Reduction in the incidence of invasive infections caused by encapsulated bacteria after the onset of the COVID-19 pandemic / Reducción de la incidencia de infecciones invasivas por bacterias capsuladas luego del inicio de la Pandemia por COVID-19

Abstract Interaction between severe acute respiratory coronavirus 2 (SARS-CoV-2) and IIEB remains under investigation. Objective: to compare IIEB incidence before and during COVID-19 pandemic, and assess incidence of coinfection with COVID-19 and case fatality. A cross-sectional study was performed on data from a centralized microbiology laboratory serving a network of healthcare centers comprising 713 pediatric and adult inpatient beds, expanded by 20% during the pandemic. Three periods were evaluated: (1) pre-pandemic: March 1, 2019-February 29, 2020; (2) pandemic year 1: March 1, 2020-February 28, 2021; (3) pandemic year 2: March 1, 2021-July 31, 2021. Descriptive statistical analysis was performed. 56502 samples (96% blood cultures) from 27224 patients were analyzed. Of these, 54 samples (from 54 patients) were positive for encapsulated bacteria. IIEB incidence was: 167.4, 32.6, and 50.4 per 100000 samples for periods 1, 2, and 3, respectively. Twelve IIEB episodes occurred during the pandemic period: 10 Streptococcus pneumoniae, and 2 Haemophilus influenzae, of which 7 were SARS-CoV-2/S. pneumoniae coinfections, with an incidence of 5.68 per 10000 COVID-19-related hospitalizations (0.056%). IIEB case fatality was 31%, 29%, and 60% for each period, respectively, 3/7 patients with coinfection died (43%). Case fatality for invasive pneumococcal disease (IPD) in patients without COVID-19, was 32.5%. Significant reduction in IIEB incidence was observed during the pandemic, coinciding with implementation of containment measures. The incidence of SARS-CoV-2/S. pneumoniae coinfection was low, with higher case fatality than IPD patients without COVID-19.

Resumen La interacción entre SARS-CoV-2 e infecciones invasivas por bacterias capsuladas (IIBC) continúa bajo estudio. Objetivos: comparar la incidencia de IIBC antes y durante la pandemia por COVID-19, evaluar la incidencia de coinfección con COVID-19 y la letalidad. Estudio transversal de registros de un laboratorio centralizado de Microbiología, que asiste a una red de centros asistenciales con 713 camas de internación para adultos y pediátricos, expandida 20% durante la pandemia. Tres periodos evaluados: 1) Pre-pandemia: 1-Marzo-2019 al 29-Febrero-2020; 2) Primer año de Pandemia: 1-Marzo-2020 al 28-Febrero-2021; 3) Pandemia 2021: 1-Marzo-2021 al 31-Julio-2021. Análisis estadístico descriptivo: Se analizaron 56.502 muestras (96% hemocultivos) correspondientes a 27.224 pacientes. De estas, 54 muestras (de 54 pacientes) fueron positivas para bacterias capsuladas. La incidencia de IIBC fue 167,4, 32,6 y 50,4 por cada 100.000 muestras para los periodos 1, 2 y 3, respectivamente. Doce IIBC ocurrieron durante la pandemia: 10 Streptococcus pneumoniae y dos Haemophilus influenzae, siete de ellos corresponden a coinfección SARS-CoV-2/S. pneumoniae, con una incidencia de 5,68 por cada 10.000 internaciones por COVID 19 (0,056%). La letalidad de las IIBC fue de 31, 29 y 60% para los tres periodos, respectivamente, 3/7 coinfectados fallecieron (43%). La letalidad por enfermedad neumocócica invasiva (ENI), sin COVID fue de 32,5%. Se evidenció una reducción significativa de la incidencia de IIBC luego del comienzo de la pandemia, coincidente con la implementación de las medidas sanitarias de contención de la pandemia. La incidencia de coinfección de SARS-CoV-2/S. pneumoniae fue baja y presentó mayor letalidad que las ENI sin COVID-19.

Reduction in the incidence of invasive infections caused by encapsulated bacteria after the onset of the COVID-19 pandemic.

Interaction between severe acute respiratory coronavirus 2 (SARS-CoV-2) and IIEB remains under investigation. Objective: to compare IIEB incidence before and during COVID-19 pandemic, and assess incidence of coinfection with COVID-19 and case fatality. A cross-sectional study was performed on data from a centralized microbiology laboratory serving a network of healthcare centers comprising 713 pediatric and adult inpatient beds, expanded by 20% during the pandemic. Three periods were evaluated: (1) pre-pandemic: March 1, 2019-February 29, 2020; (2) pandemic year 1: March 1, 2020-February 28, 2021; (3) pandemic year 2: March 1, 2021-July 31, 2021. Descriptive statistical analysis was performed. 56 502 samples (96% blood cultures) from 27224 patients were analyzed. Of these, 54 samples (from 54 patients) were positive for encapsulated bacteria. IIEB incidence was: 167.4, 32.6, and 50.4 per 100000 samples for periods 1, 2, and 3, respectively. Twelve IIEB episodes occurred during the pandemic period: 10 Streptococcus pneumoniae, and 2 Haemophilus influenzae, of which 7 were SARS-CoV-2/S. pneumoniae coinfections, with an incidence of 5.68 per 10000 COVID-19-related hospitalizations (0.056%). IIEB case fatality was 31%, 29%, and 60% for each period, respectively, 3/7 patients with coinfection died (43%). Case fatality for invasive pneumococcal disease (IPD) in patients without COVID-19, was 32.5%. Significant reduction in IIEB incidence was observed during the pandemic, coinciding with implementation of containment measures. The incidence of SARS-CoV-2/S. pneumoniae coinfection was low, with higher case fatality than IPD patients without COVID-19.

