Abemaciclib as adjuvant treatment for high-risk early breast cancer / Abemaciclib en adyuvancia para el tratamiento del cáncer de mama precoz de alto riesgo

Objective: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorization (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. Method: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label, and multicenter phase III study. A total of 5637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive, and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1–3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67≥20%. Patients were randomized (1:1) to receive adjuvant abemaciclib+endocrine therapy (n = 2808) or endocrine therapy alone (n = 2829) for 2 years, with endocrine therapy prescribed for at least 5 years. Results: With a median follow-up of 15.5 months, abemaciclib+endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone [HR = 0.747 (95% CI 0.598–0.932), P = 0.0096]; achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3 years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%), and diarrhea (7.8% vs. 0.2%). Conclusions: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for...(AU)

Objetivo: Adaptar el informe GHEMA de abemaciclib, un inhibidor de quinasas dependientes de ciclinas 4 y 6, con autorización de la Agencia Europea del Medicamento en abril de 2022 para el tratamiento adyuvante de pacientes adultos con cáncer de mama precoz, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo, con afectación ganglionar y riesgo elevado de recaída; en combinación con hormonoterapia. Método: La eficacia y seguridad de abemaciclib se evaluó en un estudio fase III multicéntrico, aleatorizado y abierto. Se incluyeron 5.637 pacientes diagnosticados de cáncer de mama precoz con ganglios positivos, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo y alto riesgo de recaída. El criterio de alto riesgo se definió como la presencia de ≥ 4 ganglios positivos, o de 1–3 ganglios y al menos una de las siguientes características: tamaño del tumor ≥5 cm, grado histológico 3 o Ki-67 ≥ 20%. Los pacientes fueron aleatorizados (1:1) a recibir durante 2 años abemaciclib + hormonoterapia (n = 2.808) u hormonoterapia sola (n = 2.829). En ambos brazos el tratamiento con hormonoterapia se mantuvo mínimo 5 años. Resultados: Con una mediana de seguimiento de 15,5 meses, abemaciclib + hormonoterapia mostró beneficio significativo frente a la hormonoterapia sola [HR = 0,747 (IC95% 0,598-0,932), p = 0,0096], con una mejora absoluta del 3,5% en la tasa de supervivencia libre de enfermedad invasiva a 2 los años. Este beneficio se mantuvo con una mediana de seguimiento de 27,7 meses, logrando una mejora en la tasa de supervivencia libre de enfermedad invasiva del 2,7% y del 5,4% a los 2 y 3 años, respectivamente. La incidencia de efectos adversos grado 3–4 fue superior en el brazo de abemaciclib (45,9% vs. 12,9%); e incluía neutropenia (19,6% vs. 0,8%), leucopenia (11,4% vs. 0,4%) y diarrea (7,8% vs. 0,2%). Conclusiones: Los resultados del ensayo pivotal son suficientes para considerar abemaciclib como...(AU)

Abemaciclib en adyuvancia para el tratamiento del cáncer de mama precoz de alto riesgo / Abemaciclib as adjuvant treatment for high-risk early breast cancer

Objective: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorization (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. Method: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label, and multicenter phase III study. A total of 5637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive, and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1–3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67≥20%. Patients were randomized (1:1) to receive adjuvant abemaciclib+endocrine therapy (n = 2808) or endocrine therapy alone (n = 2829) for 2 years, with endocrine therapy prescribed for at least 5 years. Results: With a median follow-up of 15.5 months, abemaciclib+endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone [HR = 0.747 (95% CI 0.598–0.932), P = 0.0096]; achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3 years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%), and diarrhea (7.8% vs. 0.2%). Conclusions: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for...(AU)

