Clinical and molecular characteristics of Streptococcus pneumoniae-associated hemophagocytic lymphohistiocytosis in children / 中华儿科杂志

Objective: To summarize the clinical features of Streptococcus pneumoniae-associated hemophagocytic syndrome (SP-HLH), and the serotypes and drug-resistant characteristics of the isolated strains. Methods: There were 15 children with SP-HLH admitted to the Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital, Capital Medical University from January 2013 to December 2020 were included in this study. Clinical data including children's general characteristics, clinical features, laboratory examinations, treatments, prognosis and the outcomes of follow-up by May 2021 were analyzed retrospectively. The serotypes and drug resistance of the isolated strains were identified. All children were divided into the clinical improvement group and the death group. Mann-Whitney U test, Fisher's exact test were used to compare the data of the two groups. Results: Among the 15 children with SP-HLH, 8 were males and 7 were females. The age of these children was 1.0 (1.0, 2.5) years. Regarding the primary infection, there were 9 cases of severe pneumonia, 3 cases of meningitis and 3 cases of blood stream infection. None of these children had received pneumoniae conjugate vaccine (PCV) and all of them were admitted to the PICU. Respiratory failure was observed in 10 patients, acute renal injury in 5, and hemolytic uremic syndrome in 3 patients. All children received glucocorticoids and high-dose intravenous immunogloblin (IVIG) in addition to anti-infective treatment. Eight of the children were cured while the other 7 died. The neutrophil count in the death group was lower than that in the clinical improvement group ((5.0 (1.7, 9.3) × 109 vs. 5.2 (3.4, 10.5) ×109/L, Z =-2.43, P<0.015), and the length of hospital stay and days of PICU stay in the death group were both shorter than those in the improvement group statistically (3 (1, 11) vs. 39 (34, 48) d, 2 (1, 4) vs. 19 (12, 31) d, Z=-3.25, -3.24, both P=0.001). Ten serotypes of Streptococcus pneumoniae were identified, including 4 strains of 19F, 3 of 19A, 1 of 23F, 1 of 15A and 1 of 14, among which 9 strains (9/10) were covered by PCV13. All strains were resistant to erythromycin yet sensitive to vancomycin and linezolid. Conclusions: SP-HLH is more common in children under the age of 3, with a high mortality rate. The death cases have lower neutrophil count and rapid disease progression. The comprehensive treatment is anti-infective combined with glucocorticoids and high-dose IVIG. The predominant serotypes are 19F and 19A and all isolated strains were susceptible to vancomycin and linezolid.

Clinical features and antibiotic sensitivity of invasive pneumococcal disease versus noninvasive pneumococcal disease in children / 中国当代儿科杂志

OBJECTIVE@#To analyze the clinical data of children with invasive pneumococcal disease (IPD) or noninvasive pneumococcal disease (NIPD), and to provide a reference for clinical diagnosis and treatment.@*METHODS@#A retrospective analysis was performed on the medical data and the drug susceptibility test results of isolated strains of 518 children who were hospitalized due to @*RESULTS@#The children with IPD had a median age of 2.2 years, and the children aged ≤5 years accounted for 80.0%. For the children with IPD, the main type of infection was meningitis which was observed in 19 children (54.3%), and the most common underlying disease was hematological malignancy in 8 children (22.9%); 14 children (40.0%) were admitted to the pediatric intensive care unit (PICU), 18 children (51.4%) experienced complications, and 8 children (22.9%) died. For the children with NIPD, the median age was 1.2 years; the main type of infection was pneumonia in 429 children (88.8%), and the most common underlying disease was congenital heart disease in 60 children (12.4%); 60 children (12.4%) were admitted to the PICU, 102 children (21.1%) experienced complications, and 11 children (2.3%) died. The IPD group had significantly higher incidence rate of complications, PICU admission rate, and mortality rate than the NIPD group (@*CONCLUSIONS@#SP infection is common in children under 5 years of age, and the children with underlying diseases including hematological malignancy are at high risk for IPD. Although the complication rate, PICU admission rate, and mortality rate of NIPD children are lower than those of IPD children, they still cannot be ignored. Penicillin may be used as an empirical treatment for children with NIPD, but not for those with IPD.

Antibioticoterapia en la Neumonía Adquirida en la Comunidad / Antibiotic therapy in community acquired pneumonia

Resumen La neumonía es una infección a nivel del parénquima pulmonar, que puede categorizarse según el lugar de contagio como adquirida en la comunidad (NAC) o nosocomial, lo cual resulta muy importante tener presente al momento de definir el manejo. Para fines del presente artículo, se hace énfasis en la NAC de etiología bacteriana, enfatizando aquellas infecciones producidas por microorganismos como: Sreptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae y Legionella sp También se hace referencia a la presentación clínica y pruebas de gabinete existentes para facilitar el diagnóstico y valorar de forma objetiva la evolución del cuadro. Se menciona la utilidad de escalas como la PSI, CURB65, SMART-COP, SCAP, entre otras, para determinar si el manejo más oportuno de la NAC es a nivel ambulatorio o intrahospitalario y, en caso de ser este último, identificar si lo más recomendado es el seguimiento en la Unidad de Cuidados Intensivos (UCI) o en salones de medicina interna. Con respecto al tratamiento, se exponen diversos esquemas de antibioticoterapia recomendados para el manejo de NAC a nivel ambulatorio, intrahospitalario y en unidad de cuidados intensivos (UCI), tales como el uso de penicilinas, inhibidores de betalactamasas, quinolonas, cefalosporinas, macrólidos, entre otros. A su vez, se mencionan los criterios que definen los tiempos de duración de los esquemas antibióticos y las recomendaciones del National Institute for Health and Care Excellence (NICE) para la educación del paciente con NAC por parte del médico tratante.

