Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

[Trained eye vs. gold standard]. / Ojo clínico vs. gold standard.

OBJECTIVE: To determine the degree of correlation between the clinical diagnosis prior to the minor surgery process and its concordance with the results of histopathology report, as well as to determine the surgical data of little clinical importance compared to that which is really necessary and cost-effective. MATERIAL AND METHOD: A descriptive, observational, retrospective and transversal study was conducted of the Minor Surgery Activities of a clinic in the Ciudad Real Health Centre I. RESULTS: A total of 124 surgical specimens were sent for clinical diagnostic comparison, of which, the main clinical diagnoses were: intradermal melanocytic nevi (34.67%), seborrheic keratosis (11.30%), and epidermoid or sebaceous cysts (10.48%). A correlation of 68% was obtained. The protocols of the work centre have been followed to carry out this study in relation to the confidentiality of the data. CONCLUSIONS: These results were analysed and compared with other similar works performed in the field of minor surgery in Primary Care, being able to affirm that there is a good correlation between the initial clinical diagnosis and the histopathology results.

Diagnostic performance of serological tests for swine brucellosis in the presence of false positive serological reactions.

Swine brucellosis caused by Brucella suis biovar 2 is an emerging disease in Europe. Currently used diagnostic tests for swine brucellosis detect antibodies to the O-polysaccharide (O-PS) of Brucella smooth lipopolysaccharide (S-LPS) but their specificity is compromised by false-positive serological reactions (FPSRs) when bacteria carrying cross-reacting O-PS infect pigs. FPSRs occur throughout Europe, and the only tool available for a specific B. suis diagnosis is the intradermal test with Brucella protein extracts free of O-PS or S-LPS. Using sera of 162 sows naturally infected by B. suis biovar 2, 406 brucellosis-free sows, and 218 pigs of brucellosis-free farms affected by FPSR, we assessed the diagnostic performance of an indirect ELISA with rough LPS (thus devoid of O-PS) and of gel immunodiffusion, counterimmunoelectrophoresis, latex agglutination and indirect ELISA with O-PS free proteins in comparison with several S-LPS tests (Rose Bengal, complement fixation, gel immunodiffusion and indirect ELISA). When adjusted to 100% specificity, the sensitivity of the rough LPS ELISA was very low (30%), and adoption of other cut-offs resulted in poor specificity/sensitivity ratios. Although their specificity was 100%, the sensitivity of protein tests (ELISA, latex agglutination, counterimmunoelectrophoresis, and gel immunodiffusion) was only moderate (45, 58, 61 and 63%, respectively). Among S-LPS tests, gel immunodiffusion was the only test showing acceptable sensitivity/specificity (68 and 100%, respectively). Despite these shortcomings, and when the purpose is to screen out FPSR at herd level, gel immunodiffusion tests may offer a technically simple and practical alternative to intradermal testing.

Studies on a suitable antibiotic therapy for treating swine brucellosis.

The aim of this work was developing effective treatments against Brucella suis biovar 2, responsible for swine brucellosis in Europe. MICs for antibiotics used classically in brucellosis and two new macrolides (tulathromycin and tildipirosin) were determined for 33 B. suis biovar 2 field and B. suis reference strains. MIC90 values ranged from 0.01 to 0.25 µg/mL. The best candidates, given alone or combined, were then evaluated in mice. Ten groups (n = 7) of BALB/c mice were inoculated (1 × 10(5) CFU/mouse) with a virulent B. suis biovar 2 field strain. All groups, excepting untreated control, were treated for 14 days with, respectively, doxycycline, dihydrostreptomycin, tulathromycin (one or two doses), or tildipirosin (one or two doses) given alone, and doxycycline combined with dihydrostreptomycin, tulathromycin, or tildipirosin. Combined tildipirosin treatment was the most effective, then selected for pig studies. Sixteen B. suis biovar 2 naturally infected sows were treated with oxytetracycline (20 mg/kg BW/daily) for 21 days. The half of these received also tildipirosin (4 mg/kg BW) in two doses with a 10-day interval. An extensive bacteriological study conducted ten days after ceasing treatments proved the efficacy of this combined oxytetracycline/tildipirosin treatment.

Performance of skin tests with allergens from B. melitensis B115 and rough B. abortus mutants for diagnosing swine brucellosis.

