamento e mesmo alguma mortalidade. Os nossos resultados mostram que o alcoolismo e os níveis de CD4 Introduction: Given Mycobacterium tuberculosis’s characteristics, the treatment of tuberculosis (TB) infection is administered over a long period of time (for six months or more) with a combination of several drugs which could cause adverse reactions (AR). These can cause significant morbidity and compromise tuberculosis treatment regimens. Aim: To determine the incidence and severity of and risk factors for major adverse reactions to antituberculosis drugs in in-hospital patients treated for active tuberculosis. Methods: Retrospective analysis of clinical records of patients admitted to Pulido Valente Hospital (Pulmonology Unit III) with active TB treated with anti-tuberculosis agents April 1999 to July 2007. Adverse reactions resulting in modification or discontinuation of treatment or hospital admission were recorded. Patients’ demographic characteristics and clinical data were used as independent variables. The relationship between independent variables and the frequency and severity of AR was studied using multivariate analysis using a logistic regression model. The data were analysed using the Student t test, one-way ANOVA and logistic regression. Statistical analysis was performed using the SPSS (Statistical Package for the Social Sciences) version 15.0. Results: We recorded 1400 in-hospital patients treated for active TB 1999 to 2007, of which 175 patients (12.5%), 118 male and 57 female, had at least one AR induced by antituberculosis agents, to a total of 192 events. Hepatotoxicity was the most prevalent AR (83/47.4%), followed by skin reactions (55/31.4%) and gastrointestinal intolerance (24/13.7%). In 76 patients (43.4%) AR caused prolonged hospital stay. Statistically significant differences (p