Abstract: Pneumonia is an infection located in lung parenchyma that can be classified according to the place of acquisition into Community-Acquired Pneumonia (CAP) or Hospital and Healthcare-Acquired Pneumonia, which is of major importance to define the physician management. In this article the main idea to present the bacterial CAP giving special importance to those caused by Sreptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae y Legionella sp. In addition, the following article approaches the clinical presentation and diverse laboratory tests to complement an accurate diagnosis and the evolution of the disease. The scores PSI, CURB65, SMART-COP and SCAP can be a very useful tool to help the physician determine if the patient needs to be hospitalized in an internal medicine service, intensive care unit or if the case can be handled as an outpatient. The antibiotics are keystone to treat the pneumonia, and different therapies designed to manage CAP in outpatients and inpatients are explained, such as amoxicillin, amoxixillin/clavulanate, azithromycin, cefdinir, moxifloxacin among others; as well as the criteria to determine the optimal duration of the treatment. As an addition the recommendations given by the National Institute for Health and Care Excellence (NICE) are provided to the physicians as a tool to improve patient's education and optimize the initial approach and management.

Infecciones invasivas por serotipos no vacunales de Streptococcus pneumoniae: una amenaza creciente / Invasive infections by non-vaccine serotypes of Streptococcus pneumoniae: a growing threat

Resumen Introducción: En México, cuando se inició la aplicación de la vacuna PCV13 (neumocócica conjugada), se cubría el 70.6% de los serotipos causantes de enfermedad invasiva por neumococo en menores de 5 años. Después de varios años, los casos de enfermedad causada por los serotipos incluidos en la vacuna han disminuido; sin embargo, se ha producido un reemplazo por los serotipos no incluidos en la vacuna. Caso clínico: Se presentan tres casos de pacientes pediátricos que desarrollaron enfermedad invasiva por serotipos no incluidos en la PCV13: uno con meningitis y bacteriemia (serotipo 15C) y dos con neumonía, uno de ellos complicado con derrame (serotipo 35B). Los pacientes fueron atendidos en un hospital pediátrico en Saltillo, Coahuila, durante el periodo de 2015 a 2018. Conclusiones: Resulta alarmante que se presenten tres casos graves por serotipos de Streptococcus pneumoniae no incluidos en la PCV13 en un solo hospital pediátrico en el norte del país. Este es un fenómeno que esta sucediendo a escala nacional e internacional: un incremento de casos de enfermedad invasiva por serotipos de neumococo no incluidos en la vacuna utilizada actualmente.

Abstract Background: In Mexico, 70.6% of serotypes causing invasive pneumococcal disease were covered since the application of the PCV13 vaccine in children under 5 years of age. After several years of immunization, cases of disease caused by the serotypes included in the vaccine have decreased. However, a replacement due to serotypes not included in the vaccine has been observed. Case report: Three cases of pediatric patients who developed invasive disease due to serotypes not included in PCV13 are described: one with meningitis and bacteremia (serotype 15C), and two with pneumonia, of which one complicated with effusion (serotype 35B). Patients were treated in a pediatric hospital in Saltillo, Coahuila, from 2015 to 2018. Conclusions: Three serious cases due to serotypes of Streptococcus pneumoniae not included in PCV13 were reported in a single pediatric hospital in a northern state of Mexico. This phenomenon is taking place nationwide and worldwide: an increase of cases of invasive disease due to pneumococcal serotypes not included in the vaccine currently used.

Descripción de 3 casos de infecciones de piel y tejidos blandos por Streptococcus pneumoniae / Description of 3 cases of skin and soft tissue infections caused by Streptococcus pneumoniae

El papel de Streptococcus pneumoniae como agente causal de infecciones de piel y tejidos blandos (IPTB) es inusual y de difícil interpretación clínica. Describimos 3 casos documentados (años 2010, 2011 y 2015) en pacientes internados en el Hospital Provincial de Pediatría de Misiones, detectados durante 10 años de vigilancia de enfermedades invasivas (EI). Estos casos correspondieron a 2 niñas de 8 y 7 meses y a un varón de 2 años con diagnóstico de absceso glúteo, celulitis preseptal y piodermitis, respectivamente. Todos eran eutróficos, con buen estado general al ingreso, uno de ellos seropositivo para virus de la inmunodeficiencia humana. Los aislamientos presentaron características de sensibilidad a antimicrobianos y serotipos que se enmarcaron dentro de la epidemiología local de las EI neumocócicas. A pesar de la baja frecuencia, la etiología de S. pneumoniae en IPTB debe considerarse. Nuestros hallazgos revalorizan el papel del laboratorio en el diagnóstico por cultivo y contribuyen a documentar el comportamiento de este patógeno.