Objetivo: Adaptar el informe GHEMA de abemaciclib, un inhibidor de quinasas dependientes de ciclinas 4 y 6, con autorización de la Agencia Europea del Medicamento en abril de 2022 para el tratamiento adyuvante de pacientes adultos con cáncer de mama precoz, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo, con afectación ganglionar y riesgo elevado de recaída; en combinación con hormonoterapia. Método: La eficacia y seguridad de abemaciclib se evaluó en un estudio fase III multicéntrico, aleatorizado y abierto. Se incluyeron 5.637 pacientes diagnosticados de cáncer de mama precoz con ganglios positivos, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo y alto riesgo de recaída. El criterio de alto riesgo se definió como la presencia de ≥ 4 ganglios positivos, o de 1–3 ganglios y al menos una de las siguientes características: tamaño del tumor ≥5 cm, grado histológico 3 o Ki-67 ≥ 20%. Los pacientes fueron aleatorizados (1:1) a recibir durante 2 años abemaciclib + hormonoterapia (n = 2.808) u hormonoterapia sola (n = 2.829). En ambos brazos el tratamiento con hormonoterapia se mantuvo mínimo 5 años. Resultados: Con una mediana de seguimiento de 15,5 meses, abemaciclib + hormonoterapia mostró beneficio significativo frente a la hormonoterapia sola [HR = 0,747 (IC95% 0,598-0,932), p = 0,0096], con una mejora absoluta del 3,5% en la tasa de supervivencia libre de enfermedad invasiva a 2 los años. Este beneficio se mantuvo con una mediana de seguimiento de 27,7 meses, logrando una mejora en la tasa de supervivencia libre de enfermedad invasiva del 2,7% y del 5,4% a los 2 y 3 años, respectivamente. La incidencia de efectos adversos grado 3–4 fue superior en el brazo de abemaciclib (45,9% vs. 12,9%); e incluía neutropenia (19,6% vs. 0,8%), leucopenia (11,4% vs. 0,4%) y diarrea (7,8% vs. 0,2%). Conclusiones: Los resultados del ensayo pivotal son suficientes para considerar abemaciclib como...(AU)

Abemaciclib as adjuvant treatment for high-risk early breast cancer.

OBJECTIVE: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorization (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. METHOD: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label, and multicenter phase III study. A total of 5637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive, and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1-3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67≥20%. Patients were randomized (1:1) to receive adjuvant abemaciclib+endocrine therapy (n = 2808) or endocrine therapy alone (n = 2829) for 2 years, with endocrine therapy prescribed for at least 5 years. RESULTS: With a median follow-up of 15.5 months, abemaciclib+endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone [HR = 0.747 (95% CI 0.598-0.932), P = 0.0096]; achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3 years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%), and diarrhea (7.8% vs. 0.2%). CONCLUSIONS: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for high-risk early breast cancer in highly selected patients. However, in order to the efficacy results present less uncertainty, we must wait for a evaluation later, in which we can have a mature determination at 3 years (with more patients at risk).

Abemaciclib as adjuvant treatment for high-risk early breast cancer. / [Artículo traducido] Abemaciclib en adyuvancia para el tratamiento del cáncer de mama precoz de alto riesgo.

OBJECTIVE: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorisation (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. METHOD: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label and multicenter phase III study. A total of 5,637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1-3positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3 or Ki-67 ≥ 20%. Patients were randomized (1:1) to receive adjuvant abemaciclib + endocrine therapy (n = 2,808) or endocrine therapy alone (n = 2,829) for 2 years, with endocrine therapy prescribed for at least 5 years. RESULTS: With a median follow-up of 15.5 months, abemaciclib + endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone (HR = 0.747 [95% CI 0.598-0.932], p = 0.0096); achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3-years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%) and diarrhea (7.8% vs. 0.2%). CONCLUSIONS: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for high-risk early breast cancer in highly selected patients. However, in order to the efficacy results present less uncertainty, we must wait for a evaluation later, in which we can have a mature determination at 3 years (with more patients at risk).

Laboratory surveillance of invasive Haemophilus influenzae disease in Argentina, 2011-2019

Abstract The incorporation of Haemophilus influenzae type b (Hib) vaccine into the Argentine National Immunization Program in 1998 resulted in a dramatic decrease in the incidence of invasive disease due to this serotype. We assessed 1405 H. influenzae (Hi) isolates causing invasive infections referred to the National Reference Laboratory between 2011 and 2019. Non-encapsulated Hi were the most common strains (44.5%), followed by types b (41.1%) and a (10.0%). Significant increase in the proportion of type b was observed, from 31.2% in 2011, to 50% in 2015, correlating with the peak incidence rate, later decreasing to 33.6% by 2019. We compared the genetic relationship between clones circulating during the period of increased Hib incidence (2011-2015) and those of the prevaccination-transition period (1997-1998). Four pulsotypes predominated in both periods, G, M, P and K, G being the most common. Multilocus sequence typing revealed that the 4 pulsotypes belonged to ST6, or one of its simple or double locus variants. Isolates from fully vaccinated individuals did not differ from those of the rest of the population studied. After ruling out aspects associated with emergence of specific clones, we concluded that factors such as low booster coverage rates, delayed vaccination schedules and use of different vaccines may have contributed to the reemergence of Hib infections.

