RESUMEN
Non-tuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis-complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide, a rising prevalence and significance of non-tuberculous mycobacterioses is recognized. The present recommendations summarise current aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of non-tuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.
Asunto(s)
Técnicas de Diagnóstico del Sistema Respiratorio/normas , Infectología/normas , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/terapia , Guías de Práctica Clínica como Asunto , Neumología/normas , Medicina Basada en la Evidencia , Alemania , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Resultado del TratamientoRESUMEN
Reported food-related symptoms of patients may sometimes be misleading. A correct delineation of food-induced symptoms is often difficult and various differential diagnoses have to be considered. We report on two cases of food-induced, predominantly respiratory symptoms (in one case life-threatening) in children with food allergy. First, a two-year-old boy with no history of allergies and suspected foreign body aspiration which was finally diagnosed as an anaphylactic reaction to fish, and secondly a six-year-old girl with multiple food allergies and allergic asthma who during an electively performed oral food challenge developed severe respiratory distress, drop in blood pressure, and asphyxia not due to an anaphylactic reaction but due to choking on an unnoticed sweet. These two cases represent challenging, life-threatening symptom constellations involving food-induced reactions in food allergic children, reminding us to question first impressions.
Asunto(s)
Obstrucción de las Vías Aéreas/diagnóstico , Anafilaxia/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Cuerpos Extraños/diagnóstico , Aspiración Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Obstrucción de las Vías Aéreas/etiología , Anafilaxia/complicaciones , Broncoscopía , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Cuerpos Extraños/complicaciones , Humanos , Masculino , Aspiración Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/etiologíaRESUMEN
Nontuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide a rising prevalence and significance of nontuberculous mycobacterioses can be recognized. The present recommendations summarise actual aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of nontuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/prevención & control , Micobacterias no Tuberculosas , Guías de Práctica Clínica como Asunto , Neumología/normas , Antibacterianos , Alemania , HumanosRESUMEN
OBJECTIVE: Interferon-gamma release assays (IGRA) are well established for diagnosing latent tuberculosis infection in adults. Evidence for their diagnostic relevance in children is still insufficient. The aim of this study was to evaluate the sensitivity and specificity of IGRA compared to the tuberculin skin test (TST) in a local population of children and adolescents presenting to our lung clinic with a specialised outpatient department. METHODS: Records from all patients evaluated for tuberculosis at our centre between 2009 and 2011 were analysed retrospectively. Complete data sets were available for 80 children and adolescents (age 3 months to 17 years) in the following diagnostic groups: active pulmonary tuberculosis (MTB, n = 13), latent tuberculosis infection (LTBI, n = 15) and controls with tuberculosis exposure (n = 40), non-tuberculous mycobacterial disease (NTM, n = 2) or other lung diseases (n = 10). RESULTS: All 13 patients with MTB were positive on both IGRA and TST. Among the LTBI patients, 14 /15 had a positive IGRA and 14 /15 a positive TST result. In the control group 0 /52 exceeded the IGRA cut-off, while three patients had a positive TST due to a cross reaction with BCG or NTM. DISCUSSION: IGRA and TST results are highly correlated in paediatric patients with active or latent tuberculosis. IGRA sensitivity was comparable to that of the TST with a higher specificity as expected. The importance of IGRA in the hospital setting to guide diagnostic algorithms in an unselected population should be further evaluated in prospective studies.
Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/sangre , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/inmunología , Prueba de Tuberculina/métodos , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Tuberculosis Latente/sangre , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
The "International Standards for Tuberculosis Care" (ISTC) were developed by the World Health Organisation (WHO) and others to provide internationally agreed and, if possible, evidence-based standards for tuberculosis care including the care by private providers who are not part of national tuberculosis programmes or health-care systems. Hence, the ISTC primarily address resource-restrained countries with high tuberculosis prevalence. In this article, the German translation of the 21 standards from 2009 is presented - addressing diagnostic and therapeutic standards, co-infection (especially with HIV) and public-health issues. The accompanying comments show how these standards have to be modified for Germany due to the medical resources available here and country-specific characteristics respectively.