The role of Streptococcus pneumoniae as a causative agent of skin and soft tissue infections (SSTI) is unusual and its clinical interpretation is difficult. We describe here three cases of SSTI due to S. pneumoniae in patients admitted to the Provincial Pediatric Hospital of Misiones, Argentina that were detected during 10 years of invasive disease (ID) surveillance documented in 2010, 2011 and 2015. These cases involved two girls aged 8 and 7 months old, and a two-year-old male child with diagnoses of gluteal abscess, preseptal cellulites and pyoderma respectively. All the patients were eutrophic and in good general condition on admission; one of them was seropositive for HIV. Antimicrobial susceptibility and serotypes were framed within the local epidemiology of invasive pneumococcal disease. Despite its low frequency, S. pneumoniae as an etiological agent of SSTI must be considered. Our findings revalue the role of the diagnostic laboratory and contribute to document the behavior of this pathogen.

Oxacillin disk diffusion testing for the prediction of penicillin resistance in Streptococcus pneumoniae / Prueba de difusión con discos de oxacilina para predecir la resistencia a la penicilina de Streptococcus pneumoniae

ABSTRACT Objective To 1) describe the correlation between the zones of inhibition in 1-µg oxacillin disk diffusion (ODD) tests and penicillin and ceftriaxone minimum inhibitory concentrations (MICs) of meningeal and non-meningeal strains of Streptococcus pneumoniae and 2) evaluate the usefulness of the ODD test as a predictor of susceptibility to penicillin in S. pneumoniae and as a quick and cost-effective method easily implemented in a routine clinical laboratory setting. Methods S. pneumoniae isolates from healthy nasopharyngeal carriers less than 2 years old, obtained in a multicentric cross-sectional study conducted in various Peruvian hospitals and health centers from 2007 to 2009, were analyzed. Using Clinical and Laboratory Standards Institute (CLSI) breakpoints, the correlation between the zones of inhibition of the ODD test and the MICs of penicillin and ceftriaxone was determined. Results Of the 571 S. pneumoniae isolates, 314 (55%) showed resistance to penicillin (MIC ≥ 0.12 µg/mL) and 124 (21.7%) showed resistance to ceftriaxone (MIC ≥ 1 µg/mL). Comparison of the ODD test zones of inhibition and the penicillin MICs, using the CLSI meningeal breakpoints, showed good correlation (Cohen’s kappa coefficient = 0.8239). Conclusions There was good correlation between ODD zones of inhibition and penicillin meningeal breakpoints but weak correlation between the ODD results and non-meningeal breakpoints for both penicillin and ceftriaxone. Therefore, the ODD test appears to be a useful tool for predicting penicillin resistance in cases of meningeal strains of S. pneumoniae, particularly in low- and middle- income countries, where MIC determination is not routinely available.

RESUMEN Objetivo 1) Describir la correlación entre las zonas de inhibición observadas en la prueba de difusión con discos de oxacilina de 1 µg y la concentración inhibitoria mínima (CIM) de penicilina y ceftriaxona frente a cepas meníngeas y no meníngeas de Streptococcus pneumoniae y 2) evaluar si la prueba de difusión con discos de oxacilina permite predecir la sensibilidad de S. pneumoniae a la penicilina y sirve como método rápido y eficaz en función de los costos, y resulta fácil de aplicar en los laboratorios clínicos ordinarios. Métodos Se analizaron colonias de S. pneumoniae aisladas de la nasofaringe de portadores sanos menores de 2 años obtenidas en un estudio transversal multicéntrico realizado en diversos hospitales y centros de salud del Perú entre los años 2007 y 2009. Se determinó la correlación entre las zonas de inhibición observadas en la prueba de difusión con discos y la CIM de la penicilina y la ceftriaxona utilizando los valores críticos definidos por el Instituto de Estándares Clínicos y de Laboratorio. Resultados De las 571 colonias aisladas de S. pneumoniae, 314 (55 %) presentaron resistencia a la penicilina (CIM ≥ 0,12 µg/ml) y 124 (21,7%), resistencia a la ceftriaxona (CIM ≥ 1 µg/ml). Se observó una buena correlación (coeficiente κ de Cohen = 0,8239) entre las zonas de inhibición de la prueba de difusión con discos y la CIM de la penicilina utilizando los valores críticos del Instituto respecto de las cepas meníngeas. Conclusiones Se encontró una buena correlación entre las zonas de inhibición de la prueba de difusión con discos y los valores críticos de CIM de la penicilina respecto de las cepas meníngeas, pero una correlación débil entre los resultados de la prueba de difusión y los valores críticos tanto de la penicilina como de la ceftriaxona respecto de las cepas no meníngeas. Por consiguiente, la prueba de difusión con discos es un método de utilidad para predecir la resistencia a la penicilina de las cepas meníngeas de S. pneumoniae, en particular en los países de ingresos bajos y medianos, donde no suele ser posible determinar la CIM.