Resumen La introducción de la vacuna contra Haemophilus influenzae tipo b (Hib) en el Programa Nacional de Inmunización de Argentina en 1998 produjo una drástica disminución de la incidencia de enfermedad invasiva causada por este serotipo. En el Laboratorio Nacional de Referencia se estudiaron 1405 aislamientos de H. influenzae causantes de enfermedad invasiva recibidos en el período 2011-2019. H. influenzae no capsulado fue el más frecuente (44,5%), seguido por los tipos b (41,1%) y a (10,0%). Se observó un aumento significativo de la proporción del tipo b, de 31,2% en 2011 a 50% en 2015, que se correlacionó con un pico de incidencia en ese mismo año. Hacia 2019, descendió a 33,6%. Con el objetivo de evaluar los clones circulantes durante el incremento de la proporción de Hib y comparar con el período prevacunal-transición, se determinó la relación genética de una selección de aislamientos de los períodos 1997-1998 y 2011-2015. El análisis por PFGE mostró 4 pulsotipos predominantes en los 2 períodos, G, M, P y K, y el pulsotipo G fue mayoritario en ambos períodos. Por MLST se demostró que los 4 pulsotipos pertenecieron al ST6 o sus variantes (simple o doble locus). Entre los aislamientos de pacientes con vacunación completa no se hallaron clones diferentes respecto del resto de la población. Se postula que las coberturas de vacunación no satisfactorias en las dosis de refuerzo, los esquemas atrasados y el uso de diferentes vacunas pudieron haber contribuido a la reemergencia de Hib.

Laboratory surveillance of invasive Haemophilus influenzae disease in Argentina, 2011-2019.

The incorporation of Haemophilus influenzae type b (Hib) vaccine into the Argentine National Immunization Program in 1998 resulted in a dramatic decrease in the incidence of invasive disease due to this serotype. We assessed 1405 H. influenzae (Hi) isolates causing invasive infections referred to the National Reference Laboratory between 2011 and 2019. Non-encapsulated Hi were the most common strains (44.5%), followed by types b (41.1%) and a (10.0%). Significant increase in the proportion of type b was observed, from 31.2% in 2011, to 50% in 2015, correlating with the peak incidence rate, later decreasing to 33.6% by 2019. We compared the genetic relationship between clones circulating during the period of increased Hib incidence (2011-2015) and those of the prevaccination-transition period (1997-1998). Four pulsotypes predominated in both periods, G, M, P and K, G being the most common. Multi-locus sequence typing revealed that the 4 pulsotypes belonged to ST6, or one of its simple or double locus variants. Isolates from fully vaccinated individuals did not differ from those of the rest of the population studied. After ruling out aspects associated with emergence of specific clones, we concluded that factors such as low booster coverage rates, delayed vaccination schedules and use of different vaccines may have contributed to the reemergence of Hib infections.

Frecuencia de Streptococcus pneumoniae aislados de enfermedad invasiva en Paraguay, serotipos y perfil de sensibilidad (2010-2018) / Frequency of Streptococcus pneumoniae isolated from invasive disease in Paraguay, serotypes and sensitivity profile (2010-2018)

