Primary bacillary resistance in multidrug-resistant tuberculosis and predictive factors associated with cure at a referral center in São Paulo, Brazil / Resistência bacilar primária em tuberculose multidrogarresistente e fatores preditivos associados à cura, em um centro de referência da cidade de São Paulo

ABSTRACT Objective: To identify transmitted or primary resistance among cases of multidrug-resistant tuberculosis and predictive factors for cure in multidrug-resistant tuberculosis after the first treatment. Method: Descriptive study of a cohort from 2006 to 2010, in a reference unit of tuberculosis in São Paulo, Brazil. The data were obtained by the revision of medical records. Clinical criteria were used to classify transmitted and acquired resistance. Extended primary resistance was also defined, in this study, as cases initially treated with a standardized scheme, but with no therapeutic success, and the pre-treatment drug susceptibility test (DST) showed presence of resistance. Results: 156 patients with multidrug-resistant tuberculosis and their respective sputum samples were eligible for the study. Only 7% of the patients were positive for the human immunodeficiency virus (HIV). Previous treatment occurred in 95% of the sample. The cure rate after the first treatment was 54%. The median bacteriological conversion time of those who healed was one month. Bacillary resistance was considered acquired resistance in 100 (64%) and transmitted resistance in 56 (36%). By logistic regression, patients who presented primary multidrug-resistant tuberculosis (odds ratio-OR = 6,29), without comorbidity (OR = 3,37) and with higher initial weight (OR = 1.04) were associated with cure after the first treatment. Conclusion: The early detection of bacillary resistance and appropriate treatment are in favor of healing. Thus, it is crucial to know exactly the primary resistance rate avoiding the use of inadequate treatments, amplification of bacillary resistance and its transmission.

RESUMO Objetivo: Identificar resistência transmitida ou primária entre casos de tuberculose multidrogarresistente e fatores preditivos associados à cura da tuberculose multidrogarresistente após o primeiro tratamento. Método: Estudo descritivo de uma coorte de 2006 a 2010, em uma unidade de referência em tuberculose no estado de São Paulo, Brasil. Os dados foram obtidos por meio de revisão de prontuários médicos. Critérios clínicos e laboratoriais foram utilizados para classificar resistência transmitida e adquirida. Resistência primária estendida por definição, neste estudo, abrange também casos inicialmente tratados com esquema padrão, porém sem sucesso terapêutico, e teste de sensibilidade colhido pré-tratamento demonstrou presença de resistência. Resultados: Foram elegíveis para o estudo 156 doentes com tuberculose multidrogarresistente e suas respectivas amostras de escarro. Apenas 7% dos doentes eram positivos ao vírus da imunodeficiência humana (HIV). Tratamento prévio aconteceu em 95% da amostra. A taxa de cura após o primeiro tratamento foi de 54%. A mediana do tempo de conversão bacteriológica dos que se curaram foi de um mês. Dos 156 doentes, 100 (64%) e 56 (36%) foram classificados como resistência adquirida e resistência transmitida, respectivamente. Pela regressão logística, os doentes que se apresentaram com tuberculose multidrogarresistente primária (razão de chance - RC = 6,29), sem comorbidade (RC = 3,37) e com maior peso inicial (RC = 1,04) foram associados ao desfecho cura ao final do primeiro tratamento. Conclusão: A detecção precoce da resistência bacilar e o tratamento adequado favorecem a cura. Dessa forma, é indispensável conhecer com exatidão a taxa de resistência primária evitando o uso de tratamentos inadequados, a ampliação da resistência bacilar e a sua transmissão.

Factores asociados a tuberculosis multidrogorresistente primaria en pacientes de Callao, Peru / Factors associated with primary multidrug-resistant tuberculosis in patients from Callao, Peru