Swine brucellosis by Brucella suis biovar 2 is an emerging disease whose control is based on serological testing and culling. However, current serological tests detect antibodies to the O-polysaccharide (O/PS) moiety of Brucella smooth lipopolysaccharide (S-LPS), and thus lack specificity when infections by Yersinia enterocolitica O:9 and other gram-negative bacteria carrying cross-reacting O/PS occur. The skin test with the protein-rich brucellin extract obtained from rough B. melitensis B115 is assumed to be specific for discriminating these false positive serological reactions (FPSR). However, B115 strain, although unable to synthesize S-LPS, accumulates O/PS internally, which could cause diagnostic problems. Since the brucellin skin test has been seldom used in pigs and FPSR are common in these animals, we assessed its performance using cytosoluble protein extracts obtained from B. abortus rough mutants in manBcore or per genes (critical for O/PS biosynthesis) and B. melitensis B115. The diagnostic sensitivity and specificity were determined in B. suis biovar 2 culture positive and brucellosis free sows, and apparent prevalence in sows of unknown individual bacteriological and serological status belonging to B. suis biovar 2 naturally infected herds. Moreover, the specificity in discriminating brucellosis from FPSR was assessed in brucellosis free boars showing FPSR. The skin test with B. abortus ΔmanBcore and B. melitensis B115 allergens performed similarly, and the former one resulted in 100% specificity when testing animals showing FPSR in indirect ELISA, Rose Bengal and complement fixation serological tests. We conclude that O/PS-free genetically defined mutants represent an appropriate alternative to obtain Brucella protein extracts for diagnosing swine brucellosis.

[Brain death: is it an appropriate term?]. / Muerte cerebral: ¿es un término adecuado?

INTRODUCTION: Brain death is generally accepted as a concept to indicate death. It was introduced about 40 years ago, and it was considered the ideal situation for donation of organs. METHODS: During this time, however, there have been problems in the understanding of this concept both in the medical profession and in the general population. University students from medical and non-medical schools were tested for their understanding of this concept. RESULTS: Our results show that less than one third of the non-medical students identified brain death as death. The data from the medical students changed as they progressed through their studies, but only 2/3 of the graduating medical class believed that brain death is death. CONCLUSION: Similar results have been seen in other universities around the world, and a renewed effort on the re-education of the concept of brain death may be worthwhile. Although we cannot extrapolate these results to the general population, the confusion is probably similar; hence an effort should be made to solve this problem.

Development of a selective culture medium for primary isolation of the main Brucella species.

Bacteriological diagnosis of brucellosis is performed by culturing animal samples directly on both Farrell medium (FM) and modified Thayer-Martin medium (mTM). However, despite inhibiting most contaminating microorganisms, FM also inhibits the growth of Brucella ovis and some B. melitensis and B. abortus strains. In contrast, mTM is adequate for growth of all Brucella species but only partially inhibitory for contaminants. Moreover, the performance of both culture media for isolating B. suis has never been established properly. We first determined the performance of both media for B. suis isolation, proving that FM significantly inhibits B. suis growth. We also determined the susceptibility of B. suis to the antibiotics contained in both selective media, proving that nalidixic acid and bacitracin are highly inhibitory, thus explaining the reduced performance of FM for B. suis isolation. Based on these results, a new selective medium (CITA) containing vancomycin, colistin, nystatin, nitrofurantoin, and amphotericin B was tested for isolation of the main Brucella species, including B. suis. CITA's performance was evaluated using reference contaminant strains but also field samples taken from brucella-infected animals or animals suspected of infection. CITA inhibited most contaminant microorganisms but allowed the growth of all Brucella species, to levels similar to those for both the control medium without antibiotics and mTM. Moreover, CITA medium was more sensitive than both mTM and FM for isolating all Brucella species from field samples. Altogether, these results demonstrate the adequate performance of CITA medium for the primary isolation of the main Brucella species, including B. suis.

