[Adverse drug reactions in multidrug-resistant tuberculosis]. / Reacciones adversas a fármacos en tuberculosis multirresistente.

Multidrug-resistant tuberculosis (MDRTB) poses difficulties in diagnosis and treatment, including increased frequency of adverse reactions to antituberculosis drugs (ADRAs), which compromise the effectiveness of treatment. This is specially complicated in the treatment of patients co-infected with HIV which includes the antiretroviral therapy plus the treatment of eventual comorbidities. A total of 121 MDRTB patients, 87 HIV-negative and 34 HIV positive, assisted in the Hospital F. J. Muñiz, Buenos Aires, during the period 2003-2007 were retrospectively studied. The incidence of ADRAs among the two groups of patients was compared. All the patients with adherence to treatment (no more than one abandon, recovered) were included in the study. Antituberculosis drugs used were: ethambutol, pyrazinamide, ofloxacin, moxifloxacin, cycloserine, ethionamide, PAS, streptomycin, kanamycin, amikacin and linezolid. The emergence of ADRAs and the proportion of severe reactions attributed to antituberculosis drugs were similar in both groups: 44.8% in HIV negative and 44.1% in HIV positive, but it was observed an additional 23.5% of adverse reactions to antiretroviral therapy in the second group. There were differences in the type of reactions and time of occurrence between the two groups. One HIV positive patient died of epidermolysis. The proportion of adverse reactions in HIV/AIDS patients increased 50% when those attributed to antiretroviral treatment were included. We conclude that the studied population showed a frequency of ADRAs higher than it would be expected in the treatment of susceptible TB, but there was no difference in its frequency among HIV-negative and positive patients.

[Multidrug-resistant tuberculosis in AIDS patients at the beginning of the millennium]. / Tuberculosis multirresistente en pacientes con SIDA a comienzos del milenio.

AIDS-related multidrug-resistant tuberculosis (MDRTB) emerged during the 90s in several countries around the world. In Argentina, the most notorious outbreak was documented in the Hospital Muñiz, which is still undergoing its aftermaths. In order to evaluate the situation in this hospital regarding MDRTB, we analysed clinical, demographic and epidemiological traits of the 53 male MDRTB-aids patients admitted during 2001-2003 at a ward especially dedicated to their isolation. Patients' mean age was 32 years, 70% lived in Buenos Aires suburbs. A history of illicit drug users or imprisonment was recorded in 68% and 26% of the patients, respectively. Severe immunodepression (CD4+ count < 100/microl) was found in 88% of the patients and 58% died. Mortality was associated with non-adherence to treatment and co-morbidity, but not with the genotype of the "M" strain, responsible for the original outbreak. Of 40 cases available for restriction fragment length polymorphism (RFLP), 29 (72.5%) resulted in cluster. RFLP patterns of 24 matched the "M" genotype. In this study, resistance to 5 or 6 drugs was found to be an indicator of disease due to the "M" strain. The "M" genotype associated significantly to previous admission at the Hospital Muñiz or imprisonment. In brief, 14 years after the detection of the first MDRTB-aids case, we report here the persistence and predominance of the original outbreak strain at the hospital. Stronger TB infection control measures are urgently needed in hospitals and jails in order to strengthen the declining trend of the MDRTB observed in our country towards the end of the last decade.

[Infectiousness and virulence of multidrug-resistant and drug susceptible tuberculosis in adult contacts]. / Infecciosidad y virulencia de la tuberculosis multirresistente o sensible a drogas antituberculosas en contactos adultos.

Patients carrying multidrug-resistant (MDR) strains of Mycobacterium tuberculosis have been considered traditionally as presenting a diminished epidemiological risk according to animal experimentation results. The experience obtained from the MDRTB/AIDS related epidemics showed MDRTB transmission to immunocompetent health care workers and adults close contacts. In this retrospective study, the infectiousness (measured as the frequency of intradermal test with PPD 2TU over 10 mm) and virulence (cases bacteriologically confirmed) among close contacts of patients with MDR and susceptible TB were evaluated. A total of 97 contacts of 37 MDRTB patients vs. 356 contacts of 100 patients with susceptible TB were studied. No statistical differences were found in PPD 2 UT positivity and TB cases between both contact groups, nor in relation to HIV seropositivity of index cases. According to these observations, MDR strains of M. tuberculosis present similar infectiousness and virulence compared with susceptible strains.