Clinical and microbiological implications of invasive pneumococcal disease in hospitalized patients (1998-2013)

Abstract Introduction Infections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. Objective The objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. Materials and methods This was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital – Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. Results The sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio = 4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio = 3.8) and when adjusted for comorbidity (Odds Ratio = 5.0) or age (Odds Ratio = 5.4). The same occurred with serotype 12F (respectively, Odds Ratio = 5.1, Odds Ratio = 5.0, and Odds Ratio = 4.7) Conclusion The present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and adequacy of immunization.

Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012

In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period.

Functional low vision in adults from Latin America: findings from population-based surveys in 15 countries / Baja visión funcional en adultos de América Latina: resultados de las encuestas poblacionales realizadas en 15 países

OBJECTIVE: To review data on functional low vision (FLV) (low vision-visual acuity (VA) < 6/18 (<20/60) to > perception of light (PL+) in the better eye-that is untreatable and uncorrectable) in adults aged 50 years or older from published population-based surveys from 15 countries in Latin America and the Caribbean. METHODS: Data from 15 cross-sectional, population-based surveys on blindness and visual impairment (10 national and five subnational) covering 55 643 people > 50 years old in 15 countries from 2003 to 2013 were reanalyzed to extract statistics on FLV. Eleven of the studies used the rapid assessment of avoidable blindness (RAAB) method and four used the rapid assessment of cataract surgical services (RACSS) method. For the 10 national surveys, age-and sex-specific prevalence of FLV was extrapolated against the corresponding population to estimate the total number of people > 50 years old with FLV. RESULTS: Age- and sex-adjusted prevalence of FLV in people > 50 years old ranged from 0.9% (Guatemala, Mexico, and Uruguay) to 2.2% (Brazil and Cuba) and increased by age. The weighted average prevalence for the 10 national surveys was 1.6%: 1.4% in men and 1.8% in women. For all 10 national studies, a total of 509 164 people > 50 years old were estimated to have FLV. Based on the 910 individuals affected, the main causes of FLV were age-related macular degeneration (weighted average prevalence of 26%), glaucoma (23%), diabetic retinopathy (19%), other posterior segment disease (15%), non-trachomatous corneal opacities (7%), and complications after cataract surgery (4%). CONCLUSIONS: FLV is expected to rise because of 1) the exponential increase of this condition by age, 2) increased life expectancy, and 3) the increase in people > 50 years old. These data can be helpful in planning and developing low vision services for the region; large countries such as Brazil and Mexico would need more studies. Prevention is a major strategy to reduce FLV, as more than 50% of it is preventable.

OBJETIVO: Analizar los datos de las encuestas poblacionales publicadas provenientes de 15 países de América Latina y el Caribe sobre baja visión funcional (BVF) (baja visión, desde una agudeza visual [AV] inferior a 6/18 [20/60] hasta > percepción de luz (PL+), en el mejor ojo, no tratable ni corregible) en adultos de 50 años de edad o mayores. MÉTODOS: Con objeto de extraer información estadística en materia de BVF, se volvieron a analizar los datos de 15 encuestas transversales poblacionales sobre ceguera y deficiencia visual realizadas del 2003 al 2013 (10 a escala nacional y cinco subnacio-nales) que abarcaron a 55 643 personas de > 50 años de edad en 15 países. Once de los estudios emplearon el método de Evaluación Rápida de la Ceguera Evitable y cuatro utilizaron el método de Evaluación Rápida de de Catarata y Servicios Quirúrgicos. Al analizar las 10 encuestas nacionales, se extrapoló la prevalencia específica por edad y sexo de la BVF frente a la población correspondiente, con objeto de calcular el número total de personas de > 50 años de edad con BVF. RESULTADOS: La prevalencia de la BVF ajustada por edad y sexo en personas de > 50 años de edad varió desde 0,9% (en Guatemala, México y Uruguay) a 2,2% (en Brasil y Cuba) y aumentó con la edad. La prevalencia promedio ponderada en las 10 encuestas nacionales fue de 1,6%: 1,4% en hombres y 1,8% en mujeres. Al considerar los 10 estudios nacionales en su conjunto, se calcularon un total de 509 164 personas de > 50 años de edad con BVF. Con base en las 910 personas afectadas, las principales causas de BVF fueron la degeneración macular relacionada con la edad (prevalencia promedio ponderada de 26%), el glaucoma (23%), la retinopatía diabética (19%), otras enfermedades del segmento posterior del ojo (15%), las opacidades corneales no tracomatosas (7%) y las complicaciones posteriores a la cirugía de la catarata (4%). CONCLUSIONES: Se prevé que la BVF aumente como consecuencia de 1) el aumento exponencial de esta afección con la edad, 2) la mayor esperanza de vida, y 3) el aumento de personas de > 50 años de edad. Estos datos pueden ser útiles para planificar y extender los servicios de atención a la disminución de la agudeza visual en la Región; países extensos, como Brasil y México, requerirían nuevos estudios. La prevención constituye una estrategia muy importante para reducir la BVF, ya que más de 50% de los casos se pueden prevenir.

