Oxacillin disk diffusion testing for the prediction of penicillin resistance in Streptococcus pneumoniae.

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.

The cost-effectiveness of human papillomavirus vaccination in the Philippines.

Cervical cancer is the second most common cancer among women in the Philippines. Human papillomavirus (HPV) vaccination provides protection from the most common cancer-causing HPV types. This analysis used a proportionate outcomes model to estimate the potential cost-effectiveness of four different HPV vaccine products-Cervarix™, Cecolin®, GARDASIL®, and GARDASIL®9-for routine HPV vaccination of 10 cohorts of 9-year-old girls from the government and societal perspectives. Model parameters included cervical cancer burden, healthcare and program costs, vaccine efficacy with and without potential cross-protection, and vaccination coverage. Univariate and probabilistic sensitivity analyses evaluated the impact of uncertainty on model results. Compared to no vaccination, HPV programs with Cecolin®, Cervarix™, and GARDASIL® are projected to be cost-effective at US$1,210, US$1,300, and US$2,043 per DALY averted, respectively, from the government perspective, and at US$173, US$263, and US$1,006 per DALY averted, respectively, from the societal perspective when cross-protection was considered. When direct comparisons were made across vaccines, GARDASIL® was dominated by Cervarix™ and Cecolin®. In a scenario where cross-protection was not considered, results were similar except that Cervarix™ and GARDASIL® were both dominated by Cecolin®. GARDASIL®9 was not cost-effective under any of the modeled scenarios.

Invasive pneumococcal diseases among hospitalized children in Lima, Peru.

OBJECTIVE: To determine the epidemiology of invasive pneumococcal disease (IPD) and the antibiotic susceptibility and serotype distribution of S. pneumoniae in pediatric patients in Lima, Peru. METHODS: A 2-year, multicenter, passive surveillance study conducted from May 2006- April 2008 in 11 public hospitals and five private laboratories in Lima, Peru, in patients less than 16 years of age with sterile site cultures yielding S. pneumoniae. Antibiotic susceptibility was performed by Etest® (AB Biodisk, Solna, Switzerland). Strains were serotyped by the Quellung reaction. RESULTS: In all, 101 IPD episodes were studied, 68.3% of which were among children less than 24 months of age. Diagnoses were: pneumonia (47.5%), meningitis (38.6%), and sepsis (7.9%). The overall case fatality rate was 22.0%; case fatality rate in meningitis was 32.4%. While 80.0% of fatal cases were in those less than 24 months of age, only 50.7% of non-fatal cases (P < 0.05) were in this age group. Resistance rates were high for trimethoprim/ sulfamethoxazole (76.2%), erythromycin (24.8%), and penicillin (22.8%). The most common serotypes were 14, 6B, 19F, 23F, and 5, which accounted for 69.7% of all strains and 87.0% of penicillin non-susceptible strains. CONCLUSIONS: IPD in hospitalized children in Lima is associated with high antimicrobial resistance levels and elevated case fatality rate, especially in young children. This baseline data will be useful for evaluating the effects of vaccine introduction.

[Antibiotic resistance and distribution of serotypes of invasive pneumococcal strains isolated from hospitalized adults in Lima, Peru]. / Resistencia antibiótica y distribución de serotipos en cepas neumocócicas invasivas en adultos hospitalizados en Lima, Perú.

OBJECTIVES.: To describe the clinical characteristics, antibiotic resistance, and distribution of serotypes of bacterial strains that cause invasive pneumococcal disease (IPD) in adults. MATERIALS AND METHODS.: Case series. Pneumococcal strains were isolated from 2009 to 2011 from hospitalized adult patients with IPD in five hospitals and two laboratories located in Lima. RESULTS.: The analysis of data from 43 patients with IPD indicated that 58.2% were older than 60 years. The most common complications were pneumonia (39.5%), meningitis (30.2%), bacteremia (13.9%), peritonitis (11.6%), and septic arthritis (4.8%). The mortality rate was 28.9%, and 72.7% of cases involved patients older than 60 years. The pneumococcal strains were resistant to the following antibiotics: penicillin, 0% and 30.8% in non-meningitis and meningitis strains, respectively; ceftriaxone, 4.5% and 16.7% in non-meningitis and meningitis strains, respectively; trimethoprim/sulfamethoxazole, 69.0%; and erythromycin, 35.7%. The most common serotypes were 19F, 23F, 6B, 14, and 6C. The percentage of vaccine strains was 44.2% for the 7-valent conjugate pneumococcal vaccine (PCV7) and PCV10, 51.2% for PCV13, and 60.4% for the 23-valent polysaccharide vaccine (PPV23). CONCLUSIONS.: Pneumococcus is an important pathogen in adults, particularly in older adults, owing to its high mortality rate.