[Evaluation of the control measures adopted against an epidemic of AIDS-related multidrug-resistant tuberculosis in a Latin-American hospital]. / Evaluación de las medidas de control adoptadas frente a la epidemia de tuberculosis multirresistente asociada al sida en un hospital hispanoamericano.

BACKGROUND: Since 1992 AIDS-related multidrug-resistant tuberculosis (MDRTB) has been detected among patients admitted to the Hospital Muñiz in Buenos Aires (Argentina). The aim of the present study was to evaluate the effectiveness of the control measures adopted against the nosocomial spread of MDRTB/AIDS, which affected 803 patients between 1992 and 2002. METHODS: An action plan was applied that included bacilloscopy screening on admission, isolation rooms for patients with TB/AIDS, an isolation ward for patients with MDRTB/AIDS, a radiometric method for the diagnosis of multidrug-resistance, a reserve supply of second line drugs, and respiratory protection for health care workers. RESULTS: Between 1995 and 2002, a statistically significant decreasing trend in cases of MDRTB/AIDS and admissions for TB/AIDS was observed (33.9% vs 80.5%). Mortality among patients with MDRTB/AIDS also significantly decreased. Bacilloscopy screening allowed the diagnosis of 63.4% of patients admitted with TB/AIDS. Respiratory isolation facilities and effective treatment of patients with MDRTB diagnosed through the radiometric method were progressively implemented. Admission of patients with AIDS showed no significant variations throughout the study period. The CD41 count of patients requiring admission did not vary significantly. CONCLUSION: The nosocomial epidemic curve of MDRTB in patients with AIDS significantly decreased, despite the persistence of susceptible patients with low CD41 levels. The decreasing tendency of MDRTB/AIDS cases could be attributed to the impact of the control measures implemented.

Reacciones adversas a fármacos en tuberculosis multirresistente / Adverse drug reactions in multidrug-resistant tuberculosis

La tuberculosis multidrogorresistente (TBMDR) plantea dificultades diagnósticas y terapéuticas; entre ellas, la mayor frecuencia de reacciones adversas a fármacos antituberculosos (RAFAs), que comprometen la eficacia del tratamiento. Más complicado es el panorama del tratamiento en pacientes con la coinfección HIV a los que a la terapia antirretroviral se suma el de las eventuales comorbilidades. Se estudiaron retrospectivamente 121 pacientes: 87 HIV negativos y 34 HIV positivos con TBMDR asistidos en el Hospital F. J. Muñiz en el período 2003-2007, comparándose la incidencia de reacciones adversas entre ambas poblaciones. Fueron incluidos todos los pacientes con adherencia al tratamiento (no más de un abandono recuperado). Los fármacos antituberculosos empleados fueron: etambutol, pirazinamida, ofloxacina, moxifloxacina, cicloserina, etionamida, PAS, estreptomicina, kanamicina, amikacina y linezolid. La aparición de RAFAs así como la proporción de reacciones graves atribuidas a drogas antituberculosas fue similar en los dos grupos (44.8% en HIV negativos y 44.1% en HIV positivos, a quienes se agregó un 23.5% adicional de RAFAs por el tratamiento antirretroviral). Se observaron algunas diferencias en el tipo de reacciones y en el momento de aparición. Un paciente HIV positivo falleció debido a epidermolisis. La proporción de reacciones adversas en HIV/sida aumentó un 50% al considerar también las atribuidas al tratamiento antirretroviral. Se concluye que la población estudiada presentó RAFAs por encima de lo esperable en tuberculosis sensible, pero no se observaron diferencias en la frecuencia de aparición entre pacientes HIV negativos y positivos.

Multidrug-resistant tuberculosis (MDRTB) poses difficulties in diagnosis and treatment, including increased frequency of adverse reactions to antituberculosis drugs (ADRAs), which compromise the effectiveness of treatment. This is specially complicated in the treatment of patients co-infected with HIV which includes the antiretroviral therapy plus the treatment of eventual comorbidities. A total of 121 MDRTB patients, 87 HIV-negative and 34 HIV positive, assisted in the Hospital F. J. Muñiz, Buenos Aires, during the period 2003-2007 were retrospectively studied. The incidence of ADRAs among the two groups of patients was compared. All the patients with adherence to treatment (no more than one abandon, recovered) were included in the study. Antituberculosis drugs used were: ethambutol, pyrazinamide, ofloxacin, moxifloxacin, cycloserine, ethionamide, PAS, streptomycin, kanamycin, amikacin and linezolid. The emergence of ADRAs and the proportion of severe reactions attributed to antituberculosis drugs were similar in both groups: 44.8% in HIV negative and 44.1% in HIV positive, but it was observed an additional 23.5% of adverse reactions to antiretroviral therapy in the second group. There were differences in the type of reactions and time of occurrence between the two groups. One HIV positive patient died of epidermolysis. The proportion of adverse reactions in HIV/AIDS patients increased 50% when those attributed to antiretroviral treatment were included. We conclude that the studied population showed a frequency of ADRAs higher than it would be expected in the treatment of susceptible TB, but there was no difference in its frequency among HIV-negative and positive patients.