Prevalencia de Streptococcus pneumoniae serotipo 19A antes y después de la introducción de la vacuna conjugada heptavalente en México / Prevalence of Streptococcus pneumoniae serotype 19A before and after the introduction of the heptavalent conjugate vaccine in Mexico

Objetivo. Conocer la prevalencia de S. pneumoniae serotipo 19A (Spn19A) antes y después de la introducción de la vacuna conjugada heptavalente (PCV7) en México. Material y métodos. Estudio descriptivo realizado con la información sobre vigilancia de enfermedades causadas por neumococos, generada por la red Sireva. Se realizó un análisis de regresión lineal con la proporción de cepas de Spn19A por año, en dos periodos. Los datos se analizaron con el paquete estadístico SPSS v.18. Resultados. Durante el periodo 2000-2012 se recuperaron 1 825 cepas de S. pneumoniae causantes de infección en población pediátrica, de las cuales 225/12.3% fueron Spn19A, y de éstos, 75/6.3% se aislaron en el periodo 2000-2008 y 150/23.6% en el periodo 2009-2012. La resistencia antimicrobiana post-vacunal aumentó para todos los fármacos, excepto a vancomicina. Conclusión. Se observó que la frecuencia de este serotipo y la resistencia a antimicrobianos aumentó posterior a la introducción de la PCV7.

Objective. To determine the prevalence of S. pneumoniae serotype 19A (Spn19A), before and after the introduction of heptavalent pneumococcal conjugate vaccine (PCV7) in Mexico. Materials and methods. Descriptive study carried out in Mexico with surveillance information of pneumococcal disease, generated from the Sireva network. We performed lineal regression analysis with the proportion of Spn19A by year in two study periods. Data were analyzed using SPSS v.18 software. Results. A total of 1825 S. pneumoniae strains causing infection in pediatric population were recovered in the period 2000-2012, 225/12.3% were Spn19A, and of these, 75/6.3% were isolated in 2000-2008 and 150/23.6% in 2009-2012. There was an increase in antimicrobial resistance post-vaccination for all drugs except vancomycin. Conclusion. It was observed that the frequency of this serotype and antimicrobial resistance increased after the introduction of PCV7.

Antimicrobial resistance in streptococcus pneumoniae: mechanisms and current epidemiology

Infections caused by Streptococcus pneumoniae are a worrisome public health problem worldwide. Young children and the elderly are the main age groups affected and the highest burden of the disease is found in developing countries. Pneumococcal infections cause 11% of the total infant deaths, representing the leading cause of child death currently preventable by vaccination. Epidemiologic information about pneumococci in Brazil is somehow restricted, but available data reinforce the worrisome occurrence of pneumococcal diseases, which are commonly treated empirically. Limitations in the diagnostic methods, along with the severity of disease contribute to this behavior. Thus, surveillance studies are crucial to define the prevalence of resistant strains both globally and in a particular region, as these strains may compromise empirical therapeutic choices. However, although different clones of penicillin non-susceptible pneumococci are internationally distributed, and considering diseases other than meningitis, the prevalence of resistance to penicillin is quite low, making this old, safe, and inexpensive drug an attractive first choice to treat pneumococcal infections. The widespread use of conjugate vaccines among children, influencing the circulation of resistant clones and the distribution of serotypes reinforces the need of surveillance studies to define the prevalence of resistance

Vigilancia epidemiológica prospectiva de la enfermedad neumocócica invasora y de la neumonía en niños de San José, Costa Rica / Prospective epidemiologic surveillance of invasive pneumoccal disease and pneumonia in children in San Jos‚, Costa Rica

Justificación y objetivo: Streptococcus pneumoniae es globalmente la primera causa de muertes inmunoprevenibles en niños menores de 5 años. Métodos: entre 2007 y 2009 se realizó una vigilancia prospectiva con base poblacional en niños de 28 días a 36 meses en San José, Costa Rica. Se determinaron la incidencia de la enfermedad neumocócica invasora y de neumonía confirmada clínicamente y por radiografía, la distribución de serotipos y la sensibilidad a los antibióticos. Resultados: participaron 8801 sujetos (mediana de edad: 13,0 meses). En 25 niños se detectó enfermedad neumocócica invasora mediante aislamiento en cultivos (22) o mediante reacción de polimerasa en cadena y un cuadro clínico compatible con enfermedad neumocócica invasora. En los casos diagnosticados únicamente por cultivo, la tasa de incidencia de enfermedad neumocócica invasora en niños de 28 días a 36 meses de edad fue de 33,7/100000 por año para los años 1 y 2 combinados. Al considerar los casos adicionales diagnosticados por reacción de polimerasa en cadena, la incidencia aumnetó a 46,/100 000. El serotipo más frecuente fue el 14 (28,6 por ciento), seguido por los serotipos 3, 4, 6A, 19A, 22F. 42,9 por ciento de los aislamientos eran insensibles a la penicilina y al cotrimoxazol. La incidencia de neumonía confirmada clínicamente y de neumonía confirmada por radiografía fue de 1968/100 000 y 551/100 000, respectivamente. Conclusión: la incidencia de enfermedad neumocócica invasora y neumonía en niños de San José es considerable. Estos datos epidemiológicos sirven como línea de base para evaluar la efectividad de nuevas vacunas antineumocócicas conjugadas.