Asunto(s)
Guías de Práctica Clínica como Asunto , Neumología/normas , Tuberculosis/terapia , Alemania , Humanos , InternacionalidadRESUMEN
Several new international recommendations have been published since the German Central Committee against Tuberculosis (DZK) published its recommendations for drug treatment of tuberculosis (TB) in 2001 and for chemoprevention of latent tuberculosis infection (LTBI) in 2004. These international publications have been integrated in the present new recommendations which describe both the treatment of active TB and preventive treatment, pointing out specific adaptations for Germany. Separate sections deal with the current management of mono-, poly-, and multiresistance or drug intolerance, of TB in children, of different forms of extrapulmonary TB, of LTBI and of special situations such as HIV infection, renal or hepatic insufficiency, infection following BCG instillation in bladder cancer or in case of adverse drug reactions. The following aspects differ from the previous recommendations: A three-drug regimen for the so-called fully susceptible minimal TB is no longer recommended in adults. A dosage of 15 mg/kg body weight of ethambutol for adults is regarded as sufficient. Four secondline drugs (supplemented by pyrazinamide, where appropriate) are recommended for multidrug-resistant tuberculosis (MDR-TB). MDR-TB should be treated over a period of at least 20 months, with an injectable drug administered for a minimum of 8 months (initial phase). Ciprofloxacine and ofloxacine are no longer used to treat TB. It is also recommended to offer an HIV test to all TB patients to complement antiretroviral therapy, if necessary, and to adapt the antituberculous therapy accordingly.
Asunto(s)
Antituberculosos/administración & dosificación , Antituberculosos/clasificación , Neumología/normas , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & control , Adulto , Niño , Alemania , Humanos , Prevención Secundaria , Tuberculosis/diagnósticoRESUMEN
The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dosage recommendations for children. No pharmacokinetic studies for these revised dosages are available for children <2 years. The aim of the study was to document the pharmacokinetics of the first-line anti-TB agents in children <2 years of age comparing previous and revised WHO dosages of isoniazid (INH; 5 versus 10 mg/kg/day), rifampin (RMP; 10 versus 15 mg/kg/day), and pyrazinamide (PZA; 25 versus 35 mg/kg/day) and to investigate the effects of clinical covariates, including HIV coinfection, nutritional status, age, gender, and type of tuberculosis (TB), and the effect of NAT2 acetylator status. Serum INH, PZA, and RMP levels were prospectively assessed in 20 children <2 years of age treated for TB following the previous and the revised WHO dosage recommendations. Samples were taken prior to dosing and at 0.5, 1.5, 3, and 5 h following dosing. The maximum drug concentration in serum (C(max)), the time to C(max) (t(max)), and the area under the concentration-time curve (AUC) were calculated. Eleven children had pulmonary and 9 had extrapulmonary TB. Five were HIV infected. The mean C(max) (µg/ml) following the administration of previous/revised dosages were as follows: INH, 3.19/8.11; RMP, 6.36/11.69; PZA, 29.94/47.11. The mean AUC (µg·h/ml) were as follows: INH, 8.09/20.36; RMP, 17.78/36.95; PZA, 118.0/175.2. The mean C(max) and AUC differed significantly between doses. There was no difference in the t(max) values achieved. Children less than 2 years of age achieve target concentrations of first-line anti-TB agents using revised WHO dosage recommendations. Our data provided supportive evidence for the implementation of the revised WHO guidelines for first-line anti-TB therapy in young children.
Asunto(s)
Antituberculosos/farmacocinética , Isoniazida/farmacocinética , Guías de Práctica Clínica como Asunto/normas , Pirazinamida/farmacocinética , Rifampin/farmacocinética , Tuberculosis/tratamiento farmacológico , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Área Bajo la Curva , Preescolar , Coinfección , Femenino , Infecciones por VIH , Humanos , Isoniazida/administración & dosificación , Isoniazida/uso terapéutico , Masculino , Estado Nutricional , Pirazinamida/administración & dosificación , Pirazinamida/uso terapéutico , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Resultado del Tratamiento , Tuberculosis/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Organización Mundial de la SaludRESUMEN
Ethionamide (ETH) treatment may cause hypothyroidism. Clinical data, serum thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were retrospectively assessed in 137 children receiving anti-tuberculosis treatment including ETH. Abnormal thyroid function tests (TFTs) were recorded in 79 (58%) children: elevated serum TSH and suppressed fT4 (n = 30), isolated elevated serum TSH (n = 20), isolated low serum fT4 (n = 28) and isolated low TSH (n = 1). The risk for biochemical hypothyroidism was higher for children on regimens including para-aminosalicylic acid and in human immunodeficiency virus infected children. TFT abnormalities are frequent in children on ETH and are mainly due to primary hypothyroidism or euthyroid sick syndrome.