Leishmaniasis cutánea / Cutaneous leishmaniasis

Las leishmaniasis son enfermedades causadas por protozoos del género Leishmania. España es uno de los países en los que la leishmaniasis es endémica. Los casos adquiridos en nuestro país (tanto cutáneos como viscerales) se deben a Leishmania infantum, pero puede haber otros causados por otras especies en viajeros o inmigrantes. Las lesiones cutáneas aparecen fundamentalmente en áreas expuestas y tienden a la curación espontánea dejando cicatriz. El diagnóstico es difícil por la inespecificidad de la clínica y el lento crecimiento del parásito en cultivo. Existen distintas opciones terapéuticas, por lo que cada caso debe ser valorado individualmente según las características de la lesión, la especie causante y el potencial de afectación mucosa. En nuestro país, la primera línea de tratamiento está constituida por los antimoniales pentavalentes intralesionales. En casos refractarios o con riesgo de diseminación mucosa debe emplearse un tratamiento sistémico (AU)

Leishmaniasis are a group of diseases caused by protozoa of the genus Leishmania. Spainis one of the countries where leishmaniasis is endemic. All cases acquired in our country(both cutaneous and visceral) are caused by Leishmania infantum, although cases due to other species may appear in travelers or immigrants. Cutaneous lesions appear mainly in exposed areas and tend to heal spontaneously leaving scars. Diagnosis is often difficult due to the non-specific clinical manifestations and the slow growth of the parasite when cultured. There are different available treatment options and each case should be individually considered,taking into account the characteristics of the lesion, the species of Leishmania and the potential for mucosal spread. In Spain, intralesional pentavalent antimonials are the first-line therapeutic option. In those cases at risk for mucosal dissemination or refractory to local therapy,systemic treatment must be given (AU)

Síndrome de escaldadura estafilocócia en un neonato / Staphylococcal scalded síndrome in a newborn

Se presenta un caso de escaldadura estafilocócica en un neonato de 12 días. El diagnóstico es principalmente clínico, basado en las lesiones cutáneas características (signo de Nikolski). La inmadurez fisiológica del neonato hace necesarios un diagnóstico y tratamiento precoces (AU)

A case of staphylococcal scalded syndrome in a 12 day old newborn is presented. The diagnosis is principally clinical, based on the characteristic skin lesions (Nikolski sign). The physiological immaturity of the newborn makes an early diagnosis and treatment necessary (AU)

Efficacy of bp26 and bp26/omp31 B. melitensis Rev.1 deletion mutants against Brucella ovis in rams.

Brucella melitensis Rev.1 is the most effective vaccine against B. ovis infection in sheep but induces antibodies interfering with B. melitensis diagnosis. Brucella BP26 and Omp31 proteins are differential diagnostic antigens. Single or double bp26 and omp31 Rev.1 deletion mutants have been proven effective against B. melitensis in sheep. Here, the CGV26 (deleted in bp26 gene) and CGV2631 (deleted in both bp26 and omp31 genes) mutants have been tested for efficacy against B. ovis in rams. Either inoculated subcutaneously or conjunctivally, both mutants conferred significant protection against B. ovis. The protection induced by CGV26 was similar to that of Rev.1 but significantly higher than that conferred by CGV2631. In conclusion, the CGV26 mutant, in association with the adequate diagnostic strategy, could be a useful alternative to Rev.1 for sheep vaccination against B. ovis infections in those countries performing simultaneously B. melitensis and B. ovis eradication campaigns.

Evaluation of a multiplex PCR assay (Bruce-ladder) for molecular typing of all Brucella species, including the vaccine strains.

An evaluation of a multiplex PCR assay (Bruce-ladder) was performed in seven laboratories using 625 Brucella strains from different animal and geographical origins. This robust test can differentiate in a single step all of the classical Brucella species, including those found in marine mammals and the S19, RB51, and Rev.1 vaccine strains.

[Increase in the incidence of bacterial pneumonia between 2001 and 2004]. / Incremento de la incidencia de neumonía bacteriana entre 2001 y 2004.

AIM: To study patients with typical community-acquired pneumonia (CAP) admitted to our hospital between 2001 and 2004 in order to analyze the incidence of this disease in our health area during this period. METHODS: A retrospective study was performed of patients with CAP admitted to our hospital from 2001 to 2004. Only those patients who fulfilled the criteria for typical pneumonia of possible bacterial origin based on clinical and radiological features and laboratory data were included. The annual incidence rates of CAP were analyzed using demographic data from our health area and from all children admitted to the infectious diseases unit of our hospital during this period. RESULTS: During the study period, 569 children were diagnosed with typical CAP: 116 in 2001, 133 in 2002, 154 in 2003 and 166 in 2004. The incidence rate was 1.3 cases/1,000 children under 14 years old/year in 2001, 1.51 in 2002, 1.69 in 2003 and 1.72 in 2004. These findings represent an increment of 25% in the incidence per 1,000/children/year and an increment of 53% in the incidence per 100 children admitted to our unit. Blood cultures were performed before antibiotic therapy was administered in 487 patients and were positive in 22 (4.5%). Streptococcus pneumoniae was isolated in 21 patients and Streptococcus pyogenes in one. Chest radiographs revealed lobar consolidation in 95% of the patients and 15 % developed pleural effusion. CONCLUSIONS: Cases of CAP of probable pneumococcal etiology increased in our health area during the study period. The number of complicated cases also increased.