Coinfection of SARS-CoV-2 with other respiratory pathogens in outpatients from Ecuador.

Worldwide, the COVID-19 pandemic caused by SARS-CoV-2 has enormously impacted healthcare systems, especially in low and middle-income countries. Coinfections with respiratory pathogens in COVID-19 patients may contribute to worse outcomes. This study identified the presence of 12 viral coinfections and pneumococcal carriers among individuals with SARS-CoV-2 infection in outpatient and community settings in Ecuador. From January 2020 to November 2021, 215 nasopharyngeal and nasal swabs were taken from individuals who reported symptoms of COVID-19 or had known exposure to someone with confirmed or suspected COVID-19. One hundred fifty-eight tested positive for SARS-CoV-2 by RT-qPCR and coinfections were detected in 12% (19/158) of SARS-CoV-2-positive patients; the most frequent coinfection was with influenza A virus at 4.4% (7/158; 95% CI: 1.2-7.6), followed by respiratory syncytial virus with 3.1% (5/158; 95% CI: 0.4-5.8), and finally rhinovirus and human coronavirus NL63 with 1.2% (2/158). Pneumococcal carriage was detected in 3.7% (6/158; 95% CI: 0.76-6.64) of SARS-CoV-2 cases. Influenza B, adenovirus, human metapneumovirus (HMPV), parainfluenza virus types 1, 2, and 3, and human coronavirus HKU1 were undetected. To our knowledge, this is the first study of coinfection of SARS-CoV-2 and respiratory pathogens performed on outpatients in Latin America. The high proportion of outpatients with viral coinfections reported in our cohort allows us to suggest that testing for SARS-CoV-2 and other common respiratory pathogens should be carried out to ensure accurate diagnoses, prompt patient treatment, and appropriate isolation.

Non-capsular based immunization approaches to prevent Streptococcus pneumoniae infection.

Streptococcus pneumoniae is a Gram-positive bacterium and the leading cause of bacterial pneumonia in children and the elderly worldwide. Currently, two types of licensed vaccines are available to prevent the disease caused by this pathogen: the 23-valent pneumococcal polysaccharide-based vaccine and the 7-, 10, 13, 15 and 20-valent pneumococcal conjugate vaccine. However, these vaccines, composed of the principal capsular polysaccharide of leading serotypes of this bacterium, have some problems, such as high production costs and serotype-dependent effectiveness. These drawbacks have stimulated research initiatives into non-capsular-based vaccines in search of a universal vaccine against S. pneumoniae. In the last decades, several research groups have been developing various new vaccines against this bacterium based on recombinant proteins, live attenuated bacterium, inactivated whole-cell vaccines, and other newer platforms. Here, we review and discuss the status of non-capsular vaccines against S. pneumoniae and the future of these alternatives in a post-pandemic scenario.

Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus.

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

Bacterial meningitis in patients with sickle cell anemia in Salvador, Bahia, Brazil: a report on ten cases

ABSTRACT Sickle cell anemia (SCA) is a common genetic blood disorder, affecting millions worldwide. According to current evidence, individuals with SCA have more than 300 times greater risk to develop bacterial meningitis (BM) than the general population. Herein we have described the characteristics of a series of BM cases in SCA patients in Salvador, Brazil, during 13 years of hospital-based surveillance. Data on clinical presentation, laboratory parameters and outcomes were collected retrospectively by reviewing medical records. From 1999 to 2011, ten SCA patients were identified among the 2511 cases of BM (10/2511; 0.40%). These patients were more likely to be male (90%) and to be younger (median age 8.5 years). The causative agents were Streptococcus pneumoniae (n = 5) and Haemophilus influenzae (n = 1). The most frequent pneumococcal serotypes were 23 F (2 cases), 14, 18 F, 23B (one case each). Common medical complications were stroke (n = 3); heart failure (n = 2), respiratory problems (n = 2), renal dysfunctions (n = 2) and leg ulcers (n = 1). This study highlights the importance of S. pneumoniae as a causative agent of meningitis in individuals with SCA and shows the diversity of comorbidities associated with this condition.

Bacterial meningitis in patients with sickle cell anemia in Salvador, Bahia, Brazil: a report on ten cases.