Asunto(s)
Antituberculosos/efectos adversos , Etionamida/efectos adversos , Síndromes del Eutiroideo Enfermo/inducido químicamente , Hipotiroidismo/inducido químicamente , Adolescente , Ácido Aminosalicílico/efectos adversos , Ácido Aminosalicílico/uso terapéutico , Antituberculosos/uso terapéutico , Niño , Preescolar , Etionamida/uso terapéutico , Femenino , Infecciones por VIH/epidemiología , Humanos , Lactante , Masculino , Estudios Retrospectivos , Pruebas de Función de la Tiroides , Tirotropina/sangre , Tiroxina/sangre , Tuberculosis/tratamiento farmacológicoRESUMEN
Ethionamide (ETH), a second-line antituberculosis drug, is frequently used in treating childhood tuberculosis. Data supporting ETH dose recommendations in children are limited. The aim of this study was to determine the pharmacokinetic parameters for ETH in children on antituberculosis treatment including ETH. ETH serum levels were prospectively assessed in 31 children in 3 age groups (0 to 2 years, 2 to 6 years, and 6 to 12 years). Within each age group, half received rifampin (RMP). Following an oral dose of ETH (15 to 20 mg/kg of body weight), blood samples were collected at 0, 1, 2, 3, 4, and 6 h following 1 and 4 months of ETH therapy. The maximum serum concentration (C(max)), time to C(max) (T(max)), and area under the time-concentration curve from 0 to 6 h (AUC(0-6)) were calculated. Younger children were exposed to lower ETH concentrations than older children at the same mg/kg body weight dose. Age correlated significantly with the AUC after both 1 month (r = 0.50, P = 0.001) and 4 months (r = 0.63, P = 0.001) of therapy. There was no difference in the AUC or C(max) between children receiving concomitant treatment with RMP and those who did not. Time on treatment did not influence the pharmacokinetic parameters of ETH following 1 and 4 months of therapy. HIV infection was associated with lower ETH exposure. In conclusion, ETH at an oral dose of 15 to 20 mg/kg results in sufficient serum concentrations compared to current adult recommended levels in the majority of children across all age groups. ETH levels were influenced by young age and HIV status but were not affected by concomitant RMP treatment and duration of therapy.
Asunto(s)
Antituberculosos/farmacocinética , Etionamida/farmacocinética , Tuberculosis/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/administración & dosificación , Antituberculosos/sangre , Antituberculosos/uso terapéutico , Niño , Preescolar , Quimioterapia Combinada , Etionamida/administración & dosificación , Etionamida/sangre , Etionamida/uso terapéutico , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/administración & dosificación , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis/complicacionesRESUMEN
In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.
Asunto(s)
Trazado de Contacto/métodos , Ensayos de Liberación de Interferón gamma , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/transmisión , Vacuna BCG/administración & dosificación , Niño , Preescolar , Alemania , Humanos , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/transmisión , Valor Predictivo de las Pruebas , Factores de Riesgo , Prueba de TuberculinaRESUMEN
In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.
Asunto(s)
Trazado de Contacto/métodos , Ensayos de Liberación de Interferón gamma , Tuberculosis/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/transmisión , Adolescente , Adulto , Factores de Edad , Antituberculosos/administración & dosificación , Vacuna BCG/administración & dosificación , Niño , Preescolar , Alemania , Humanos , Tuberculosis Latente/diagnóstico , Valor Predictivo de las Pruebas , Factores de Riesgo , Prueba de Tuberculina , Tuberculosis/diagnóstico , Tuberculosis/transmisión , Adulto JovenRESUMEN
BACKGROUND: Rifampicin (RMP) is an essential drug in paediatric anti-tuberculosis treatment. The current World Health Organization (WHO) guidelines recommend an oral dosage of 10 (8-12) mg per kg body weight. OBJECTIVE: To present a study investigating RMP serum levels in children after oral medication of RMP alone and after combination treatment with ethambutol (EMB). DESIGN: RMP serum levels in children of different age groups were determined after a single oral administration of 10 mg/kg RMP alone as well as after combination with 35 mg/kg EMB. RESULTS: RMP serum levels were lower than those expected in adults receiving a similar oral dose. RMP serum levels in combination treatment were even lower than in monotherapy. CONCLUSION: Currently recommended RMP dosages in childhood tuberculosis lead to serum levels lower than those recommended for adults, probably due to different pharmacokinetics and pharmacodynamics in children. In children, it appears to be more valid to calculate RMP dosage on the basis of body surface area rather than body weight, leading to higher dosages especially in younger children.