Streptococcus pneumoniae sigue siendo una de las causas más importantes de morbilidad y mortalidad en niños y adultos alrededor del mundo. El objetivo del estudio fue describir la frecuencia de aislamiento de S. pneumoniae en enfermedad invasiva, distribución de serotipos y sensibilidad antimicrobiana en Paraguay (2010-2018). Se estudiaron 793 cepas de S. pneumoniae aisladas de pacientes de todas las edades con enfermedad invasiva en Paraguay, provenientes de los diferentes centros centinelas y colaboradores en el marco de la vigilancia de meningitis y neumonías, durante el periodo 2010-2018. La frecuencia general según diagnóstico resultó 74.9% de neumonías (n=594), 18.4% de meningitis (n=146) y 6.7% de sepsis (n=53). El serotipo 14 fue más frecuente con 174 aislamientos (22.0%), seguido del serotipo 19A con 84 aislamientos (10.6%), el serotipo 3 con 66 aislamientos (8.3%) y el 6A con 37 aislamientos (4.7%). En meningitis se registró una frecuencia general de resistencia a penicilina del 32,2% y de ceftriaxona del 1,4%. En los casos de no meningitis la resistencia a penicilina fue del 0,8% y ceftriaxona del 0,3%. Los resultados de serotipos y sensibilidad antimicrobiana proporcionarán información necesaria para la implementación de estrategias de prevención y tratamiento de la enfermedad neumocócica en nuestro país, por lo que es necesaria una vigilancia continua para evaluar la carga de enfermedad, los serotipos circulantes y el aumento de la resistencia a los antibióticos

Streptococcus pneumoniae remains one of the most important causes of morbidity and mortality in children and adults worldwide. The objective of the study was to describe the frequency of isolation of S. pneumoniae in invasive disease, serotype distribution and antimicrobial susceptibility in Paraguay (2010-2018). We studied 793 strains of S. pneumoniae isolated from patients of all ages with invasive disease in Paraguay, from different sentinel centers and collaborators in the framework of meningitis and pneumonia surveillance during the period 2010-2018. The general frequency according to diagnosis was 74.9% of pneumonia (n = 594), 18.4% of meningitis (n = 146) and 6.7% of sepsis (n = 53). Serotype 14 was more frequent with 174 isolates (22.0%), followed by serotype 19A with 84 isolates (10.6%), serotype 3 with 66 isolates (8.3%) and 6A with 37 isolates (4.70%). In meningitis, there was a general frequency of penicillin resistance of 32.2% and ceftriaxone of 1.4%. In cases of non-meningitis, penicillin resistance was 0.8% and ceftriaxone 0.3%. The results of serotypes and antimicrobial sensitivity will provide necessary information for the implementation of prevention strategies and treatment of pneumococcal disease in our country, therefore it is necessary to continue monitoring in order to assess the burden of the disease, circulating serotypes and increased antibiotic resistance

[Invasive disease due to Streptococcus pyogenes: Changes in incidence and prognostic factors]. / Enfermedad invasiva por Streptococcus pyogenes: cambios en la incidencia y factores pronósticos.

INTRODUCTION: Invasive group A streptococcal disease (iGASD) is a serious infection in children. Several studies have shown an increased incidence in the past years. OBJECTIVE: To evaluate the characteristics and outcome of iGASD in children, and to determine changes in incidence or severity. MATERIAL AND METHODS: A retrospective study was conducted on children≤16 years evaluated in a tertiary paediatric hospital in Madrid, and diagnosed with iGASD (June 2005-July 2013). An analysis was made of the demographics, symptomatology, microbiology, and treatment. The changes throughout the period studied were evaluated, as well as parameters associated with disease severity. RESULTS: The study included a total of 55 children with iGASD, with 33 (60%) females, and a median age of 48.5 (20.5-88.9) months. The most frequent clinical syndromes were cellulitis/subcutaneous abscess (21.8%), ENT abscess (20%), pneumonia (16.4%), osteoarticular infection (16.4%), and mastoiditis (12.7%). The incidence of iGASD (cases/105 emergencies/year) increased from 5.6 (4.2-7.2) between June 2005-May 2009 to 18.9 (15.1-26) between June 2009-May 2013; P=.057. Surgery and admission to PICU was required by 35 (63.6%) and 10 (18.2%) patients, respectively. Children in PICU were younger (26.5 vs 52.6 months, P=.116), had a higher C-reactive protein (24.5 vs 10.7mg/dl, P<.001) and higher frequency of pneumonia (60 vs 7%, P<.001). In the multivariate analysis, only C-reactive protein was a risk factor for admission to PICU (OR: 1.14 [1.004-1.286], P=.04). There were no sequelae. CONCLUSIONS: An increased incidence of iGASD was observed in the children in this study. Lower age, pneumonia, and higher C-reactive protein were associated with disease severity in this series.