Susceptibilidad antimicrobiana, serotipos capsulares y relación clonal entre cepas invasoras de Streptococcus pneumoniae aisladas de pacientes adultos de la Región del Bío-Bío, Chile: Período 2005-2006 / Antimicrobial susceptibility, capsular serotypes and clonal relationship of invasive Streptococcus pneumoniae isolates in adult population of the Bio-Bio Region, Chile: 2005-2006

Las infecciones ocasionadas por Streptococcus pneumoniae constituyen un problema de salud pública. En nuestro país existe escasa información sobre aislados de procesos bacteriémicos en población adulta. Se estudió la susceptibilidad, serotipos y relación clonal de 56 aislados de S. pneumoniae desde hemocultivos, entre enero 2005 y agosto 2006, de pacientes adultos de la intercomuna Concepción-Talcahuano, Región del Bío-Bío, Chile. Se encontró resistencia a tetraciclina (21,4 por ciento), cotrimoxazol (18 por ciento), eritromicina (18 por ciento), cloranfenicol (7 por ciento) y a penicilina en un solo aislado procedente de un foco meníngeo (2 por ciento). La totalidad mostró susceptibilidad a cefotaxima, levofloxacina, moxifloxacina y vancomicina. Se demostró una amplia variedad de serotipos capsulares, con predominio de los serotipos 1, 5, 23F, 7F y 3. El análisis de macrorestricción y electroforesis en campo pulsado reveló 31 patrones electroforéticos con 12 grupos clona-les, descartando un clon predominante. De acuerdo a los resultados, al menos 80 por ciento de los serotipos de aislados de S. pneumoniae de procesos bacteriémicos están incluidos en la vacuna comercial disponible.

Streptococcus pneumoniae infections constitute a public health problem. In our country there is scarce information regarding isolates from bacteraemic episodes in adult population. The antibiotic susceptibility, sero-types and clonal relationship of 56 isolates of S. pneumoniae from adult patients with bacteraemic infections in Concepcion-Talcahuano, Bio-Bio Region, Chile, were studied. Resistance to tetracycline (21.4 percent), trimethoprim/ sulfamethoxazole (18 percent), erythromycin (18 percent), chloramphenicol (7 percent) and 1 penicillin resistant isolate from a meningeal focus (2 percent) was found. Also, all the isolates were susceptible to cefotaxime, levofloxacin, moxifloxacin and vancomycin. A wide variety of capsular serotypes was demonstrated, with predominance of serotypes 1, 5, 23F, 7F and 3. The macrorestriction analysis by pulse field electrophoresis revealed 31 electrophoretic patterns and 12 clonal groups, discarding a predominant clone. According to the results, at least, 80 percent of the S. pneumoniae serotypes isolated from bacteraemic adult patients are included in the available commercial vaccine.

Invasive pneumococcal disease in a third level pediatric hospital in Mexico City: epidemiology and mortality risk factors / Enfermedad neumocócica invasora en un hospital pediátrico de tercer nivel en la Ciudad de México: características epidemiológicas y factores de riesgo asociados con mortalidad

Objective. To assess the epidemiologic characteristics of invasive pneumococcal diseases (IPD) among a population in a pediatric hospital in Mexico City and analyze mortality-related risk factors, serotype distribution and antibiotic susceptibility related to S.pneumoniae. Material and Methods. We performed a retrospective review of IPD cases at a third level pediatric hospital between 1997-2004. Results. A total of 156 patients were included. The mortality rate was 27.5 percent and was associated with six pneumococcal serotypes: 14, 6B, 23F, 6A, 19F and 19A. There was no relationship between mortality and antimicrobial susceptibility pattern. A total of 28.2 percent of isolates were resistant to penicillin and 24.6 percent were resistant to cefotaxime. A statistically significant relationship was observed between mortality and previous underlying disease (CI 95 percent; 2.5-18.3; p< 0.05) using a multivariate logistic regression model. Conclusions. Our outcomes show that IPD mortality in our population is closely related to underlying disease and to six serotypes, five of which are included in the 7-valent pneumococcal conjugate vaccine.

Objetivo. Conocer la epidemiología de la enfermedad neumocócica invasora (ENI) en un hospital pediátrico y analizar los factores de riesgo relacionados con la mortalidad, la distribución de serotipos y el patrón de susceptibilidad de S. pneumoniae. Material y métodos. Revisión retrospectiva de los casos de ENI en un hospital pediátrico de tercer nivel, entre 1997 y 2004. Resultados. En 156 pacientes la mortalidad fue de 27.5 por ciento. Los serotipos de neumococo más frecuentemente relacionados con la mortalidad fueron: 14, 6B, 23F, 6A, 19F y 19A; no hubo relación de mortalidad con la resistencia a antibióticos. El 28.2 por ciento mostró resistencia a penicilina y 24.6 por ciento a cefotaxima. A través del modelo multivariado, se encontró una relación estadísticamente significativa entre la mortalidad y enfermedad previa (IC 95 por ciento; 2.5-18.3; p<0.05). Conclusiones. La mortalidad asociada a la ENI tuvo relación significativa con antecedente de una enfermedad previa y con seis serotipos, cinco incluidos en la vacuna neumocócica conjugada 7-valente.