Asunto(s)
Antibióticos Antituberculosos/sangre , Antibióticos Antituberculosos/farmacocinética , Antituberculosos/farmacocinética , Etambutol/farmacocinética , Rifampin/sangre , Rifampin/farmacocinética , Tuberculosis Pulmonar/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Antibióticos Antituberculosos/administración & dosificación , Antituberculosos/administración & dosificación , Superficie Corporal , Niño , Preescolar , Cálculo de Dosificación de Drogas , Quimioterapia Combinada , Etambutol/administración & dosificación , Humanos , Guías de Práctica Clínica como Asunto , Rifampin/administración & dosificación , Resultado del Tratamiento , Tuberculosis Pulmonar/sangreRESUMEN
Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.
Asunto(s)
Pruebas Inmunológicas/métodos , Mycobacterium tuberculosis/inmunología , Selección de Paciente , Tuberculosis/diagnóstico , Tuberculosis/inmunología , Antígenos Bacterianos , Antituberculosos/farmacología , Trazado de Contacto , Medicina Basada en la Evidencia , Humanos , Tamizaje Masivo/métodos , Técnicas de Diagnóstico Molecular , Valor Predictivo de las Pruebas , Prueba de Tuberculina , Tuberculosis/tratamiento farmacológico , Tuberculosis/transmisiónRESUMEN
In spite of a decline in the western industrialised countries, tuberculosis remains one of the commonest causes of childhood mortality in the world. In most cases, children become infected by adults in their immediate environment. The clinical manifestation as a consequence of the primary infection reflects the community transmission of tuberculosis. Children with untreated infection remain a lifelong pool for future disease and therefore infectivity. Thus, prevention and therapy of latent tuberculosis infection are fundamental duties of the public health system. The risk of developing active disease following infection with MYCOBACTERIUM TUBERCULOSIS is especially high in children. Compared to adults, childhood tuberculosis manifests differently and is often more severe. At the same time, the diagnosis is complicated by the unspecific clinical presentation and difficulty of culture confirmation in children. This article gives an overview of the special features of the epidemiology, clinical presentation, diagnosis and management of childhood tuberculosis.
Asunto(s)
Ensayos Clínicos como Asunto/tendencias , Tuberculosis/diagnóstico , Tuberculosis/terapia , Niño , Humanos , Tuberculosis/epidemiologíaRESUMEN
Multi-colour flow cytometry was applied to determine T-cell-specific interferon-gamma, interleukin-2 and tumour necrosis factor-alpha expression in children with tuberculosis and non-tuberculosis mycobacterial lymphadenopathy (NTM-L). In vitro stimulation of peripheral blood mononuclear cells with purified protein derivative from Mycobacterium tuberculosis (tuberculin) and M. avium (sensitin) revealed differential recognition of tuberculin and sensitin in both study groups. Ratios of tuberculin-specific and sensitin-specific T-cell proportions in individual patients discriminated between children with tuberculosis or NTM-L. These findings have the potential to improve the differential diagnosis of mycobacterial infections.
Asunto(s)
Antígenos/inmunología , Enfermedades Linfáticas/inmunología , Infecciones por Mycobacterium/inmunología , Linfocitos T/inmunología , Tuberculina/inmunología , Tuberculosis Ganglionar/inmunología , Células Cultivadas , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Lactante , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Leucocitos Mononucleares/inmunología , Masculino , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Pyrazinamide (PZA) is one of the first-line drugs in anti-tuberculosis treatment. In the present study, PZA serum levels in 34 children aged 1 to 14 years were measured either after oral application of PZA alone or after combination therapy with isoniazid and rifampicin. Serum levels did not differ statistically with age, in PZA monotherapy or in combination therapy. With a dosage of 30 mg/kg PZA, efficient serum levels were reached. Because PZA is distributed uniformly in the body, serum levels are related to body weight, and a dose of 30 mg/kg bodyweight is appropriate in children.