Sickle cell anemia (SCA) is a common genetic blood disorder, affecting millions worldwide. According to current evidence, individuals with SCA have more than 300 times greater risk to develop bacterial meningitis (BM) than the general population. Herein we have described the characteristics of a series of BM cases in SCA patients in Salvador, Brazil, during 13 years of hospital-based surveillance. Data on clinical presentation, laboratory parameters and outcomes were collected retrospectively by reviewing medical records. From 1999 to 2011, ten SCA patients were identified among the 2511 cases of BM (10/2511; 0.40%). These patients were more likely to be male (90%) and to be younger (median age 8.5 years). The causative agents were Streptococcus pneumoniae (n=5) and Haemophilus influenzae (n=1). The most frequent pneumococcal serotypes were 23F (2 cases), 14, 18F, 23B (one case each). Common medical complications were stroke (n=3); heart failure (n=2), respiratory problems (n=2), renal dysfunctions (n=2) and leg ulcers (n=1). This study highlights the importance of S. pneumoniae as a causative agent of meningitis in individuals with SCA and shows the diversity of comorbidities associated with this condition.

Optimal Conditions for Streptococcus pneumoniae Culture: In Solid and Liquid Media.

Control of Streptococcus pneumoniae is mainly achieved by the use of existing vaccines. Capsular polysaccharides are the major antigenic component and are also the main virulence factor.Capsular polysaccharides must fulfill requirements of purity, uniformity, and an accurate molecular weight to be used as vaccine antigens. Vaccine production largely relies on cultivation of the pathogen in appropriate conditions.Here we describe widely used techniques to culture S. pneumoniae based on solid or complex liquid media, which are successfully applied in the diagnosis of the pathogen and in development and production of S. pneumoniae vaccines. Furthermore, we present a new chemically defined medium that can be used at lab scale.

Microbiological and immunological profile of patients with severe lupus flares related to bloodstream infections: a retrospective cohort study.

Background This study aimed to address whether bloodstream infections are a risk factor for the development of severe lupus flares, as well as clinical, immunological and microbiological features of patients with bloodstream infections that develop severe lupus flares. Methods We performed a retrospective cohort study comparing 87 systemic lupus erythematosus (SLE) patients with bloodstream infections and 87 hospitalized SLE patients without bloodstream infections as a comparison group. All patients were followed up for at least 3 months or until one of the primary outcomes was developed (severe SLE flare according to SELENA/SLEDAI score or death). Microbiological features of all bloodstream infections were recorded. The disease status at the end of follow up was registered. Results A total of 23 patients (13.2%) developed a severe flare during follow up; among them, 20 (87%) had an associated episode of bloodstream infection ( p < 0.001). The most frequent flares were renal (43.4%) and severe thrombocytopenia (26%). After multivariate analysis, baseline-independent factors associated with severe SLE flare were bloodstream infection [hazard ratio (HR) 7.3, 95% confidence interval (CI) 2.13-24.95; p = 0.002]. Among patients with bloodstream infections, low C4 levels (HR 2.43, 95% CI 1.04-5.69: p = 0.04) and Streptococcus pneumoniae were associated with severe SLE flare (HR 3.41, 95% CI 1.68-6.91; p = 0.012). Conclusions SLE patients with bloodstream infections, especially due to S. pneumoniae, and low C4 levels, are at higher risk for development of severe SLE flares.

Key features of invasive pneumococcal isolates recovered in Lima, Peru determined through whole genome sequencing.

Before PCV7 introduction, invasive pneumococcal disease (IPD) was responsible for approximately 12,000-18,000 deaths annually among children <5years in Latin America. In Peru, PCV7 was introduced in 2009. We used whole genome sequencing to deduce key features of invasive strains collected in Lima, Peru from 2006 to 2011. We sequenced 212 IPD isolates from 16 hospitals in Lima pre (2006-2009; n=133) and post (2010-2011; n=79) PCV7 introduction; 130 (61.3%) isolates were from children≤5years old. CDC's Streptococcus lab bioinformatics pipeline revealed serotypes, sequence types (STs), pilus genes, PBP types and other resistance determinants. During the pre-PCV7 period, serotype 14 was the most common serotype (24.8%), followed by 6B (20.3%), 19F (10.5%), and 23F (6.8%). Post-PCV7, the proportion of PCV7 serotype 6B decreased significantly (to 6.3%), while 19F (16.3%), 14 (15.0%), 23F (7.5%), and 19A (7.5%) were the most common serotypes; only serotypes 3 and 10A increased significantly. Overall, 82% (n=173) of all isolates carried at least one resistance determinant, including 72 (34%) isolates that carried resistance determinants against 3 or more antimicrobial classes; of these 72 isolates, 56 (78%) belonged to a PCV7 serotype. Eighty-two STs were identified, with 53 of them organized in 14 clonal complexes. ST frequencies were distributed differently pre and post-PCV7 introduction, with only 18 of the 57 STs identified in years 2006-2009 isolates also observed in years 2010-2011 isolates. The apparent expansion of a 19F/ST1421 lineage with predicted ß-lactam resistance (PBP type 13:16:20) and carrying resistance determinants against four additional antimicrobial classes was observed.