Caracterización de la enfermedad invasiva por haemophilus influenzae, neumococo y meningococo en pediatría: estudio de casos-controles / Characterization of invasive disease caused by haemophilus influenzae, pneumococcus, and meningococcus in pediatrics: a case-control study

INTRODUCCIÓN Las enfermedades invasivas constituyen una importante causa de morbimortalidad y costos del sistema de salud en países en vías de desarrollo. Los principales agentes responsables son Haemophilus influenzae (Hi)b, Neisseria meningitidis (Nm) y Streptococcus pneumoniae (Spn). OBJETIVOS Describir la epidemiología y factores de riesgo de la enfermedad invasiva bacteriana (EIB) en la población que se atiende en el Hospital Pediátrico Provincial de Misiones. MÉTODOS Se realizó un estudio observacional prospectivo de casos y controles, identificando a pacientes con diagnóstico de EIB entre enero de 2015 y marzo de 2016. Se recogieron datos clínicos, de laboratorio y epidemiológicos, que fueron analizados con Epi Info 7. El protocolo fue aprobado por el Comité de Ética. RESULTADOS Se confirmaron 24 casos 11 correspondieron a Spn, 12 a Hi y 1 a Nm. En EIB a Spn no se observó preponderancia de grupos etarios; un 73% eran varones. Spn se identificó por aislamiento en el 100% de los casos, con LPP como sitio de mayor recuperación. Predominaron las neumonías con derrame pleural (7) y hubo un paciente óbito a causa de meningitis. Se identificaron 12 pacientes con EIB a Hi, con 7 varones y 10 lactantes. Hi se aisló en 10 casos, con HMC como líquido con mayor recuperación. Un total de 9 cepas correspondieron al serotipo b. En 2015 predominaron las infecciones a foco pulmonar, y en 2016 las meningitis. Hubo 3 pacientes que obitaron. Se registró 1 caso de EIB a Nm en un varón de 10 meses de edad, con meningitis. Nm desarrolló en LCR y fue seroagrupado como Nm W135. No se observó relación estadísticamente significativa (nivel de confianza del 95%) entre la EIB a capsulados y los factores de riesgo intrínsecos y extrínsecos al paciente. La oportunidad de riesgo no evidenció diferencias entre casos y controles. DISCUSIÓN Se observa un comportamiento diferente de las cepas respecto a años anteriores. Se debe aumentar el número de pacientes para analizar factores de riesgo.

Invasive disease by Streptococcus pyogenes: patients hospitalized for 6 years. / Enfermedad invasiva por Streptococcus pyogenes: ingresos durante 6 años.

INTRODUCTION AND OBJECTIVE: The last years an increase of severe cases of invasive disease (ID) due to Streptococcus pyogenes or streptococcus b-hemolytic group A (SGA) had been detected. The aim of this study was to analyze the epidemiology and the clinical features of ID due to SGA in a tertiary Pediatric Hospital. MATERIAL AND METHODS: Retrospective study in a Pediatric hospital, of all in-patients with final diagnosis of ID due to SGA during 6 years (2009-2014). To consider ID, SGA had to be isolated in sterile samples; in patients with fascitis necroticans in skin samples or in any sample in patients with the diagnostic of Streptococcal Toxic Shock Syndrome (STSS). The SSTS was defined as hypotension and at least 2 of these criteria: renal failure, hepatic failure, acute respiratory distress, tissue necrosis or desquamative erythematous rash. Demographic data, type of infection, risk factors, clinical presentation, analytical data at admission, treatment, need for admission to a pediatric intensive care unit, microbiological data, hospital stay and evolution were collected. RESULTS: Fifty-two (52) cases were included (12/10,000 of all inpatients); 3 years-old was the medium age (p25-75: 1.4-6.9 years); 28 (53.8%) were boys. Fourteen patients (26.9%) had risk factors. Fever was the major symptom (51 patients, 98.1%). The skin lesions were the most frequent clinical manifestations found (21; 40.4%). In 50 (96%) cases, SGA was isolated in at least one sterile sample. Skin and soft tissue infections were diagnosed in 14 patients (26.9%), 14 (26.9%) pneumonias, 12 (23.1%) bones and joints infections, 10 (19.2%) SSTS, 6 (11.5%) occult bacteremia, 4 (7.7%) meningitis and 2 (3.8%) sepsis. Surgery was required in 18 cases (34.6%) and 17 patients (32.7%) needed intensive care. The medium hospital stay was 9.5 days (p25-75: 8-15 days). Three patients presented sequels and one patient died. CONCLUSION: The ID due to SGA was a rare but serious reason for hospital admission. Skin and soft tissue infections, and pleuroneumonia were the most common forms of ID. The mortality of our sample was low despite the serious clinical manifestations.