Asunto(s)
Antituberculosos/farmacocinética , Isoniazida/uso terapéutico , Pirazinamida/farmacocinética , Rifampin/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológico , Adolescente , Antituberculosos/administración & dosificación , Antituberculosos/sangre , Antituberculosos/uso terapéutico , Niño , Preescolar , Quimioterapia Combinada , Humanos , Lactante , Isoniazida/administración & dosificación , Isoniazida/sangre , Pirazinamida/administración & dosificación , Pirazinamida/sangre , Rifampin/administración & dosificación , Rifampin/sangre , Tuberculosis Pulmonar/metabolismoAsunto(s)
Trazado de Contacto/métodos , Monitoreo del Ambiente/normas , Vigilancia de la Población/métodos , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Monitoreo del Ambiente/métodos , Monitoreo Epidemiológico , Alemania/epidemiología , HumanosRESUMEN
SETTING: Ethambutol (EMB) is used as a fourth drug in paediatric anti-tuberculosis treatment. In current recommendations the dosage of EMB is calculated per kg body weight. OBJECTIVE: To present two studies investigating an appropriate EMB dosage in children, and observational data on its toxicity and efficacy. DESIGN: EMB serum levels in children of different age groups were determined after single oral administration of EMB alone as well as after EMB combined with rifampicin, and optimal dosages were established. The efficacy and toxicity of these EMB dosages were examined retrospectively. RESULTS: EMB serum levels were lower than those expected in adults receiving a similar oral dose, due to different pharmacokinetics and pharmacodynamics in childhood. Thereafter, children were treated with EMB doses calculated by body surface (867 mg/m2). Ocular toxicity occurred in 0.7% of cases and relapses in 0.8%. CONCLUSION: Current recommended EMB dosages in childhood tuberculosis lead to subtherapeutic serum levels. It appears to be more valid to calculate the EMB dosage on the basis of body surface rather than body weight, leading to higher dosages especially in younger children. With these dosages, therapeutic serum levels are reached in all age groups, leading to a high efficacy of anti-tuberculosis treatment without increased ocular toxicity.
Asunto(s)
Antituberculosos/administración & dosificación , Antituberculosos/sangre , Etambutol/administración & dosificación , Etambutol/sangre , Oftalmopatías/inducido químicamente , Tuberculosis/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Factores de Edad , Antituberculosos/efectos adversos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Etambutol/efectos adversos , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Recurrencia , Estudios Retrospectivos , Rifampin/administración & dosificación , Tuberculosis/sangreRESUMEN
BACKGROUND: Diagnosis of childhood tuberculosis (TB) is challenging. The widely used tuberculin skin test (TST) may produce -positive results because of cross-reactivity with nontuberculous mycobacteria or bacille Calmette-Guerin vaccination, resulting in unnecessary treatment. Two recently developed interferon- gamma release assays (IGRAs) show good diagnostic accuracy for active TB in adults; pediatric data are limited, particularly in areas with a low incidence of TB. We assessed the diagnostic accuracy of IGRAs for TB in children in an area with a low incidence of TB. METHODS: In a hospital-based study, the diagnostic accuracy of the TST and 2 IGRAs (T SPOT-TB [T-SPOT; Oxford Immunotec] and QuantiFERON-TB Gold In-Tube [QFT-IT; Cellestis]) were assessed in a cohort of 73 children (median age, 39 months); 28 children with bacteriologically confirmed TB were compared with children without TB (23 with bacteriologically confirmed nontuberculous mycobacterial lymphadenitis and 22 with other nonmycobacterial respiratory tract infections). RESULTS: The specificity for TB of QFT-IT was 100% (95% confidence interval [CI], 91%-100%), and the specificity of T-SPOT was 98% (95% CI, 87%-100%), both of which were considerably higher than the specificity of TST (58%; 95% CI, 42%-73%). The specificity of the TST was 10.5% (95% CI, 1%-33%) in children with nontuberculous mycobacterial lymphadenitis and was 100% (95% CI, 83%-100%) in children with other nonmycobacterial respiratory tract infections. The sensitivity of both QFT-IT and T-SPOT was 93% (95% CI, 77%-99%), and the sensitivity of the TST was 100% (95% CI, 88%-100%). Agreement between the IGRAs was 95.6% ( kappa =0.91); 6.8% of the IGRAs showed indeterminate results. CONCLUSIONS: Both IGRAs showed high diagnostic value in bacteriologically confirmed childhood TB. Their advantage in this study, when performed in addition to the TST, was the ability to distinguish -positive TST results caused by nontuberculous mycobacterial disease, thereby reducing overdiagnosis of TB and guiding clinical management.