Changing trends in serotypes of S. pneumoniae isolates causing invasive and non-invasive diseases in unvaccinated population in Mexico (2000-2014).

OBJECTIVE: Introduction of pneumococcal conjugate vaccines (PCV) targeted against a limited number of serotypes substantially decreased invasive (IPD) and non-invasive pneumococcal diseases (NIPD) but it was accompanied by non-vaccine type replacement disease. After 9 years of introduction of PCV in Mexico, we analyze the evidence of the indirect effects on IPD and NIPD serotype distribution among groups not targeted to receive the vaccine. METHODS: From January 2000 to December 2014, pneumococcal strains isolated from IPD and NIPD cases from patients ≥5 years of age from participant hospitals of the SIREVA II (Sistema Regional de Vacunas) network were serotyped. A regression analysis was performed considering year and proportion of serotypes included in the different vaccine formulations (PCV7, PCV10 and PCV13). The slope was obtained for each regression line and their correspondent p-value. The proportion of each serotype in the pre-PCV7 and post-PCV7 periods was evaluated by χ2 test. RESULTS: From a total of 1147 pneumococcal strains recovered, 570 corresponded to the pre-PCV7 and 577 to the post-PCV7 periods. The proportion of vaccine serotypes included in the three PCV formulations decreased by 2.4, 2.6 and 1.3%, respectively per year during the study period. A significant increase of serotype 19A was observed in the post-vaccine period in all age groups. CONCLUSIONS: A percentage of annual decline of serotypes causing IPD and NIPD included in PCV was detected among groups not targeted to receive the vaccine, probably due to herd effect. Considering pneumococcal serotype distribution is a dynamic process, we highlight the importance of surveillance programs.

Streptococcus pneumoniae sensibilidade a antimicrobianos e detecção de genes de resistência em isolados de crianças com pneumonia adquirida na comunidade em Fortaleza, Ceará

A infecção respiratória aguda (IRA) é uma síndrome clínica, em que cerca de 80% dasmortes são atribuídas à pneumonia, uma doença grave que atinge o trato respiratórioinferior. O agente etiológico comumente isolado na pneumonia adquirida nacomunidade (PAC) é o Streptococcus pneumoniae (S. pneumoniae). As doençaspneumocócicas começam com a colonização do S. pneumoniae na nasofaringe, podendoprogredir para doença invasiva. Nas últimas décadas, o aumento do número de cepas deS. pneumoniae resistentes a antibióticos β-lactâmicos e a macrolídeos tem dificultado otratamento das infecções pneumocócicas. Os objetivos desse estudo foram determinar àprevalência de portadores de S. pneumoniae em crianças com PAC, o perfil desensibilidade a antimicrobianos e distribuição dos sorotipos, em Fortaleza, Brasil. Ascepas de S. pneumoniae foram isoladas de aspirados de nasofaringe de crianças comPAC atendidas no Hospital Infantil Albert Sabin (HIAS). Para a determinação dasConcentrações Inibitórias Mínimas (CIM) foi utilizado o método de E-test para osseguintes antimicrobianos: penicilina, ceftriaxona, sulfametoxazol/trimetoprim,amoxicilina, clindamicina e eritromicina. A genotipagem das cepas de S. pneumoniaefoi realizada pela técnica de multiplex PCR. De 527 amostras de crianças com PAC,foram isolados S. pneumoniae em 30,17%...

Acute respiratory infection is a clinical syndrome in which about 80% of deathsattributed to pneumonia, which is a serious disease that affects the lower respiratorytract. The etiologic agent commonly isolated in community-acquired pneumonia isStreptococcus pneumoniae (S. pneumoniae). Pneumococcal disease begins withcolonization of S. pneumoniae in the nasopharynx, which may progress to invasivedisease markedly. In recent decades, the increasing number of strains of S. pneumoniaeresistant to -lactam antibiotics and macrolides has hampered the treatment ofpneumococcal infections. The objectives of this study were to determine: (1) theprevalence of carriers of S. pneumoniae in children with community-acquiredpneumonia; (2) the profile of the sensitivity of the causative agent and the antimicrobial;(3) the distribution of serotypes existing in Fortaleza. The strains of S. pneumoniae wereisolated from nasopharyngeal aspirates from children with community-acquiredpneumonia treated at Children's Hospital Albert Sabin public. Penicillin, ceftriaxone,sulfamethoxazole / trimethoprim, amoxicillin, clindamycin and erythromycin: Todetermine the minimum inhibitory concentration method the E-test for the followingantimicrobials were used. Genotyping of the strains of S. pneumoniae was performed bymultiplex PCR. A total of 527 samples with carriers of community-acquired pneumoniain children were isolated 30.17% of strains of S...