Serotipos de Streptococcus pneumoniae responsables de enfermedad invasiva en niños cubanos / Streptococcus pneumoniae serotypes responsible for invasive disease affecting Cuban children

Introducción: Streptococcus pneumoniae es causa importante de morbilidad y mortalidad a nivel mundial, fundamentalmente en niños < 5 años. En Cuba aún no se introdujo la vacunación antineumocócica, pero desde 2014, con el propósito de sentar las bases para la evaluación de su impacto, se lleva a cabo un protocolo de vigilancia centinela de la enfermedad neumocócica invasiva en niños ≤ 5 años. Objetivos: notificar los serotipos de S. pneumoniae responsables de enfermedad neumocócica invasiva en la población pediátrica cubana, y valorar la contribución de ese protocolo a la vigilancia. Métodos: se determinaron los serotipos de todos los aislamientos pediátricos invasivos y los recuperados de otitis media aguda, recibidos en el Laboratorio Nacional de Referencia de Neumococo, del Instituto de Medicina Tropical Pedro Kourí, entre 2013-2015. Se utilizó el método de hinchazón capsular empleando el juego de reactivos Pneumotest. Resultados: se notificaron 141 aislamientos invasivos en edad pediátrica. Predominaron los responsables de neumonías (76 vs. 49 aislamientos meníngeos) y la mayoría de estos fueron aportados por los hospitales involucrados en la vigilancia centinela (75 por ciento; 57/76). El 85,8 por ciento de los aislamientos quedaron contenidos en siete serotipos, que por orden de frecuencia fueron: 14, 19A, 6A, 19F, 6B, 3 y 23F. La cobertura serotípica de las diferentes vacunas neumocócicas multivalentes con posibilidades de ser empleadas se estimó entre 54 y 90 por ciento. Conclusiones: tras la introducción de la vacunación cabría esperar una reducción de la enfermedad neumocócica invasiva debida a los serotipos contenidos en las vacunas conjugadas disponibles, pero se insiste en la necesidad de fortalecer la vigilancia clínico-epidemiológica que se hace hoy de esta entidad en el país(AU)

Introduction: Streptococcus pneumoniae is a significant cause of morbidity and mortality worldwide mainly in children younger than 5 years. The pneumococcal vaccination has not been yet put into practice in Cuba; however, since 2014 a protocol of sentinel surveillance of the invasive pneumococcal disease in children aged 5 years or less is being implemented to lay the foundations for the evaluation of the impact of this vaccine. Objectives: to report on the S. pneumoniae serotypes responsible for the invasive pneumococcal disease in the Cuban pediatric population and to assess the contribution of this protocol to surveillance. Methods: the serotypes of all the invasive pediatric isolates and the recovered ones of acute otitis media were determined by the national laboratory of pneumococcal reference of Pedro Kourí Institute of Tropical Medicine from 2013 to 2015. The capsular swelling method was used with the Penumotest reagent set. Results: one hundred and forty one invasive isolates were reported at pediatric ages. The isolates causing pneumonia predominated (76 vs. 49 meningeal isolates) and most of them were provided by hospitals involved in the sentinel surveillance project (57 out of 76; 75 percent). In this regard, 85.8 percent of isolates belonged to seven serotypes that were in order of frequency the following: 14, 19A, 6A, 19F, 6B, 3 and 23F. The serotype coverage of the various multivalent pneumococcal vaccines of possible use was estimated at 54-90 percent. Conclusions: after the introduction of the vaccinations, one might expect that a reduction of the invasive pneumococcal disease occurs due to the serotypes included in the available conjugate vaccines, but emphasis is made on the need of strengthening at present the clinical and epidemiological surveillance system for this disease nationwide(AU)