OBJETIVOS.: Describir las características clínicas, resistencia antibiótica y distribución de serotipos de cepas causantes de enfermedad neumocócica invasiva (ENI) en adultos. MATERIALES Y MÉTODOS.: Estudio tipo serie de casos. Se recolectaron cepas de neumococo de pacientes adultos hospitalizados con ENI en cinco hospitales nacionales y dos laboratorios de Lima durante los años 2009-2011. RESULTADOS.: Se estudiaron datos de 43 pacientes con ENI, el 58,2% fueron mayores de 60 años. Los diagnósticos fueron neumonía 39,5%, meningitis 30,2%, bacteriemia 13,9%, peritonitis 11,6%, artritis séptica 4,8%. El porcentaje de fallecidos fue 28,9%, de los cuales el 72,7% fueron mayores de 60 años. Las cepas de neumococo presentaron la siguiente resistencia: penicilina 0% en cepas no meningitis y 30,8% en cepas meningitis; ceftriaxona 4,5% y 16,7% de resistencia intermedia en cepas no meningitis y cepas meningitis respectivamente; 69% a trimetoprim/sulfametoxazol y 35,7% a eritromicina. Los serotipos más comunes fueron 19F, 23F, 6B, 14 y 6C. El porcentaje de cepas vacunales fue 44,2% para la vacuna conjugada siete-valente (PCV7) y para la PCV10, 51,2% para PCV13 y 60,4% para la vacuna polisacárida veintitrés-valente (PPV23). CONCLUSIONES.: El neumococo es un patógeno relevante en adultos, en especial en los adultos mayores, debido a su elevada mortalidad.

[Epidemiologic, clinical and bacteriologic characteristics of pneumococcal meningitis in pediatric patients from Lima, Peru]. / Características epidemiológicas, clínicas y bacteriológicas de meningitis neumocócica en pacientes pediátricos de Lima, Perú.

OBJECTIVES.: To describe the clinical characteristics, lethality, antibiotic susceptibility, and serotype distribution of pneumococcal meningitis in pediatric patients in Lima, Peru. MATERIALS AND METHODS.: A case series of pneumococcal meningitis in children less than 16 years of age from two prospective, multicenter, passive surveillance studies of invasive pneumococcal diseases held in Lima-Peru from 2006 to 2008 and 2009 to 2011. RESULTS.: We report 44 pneumococcal meningitis episodes; 68.2% of them were in children less than 2 years old. The overall case fatality rate was 32.6%; 92.9% of fatal cases were in children less than 2 years of age (p<0.05). Malnutrition was associated with fatal cases (p<0.05). 64.3% of fatal cases died within the first two days. 41.9% of pneumococcal isolates were resistant to penicillin, 23.3% were intermediate resistant to ceftriaxone (none were highly resistant) and 9.3% were resistant to chloramphenicol. The most common serotypes were 6B, 14, 19F and 23F, which accounted for 68.3% of all strains; 84.1% of strains were PCV13 serotypes. CONCLUSIONS.: Pneumococcal meningitis continues to be a lethal disease, especially in children less than 2 years of age. Since almost two third of lethal cases lead to death within the first 48 hours, prompt diagnosis and management is critical, as well as assurance of immunization with pneumococcal vaccine.