O exercício aeróbio atenua a inflamação pulmonar induzida pelo Streptococcus pneumoniae / Aerobic exercise attenuates pulmonary inflammation induced by Streptococcus pneumoniae

O treinamento aeróbio moderado tem sido reconhecido como um importante estimulador do sistema imune, no entanto o efeito deste na infecção bacteriana não tem sido extensivamente estudado. Nosso objetivo foi avaliar se o exercício aeróbio moderado prévio à infecção por S. pneumoniae influencia a resposta inflamatória pulmonar. Camundongos BALB/C foram divididos em 4 grupos: Controle (animais sedentários; não infectados); S. pneumoniae (animais sedentários e posteriormente infectados); Exercício (animais treinados; não infectados); Exercício + S. pneumoniae (animais treinados e posteriormente infectados). Os animais foram submetidos a um programa de treinamento físico aeróbio durante 4 semanas, e 72 horas após a última sessão de exercício, os animais receberam instilação nasal de S. pneumoniae (linhagem M10) e foram avaliados 12 horas (fase aguda) ou 10 dias (fase tardia) após a instilação. Na fase aguda, o grupo S. pneumoniae apresentou um aumento de: resistência e elastância do sistema respiratório, número total de células, neutrófilos, linfócitos e macrófagos no lavado broncoalveolar (BAL), células polimorfonucleares no parênquima pulmonar e TNF-alfa e IL-1beta no homogenato pulmonar. O exercício físico atenuou significantemente esses parâmentros. Além disso, o exercício físico resultou em aumento da expressão de enzimas antioxidantes no pulmão (CuZnSOD and MnSOD). Na fase tardia, o grupo Exercício + S. pneumoniae apresentou redução no número total de células e macrófagos no BAL, células polimorfonucleares no parênquima pulmonar e IL-6 no homogenato pulmonar comparado ao grupo S. pneumoniae. Nossos resultados sugerem um efeito protetor do exercício aeróbio moderado contra a infecção bacteriana pulmonar. Esse efeito é provavelmente secundário ao efeito do exercício no balanço oxidante-antioxidante.

Moderate aerobic exercise training has been recognized as an important stimulator of the immune system, but its effect on bacterial infection has not been extensively studied. Our aim was to determine whether moderate aerobic exercise training prior to S. pneumoniae infection influences pulmonary inflammatory responses. BALB/c mice were divided into 4 groups: Control (sedentary without infection); S. pneumoniae (sedentary with infection); Exercise (aerobic training without infection); Exercise + S. pneumoniae (aerobic training with infection). Animals underwent aerobic exercise training for 4 weeks. 72 h after last exercise training, animals received a challenge with S. pneumoniae (strain M10) and were evaluated either 12 h (acute phase) or 10 days (late phase) after instillation. In acute phase, S. pneumoniae group had an increase in respiratory system resistance and elastance; number of total cells, neutrophils, lymphocytes and macrophages in bronchoalveolar lavage fluid (BAL); polymorphonuclear cells in lung parenchyma; and levels of TNF-alfa and IL-1beta in lung homogenates. Exercise training significantly attenuated the increase in all of these parameters. In addition, exercise induced an increase in expression of antioxidant enzymes (CuZnSOD and MnSOD) in lungs. In late phase, Exercise + S. pneumoniae group exhibited a reduction in number of total cells and macrophages in BAL, in polymorphonuclear cells in lung parenchyma and in levels of IL-6 in lung homogenates compared to S. pneumoniae group. Our results suggest a protective effect of moderate exercise training against respiratory infection with S. pneumoniae. This effect is most likely secondary to an effect of exercise on oxidant-antioxidant balance.

Cambios en el Patrón Epidemiológico y resistencia Bacteriana de la Meningitis Bacteriana Aguda en Niños en un hospital de referencia

Introducción. Pos-introducción de la vacuna anti-H. influenzae tipo b (HIB) se ha observado en Latinoamérica significantes cambios en el perfil epidemiológico y de la susceptibilidad de los gérmenes causantes de meningitis bacteriana aguda. No se disponen de estudios similares en el Paraguay. Objetivo: Estudiar el panorama epidemiológico actual de la meningitis bacteriana aguda en el Paraguay, posterior a la introducción de la vacuna anti-HIB en el país, en un hospital de referencia. Materiales y métodos: Estudio observacional y retrospectivo en el que se incluyeron todos los casos de meningitis bacteriana aguda en niños 3 meses hospitalizados en el IMT desde enero de 1993 a junio del 2006. Se analizaron las fichas clínicas de los pacientes (pts) incluyendo datos demográficos, etiológicos y la evolución clínica. Los pts fueron estratificados según el año de hospitalización en tres periodos: Periodo I (PER I), que incluyó los que se hospitalizaron entre 1993 y 1997, PER II entre 1998 y 2002 y PER III del 2003 a 2006. Se determinó la CIM a penicilina (PEN) y cefotaxima (CFX) de los aislados de S. pneumoniae (Spn) por el método ipsilométrico (E-test) realizándose la serotipificación por la reacción de Quellung. Resultados: En el periodo de estudio se hospitalizaron 394 pts con meningitis bacteriana aguda. La edad media fue 2.9 + 4 años, con discreto predominio del sexo masculino (relación 1.2/1). La serotipificación realizada en 31 cepas de Spn (a partir del 2000) mostró que solo 50% de los serotipos correspondieron a los incluidos en la vacuna conjugada antineumocóccica actualmente disponible, siendo el 14 (9/31, 29%) el más frecuente. Conclusiones: La introducción de vacuna anti Hib ha producido un importante cambio epidemiológico de la meningitis bacteriana aguda en nuestra institución, constituyendo actualmente el S. pneumoniae el principal causante de meningitis bacteriana aguda. Se siguen observando, sin embargo, casos esporádicos de meningitis bacteriana aguda por HIB. Aunque se constata un significativo incremento de la resistencia de Spn a PEN, la resistencia a CTX se halla todavía <10%.