Infección grave por Staphylococcus aureus meticilino sensible productor de leucocidina de Panton-Valentine: reportes de dos casos / Severe infection by methicillin sensitive Staphylococcus aureus producing Panton-Valentine leukocidin: reports of two cases

Staphylococcus aureus es uno de los principales agentes etiológicos de infecciones en niños provenientes de la comunidad y del ámbito hospitalario. La gravedad de estos cuadros se asocia a factores de virulencia, entre los que se encuentra la leucocidina de Panton-Valentine. Tanto Staphylococcus aureus resistente como sensible a la meticilina producen esta leucocidina, aunque con frecuencia variable. Presentamos a dos niños con infección grave por Staphylococcus aureus sensible a la meticilina productor de leucocidina de Panton-Valentine con complicaciones osteoarticulares y endovasculares. Es fundamental la sospecha diagnóstica, el tratamiento antibiótico adecuado y el manejo quirúrgico precoz para mejorar el abordaje de estas infecciones. Se debe mantener la vigilancia epidemiológica para detectar la frecuencia de las infecciones causadas por estas bacterias.

Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria.

Puesta al día en vacunación antineumocócica en adultos / Update on pneumococcal vaccination in adults

La enfermedad invasiva por Streptococcus pneumoniae constituye una importante causa de morbilidad y mortalidad, y es la primera causa de muerte prevenible mediante vacunación en el mundo, no solo en niños sino en todas las edades. Tanto la vacuna polisacárida como la vacuna conjugada antineumocócicas han demostrado reducción de las tasas de enfermedad invasiva en adultos. En los últimos años, a la luz de nueva evidencia disponible, los esquemas de vacunación antineumocócica para esta población han sufrido modificaciones. Este documento ofrece una actualización sobre las recomendaciones de vacunación a través de los fundamentos que han llevado a dicho cambio. (AU)

The Streptococcus pneumoniae invasive disease is a major cause of morbidity and mortality, being the leading cause of vaccine-preventable death in the world, not only in children but in all ages. Both the polysaccharide vaccine and pneumococcal conjugate vaccine have shown reduced rates of invasive disease in adults. In recent years, in light of new evidence available, schedules of pneumococcal vaccination for this population have changed. This document provides an update on vaccine recommendations through the rational that have led to this change. (AU)

Diecinueve años de vigilancia de enfermedad invasiva neumocócica en un hospital pediátrico de Mendoza, Argentina / Nineteen-years of pneumococcal invasive disease surveillance in a children’s hospital in Mendoza, Argentina

Estudiamos 537 niños internados en el Hospital Dr. Notti, entre 1993 y 2011, con enfermedad invasiva neumocócica. La mediana de edad fue 19 meses (R = 0-192 m); 34,82% fueron < 1 año y 23,46%, t 60 meses. Predominaron neumonía con y sin derrame (48,04%) y meningitis (29,05%), con una letalidad de 6,14%. El 56,86% de los serotipos identificados fueron 14, 5 y 1. Mostraron sensibilidad a la penicilina el 99,74% de cepas no meníngeas y a la ceftriaxona, el 98,08% de cepas meníngeas. Los factores de riesgo en neumonía con derrame se asociaron a la edad t 60 meses, RR 1,47 (1,06-2,04), p 0,02, serotipos 5, RR 2,57 (1,71-3,87), p 0,0001 y 1 RR 1,86 (1,17-2,96), p 0,014 y en las meningitis, principalmente a < 1 año, RR 2,35 (1,87-3,06), p 0,0000 y serotipo 18C, RR 2,19 (1,3-3,7), p 0,024. Conclusión. El Streptococcus pneumoniae representó un problema importante en menores de un año, en quienes predominó la meningitis y causó más de la mitad de las muertes, y en mayores de 60 meses, en los que prevalecieron neumonías con derrame. La mayoría fueron sensibles a la penicilina y a la ceftriaxona.