[Antibiotic resistance of streptococcus pneumoniae among healthy nasopharyngeal carriers in seven regions of Peru]. / Resistencia antibiótica de streptococcus pneumoniae en portadores nasofaríngeos sanos de siete regiones del Perú

OBJECTIVES: To determine the pattern of antibiotic susceptibility of isolated Streptococcus pneumoniae strains of healthy nasopharyngeal carriers younger than 2 years in seven regions of Peru. MATERIALS AND METHODS: Between 2007 and 2009, nasopharyngeal swab samples were collected among 2123 healthy children aged 2-24 months in growth and development medical practices (CRED) and vaccination offices of hospitals and health centers in Lima, Piura, Cusco, Abancay, Arequipa, Huancayo, and Iquitos. The resistance to ten antibiotics through disk diffusion sensitivity testing of isolated pneumococcus strains was determined. RESULTS: 572 strains were isolated. High rates of resistance to co-trimoxazole (58%), penicillin (52.2% non-sensitive); tetracycline (29,1%); azithromycin (28,9%), and erythromycin (26,3%). Resistance to chloramphenicol was low (8.8%). Multiresistance was found at 29.5%. Resistance to azithromycin and penicillin was different in all seven regions (p<0,05), the highest percentage of non-sensitive strains being found in Arequipa (63,6%), whereas the lowest percentage was found in Cusco (23.4%). CONCLUSIONS: High levels of resistance found to penicillin, co-trimoxasole and macrolides in isolated pneumococcus strains of healthy carriers in all studied regions, and their association to a previous use of antibiotics, represent a significant public health problem in our country. This emphasizes the need to implement nationwide strategies to reduce the irrational use of antibiotics, especially among children. It is necessary to complement data of resistance to penicillin with the determination of minimal inhibitory concentration to make proper therapeutic recommendations.

Resistencia antibiótica y distribución de serotipos en cepas neumocócicas invasivas en adultos hospitalizados en Lima, Perú / Antibiotic resistance and distribution of serotypes of invasive pneumococcal strains isolated from hospitalized adults in Lima, Peru

RESUMEN Objetivos. Describir las características clínicas, resistencia antibiótica y distribución de serotipos de cepas causantes de enfermedad neumocócica invasiva (ENI) en adultos. Materiales y métodos. Estudio tipo serie de casos. Se recolectaron cepas de neumococo de pacientes adultos hospitalizados con ENI en cinco hospitales nacionales y dos laboratorios de Lima durante los años 2009-2011. Resultados. Se estudiaron datos de 43 pacientes con ENI, el 58,2% fueron mayores de 60 años. Los diagnósticos fueron neumonía 39,5%, meningitis 30,2%, bacteriemia 13,9%, peritonitis 11,6%, artritis séptica 4,8%. El porcentaje de fallecidos fue 28,9%, de los cuales el 72,7% fueron mayores de 60 años. Las cepas de neumococo presentaron la siguiente resistencia: penicilina 0% en cepas no meningitis y 30,8% en cepas meningitis; ceftriaxona 4,5% y 16,7% de resistencia intermedia en cepas no meningitis y cepas meningitis respectivamente; 69% a trimetoprim/sulfametoxazol y 35,7% a eritromicina. Los serotipos más comunes fueron 19F, 23F, 6B, 14 y 6C. El porcentaje de cepas vacunales fue 44,2% para la vacuna conjugada siete-valente (PCV7) y para la PCV10, 51,2% para PCV13 y 60,4% para la vacuna polisacárida veintitrés-valente (PPV23). Conclusiones. El neumococo es un patógeno relevante en adultos, en especial en los adultos mayores, debido a su elevada mortalidad.

ABSTRACT Objectives. To describe the clinical characteristics, antibiotic resistance, and distribution of serotypes of bacterial strains that cause invasive pneumococcal disease (IPD) in adults. Materials and methods. Case series. Pneumococcal strains were isolated from 2009 to 2011 from hospitalized adult patients with IPD in five hospitals and two laboratories located in Lima. Results. The analysis of data from 43 patients with IPD indicated that 58.2% were older than 60 years. The most common complications were pneumonia (39.5%), meningitis (30.2%), bacteremia (13.9%), peritonitis (11.6%), and septic arthritis (4.8%). The mortality rate was 28.9%, and 72.7% of cases involved patients older than 60 years. The pneumococcal strains were resistant to the following antibiotics: penicillin, 0% and 30.8% in non-meningitis and meningitis strains, respectively; ceftriaxone, 4.5% and 16.7% in non-meningitis and meningitis strains, respectively; trimethoprim/sulfamethoxazole, 69.0%; and erythromycin, 35.7%. The most common serotypes were 19F, 23F, 6B, 14, and 6C. The percentage of vaccine strains was 44.2% for the 7-valent conjugate pneumococcal vaccine (PCV7) and PCV10, 51.2% for PCV13, and 60.4% for the 23-valent polysaccharide vaccine (PPV23). Conclusions. Pneumococcus is an important pathogen in adults, particularly in older adults, owing to its high mortality rate.

