Pneumococcal infective endocarditis in Brazil: a multicenter study on a severe condition.

BACKGROUND: Streptococcus pneumoniae bacteremia may result in Infective Endocarditis (IE). In the pre-antibiotic era, it caused 10 %‒15 % of IE, decreasing to < 3 % after penicillin availability. Although infrequent, it causes aggressive disease. METHODS: Retrospective analysis of endocarditis databases, prospectively implemented in 4 Brazilian institutions, 2005‒2023. RESULTS: From the prospective cohorts comprising 2321 adult patients with IE, we identified 11 (0.47%) with pneumococcal IE. Males represented 7/11 and mean age was 54 years (22‒77). All had native valve involvement; perivalvular abscess was present in 6/11. Only one patient had concurrent meningitis. Beta-lactams were the antibiotics used in 10/11. All had surgical indication, but only 6 had it, as the others were seriously ill. Overall, in hospital mortality was 6/11, but only 1/6 of those who underwent surgery died, compared to 5/5 of those who had an indication for surgery and did not have it. CONCLUSIONS: The high mortality rates and need for surgical intervention emphasize the need to promptly identify and manage pneumococcal endocarditis. Physicians ought to recommend vaccination to all patients at risk for severe pneumococcal disease.

The Crisis of Macrolide Resistance in Pneumococci in Latin America.

Macrolide antibiotics are recommended for the treatment of pneumococcal pneumonia and invasive pneumococcal disease (IPD). Prior to 2000, ∼10% of Streptococcus pneumoniae strains isolated from IPD cases in Latin American countries were resistant to macrolides. The mechanism of resistance to macrolides was associated mainly with the efflux pump known as the macrolide efflux genetic assembly, since most pneumococcal strains carried the mef(A/E) gene, whereas <6% strains carried both the methylase gene ermB and mef(A/E). In the first decade of this century, a significant increase in the prevalence of macrolide resistance was observed in pneumococcal strains in both Mexico and Peru. Approximately 30% of S. pneumoniae strains in these countries were already resistant to erythromycin, while the prevalence in Colombia, Argentina, and Brazil remained below 10%. During the last decade, we have been experiencing a worrisome increase in pneumococcal strains carrying resistance to macrolides, with a prevalence of up to 80% for resistance to erythromycin. The mechanism for disseminating macrolide resistance has evolved. Currently, more than 55% of invasive S. pneumoniae macrolide-resistant strains carry both the ermB and the mef(A/E)/mel genes. Lessons learned from the current macrolide resistance crisis in Latin America can inform interventions in other regions.

Dynamics of Pediatric Antibiotic Use Differ between High- and Low-Prescribing Clinics after Pneumococcal Conjugate Vaccines.

OBJECTIVE: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age. METHODS: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated. RESULTS: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC]). CONCLUSIONS: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption.

[Primary pneumococcal peritonitis in a pediatric hospital from Argentina]. / Peritonitis primaria por neumococo en un hospital pediátrico de Argentina.

Pneumococcal peritonitis represents a small subset of patients suffering from invasive pneumococcal disease (IPD). We describe 5 cases of primary peritonitis documented in the pediatric hospital over 15 years (2005-2020) of IPD surveillance. The patients, 3girls and 2boys with a mean age of 5 years, experienced peritoneal signs and symptoms; 3of them suffered from nephrotic syndrome. Based on the local resistance profiles, all isolates were sensitive to beta-lactams, one strain showed resistance to cotrimoxazole and tetracycline while another strain, to cotrimoxazole only. Serotypes found in 4/5 strains (one was non-viable) were: 1, 19F, 15C and 23A. Children were treated with third-generation cephalosporins or ampicillin, gentamicin and metronidazole and all of them evolved favorably. Pneumococcal etiology should be included in the differential diagnosis of acute abdominal pain in children. Our study aims to contribute to the knowledge of this condition and to the local epidemiology of IPD.

Multiplex real-time PCR using SYBR Green: Unspecific intercalating dye to detect antimicrobial resistance genes of Streptococcus pneumoniae in cerebrospinal fluid.