Five hundred and thirty-seven children admitted to Hospital Dr. Notti and diagnosed with invasive pneumococcal disease between 1993 and 2011 were studied. Their median age was 19 months (range= 0-192 months); 34.82% were <1 year old and 23.46%, ≥60 months old. Pneumonia with or without effusion (48.04%) and meningitis (29.05%) were the most predominant conditions, with a case fatality rate of 6.14%. Identified serotypes corresponded to 14, 5 and 1 in 56.86% of cases. Sensitivity to penicillin was observed in 99.74% of non-meningeal strains, while sensitivity to ceftriaxone was found in 98.08% of meningeal strains. Risk factors in pneumonia with effusion were associated to age ≥60 months old, RR: 1.47 (1.06-2.04), p= 0.02, to serotype 5, RR: 2.57 (1.71-3.87), p= 0.0001, and to serotype 1, RR: 1.86 (1.17-2.96), p= 0.014; in the case of meningitis, risk factors were mainly associated to age <1 year old, RR: 2.35 (1.87-3.06), p= 0.0000, and to serotype 18C, RR: 2.19 (1.3-3.7), p= 0.024. Conclusion. Streptococcus pneumonia was a major problem in infants younger than one year old, who predominantly developed meningitis which caused half of deaths, and in children older than 60 months old, who had a prevalence of pneumonia with effusion. Most cases were sensitive to penicillin and ceftriaxone

[Influence of age on the clinical manifestations of invasive pneumococcal disease and antibiotic resistance rates]. / Influencia de la edad en la enfermedad neumocócica invasiva y en la resistencia a antimicrobianos.

BACKGROUND AND OBJECTIVE: Invasive pneumococcal disease (IPD) shows different epidemiological characteristics depending on age and pneumococcus serotype. The aims of the work were to analyze the clinical manifestations and mortality associated with IPD, the serotype isolated and the antibiotic resistance rates in different age groups. PATIENTS AND METHOD: Retrospectively, 141 patients with IPD diagnosed between 2002 and 2008 were studied. Patients were classified in 4 age groups: ≤ 2 year-old, 3-14 year-old, 15-64 year-old and ≥ 65 year-old. RESULTS: Pneumonia was the most common manifestation in all age groups (71%). Pneumococcal meningitis was more prevalent in patients ≤ 2 year-old (28 vs. 9%, P=.054) and empyema was more frequent in those between 3-14 year-old (31 vs. 5%, P<.001). Mortality was associated with age ≥ 65 year-old (odds ratio [OR] 7, 95% confidence interval [95% CI] 1.9-28.9), primary bacteremia (OR 7, 95% CI 1.9-28.9) and orotracheal intubation (OR 9, 95% CI 1.9-41.1). The more prevalent serotypes among patients ≤ 2 year-old were 14, 19A and 19F. The serotype 1 was most common in patients between 3-14 year-old and serotype 3 in those ≥ 65 year-old. A higher rate of non-susceptible penicillin strains was observed in pediatric population (42 vs. 19%, P=.007). CONCLUSIONS: Age was related to the clinical manifestations, mortality and antibiotic resistance rates. Primary bacteremia was one of the risk factors of mortality.

Absceso hepático como presentación inicial de la enfermedad invasora por Streptococcus pneumoniae / Hepatic abscess as first manifestation of pneumococcal invasive disease

Pneumococcal invasive disease is an important cause of morbidity and mortality in different population groups. Most cases originate from an airway infection. We describe a patient with diabetes mellitus who presented a liver abscess as first manifestation of pneumococcal invasive disease, without respiratory symptoms. The patient was treated with percutaneous drainage and systemic antibiotics with good results. Streptococcus pneumoniae should be considered among the possible etiologies of hepatic abscess, even in absence of respiratory symptoms.

La enfermedad invasora por Streptococcus pneumoniae es una causa importante de morbi-mortalidad en diferentes grupos poblacionales. La mayor parte de los casos se origina a partir de un foco infeccioso primario de origen respiratorio. Se describe el caso de un paciente diabético en el cual esta grave enfermedad se presentó de manera inicial como un absceso hepático sin manifestaciones respiratorias asociadas. El enfermo respondió de manera apropiada al tratamiento quirúrgico percutáneo y a la administración de antimicrobianos sistémicos. Se propone la consideración de S. pneumoniae entre las etiologías posibles de los abscesos hepáticos en sujetos con factores de riesgo para enfermedad invasora por este microorganismo, aún en ausencia de síntomas respiratorios.