[Pneumococcal serotypes in carrier children prior to the introduction of anti-pneumococcal vaccines in Peru]. / Serotipos de neumococo en niños portadores antes de la vacunación antineumocócica en el Perú.

OBJECTIVES: To determine the carriage rate and serotype distribution of Streptococcus pneumoniae in the nasopharynx of healthy children younger than 2 years prior to the universal use of the pneumococcal conjugate vaccines in Peru. MATERIALS AND METHODS: Between 2007 and 2009 we collected nasopharyngeal swab samples from 2,123 healthy children aged 2 to 24 months in the vaccination and healthy children consultation offices of pediatric hospitals and health centers in 7 cities in Peru: on the coast (Lima, Piura), highlands (Cusco, Abancay, Arequipa and Huancayo) and amazon basin (Iquitos). The pneumococcal strains were isolated and identified at the central laboratory of the project in Lima, and serotyped by Quellung reaction in the pneumococcal reference laboratory at the Center for Diseases Control and Prevention (CDC). RESULTS: We found 27% (573/2123) of pneumococcal nasopharyngeal healthy carrier children. Among the 526 analyzed strains, we found 42 serotypes; the most common were: 19F (18.1%), 6B (14.3%); 23F (8.9%) and 14 (6.5%). CONCLUSIONS: The distribution of vaccine serotypes in the analyzed strains was of 50% for the serotypes present in the seven-valent vaccine, 50.2% for the serotypes present in the ten-valent vaccine and 57.2% for those present in the thirteen-valent vaccine.

Características epidemiológicas, clínicas y bacteriológicas de meningitis neumocócica en pacientes pediátricos de Lima, Perú / Epidemiologic, clinical and bacteriologic characteristics of pneumococcal meningitis in pediatric patients from Lima, Peru

RESUMEN Objetivos. Describir las características clínicas, letalidad, susceptibilidad antibiótica y distribución de serotipos de meningitis neumocócica en pacientes pediátricos de Lima, Perú. Materiales y Métodos. Serie de casos de meningitis neumocócica en niños menores de 16 años. Los datos fueron obtenidos de dos estudios multicéntricos prospectivos, de vigilancia pasiva de enfermedad neumocócica invasiva realizados en Lima-Perú desde los años 2006 al 2008, y del 2009 al 2011. Resultados. Reportamos 44 episodios de meningitis neumocócica; 68,2% fueron en niños menores de 2 años. La tasa de letalidad fue 32,6; y 92,9% de los casos letales ocurrieron en niños menores de dos años (p<0,05). La desnutrición estuvo asociada a los casos letales (p<0,05). El 64,3% de los casos fatales murieron dentro de los 2 primeros días. El 41,9% de los cultivos con neumococo fueron resistentes a la penicilina, 23,3% mostró resistencia intermedia a ceftriaxona (ninguno mostró resistencia completa) y 9,3% mostró resistencia a cloranfenicol. Los serotipos más frecuentes fueron 6B, 14, 19F y 23F, los cuales constituyeron el 68,3% de todas las cepas; 84,1% de las cepas encontradas están incluidas en los serotipos de la vacuna 13 valente. Conclusiones. La meningitis neumocócica continúa siendo una enfermedad letal, especialmente en niños menores de 2 años. Dado que aproximadamente dos tercios de los casos letales fallecen en las primeras 48 h, es crítico un diagnóstico y tratamiento oportuno, así como asegurar el cumplimiento de la inmunización con la vacuna neumocócica.