[Staphylococcal scalded skin syndrome]. / Síndrome de escaldadura estafilocócica.

INTRODUCTION: Staphylococcal scalded skin syndrome is a rare disease caused by Staphylococcus aureus that produces exfoliative toxins. There are few epidemiological data in our environment. PATIENTS AND METHODS: We present an observational cohort study. We review the cases of staphylococcal scalded skin syndrome monitored at La Paz Children Hospital during the last ten years (January 1997 to December 2006). RESULTS: We obtained 26 patients, 7 in the first 5 years and 19 more in the following years. The mean age at diagnosis was 19 months. Four cases (15%) occurred during the neonatal period. Sixty-seven percent of the cases were diagnosed during spring and summer. Main clinical signs were: erythroderma with blisters and posterior desquamation (100%), perioral fissures (54%), fever (46%), conjunctivitis (42%) and palpebral edema (31%). No significant increases in leukocytes (mean: 11,341/.l) or C-reactive protein (mean: 9 mg/l) were found on blood analysis. Diagnosis was made by clinical findings. S. aureus was isolated in nasal or conjunctival samples on 59% of cases. All strains were sensitive to cloxacillin, clindamycin and vancomycin. The patients were treated with cloxacillin with good progress. CONCLUSIONS: Staphylococcal scalded skin syndrome seems to be more common in the last few years. It must be suspected in children with acute erythroderma and perioral or conjunctival lesions. Treatment with cloxacillin leads to healing without sequelae.

Incremento de la incidencia de neumonía bacteriana entre 2001 y 2004 / Increase in the incidence of bacterial pneumonia between 2001 and 2004

Objetivo: Estudiar los pacientes ingresados en nuestro hospital por neumonía típica adquirida en la comunidad (NAC) en los últimos 4 años y analizar la incidencia en este período. Métodos: Se seleccionaron retrospectivamente todas las NAC ingresadas en nuestro hospital entre los años 2001 y 2004. Se analizaron exclusivamente aquellas que cumplían criterios clínico-analítico-radiológicos de neumonía típica de posible origen bacteriano. Se analiza la incidencia de NAC según los datos de población de nuestra área sanitaria y del número de ingresos totales en la unidad de enfermedades infecciosas. Resultados: Se diagnosticaron un total de 569 NAC que cumplían criterios de bacteriana: 116 casos en 2001, 133 casos en 2002, 154 casos en 2003 y 166 casos en 2004. La incidencia fue de 1,38 casos/1.000 niños < 14 años de edad/año en 2001, 1,51 en 2002, 1,69 en 2003 y 1,72 en 2004. Esto supone un incremento de la incidencia del 25 % por 1.000 niños/año en nuestra área sanitaria y un incremento de la incidencia del 53 % por 100 ingresos en la unidad. Se realizó hemocultivo antes de la antibioterapia en 487 casos, de los cuales fueron positivos 22 (4,5 %), 21 para Streptococcus pneumoniae y 1 para Streptococcus pyogenes. El 95 % de los pacientes presentaba en la radiografía de tórax una imagen de consolidación. El 15 % de los pacientes tuvo derrame pleural. Conclusiones: En los últimos años hemos observado un aumento del número de casos de neumonía de posible origen neumocócico en España, al mismo tiempo que también se ha producido un incremento de los casos complicados (AU)