Avances en el desarrollo de las vacunas neumocócicas conjugadas: [revisión] / Update on pneumococcal conjugate vaccines: [review]

El estreptococcus pneumoniae se encuentra entre los mayores patógenos causantes de infecciones invasoras y no invasoras en los dos extremos de la vida: en niños menores de 5 años y en personas mayores de 65 años de edad. Las principales manifestaciones asociadas a infecciones neumocócicas son: neumonía, bacteriemia febril, septicemia, otitis media y meningitis. Esta bacteria es uno de los principales agentes involucrados en la mortalidad infantil, con un estimado de 1000000 de muertes globales por año, en niños menores de 5 años de edad, la mayoría provenientes de países en vías de desarrollo, por lo que es considerada como un serio problema para la salud pública alrededor del mundo. En el 2000 se introdujo al mercado de los Estados Unidos de Norte América, la primera vacuna neumocócica conjugada, que a diferencia de la ya disponible vacuna neumocócica polisacárida, es capaz de proporcionar una respuesta inmune efectiva para la protección de niños menores de 2 años. La eficacia reportada para la vacuna conjugada heptavalente en los ensayos clínicos iniciales fue de un 97.4 por ciento contra la enfermedad neumocócica invasora producida por los serotipos incluidos en la vacuna, 4, 9V, 14, 19F, 23F, 18C y 6B. En la actualidad diferentes entidades regulatorias, incluyendo la Agencia Europea de Medicamentos, EMEA, han autorizado la comercialización de la vacuna conjugada 10-valente, en la que, además de los serotipos descritos para la vacuna 7-valente, se incluyen los serotipos 1, 5 y 7F; de estos diez serotipos, ocho se encuentran conjugados con la proteína transportadora D, un elemento que se encuentra en la porción externa del Haemophilus influenzae. La otra nueva vacuna conjugada que está en fase de análisis por diferentes entidades regulatorias, incluyendo la Administración de Alimentos y Drogas de los Estados Unidos...

Streptococcus pneumoniae is one of the major pathogens causing invasive and non invasive infections in children younger than 5 years as well as in the elderly. Primary clinical syndromesassociated with pneumococcal infections are pneumonia, bacteremia, acute otitis media andmeningitis. This microorganism contributes importantly to morbidity and mortality among children under 5years of age, it is estimated that 1,000, 000 deaths occurs per year in that age range alone, mostly from developing countries, thus becoming a serious public health problem around the globe. In year 2000 the first heptavalent conjugated pneumococcal vaccine was licensed in the United States of America, it differed from the already available polysaccharide pneumococcal vaccine,by its ability to provide an effective immune response for the protection of children under the age of 2. The efficacy of the heptavalent conjugated vaccine reported in initial clinical trials was 97,4% against invasive pneumococcal disease related to vaccine serotypes (4, 9V, 14, 19F, 23F, 18C and 6B). Different health authorities worldwide, including the European Medicines Agency(EMEA) had approved the introduction of a 10-valent formulation which includes all 7 PCV7 serotypes plus serotypes 1, 5 and 7F; 8 serotypes are conjugated with protein D as a novel carrier, an element found in the outer core of the non-typeable Haemophilus influenzae. Another new conjugated vaccine is being assessed by several regulatory entities such as the Food and Drug Administration (FDA) and EMEA and in Chile is already approved. This 13-valent formulation includes the 10 serotypes contained in the 10-valent vaccine plus serotypes 3, 6A and 19A, all conjugated to the carrier protein CRM197. These new formulations pretend to enhance vaccine coverage against S. pneumoniae including the frequent serotypes in developing countries (1 and 5) and emerging serotypes such as serotypes 3, 6A, 17F and 9A after a decade of PCV7 immunization.

Antimicrobial resistance in clinical isolates of Streptococcus pneumoniae in a tertiary hospital in Kuwait, 1997-2007: Implications for empiric therapy

This study evaluated antibiotic resistance trends in Streptococcus pneumoniae isolated in a tertiary hospital in Kuwait and its implications for empiric therapy. Antimicrobial susceptibility of 1353 strains of S. pneumoniae isolated from clinical specimens during 1997-2007 was performed by disc diffusion method. MIC was determined by E test. The results were compared for 1997-2001, 2002-2005 and 2006-2007. The prevalence of resistance for the respective periods were as follows: penicillin, 51.3%, 61.3% and 54.5%; erythromycin, 31.2%, 36.7% and 37.7%; tetracycline, 30.8%, 45.3% and 41.3%; co-trimoxazole, 49.5%, 58.5% and 62.8%; clindamycin, 20.4%, 20.6% and 24.5% and chloramphenicol, 8.1%, 8.9% and 3.7%. All were susceptible to vancomycin and rifampicin. For oxacillin-resistant isolates, penicillin resistance was rare [0.8%] with the new non-meningeal breakpoint. However, using the meningeal breakpoints, resistance increased for penicillin from 0.6%, to 28.7%, for cefotaxime from none to 16.5%, and for ceftriaxone from none to 7%. Intermediate resistance to meropenem increased from 1.7% to 22.4%. Multiple drug resistance increased from 22.4% to 37.8%. The study demonstrated that antimicrobial resistance of S. pneumoniae is increasing in Kuwait. However, the results of MIC determinations indicated that penicillin can still be used for therapy of non-meningeal infections. High prevalence of erythromycin resistance suggests that therapy of pneumonia with a macrolide alone may result in failure and should be based on results of susceptibility testing