Estudio multicéntrico, abierto y prospectivo con cefadroxilo de pacientes con infecciones en tejidos blandos, residentes en grandes ciudades de la Argentina / Multicentric, open and prospective trial related to the adhesion to the treatment with cefadroxil of patients with infections of soft tissues living in peripheric and/or marginal areas of large cities of the Argentine Republic

Desde las últimas décadas se observa un incrmento cada vez mayor de resistencia microbiana a los quimioterápicos ocasionada por malas prescripciones, falta de adherencia al tratamiento, automedicación, entre otros. El cefadroxilo, comparte las cualidades de la cefalexina, pero además las concentraciones séricas y urinarias mas sostenidas permiten el tratamiento de infecciones con una a dos dosis diarias. Dicha particularidad farmacocinética otorga un beneficio para el paciente que permite asegurar la adherencia al tratamiento.

Tuberculosis multirresistente en pacientes con SIDA a comienzos del milenio / Multidrug-resistant tuberculosis in AIDS patients at the beginning of the millennium

La tuberculosis multirresistente (TBMR) asociada al sida emergió durante los años 90 en varios países del mundo. En Argentina, el brote más importante se originó en el Hospital Muñiz y susconsecuencias persisten hasta ahora. Con el objeto de evaluar la situación de la TBMR en este hospital, analizamoslas características clínico-demográfico-epidemiológicas de los 53 pacientes masculinos con TBMR/sida internados por primera vez en el trienio 2001-2003 con relación al genotipo del polimorfismo de longitud de fragmentos de restricción (RFLP) IS6110 de los aislamientos. La edad promedio de los pacientes fue 32 años, 37 (70%) residían en el conurbano bonaerense, 36 (68%) eran usuarios de drogas ilícitas y 14 (26.4%) tenían antecedentes carcelarios. El 88% presentó grave inmunodepresión (CD4+<100/μl) y el 58.5% falleció. La mortalidadse asoció a baja adherencia al tratamiento y a comorbilidades, pero no a enfermedad por Mycobacteriumtuberculosis cepa “M”, causante del brote original. De los 40 casos analizados por RFLP, 29 (72.5%) conformaron clusters y 24 presentaban el genotipo “M”. La resistencia a 5 o 6 drogas resultó un indicador de enfermedad por esa cepa. El genotipo “M” se asoció significativamente a internaciones previas en el Hospital Muñiz oencarcelamiento. En síntesis, 14 años después de ocurrido el primer caso de TBMR/sida, se constata la persistenciay predominancia en el hospital de la cepa responsable del brote. Se requiere una intensificación de las medidas de control de la diseminación institucional de la tuberculosis para consolidar la tendencia decrecientede la TBMR observada en el país en la última década

Aids-related multidrug-resistant tuberculosis (MDRTB) emerged during the 90s in several countries aroundthe world. In Argentina, the most notorious outbreak was documented in the Hospital Muñiz, which is still undergoing its aftermaths. In order to evaluate the situation in this hospital regarding MDRTB, we analysed clinical,demographic and epidemiological traits of the 53 male MDRTB-aids patients admitted during 2001-2003 at award especially dedicated to their isolation. Patients’ mean age was 32 years, 70% lived in Buenos Aires suburbs. A history of illicit drug users or imprisonment was recorded in 68% and 26% of the patients, respectively.Severe immunodepression (CD4+ count <100/μl) was found in 88% of the patients and 58% died. Mortality wasassociated with non-adherence to treatment and co-morbidity, but not with the genotype of the “M” strain, responsible for the original outbreak. Of 40 cases available for restriction fragment length polymorphism (RFLP),29 (72.5%) resulted in cluster. RFLP patterns of 24 matched the “M” genotype. In this study, resistance to 5 or 6 drugs was found to be an indicator of disease due to the “M” strain. The “M” genotype associated significantlyto previous admission at the Hospital Muñiz or imprisonment. In brief, 14 years after the detection of the firstMDRTB-aids case, we report here the persistence and predominance of the original outbreak strain at the hospital.Stronger TB infection control measures are urgently needed in hospitals and jails in order to strengthenthe declining trend of the MDRTB observed in our country towards the end of the last decade