Abstract Introduction. Post-introduction of the anti-H. influenzae type b (HIB) vaccine has been observed in Latin America a significant changes in the epidemiological profile and susceptibility of germs that cause acute bacterial meningitis. No similar studies have in Paraguay. Aim: Study the current epidemiological situation of acute bacterial meningitis in a referral hospital after the introduction of Hib vaccine in Paraguay. Materials and methods: observational, retrospective study in which all cases of acute bacterial meningitis in children 3 months hospitalized in the IMT from January 1993 to June 2006 included the medical records of patients were analyzed (pts) including demographics, etiologic and clinical outcome. Pts were stratified by year of hospitalization in three periods: Period I (PER I), which included those who were hospitalized between 1993 and 1997, PER II between 1998 and 2002 and PER 2003 to 2006. III CIM was determined penicillin (PEN) and cefotaxime (CFX) isolates of S. pneumoniae (SPN) for the ipsilométrico method (E-test) carried out by the reaction serotyping Quellung. Results: During the study period 394 pts with acute bacterial meningitis were hospitalized. The mean age was 2.9 ± 4 years, with discreet predominance of males (ratio 1.2 / 1). Serotyping performed in 31 strains of Spn (since 2000) it showed that only 50% corresponded to serotypes included in the pneumococcal conjugate vaccine currently available, with 14 (9/31, 29%) the most frequent. Conclusions: The introduction of Hib vaccine has been a major epidemiological change of acute bacterial meningitis in our institution, now constituting the S. pneumoniae the leading cause of acute bacterial meningitis. Are still evident, however, sporadic cases of acute bacterial meningitis HIB. Although a significant increase in resistance of Spn PEN, CTX resistance is observed is still only <10%.

Spectrum and potency of ceftaroline against leading pathogens causing community-acquired respiratory tract and skin and soft tissue infections in Latin America, 2010

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with in vitro bactericidal activity against Gram-positive organisms, including methicillinsusceptible and -resistant Staphylococcus aureus, β-haemolytic and viridans group streptococci, and Streptococcus pneumoniae, as well as common Gram-negative organisms. In this study a total of 986 isolates collected in 2010 from patients in 15 medical centers in five Latin American countries from the Assessing Worldwide Antimicrobial Resistance Evaluation Program were identified as community-acquired respiratory tract or skin and soft tissue infection pathogens. Ceftaroline was the most potent agent tested against S. pneumoniae with a MIC90 value (0.12 µg/mL) that was eight-fold lower than ceftriaxone, levofloxacin, and linezolid. Its spectrum of coverage (100.0% susceptible) was similar to tigecycline, linezolid, levofloxacin and vancomycin. Against Haemophilus influenzae and Moraxella catarrhalis, ceftaroline was the most active agent tested. The activity of ceftaroline against S. aureus (including MRSA) was similar to that of vancomycin and tetracycline (MIC90,1 µg/mL) and linezolid (MIC90,2 Jg/mL). The 1-haemolytic streptococci exhibited 100.0% susceptibility to ceftaroline. Ceftaroline activity against Escherichia coli, Klebsiella spp., and Enterobacter spp. was similar to that of ceftriaxone and ceftazidime. These parenteral cephalosporin agents have potent activity against non-extended-spectrum These parenteral cephalosporin agents have potent activity against non-extended-spectrum-lactamase-phenotype strains, but are not active against extended-spectrum β-lactamase-phenotype strains. These results confirm the in vitro activity of ceftaroline against pathogens common in communityacquired respiratory tract and skin and soft tissue infection in Latin America, and suggest that ceftaroline fosamil could be an important therapeutic option for these infections.

Spectrum and potency of ceftaroline against leading pathogens causing community-acquired respiratory tract and skin and soft tissue infections in Latin America, 2010.