Introducción:En el Perú, Lima y Callao constituyen regiones con riesgo alto de transmisión activa de tuberculosis. La tuberculosismultidrogorresistente se presenta en el 5,54% de los casos nuevos de tuberculosis pulmonar (TB MDR primaria) en Lima y Callao. Susfactores de riesgo no han sido estudiados en pacientes del Callao.Objetivos:Determinar los factores de riesgo para TB MDR primariaen pacientes atendidos en centros de salud de Callao, durante los años 2009- 2010.Diseño:Estudio caso control.Lugar:Centros deSalud de Callao.Participantes:Participaron 29 pacientes con TB MDR primaria y 37 con tuberculosis sensible, según los registros delPrograma de Control de Tuberculosis y las historias clínicas ubicadas en los centros de salud.Intervenciones:Toda la información fueobtenida de fuentes secundarias. En el análisis bivariado se calculó el OR de cada covariable. Para el cálculo de los OR multivariadosse utilizó modelos de regresión logística.Principales medidas de resultados:Factores de riesgo para TB MDR.Resultados:En elanálisis bivariado, el haber tenido contacto con pacientes TB MDR o XDR fue un factor de riesgo significativo (OR: 5,56; IC95%: 1,05a 29,27); lo mismo se demostró en el análisis multivariado (OR: 14,56; IC95%: 1,52 a 139,54). Además, en el análisis multivariado, lavariable edad≥40 años mostró ser un factor protector significativo (OR: 0,94; IC95%: 0,90 a 0,99).Conclusiones:El tener contactocon pacientes TB MDR/XDR fue factor de riesgo y una edad menor a 40 años un factor protector para contraer TB MDR primaria enlos pacientes del Callao estudiados.

Introduction: Lima and Callao are high risk areas for tuberculosis active transmission in Peru. Multidrug-resistant tuberculosis represents 5.54 per cent of the new cases of pulmonary tuberculosis (primary MDR-TB) in Lima and Callao. Involved risk factors have not been studied in patients from Callao. Objectives: To determine risk factors for primary MDR-TB in patients attending health care facilities in Callao during 2009-2010. Design: Case-control study. Setting: Health care facilities from Callao. Participants: Twenty nine primary MDR-TB patients and 37 drug-sensitive TB patients were studied through assessment of the Tuberculosis Control Program Registries and healthcare facilities’ clinical records. Interventions: Information was obtained from secondary sources. Odds-ratios were calculated by bivariate analysis. Logistic regression models were used to calculate multivariate odd-ratios. Main outcome measures: Risk factors for primary MDR-TB. Results: Prior contact with a MDR-TB or XDR-TB patient was a significant risk factor (OR: 5.56; 95 per cent CI: 1.05-29.27) in bivariate analysis; the same was found in multivariate analysis (OR: 14.56; 95 per cent CI: 1.52–139.54). Being 40 or more years old was a significant protective factor in multivariate analysis (OR: 0.94; 95 per cent CI: 0.90–0.99). Conclusions: Previous contact with a MDR-TB or XDR-TB patient was a risk factor, and being 40 or more years old was a protective factor for primary MDR-TB in Callao patients studied.

Extrapulmonary multidrug resistant tuberculosis presenting as chest wall abscess - A rare case report.

Summary: Even though the prevalence of pulmonary drug resistant tuberculosis is showing an increasing trend globally, only a few case reports of extrapulmonary tuberculosis caused by drug resistant mycobacteria have been documented over the last decade. Extrapulmonary tuberculosis is not infrequent and may cause considerable morbidity and mortality. Tuberculous abscess over chest wall is commonly due to the spread from an adjacent affected lymph node group. Multidrug resistance poses a great challenge to the physicians in managing such a condition and significantly affects the prognosis. Here we report a rare presentation of multidrug resistant tuberculosis as anterior chest wall abscess in a young male.

Smoking effects on clinical manifestations and drug resistance patterns in pulmonary TB patients

Considering the rising trend of tuberculosis [TB] and cigarette smoking, an evaluation of the clinical manifestations and drug resistance patterns in TB patients with regard to smoking status seemed beneficial. Clinical manifestations and drug resistance patterns were studied in 872 new pulmonary TB patients classified as non-smokers, ever-smokers, and passive smokers during 3 years at the National Research Institute of Tuberculosis and Lung Disease. Both univariate and multivariate analyses were performed. Ever-smokers were mostly male [p<0.001], Iranian [p<0.001], and drug and alcohol users [p<0.001]. They were found to have a longer patient delay [15.9 versus 8.7 and 6.3 days, p=0.008], shorter diagnostic delay [106.8 versus 132.6 and 156 days, p=0.01], greater weight loss [p=0.01], and higher sputum expectoration [p<0.001]. Notably, the degree of smear positivity was associated with smoking [p<0.001] in both univariate and multivariate analyses. No statistical significance was found for the aforementioned factors among non-smokers and passive smokers. Some of the clinical manifestations of TB are significantly different with regard to the patients' smoking status.The degree of sputum smear positivity for acid fast bacilli was higher and patient delay was longer in ever-smoker patients