ABSTRACT Objectives. To describe the clinical characteristics, lethality, antibiotic susceptibility, and serotype distribution of pneumococcal meningitis in pediatric patients in Lima, Peru. Materials and Methods. A case series of pneumococcal meningitis in children less than 16 years of age from two prospective, multicenter, passive surveillance studies of invasive pneumococcal diseases held in Lima-Peru from 2006 to 2008 and 2009 to 2011. Results. We report 44 pneumococcal meningitis episodes; 68.2% of them were in children less than 2 years old. The overall case fatality rate was 32.6%; 92.9% of fatal cases were in children less than 2 years of age (p<0.05). Malnutrition was associated with fatal cases (p<0.05). 64.3% of fatal cases died within the first two days. 41.9% of pneumococcal isolates were resistant to penicillin, 23.3% were intermediate resistant to ceftriaxone (none were highly resistant) and 9.3% were resistant to chloramphenicol. The most common serotypes were 6B, 14, 19F and 23F, which accounted for 68.3% of all strains; 84.1% of strains were PCV13 serotypes. Conclusions. Pneumococcal meningitis continues to be a lethal disease, especially in children less than 2 years of age. Since almost two third of lethal cases lead to death within the first 48 hours, prompt diagnosis and management is critical, as well as assurance of immunization with pneumococcal vaccine.

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

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

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.

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.

Resistencia antibiótica de streptococcus pneumoniae en portadores nasofaríngeos sanos de siete regiones del Perú / Antibiotic resistance of streptococcus pneumoniae among healthy nasopharyngeal carriers in seven regions of Peru

Objetivos. Determinar el patrón de susceptibilidad antibiótica de cepas de Streptococcus pneumoniae aisladas de portadores nasofaríngeos sanos menores de 2 años de siete regiones del Perú. Materiales y métodos. Entre el 2007 y 2009 se tomaron muestras de hisopado nasofaríngeo a 2123 niños sanos entre 2 y 24 meses de edad en los consultorios de crecimiento y desarrollo (CRED) y vacunación de hospitales y centros de salud de Lima, Piura, Cusco, Abancay, Arequipa, Huancayo, e Iquitos. Se determinó la resistencia a diez antibióticos mediante la prueba de disco-difusión de las cepas de neumococo aisladas. Resultados. Se aislaron 572 cepas. Se encontró altas tasas de resistencia a cotrimoxazol (58%); penicilina (52,2% no-sensibles); tetraciclina (29,1%); azitromicina (28,9%), y eritromicina (26,3%). La resistencia a cloranfenicol fue baja (8,8%). Se encontró 29,5% de multirresistencia. La resistencia a la azitromicina y a la penicilina fue diferente en las siete regiones (p<0,05), hallándose el mayor porcentaje de cepas no-sensibles a penicilina en Arequipa (63,6%), mientras que el menor fue en Cusco (23,4%). Conclusiones. Los elevados niveles de resistencia encontrados para penicilina, cotrimoxazol y macrólidos en cepas de neumococo aisladas de portadores sanos en todas las regiones estudiadas, y su asociación con uso previo de antibióticos, representan un importante problema de salud pública en nuestro país. Esto resalta la necesidad de implementar, a nivel nacional, estrategias para disminuir el uso irracional de antibióticos, sobre todo en la población pediátrica. Es necesario complementar los datos de resistencia a penicilina con la determinación de la concentración mínima inhibitoria para hacer las recomendaciones terapéuticas respectivas.

Objectives. To determine the pattern of antibiotic susceptibility of isolated Streptococcus pneumoniae strains of healthy nasopharyngeal carriers younger than 2 years in seven regions of Peru. Materials and methods. Between 2007 and 2009, nasopharyngeal swab samples were collected among 2123 healthy children aged 2-24 months in growth and development medical practices (CRED) and vaccination offices of hospitals and health centers in Lima, Piura, Cusco, Abancay, Arequipa, Huancayo, and Iquitos. The resistance to ten antibiotics through disk diffusion sensitivity testing of isolated pneumococcus strains was determined. Results. 572 strains were isolated. High rates of resistance to co-trimoxazole (58%), penicillin (52.2% non-sensitive); tetracycline (29,1%); azithromycin (28,9%), and erythromycin (26,3%). Resistance to chloramphenicol was low (8.8%). Multiresistance was found at 29.5%. Resistance to azithromycin and penicillin was different in all seven regions (p<0,05), the highest percentage of non-sensitive strains being found in Arequipa (63,6%), whereas the lowest percentage was found in Cusco (23.4%). Conclusions. High levels of resistance found to penicillin, co-trimoxasole and macrolides in isolated pneumococcus strains of healthy carriers in all studied regions, and their association to a previous use of antibiotics, represent a significant public health problem in our country. This emphasizes the need to implement nationwide strategies to reduce the irrational use of antibiotics, especially among children. It is necessary to complement data of resistance to penicillin with the determination of minimal inhibitory concentration to make proper therapeutic recommendations.