Aim: To study patients with typical community-acquired pneumonia (CAP) admitted to our hospital between 2001 and 2004 in order to analyze the incidence of this disease in our health area during this period. Methods: A retrospective study was performed of patients with CAP admitted to our hospital from 2001 to 2004. Only those patients who fulfilled the criteria for typical pneumonia of possible bacterial origin based on clinical and radiological features and laboratory data were included. The annual incidence rates of CAP were analyzed using demographic data from our health area and from all children admitted to the infectious diseases unit of our hospital during this period. Results: During the study period, 569 children were diagnosed with typical CAP: 116 in 2001, 133 in 2002, 154 in 2003 and 166 in 2004. The incidence rate was 1.3 cases/1,000 children under 14 years old/year in 2001, 1.51 in 2002, 1.69 in 2003 and 1.72 in 2004. These findings represent an increment of 25 % in the incidence per 1,000/children/year and an increment of 53 % in the incidence per 100 children admitted to our unit. Blood cultures were performed before antibiotic therapy was administered in 487 patients and were positive in 22 (4.5 %). Streptococcus pneumoniae was isolated in 21 patients and Streptococcus pyogenes in one. Chest radiographs revealed lobar consolidation in 95 % of the patients and 15 % developed pleural effusion. Conclusions: Cases of CAP of probable pneumococcal etiology increased in our health area during the study period. The number of complicated cases also increased (AU)

Evaluation of two serological methods for potency testing of whole cell pertussis vaccines.

The European Pharmacopoeia (Ph. Eur.) and the World Health Organization (WHO) require the performance of extensive quality control testing including a potency test before a vaccine batch is released for human use. Whole cell pertussis (wP) vaccine potency is assessed by a mouse protection test (MPT) based on the Kendrick test. This test compares the vaccine dose necessary to protect 50% of mice against the effect of a lethal intracerebral dose of Bordetella pertussis and the dose of a suitable reference vaccine needed to give the same protection level. Due to the large variability in the results of this test and the severe distress which is inflicted on the many animals involved, its replacement by an alternative method is highly desirable. At the initiative of the European Directorate for the Quality of Medicines and HealthCare (EDQM) of the Council of Europe, in collaboration with the WHO and the In-vitro toxicology Unit/European Centre for the Validation of Alternative Methods (ECVAM) of the European Commission (EC) Joint Research Centre-Institute for Health and Consumer Protection (JRC-IHCP), wP vaccine specialists from all over the world were invited to present an overview of candidate alternatives at a symposium organised in Geneva (Switzerland) in March 2005. Although no alternative method was found suitable for immediate implementation of batch potency control, the Pertussis Serological Potency Test (PSPT), initially developed in mice and recently transferred to guinea pigs (gps), was identified as a model of interest. Using the PSPT in gps to test several components of combined vaccines such as Diphtheria-Tetanus-wP vaccines in the same animal series would allow further implementation of the European 3Rs policy to batch potency control, by additional method refinement and reduction of animal use. The present study evaluated 2 features of the serological response to wP vaccination: 1) the overall antibody response as measured by a "whole cell" ELISA (PSPT-wC-ELISA) which uses the B. pertussis 18323 challenge strain prescribed for the MPT to coat the assay plates and 2) the functional neutralising antibodies to pertussis toxin (PT, one of the main virulence factors of B. pertussis), as measured by the Chinese Hamster Ovary (CHO) cell assay. The results showed that 1) the gp model can be used for wP vaccine potency testing; 2) despite good repeatability and precision, the CHO cell assay did not generate results comparable to the MPT. Moreover, the CHO cell assay showed significant differences in the ability of wP vaccines to induce neutralising anti-PT antibodies, which did not correlate to the overall antibody response evaluated by PSPT-wC-ELISA; 3) comparable potencies were obtained in the MPT and the PSPT-wC-ELISA. This study, supported by the previous ones correlating the PSPT-wC-ELISA in mice with the MPT, confirms that PSPT-wC-ELISA in gps is a promising approach for batch release potency testing of wP vaccines for which consistency in production has already been demonstrated by the MPT. However, a large scale validation study is required prior to the adoption of PSPT-wC-ELISA as a compendial reference method for wP vaccines batch release control.

[Multidrug-resistant tuberculosis in the pediatric age group]. / Tuberculosis mutirresistente en la edad pediátrica.