Meningitis caused by Streptococcus pneumoniae is still a disease of great impact on Public health, which requires immediate diagnosis and treatment. However, the culture of clinical specimens is often negative and antibiotic susceptibility testing (AST) must be performed with isolated strains. Multiplex real-time polymerase chain reaction (qPCR) has high sensitivity and specificity, produces faster results to identify the pathogen, and it can also be an important tool to identify resistance antibiotic genes earlier than AST, especially in the absence of an isolated strain. This study developed a multiplex qPCR assay, using SYBR Green as a nonspecific dye, to detect antibiotic resistance genes to predict pneumococcal susceptibility/resistance in cerebrospinal fluid (CSF) samples from meningitis patients. From 2017 to 2020, CSF samples were cultured and analyzed by qPCR to detect the main three bacteria causing meningitis. Isolated and reference strains were applied in SYBR Green qPCR multiplex to detect pbp2b, ermB, and mef genes, and the results were compared with the AST. Pneumococcal-positive CSF samples (lytA-positive gene) without isolated strains were also tested to evaluate the antimicrobial susceptibility profile in the region from 2014 to 2020. From the received 873 CSF samples; 263 were cultivated, 149 were lytA-positive in the qPCR, and 25 produced viable isolated pneumococci strains, which were evaluated by AST. Melting temperature for each gene and the acceptance criteria were determined (pbp2b: 78.24-79.86; ermB: 80.88-82.56; mef: 74.85-76.34 ºC). A total of 48/51 strains presented a genetic profile in agreement with the AST results. Resistant strains to erythromycin and clindamycin were ermB-positive, and two were also mef-positive, indicating both resistance mechanisms were present. In the retrospective study of the genetic profile of resistance, 82 lytA-positive CSF samples plus 4 strains were applied in the SYBR Green qPCR multiplex: 51% of samples presented the wild genotype (pbp2b positive and ermB/mef negative); 15% were negative for all the three evaluated, indicating pneumococci resistant to penicillin; and 17% represented the multidrug-resistant pneumococci (pbp2b negative and ermB positive or pbp2b negative and ermB and mef positive). Therefore, SYBR Green qPCR multiplex proved to be a reliable tool to identify resistance genes in S. pneumoniae and would be less expensive than multiplex qPCR using specific probes. This could be easily introduced into the routine of diagnostic laboratories and provide a strong presumption of pneumococcal resistance, especially in the absence of isolated strains.

Invasive pneumococcal disease in patients from a pediatric hospital in Peru, 2017-2020. / Enfermedad neumocócica invasiva en pacientes de un hospital pediátrico de Perú, 2017-2020.

OBJECTIVES.: Motivation for the study: there are few reports describing cases of invasive pneumococcal disease after the introduction of the 13-valent conjugate vaccine in Peru. Main findings: cases of invasive pneumococcal disease are still reported in children, more frequently in children under five years of age. The most frequent clinical form was bacteremia and there was greater antibiotic resistance to erythromycin, trimethoprim-sulfamethoxazole, and penicillin. Implications: our findings suggest the need to maintain epidemiological surveillance of invasive pneumococcal disease and to measure the impact of vaccination against pneumococcus in children. This study aimed to describe the clinical characteristics, serotypes, and antibiotic susceptibility in patients with invasive pneumococcal disease (IPD). The medical records of patients with IPD who were hospitalized at the Instituto Nacional de Salud del Niño-Breña (Lima, Peru) were reviewed. We evaluated 29 patients. The median age was 1.9 years (interquartile range: 1 to 4 years). Of the sample, 51.7% were women and the most frequent clinical form of IPD was bacteremia in 18 (62.1%) patients; 65.5% had a complete vaccination schedule, according to the Peruvian Ministry of Health. Germ isolation was performed from blood samples in 82.8% of patients. Antibiotic resistance to erythromycin (55.2%) was the most frequent, followed by resistance to trimethoprim-sulfamethoxazole (48.3%) and penicillin (24.1%). The isolated serotypes were 6C, 19A, 23A and 24F. One patient died of meningitis. In conclusion, IPD was more frequent in children aged one to five years and the most frequent clinical form was bacteremia. Five serotypes reported in previous studies were found to be resistant to penicillin and erythromycin.

OBJETIVOS.: Motivación para realizar el estudio: existen pocos reportes que describan casos de la enfermedad neumocócica invasiva posterior a la introducción de la vacuna conjugada 13-valente en Perú. Principales hallazgos: aún se reportan casos de enfermedad neumocócica invasiva en niños, con mayor frecuencia en menores de cinco años. La forma clínica más frecuente fue la bacteriemia y hubo mayor resistencia antibiótica a eritromicina, trimetoprim-sulfametoxazol y penicilina. Implicancias: los hallazgos de este estudio sugieren la necesidad de mantener la vigilancia epidemiológica de la enfermedad neumocócica invasiva; además, de medir el impacto de la vacunación contra el neumococo en niños. El propósito del presente estudio fue describir las características clínicas, serotipos y susceptibilidad antibiótica en pacientes con enfermedad neumocócica invasiva (ENI). Se revisaron las historias clínicas de los pacientes con ENI hospitalizados en el Instituto Nacional de Salud del Niño-Breña (Lima, Perú). Se evaluaron a 29 pacientes. La mediana de edad fue 1,9 años (rango intercuartílico 1 a 4 años). El 51,7% eran mujeres y la forma clínica de la ENI más frecuente fue la bacteriemia en 18 (62,1%) pacientes. El 65,5% tenía el esquema de vacunación completo, según el Ministerio de Salud de Perú. El 82,8% del aislamiento del germen fue de sangre. La resistencia antibiótica fue más frecuente a la eritromicina (55,2%), trimetoprim-sulfametoxazol (48,3%) y penicilina (24,1%). Los serotipos registrados fueron 6C, 19A, 23A y 24F. Un paciente falleció por meningitis. En conclusión, la ENI fue más frecuente en niños de uno a cinco años y en la forma clínica de bacteriemia. Se encontraron cinco serotipos reportados en estudios previos con resistencia a penicilina y eritromicina.