Serotipos de neumococo en niños portadores antes de la vacunación antineumocócica en el Perú / Pneumococcal serotypes in carrier children prior to the introduction of anti-pneumococcal vaccines in Peru

Objetivos. Determinar la frecuencia y distribución de serotipos de S. pneumoniae en portadores nasofaríngeos sanos menores de dos años previa al uso universal de la vacuna conjugada antineumocócica en el Perú. Materiales y métodos. Entre los años 2007 y 2009 se tomaron muestras de hisopado nasofaríngeo a 2123 niños sanos entre 2 y 24 meses de edad en los consultorios de crecimiento y desarrollo o vacunación de hospitales y centros de salud de siete ciudades del Perú: costa (Lima, Piura); sierra (Cusco, Abancay, Arequipa y Huancayo) y selva (Iquitos). Las cepas de neumococo fueron aisladas e identificadas en el laboratorio central del proyecto en Lima y serotipificadas por reacción de Quellung en el Laboratorio de Referencia de Neumococo del Centro de Control y Prevención de Enfermedades. Resultados. Se encontró 27,0% (573/2123) de portadores nasofaríngeos sanos de neumococo. En las 526 cepas analizadas se encontraron 42 serotipos; los más frecuentes fueron: 19F (18,1%), 6B (14,3%); 23F (8,9%) y 14 (6,5%). Conclusiones. La distribución de serotipos vacunales en las cepas analizadas fue de 50,0% para los serotipos presentes en la vacuna conjugada heptavalente; 50,2% para los serotipos presentes en la vacuna decavalente y 57,2% para la vacuna 13-valente.

Objectives. To determine the carriage rate and serotype distribution of Streptococcus pneumoniae in the nasopharynx of healthy children younger than 2 years prior to the universal use of the pneumococcal conjugate vaccines in Peru. Materials and methods. Between 2007 and 2009 we collected nasopharyngeal swab samples from 2,123 healthy children aged 2 to 24 months in the vaccination and healthy children consultation offices of pediatric hospitals and health centers in 7 cities in Peru: on the coast (Lima, Piura), highlands (Cusco, Abancay, Arequipa and Huancayo) and amazon basin (Iquitos). The pneumococcal strains were isolated and identified at the central laboratory of the project in Lima, and serotyped by Quellung reaction in the pneumococcal reference laboratory at the Center for Diseases Control and Prevention (CDC). Results. We found 27% (573/2123) of pneumococcal nasopharyngeal healthy carrier children. Among the 526 analyzed strains, we found 42 serotypes; the most common were: 19F (18.1%), 6B (14.3%); 23F (8.9%) and 14 (6.5%). Conclusions. The distribution of vaccine serotypes in the analyzed strains was of 50% for the serotypes present in the seven-valent vaccine, 50.2% for the serotypes present in the ten-valent vaccine and 57.2% for those present in the thirteen-valent vaccine.

Invasive pneumococcal diseases among hospitalized children in Lima, Peru / Enfermedades neumocócicas invasoras en niños hospitalizados en Lima, Perú