Clinical behavior of Streptococcus pneumoniae meningoencephalitis / Comportamiento clinico y terapéutico de la meningoencefalitis por Streptococcus pneumoniae

OBJECTIVE: There was an increased number of cases of meningoencephalitis caused by Streptococcus pneumoniae, after the successful vaccination campaigns against Neisseria meningitidis and Haemophilus influenzae. This paper aims at describing the clinical characteristics, the laboratory findings, the complications, and the therapeutic management of these patients, who have been suffering from this disease since 1993 to 2006. METHOD: Twelve children with Streptococcus pneumoniae meningoencephalitis admitted to the pediatric hospital of San Miguel del Padron, City of Havana in this period were assessed. RESULTS: Children under one year are the most frequently affected. Septic shock and brain edema were the most severe complications. Three patients died, implying that this disease has a serious course. Early treatment of brain edema is very important to reduce mortality. The elective drugs for treatment of these cases of Streptococcus pneumoniae meningoencephalitis were vancomycin combined with cephalosporin, cefotaxime or ceftriaxone type. CONCLUSION: Patients with Streptococcus pneumoniae meningoencephalitis show clinical characteristics, complications, and sequels that are different to other bacterial meningoencephalitis, meaning that they could be helpful for physicians considering the differential diagnosis of meningoencephalitis.

OBJETIVO: Existe un incremento de la meningoencefalitis producida por Streptococcus pneumoniae, después de las campañas exitosas de vacunación contra Neisseria meningitidis y Haemophilus influenzae. El objetivo de este trabajo es describir las caracteristicas clinicas, los hallazgos de laboratorio, las complicaciones y el manejo terapéutico de los pacientes que sufrieron esta enfermedad desde 1993 a 2006. MÉTODO: Se estudiaron doce niños con meningoencefalitis por Streptococcus pneumoniae ingresados en el Hospital Pediátrico de San Miguel del Padrón, Ciudad de La Habana en este periodo. RESULTADOS: Los niños menores de un año son los más frecuentemente afectados. El shock séptico y el edema cerebral las mayores complicaciones. Tres pacientes fallecieron. Esta enfermedad ha tenido un curso serio. El tratamiento temprano del edema cerebral es muy importante para reducir la mortalidad. Los medicamentos de elección para tratar la meningoencefalitis por Strepcococcus pneumoniae en los casos estudiados fueron la vancomicina combinada con cefalosporina del tipo de la cefatoxima o la ceftriaxona. CONCLUSION: Los pacientes con meningoencefalitis por Streptoccocus pneumoniae exhibieron características clínica, complicaciones y secuelas las cuales se diferencian de otras meningoencefalitis bacterianas. Por eso estos elementos pueden ayudar a los médicos en el diagnóstico diferencial

Cotrimoxazole resistance in Streptococcus pneumoniae isolated from sputum of HIV-positive patients / Resistencia al Cotrimoxazol del Streptococcus pneumoniae aislado del esputo de pacientes VIH positivos en Lagos

The prevalence and cotrimoxazole susceptibility of Streptococcus pneumoniae isolated from sputum of 100 HIV-positive patients attending the Nigeria Institute of Medical Research clinic was investigated using standard microbiological methods. Eleven of the sputum specimens grew Streptococcus pneumoniae. Antimicrobial susceptibility test showed that all the isolates were sensitive to amoxicillin, augmentin, erythromycin and chloramphenicol but were resistant to cotrimoxazole. Continuous surveillance of S pneumoniae in sputum samples of HIV-positive subjects in this environment is necessary in order to regulate treatment regimen, considering that cotrimoxazole is the drug recommended by WHO for respiratory infections in HIV patients.

Usando métodos microbiológicos convencionales, se investigó la prevalencia y la susceptibilidad al cotrimoxazol, del neumococo Streptococcus pneumoniae aislado a partir del esputo de 100 pacientes VIH-positivos que asistían a la clínica del Instituto Nigeriano de Investigaciones Médicas, Once de las muestras de esputo desarrollaron Streptococcus pnemoniae. La prueba de susceptibilidad antimicrobiana mostró que todos los aislados eran sensibles a la amoxicilina, la augmentina, la eritromicina, y el cloranfenicol, pero resistentes al cotrimoxazol. La vigilancia continua de S pneumoniae en las muestras de esputo de sujetos VIH positivos en este ambiente, es necesaria para regular el régimen del tratamiento, tomando en consideración que el cotrimoxazol es el medicamento recomendado por la OMS para las infecciones respiratorias en los pacientes de VIH.