AIMS: To study the clinical and epidemiological features in eight pediatric patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed from 1994 to 2005 in three hospitals in Madrid (Spain). METHODS: A retrospective study was performed in patients aged less than 15 years old with positive culture for multidrug-resistant Mycobacterium tuberculosis and patients with negative cultures diagnosed after contact with MDR-TB. RESULTS: Pulmonary tuberculosis was diagnosed in seven patients and arthritis in one. Fifty percent of the patients were immigrants and an adult source case was found in four (50%). M. tuberculosis was isolated in gastric juice in four patients and in synovial biopsy in one. In three patients cultures were negative but these patients had previously been in contact with MDR-TB. Two strains were resistant to isoniazid and rifampicin, four were resistant to isoniazid, rifampicin and streptomycin, one was resistant to isoniazid, rifampicin, streptomycin and pyrazinamide, and one was resistant to 11 drugs. Six patients initially received conventional treatment without improvement. Patients received therapy for 15 months (range: 12 to 18) with 3 to 5 drugs according to the sensitivity study. The following adverse effects were observed: creatine phosphokinase increase (one patient), tendinitis (one patient), alteration of visual evoked responses (one patient) and transitory psychosis (one patient). One patient required pulmonary lobectomy. All patients responded satisfactorily to medical treatment. CONCLUSIONS: MDR-TB should be suspected in patients not responding to TB treatment, especially those from countries with high resistance rates. In patients with negative cultures, treatment should rely on the results of a sensitivity study in the adult source case. MDR-TB requires the use of second-line anti-TB drugs for prolonged periods with possible toxic effects.

Tuberculosis mutirresistente en la edad pediátrica / Multidrug-resistant tuberculosis in the pediatric age group

Objetivos Estudiar las características clínicas y epidemiológicas de 8 pacientes pediátricos con tuberculosis multirresistente (TB-MDR) diagnosticados en 3 hospitales de Madrid entre 1994 y 2005. Métodos Estudio retrospectivo que incluye pacientes menores de 15 años con aislamiento de Mycobacterium tuberculosis multirresistente y sin aislamiento que empezaron tras contacto con TB-MDR. Resultados Se diagnosticaron 7 tuberculosis pulmonares y una artritis. El 50 % eran inmigrantes y en el 50 % se confirmó contacto con adulto enfermo. Se aisló M. tuberculosis en jugo gástrico (4) y biopsia sinovial (1). En 3 pacientes no se consiguió aislamiento, pero se confirmó contacto con TB-MDR. Dos cepas presentaron resistencia a isoniazida (H) y rifampicina (R), cuatro a H, R y estreptomicina (S), una a H, R, S y pirazinamida (Z) y una a 11 fármacos. Seis pacientes recibieron tratamiento convencional inicial sin presentar mejoría. Una vez conocida la sensibilidad de la cepa, se administró tratamiento durante una media de 15 meses (rango: 12-18 meses) con 3-5 fármacos efectivos. Los efectos secundarios observados fueron: aumento de creatinfosfocinasa (1), tendinitis (1), alteración de potenciales visuales (1) y psicosis transitoria (1). Un paciente requirió lobectomía. Todos los pacientes evolucionaron satisfactoriamente. Conclusiones La TB-MDR debe sospecharse en casos con mala evolución, especialmente si proceden de zonas con altas tasas de resistencia. En niños enfermos con cultivos negativos y expuestos a TB-MDR, el tratamiento se realizará según el estudio de resistencias del caso índice. La resistencia limita las opciones terapéuticas y conlleva la utilización de fármacos con posibles efectos tóxicos

Aims To study the clinical and epidemiological features in eight pediatric patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed from 1994 to 2005 in three hospitals in Madrid (Spain). Methods A retrospective study was performed in patients aged less than 15 years old with positive culture for multidrugresistant Mycobacterium tuberculosis and patients with negative cultures diagnosed after contact with MDR-TB. Results Pulmonary tuberculosis was diagnosed in seven patients and arthritis in one. Fifty percent of the patients were immigrants and an adult source case was found in four (50 %). M. tuberculosis was isolated in gastric juice in four patients and in synovial biopsy in one. In three patients cultures were negative but these patients had previously been in contact with MDR-TB. Two strains were resistant to isoniazid and rifampicin, four were resistant to isoniazid, rifampicin and streptomycin, one was resistant to isoniazid, rifampicin, streptomycin and pyrazinamide, and one was resistant to 11 drugs. Six patients initially received conventional treatment without improvement. Patients received therapy for 15 months (range: 12 to 18) with 3 to 5 drugs according to the sensitivity study. The following adverse effects were observed: creatine phosphokinase increase (one patient), tendinitis (one patient), alteration of visual evoked responses (one patient) and transitory psychosis (one patient). One patient required pulmonary lobectomy. All patients responded satisfactorily to medical treatment. Conclusions MDR-TB should be suspected in patients not responding to TB treatment, especially those from countries with high resistance rates. In patients with negative cultures, treatment should rely on the results of a sensitivity study in the adult source case. MDR-TB requires the use of second- line anti-TB drugs for prolonged periods with possible toxic effects