OBJECTIVE: To determine the epidemiology of invasive pneumococcal disease (IPD) and the antibiotic susceptibility and serotype distribution of S. pneumoniae in pediatric patients in Lima, Peru. METHODS: A 2-year, multicenter, passive surveillance study conducted from May 2006- April 2008 in 11 public hospitals and five private laboratories in Lima, Peru, in patients less than 16 years of age with sterile site cultures yielding S. pneumoniae. Antibiotic susceptibility was performed by Etest® (AB Biodisk, Solna, Switzerland). Strains were serotyped by the Quellung reaction. RESULTS: In all, 101 IPD episodes were studied, 68.3 percent of which were among children less than 24 months of age. Diagnoses were: pneumonia (47.5 percent), meningitis (38.6 percent), and sepsis (7.9 percent). The overall case fatality rate was 22.0 percent; case fatality rate in meningitis was 32.4 percent. While 80.0 percent of fatal cases were in those less than 24 months of age, only 50.7 percent of non-fatal cases (P < 0.05) were in this age group. Resistance rates were high for trimethoprim/ sulfamethoxazole (76.2 percent), erythromycin (24.8 percent), and penicillin (22.8 percent). The most common serotypes were 14, 6B, 19F, 23F, and 5, which accounted for 69.7 percent of all strains and 87.0 percent of penicillin non-susceptible strains. CONCLUSIONS: IPD in hospitalized children in Lima is associated with high antimicrobial resistance levels and elevated case fatality rate, especially in young children. This baseline data will be useful for evaluating the effects of vaccine introduction.

OBJETIVO: Determinar la epidemiología de la enfermedad neumocócica invasora y la sensibilidad a los antibióticos y la distribución de los serotipos de S. pneumoniae en pacientes pediátricos en Lima, Perú. MÉTODOS: Estudio multicéntrico de vigilancia pasiva durante dos años, entre mayo del 2006 y abril del 2008, en 11 hospitales públicos y 5 consultorios privados de Lima, en pacientes menores de 16 años con cultivos de sitios estériles positivos para S. pneumoniae. Se determinó la sensibilidad a los antibióticos mediante Etest® (AB Biodisk, Solna, Suiza). Se serotipificaron las cepas mediante la reacción de Quellung. RESULTADOS: En total, se estudiaron 101 episodios de enfermedad neumocócica invasora, 68,3 por ciento de ellos en niños menores de 24 meses, con los siguientes diagnósticos: neumonía (47,5 por ciento), meningitis (38,6 por ciento) y septicemia (7,9 por ciento). La tasa de letalidad general fue de 22,0 por ciento y la tasa de letalidad por meningitis de 32,4 por ciento. Si bien 80,0 por ciento de los casos mortales ocurrió en menores de 24 meses, solo 50,7 por ciento de los casos no mortales (P < 0,05) ocurrió en este grupo de edad. Las tasas de resistencia fueron elevadas para trimetoprima-sulfametoxazol (76,2 por ciento), eritromicina (24,8 por ciento) y penicilina (22,8 por ciento). Los serotipos más comunes, 14, 6B, 19F, 23F y 5, representaron 69,7 por ciento de todas las cepas, y 87,0 por ciento de las cepas no sensibles a la penicilina. CONCLUSIONES: La enfermedad neumocócica invasora en niños hospitalizados en Lima se asocia con altos niveles de resistencia a los antimicrobianos y una tasa de letalidad elevada, especialmente en niños pequeños. Estos datos iniciales serán útiles para evaluar los efectos de la introducción de las vacunas.

Tuberculosis congénita / Congenital tuberculosis

Se recopilan 9 casos de tuberculosis congenita, que cumplen con los postulados de Beitzke, resultado de una encuesta efectuada en los hospitales de Lima que cuentan con Servicios de Neonatología, de una revisión de la literatura médica nacional y del aporte de 2 recién nacidos en el Hospital E. Rebagliati. 3 de los 9 casos encontrados correspondieron a la forma de infección congenita producida por diseminación hematógena placentaria, y los otros 6 a la adquirida por aspiración de secreciones infectadas durante el parto. Todos ellos fueron Recien Nacidos de Bajo Peso (menos de 2500 gr). La clínica fue variable pero con frecuencia se presentaron fiebre, falta de ganancia de peso, hepatomegalia y cuadro respiratorio. La mortalidad ocurrió en 7 de los 9 pacientes y el diagnostico se hizo con la necropsia. Los 2 casos sobrevivientes recibieron multiples drogas antituberculosas, hecho que confirma la falta de información para recomendar un régimen preferido de tratamiento, agregado a la administración de Izoniazida. El diagnóstico precoz y el tratamiento adecuado son los elementos cardinales para disminuir la elevada mortalidad de la tuberculosis congenita.