Papel da tuberculose domiciliar no surgimento da tuberculose multirresistente / The role of household contact in the appearance of multidrug-resistant tuberculosis

INTRODUÇAO: A tuberculose multirresistente é uma preocupação em todo o mundo. A identificação de fatores de risco associados pode contribuir para o seu controle. OBJETIVO: Avaliar se o contato com tuberculose domiciliar é fator de risco para tuberculose multirresistente. MÉTODO: Estudo caso-controle de base populacional de modo retrospectivo. Foi considerado multirresistente o bacilo resistente a pelo menos rifampicina+isoniazida, e tuberculose sensível o caso no qual houvesse sido feito o primeiro tratamento num período semelhante ao primeiro tratamento do caso com tuberculose multirresistente, mas que estivesse curado no momento da entrevista. Os casos foram selecionados através dos testes de sensibilidade realizados no Laboratório Central do Estado do Ceará de 1990 a 1999, pelo método das proporções. Os controles foram selecionados entre os bacilíferos do livro de registro do Programa de Controle da Tuberculose, em período semelhante. Foi pesquisada a história de tuberculose na família. Os casos de Tuberculose na família foram divididos em 03 subgrupos: tuberculose curada, tuberculose abandonada e tuberculose multirresistente. RESULTADOS: 266 casos de tuberculose multirresistente foram diagnosticados. Identificamos 153 pacientes, dos quais, 19 foram excluídos. O grupo de casos e controle foi de 134 e 185 pacientes, respectivamente. Através do teste exato de Fisher não foi encontrada associação entre tuberculose multirresistente e contato com tuberculose na família (p=0,1190). Estudando os subgrupos, encontramos que o contato com pacientes curados de tuberculose estava associado com tuberculose sensível (p<0,0001), enquanto que o abandono do tratamento da tuberculose na família e a tuberculose multirresistente na família estavam associados com a tuberculose multirresistente, p<0,0160 e p<0,0300 respectivamente. CONCLUSAO: A existência na família de casos de tuberculose multirresistente e de casos de tuberculose com abandono de tratamento é fator de risco para tuberculose multirresistente e, portanto, constitui problema de saúde pública.

Fatores associados aos tratamentos inadequados em grupo de portadores de tuberculose multirresistente / Factors associated with inadequate treatment in a group of patients with multidrug-resistant tuberculosis

INTRODUÇAO: A tuberculose multirresistente é uma ameaça ao controle da tuberculose em todo o mundo. Tratamento inadequado é freqüentemente apontado como fator de risco para tuberculose multirresistente. OBJETIVO: Identificar fatores associados ao tratamento inadequado em portadores de tuberculose multirresistente. MÉTODO: Foram levantados e identificados os testes de sensibilidade para tuberculose, realizados no Laboratório Central do Estado do Ceará de 1990 a 1999. Foi realizado um estudo retrospectivo e prospectivo, em grupo de portadores de tuberculose multirresistente, comparando as características dos pacientes com tratamento adequado com as dos com tratamentos inadequados. Foi considerado multirresistente o bacilo resistente a pelo menos rifampicina + isoniazida e utilizado o método das proporções. RESULTADOS: Dos 1.500 testes de sensibilidade realizados, 266 eram multirresistentes. Destes, identificaram-se apenas 153 pacientes, dos quais 19 foram excluídos, restando, no estudo, 134 pacientes. Pela análise univariada os fatores associados significativamente ao tratamento inadequado foram: não-adesão ao tratamento, pobreza extrema, intolerância medicamentosa, falha no atendimento, falta de medicação, dois ou mais tratamentos anteriores, lesões radiológicas bilaterais e grandes cavidades pulmonares. Foi encontrada ainda associação (p < 0,001) de alcoolismo e/ou tabagismo com a não-adesão. Na análise multivariada, permaneceram associados ao tratamento inadequado: dois ou mais tratamentos anteriores (p < 0,0001, OR = 5,9; IC 95 por cento: 2,5-13,7), grandes cavidades pulmonares (p < 0,0217, OR = 2,7; IC 95 por cento: 1,2-6,1) e lesões radiológicas bilaterais (p < 0,0226, OR = 3,2; IC 95 por cento: 1,4-7,4). CONCLUSAO: Neste estudo, observou-se que os fatores associados aos tratamentos inadequados são de grande abrangência. Deve existir uma tentativa para controlar melhor a doença, principalmente nos pacientes em retratamento e nos portadores de grandes cavidades e/ou lesões bilaterais na radiografia torácica.