Deltametrina no tratamento das ectoparasitoses: estudo multicêntrico realizado a nível nacional / Deltametrin in the treatment of ectoparasitosis: multicenter study performed at national level

A notável recorrência de pediculose, com seu típico padräo endemo-epidêmico, principalmente nos meios escolares, é bem conhecida e também observada em nosso país. O desenvolvimento de resistência por parte dos parasitos aos inseticidas clorados é considerado a causa mais provável deste fenômeno. Portanto, vem daí nosso interesse em avaliar a atividade terapêutica da deltametrina, novo ectoparasiticida altamente potente e praticamente atóxico, ativo sobre todos os artrópodes. Com este objetivo foi realizado um estudo multicêntrico em vários centro urbanos, totalizando 563 pacientes com as seguintes parasitoses: 540 com pediculose do couro cabeludo, 2 com pediculose pubiana, 1 caso com ambos os tipos de pediculose e 20 casos de escabiose. O tratamento consistiu na aplicaçäo tópica de loçäo de deltametrina a 0,2%, nos pacientes infestados de piolhos, à noite, com lavagem dos cabelos e couro cabeludo com shampoo contendo deltametrina, na manhä seguinte. A erradicaçäo dos parasitos foi obtida em 99,45% dos pacientes tratados. A tolerância à deltametrina foi excelente. Concordantes com os resultados obtidos por outros pesquisadores, os nossos demonstram uma atividade extraordinária da deltametrina sobre P. capitis, P. pubis e S. scabiei, levando à cura em praticamente todos os casos

Infecciosidad y virulencia de la tuberculosis multirresistente o sensible a drogas antituberculosas en contactos adultos / Infectiousness and virulence of multidrug-resistant and drug susceptible tuberculosis in adult contacts

Patients carrying multidrug-resistant (MDR) strains of Mycobacterium tuberculosis have been considered traditionally as presenting a diminished epidemiological risk according to animal experimentation results. The experience obtained from the MDRTB/AIDS related epidemics showed MDRTB transmission to immunocompetent health care workers and adults close contacts. In this retrospective study, the infectiousness (measured as the frequency of intradermal test with PPD 2TU over 10 mm) and virulence (cases bacteriologically confirmed) among close contacts of patients with MDR and susceptible TB were evaluated. A total of 97 contacts of 37 MDRTB patients vs. 356 contacts of 100 patients with susceptible TB were studied. No statistical differences were found in PPD 2 UT positivity and TB cases between both contact groups, nor in relation to HIV seropositivity of index cases. According to these observations, MDR strains of M. tuberculosis present similar infectiousness and virulence compared with susceptible strains (AU)#S#a

Mejoria pronóstica de pacientes con tuberculosis multirresistente asociada a enfermedad por HIV/SIDA tratados con terapia antirretroviral de alta eficacia / Improved prognosis in HIV/AIDS related multi-drug resistant tuberculosis patients treated with highly active antiretroviral therapy

A prospective cohort study was carried out in patients assisted in the F. J. Muniz Infectious Disease Hospital, with the aim of determining the effectiveness of highly active antiretroviral therapy (HAART) implemented as soon as the sputum smear microscopy became negative (1 to 3 months) in the survival improvement of HIV/AIDS related multidrug-resistant tuberculosis patients. The cohort was recruited from June 1997 to February 1999 and compared with a pre-HAART control group that consisted of 43 patients. The follow-up of the patients was terminated June 2000. A total of 48 patients who received HAART precociously were included. The mortality rate in this group was 31.2 per cent and the survival time of deceased patients 15.8 +/- 8.5 months. The T lymphocytes CD4+ count was initially 40.1 +/- 30.2/microL, while at the end of the observation period it was 140.4 +/- 73.04/microL and 79.1 per cent of these patients presented undetectable viral load. In the control group the overall mortality was 90.7 per cent and the survival time of deceased patients 8.95 +/- 3.72 months. We conclude that the early anti-retroviral therapy, together with the treatment of the multidrug-resistant tuberculosis and of other AIDS associated diseases represent a useful approach to achieve a longer and better survival in these severely immunodepressed patients.