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with in vitro bactericidal activity against Gram-positive organisms, including methicillin-susceptible and -resistant Staphylococcus aureus, ß-haemolytic and viridans group streptococci, and Streptococcus pneumoniae, as well as common Gram-negative organisms. In this study a total of 986 isolates collected in 2010 from patients in 15 medical centers in five Latin American countries from the Assessing Worldwide Antimicrobial Resistance Evaluation Program were identified as community-acquired respiratory tract or skin and soft tissue infection pathogens. Ceftaroline was the most potent agent tested against S. pneumoniae with a MIC90 value (0.12µg/mL) that was eight-fold lower than ceftriaxone, levofloxacin, and linezolid. Its spectrum of coverage (100.0% susceptible) was similar to tigecycline, linezolid, levofloxacin and vancomycin. Against Haemophilus influenzae and Moraxella catarrhalis, ceftaroline was the most active agent tested. The activity of ceftaroline against S. aureus (including MRSA) was similar to that of vancomycin and tetracycline (MIC90, 1µg/mL) and linezolid (MIC90, 2µg/mL). The ß-haemolytic streptococci exhibited 100.0% susceptibility to ceftaroline. Ceftaroline activity against Escherichia coli, Klebsiella spp., and Enterobacter spp. was similar to that of ceftriaxone and ceftazidime. These parenteral cephalosporin agents have potent activity against non-extended-spectrum ß-lactamase-phenotype strains, but are not active against extended-spectrum ß-lactamase-phenotype strains. These results confirm the in vitro activity of ceftaroline against pathogens common in community-acquired respiratory tract and skin and soft tissue infection in Latin America, and suggest that ceftaroline fosamil could be an important therapeutic option for these infections.

Caracterização molecular de sorotipos não-vacinais de Streptococcus pneumoniae isolados de pacientes com meningite em Salvador, antes e após a implementação da vacina conjugada PCV-10 / Molecular characterization of non-vaccine serotypes of Streptococcus pneumoniae isolates from meningitis patients in Salvador, before and after implementation of the conjugate vaccine PCV-10

O advento das vacinas pneumocócicas conjugadas veio contribuir de forma decisiva para a redução da incidência dos casos de doença invasiva por S. pneumoniae em vários países do mundo. Em contrapartida, tem-se verificado um aumento de casos decorrentes de sorotipos não vacinais, que escapam da vacina e reduzem o seu efeito a partir da expansão de clones pré-existentes com consequente substituição de sorotipos e/ou do fenômeno de troca capsular (capsular switching). No Brasil, a vacina conjugada 10-valente (PCV10) foi introduzida no calendário nacional de imunização a partir de 2010. Este estudo teve como objetivo caracterizar através de técnicas fenotípicas e moleculares os sorotipos não-vacinais (SNVT) de S.pneumoniae, isolados de pacientes com meningite nos períodos anterior (janeiro/2008 - junho/2010) e posterior (julho/2010 - dezembro/2012) à implementação da vacina pneumocócica conjugada 10-valente (PCV10), na cidade de Salvador, Bahia. Os isolados de S. pneumoniae foram identificados através de métodos microbiológicos clássicos e a determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a oito antimicrobianos foi realizada através da técnica de microdiluição em caldo e a caracterização genotípica por intermédio das técnicas de PFGE e MLST...

The licensure and subsequent widespread use of pneumococcal conjugate vaccines have contributed for the reduction in the overall incidence of invasive pneumococcal disease worldwide. However, the emergence of Streptococcus pneumoniae nonvaccine serotypes (SNVT), which escape from the vaccine by the expansion of pre-existing clones following serotype replacement and/or by capsular switching is a matter of concern. In 2010, Brazil introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into its routine National Immunization Program. Our aim was to characterize the phenotypic and genotypic profile of S. pneumoniae non-vacine serotypes (SNVT) isolated from patients with meningitis before (January 2008 – June 2010) and after (July 2010 – December 2012) the introduction of PCV10 in Salvador, Bahia. The pneumococcal isolates were identified by classical microbiological methods and submitted to capsular deduction by multiplex-PCR and/or Quellung reaction. The antimicrobial susceptibility was performed the broth microdilution method. The genotypic profile was assessed by PFGE and MLST...

Avaliação de resultados discrepantes obtidos na execução de PCR em tempo real em amostras de pacientes com suspeita clínica de meningite bacteriana / Inconsistent results in real-time PCR in analyzing samples from patients with suspected bacterial meningitis

O princípio básico para obter resultado confiável é a compatibilidade entre as réplicas e sua reprodutibilidade. Na rotina diagnóstica por PCR em tempo real (PCR-TR), em que centenas de amostras são processadas, a obtenção de resultados com Cts tardios ou réplicas que diferem entre si por mais de três unidades, são inevitáveis. Das 3.000 amostras processadas em 2010, em duplicata, na rotina diagnóstica das meningites bacterianas por PCR-TR na pesquisa de N. meningitidis, S. pneumoniae e H. influenzae,157 (5,2 %), apresentaram inconsistência entre as réplicas (diferença entre Cts maior do que 3) e/ou altos valores de Cts; e os ensaios foram retestados. O presente trabalho investigou estes resultados obtidos, os benefícios destas repetições e as possíveis razões da ocorrência dos resultados discrepantes. Verificou-se que, apenas 18 (11 %) das amostras submetidas à repetição, apresentaram resultados positivos. Erros humanos inerentes à pipetagem, como o uso de pipetas não calibradas, a baixa concentração de DNA alvo nas amostras, a degradação da sonda ou mesmo a possível contaminação aleatória são fatores que contribuem para induzir resultados discrepantes. A realização do ensaio de PCR-TR com amostras em duplicata e a repetição de ensaios com resultados discordantes é um artifício eficiente para avaliar e definir estes resultados.(AU)