Risk factors for acquired multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) is a severe and feared problem, that is difficult to control and has shown a tendency to increase worldwide. OBJECTIVE: To analyze the risk factors for acquired MDR-TB. CASUISTIC AND METHODS: A retrospective population-based case-control study was conducted. A bacillus was considered multidrug-resistant whenever it was resistant at least to rifampin (RFP) + isoniazid (INH), and a case was considered as sensitive tuberculosis (TB) if it had undergone the first treatment during a similar period as the first treatment of an MDR-TB case, but was cured at the time of the interview. Case selection was made based on the list of Sensitivity Tests (ST) performed at the Central Public Health Laboratory of the State of Ceará, from 1990 through 1999. The Proportion Method was used to investigate resistance to the six antituberculosis drugs (isoniazid, rifampin, pyrazinamide, ethambutol, ethionamide, streptomycin) used as the standard treatment in Brazil. Controls were selected from the registry of the TB Control Program. Univariate and multivariate analysis were performed, with p < 0.05 considered significant. RESULTS: Out of the 1,500 STs performed during the studied period, 266 strains were multidrug-resistant; 153 patients were identified, 19 of which were excluded. The Group of Cases comprised 134 patients, and the Group of Controls comprised 185. Multivariate analysis helped to detect the following risk factors: lack of home sewer system, alcoholism + smoking, number of previous treatments, irregular treatment, and lung cavities. CONCLUSION: These five factors are important for the development of acquired MDR-TB, and an attempt to neutralize them might contribute to control TB.

Drug defaulters in pulmonary tuberculosis

To recognize the factors behind premature stoppage of anti-tuberculous drugs in drug defaulters. Cases of pulmonary tuberculosis who discontinued anti-tuberculous drugs for atleast on month, developed tuberculosis again and anti-tuberculous drugs had to be resumed were labelled as drug defaulters and studied in details. In-patients of Tuberculosis Hospital, Khulna [A Divisional Tuberculosis Hospital], Bangladesh. One hundred and seventy nine cases of drug defaulters who discontinued anti-tuberculous drugs earlier were studied during the period January 1996 to June 1998. Clinical characteristics, anti-tuberculous and associated drugs prescribed and reasons behind premature stoppage of drugs in drug defaulters. The age of 179 [males 119 and females 60] cases ranged from 11-65 years with a mean +/- SDof 35.8 +/- 12.7 years. 30.3% of the male cases were farmers. 167 [93.3%] cases initially started a good short course regimen, but discontinued later on. 110 [61.5%] cases discontinued after one month and further 42 [23.5%] cases within another one month. Maximum 72 [40.2%] number of cases discontinued therapy due to financial constraints. Other reasons for defaulting were, poor briefing in 41 [22.9%], ignorance 31 [17.3%], adverse effects of drugs 18 [10.1%], apparent subjective improvement 11 [6.1%] and scarcity of drugs in 6 [3.4%]. Since drug defaulters may play a vital role in the emergence of multi-drug resistant tuberculosis, the reasons behind premature discontinuation of drugs need to be identified and appropriately dealt with. Since cost is the major factor, anti-tuberculous drugs should be made available free of cost under direct supervision, if possible and the cases should also be reviewed periodically

Nodal radiotherapy in refractory tuberculosis in an AIDS patients

A 25-year-old female with transfusion-associated acquired immunodeficiency syndrome (AIDS) treated with zidovudine (AZT) developed cervical lymph node enlargement. The histological study disclosed granulomas and the culture revealed M. tuberculosis. The patient was treated with isoniazid, rifampicin and pirazynamide and the lymphadenomegaly resolved. Five years later, with a CD4 cell count of 245, the lymph node enlargement reappeared, the biopsy and special studies confirming tuberculosis (TB). She was then given cirpofloxacin, azithromicin, ethambutol, amikacin and pirazyn amide without success. In two instances the enlarged nodes were surgically removed. Facing progressive osbtruction of both the airway and the esophagus, localized radiotheraphy (1800 cGy in nine fractions) to the right aspect of the neck was delivered with dramatic resolution of the node elargement; however, dissemination of the infection leading to a severe lung infiltration and respiratory failure ended the life of the patient