The basic principle for obtaining a reliable result is the consistency found among the replicas and its reproducibility. In a diagnostic routine by using real-time PCR (RT-PCR), when hundreds samples are processed, and results with late Cts or replicas that differ by more than three units are inevitable. Of 3,000 samples processed in 2010, in duplicate, in the diagnostic routine of bacterial meningitis by RT-PCR for detecting N. meningitidis, S. pneumoniae and H. influenzae, 157 (5.2 %) samples showed inconsistencyamong replicas (difference between Cts higher than three units) and/or high Cts values; and the samples were retested. This study assessed these results, the benefits of its repetitions and probable reasons for the occurrence of these discrepant results. Among the retested samples, 18 (11 %) only showed positive results. Human errors inherent to pipetting, use of non-calibrated pipettes, low concentration of target DNA in the analyzed samples, probe degradation or even random contamination are factors which contribute to induce the discrepant results. Performing RT-PCR assay with samples in duplicate and retesting thesamples showing discordant results constitute a device for efficiently evaluating and defining these results.(AU)

Tratamiento de la neumonía por Streptococcus pneumoniae y consideraciones de resistencia / Streptococcus pneumoniae pneumonia treatment and resistence considerations

Streptococcus pneumoniae is the most common bacterial cause of pneumonia in children and has become a topic of controversy for epidemiological changes that have been seen in recent years with the advent of the vaccine and the emergence of serotypes that cause increased morbidity which were not covered by the heptavalent vaccine. Also there have been changes in the concepts of resistance in recent years. This has led to the reevaluation of the use of specific antibiotics for management.

El Streptococcus pneumoniae es la causa bacteriana más frecuente de neumonía en los niños y se ha convertido en un tema de controversia por los cambios epidemiológicos que se han visto en los últimos años con el advenimiento de la vacuna y el surgimiento de serotipos que causan mayor morbilidad que no estaban cubiertos por la vacuna heptavalente. Igualmente se han presentado cambios en los conceptos de resistencia en los últimos años. Esto ha motivado la reevaluación del uso de los antibióticos específicos para su manejo.

Comparación de la respuesta inmunológica frente a cepas de S. pneumoniae, evaluada por hemaglutinación, en niños inmunizados con vacuna neumocócica heptavalente (dos primovacunaciones con o sin refuerzo) / Comparison of the immune response against strains of S. pneumoniae, assessed by hemagglutination, in children immunized with heptavalent conjugated pneumococcal vaccine (two primary vaccinations with or without reinforcement)

Introducción. Diferentes esquemas de inmunización con la vacuna antineumocócica heptavalente han probado su eficacia. Aunque se recomiendan pautas vacunales de dos o tres primovacunaciones con su respectivo refuerzo adicional, aún hay niños con primovacunaciones sin refuerzo. El objetivo de este trabajo fue comparar la respuesta inmunológica contra S. pneumoniae en niños bajo distintos esquemas de inmunización (dos o tres dosis) con vacuna antineumocócica heptavalente. Métodos. Se realizó un estudio observacional y transversal para comparar la respuesta inmunológica entre los grupos A (dos primovacunaciones sin refuerzo) y B (dos primovacunaciones con refuerzo). Se analizó la respuesta inmunológica escasa por medio de hemaglutinación positiva (dilución ≤ 1:2). Se calculó la razón de momios (OR) y se aplicó la prueba exacta de Fisher. Resultados. No se encontraron diferencias clínicas entre los grupos A (n = 14) y B (n = 15). Hubo mayor proporción de respuesta inmunológica escasa en el grupo A [57% vs 13%; OR 8.7 (IC 95% 1.3-53.8); p = 0.017]. Conclusiones. La respuesta inmunológica escasa contra S. pneumoniae es mayor en los esquemas de dos dosis de primovacunación sin refuerzo que cuando se utilizan dos dosis de primovacunación con refuerzo.

Background. Different patterns of heptavalent conjugated pneumococcal vaccine immunization have proven effective. Although three and four doses are recommended, there are still children who are administered schemes of two primary vaccination doses without reinforcement. The aim of this study was to compare the immune response against S. pneumoniae in children (group A and group B) submitted to different immunization schemes (two primary vaccination doses with or without reinforcement). Methods. We conducted an observational, cross-sectional study comparing the immune response between group A and group B, analyzing the weak immune response with positive hemagglutination dilution ≤1:2. Odds ratio (OR) and Fisher's exact test were used. Results. There were no clinical differences between group A (n = 14) and group B (n = 15). There was a higher proportion of weak immune response in group A (57% vs. 13%, OR 8.7 (95% CI 1.3-53.8, p = 0.017). Conclusions. Weak immune response against S. pneumoniae is higher in schemes primed with two doses of heptavalent conjugated pneumococcal vaccine without reinforcement than using the two-dose schedule + a booster of heptavalent conjugated pneumococcal vaccine.