Resistance to ß-lactams in Streptococcus pneumoniae.

Streptococcus pneumoniae is an important causal agent of pneumonia, meningitis, sepsis, bacteremia, and otitis media. Penicillin resistance rates in S. pneumoniae have remained stable in Argentina in the last years. In the late '90s more isolates with MIC of penicillin ≥2µg/ml were observed; however, their frequency has decreased in recent years. The phenotypic expression of penicillin resistance is due to a modification in penicillin-binding proteins associated with a mosaic structure in the coding genes. The expansion of successful resistant clones varies among the different regions and is influenced by the use of antibiotics, vaccines, particularly conjugated ones, as well as population density. Parenteral treatment with high doses of penicillin G continues to be effective for the treatment of pneumonia and bacteremia, oral aminopenicillins for otitis media and sinusitis and third generation cephalosporins for meningitis.

Fluoroquinolone treatment as a protective factor for 10-day mortality in Streptococcus pneumoniae bacteremia in cancer patients.

To evaluate the prognostic factors in adult cancer patients with pneumococcal bacteremia, describe episode features and the phenotypic characteristics of the isolated strains. We evaluated the episodes in patients admitted to a cancer hospital between 2009 and 2015. The outcomes were defined as 48 h mortality and mortality within 10 days after the episode. The variables evaluated were: age, sex, ethnicity, ECOG, Karnofsky score, SOFA, cancer type, metastasis, chemotherapy, radiotherapy, neutropenia, previous antibiotic therapy, community or healthcare-acquired infection, comorbidities, smoking, pneumococcal vaccination, infection site, presence of fever, polymicrobial infection, antimicrobial susceptibility, serotype and treatment. 165 episodes were detected in 161 patients. The mean age was 61.3 years; solid tumors were the most prevalent (75%). 48 h and 10-day mortality were 21% (34/161) and 43% (70/161) respectively. The 48 h mortality- associated risk factors were SOFA and polymicrobial bacteremia; 10-day mortality-associated risk factors were fever, neutropenia, ECOG 3/4, SOFA and fluoroquinolones as a protective factor. Pneumococcal bacteremia presented high mortality in cancer patients, with prognosis related to intrinsic host factors and infection episodes features. Fluoroquinolone treatment, a protective factor in 10-day mortality, has potential use for IPDs and severe community-acquired pneumonia in cancer patients.

[Pneumococcal osteoarticular infections in children admitted to a Pediatric Reference Hospital from Misiones, Argentina. Thirteen years of surveillance]. / Infección neumocócica osteoarticular en niños atendidos en un hospital pediátrico de referencia de Misiones, Argentina. Trece años de vigilancia.

Streptococcus pneumoniae is a rare cause of osteoarticular infections. We describe 5documented cases that occurred in 2005, 2009, 2011, 2015 and 2017 in patients admitted to the Pediatric Provincial Reference Hospital of Misiones. These cases corresponded to a 4-year-old boy and 4 girls aged 11, 10, 6 years and 4 months with a diagnosis of osteomyelitis of the scapula and humerus, arthritis of the hip, ankle and osteomyelitis of the distal fibula. All of them were in good general condition on admission and one of them was seropositive for human immunodeficiency virus. All the recovered isolates were susceptible to ß-lactams and only one isolate showed joint resistance to macrolides and tetracycline. Three isolates were serotyped, 2of which carried vaccine serotypes (19F and 7F). Despite its low frequency, the etiology of S.pneumoniae should be considered among the osteoarticular infections. Our findings enhance the role of the Bacteriology laboratory in the diagnosis by microbiological culture and contribute to documenting the epidemiological behavior of this pathogen.

Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection.

Resolution failure of exacerbated inflammation triggered by Influenza A virus (IAV) prevents return of pulmonary homeostasis and survival, especially when associated with secondary pneumococcal infection. Therapeutic strategies based on pro-resolving molecules have great potential against acute inflammatory diseases. Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator that acts on its Mas receptor (MasR) to promote resolution of inflammation. We investigated the effects of Ang-(1-7) and the role of MasR in the context of primary IAV infection and secondary pneumococcal infection and evaluated pulmonary inflammation, virus titers and bacteria counts, and pulmonary damage. Therapeutic treatment with Ang-(1-7) decreased neutrophil recruitment, lung injury, viral load and morbidity after a primary IAV infection. Ang-(1-7) induced apoptosis of neutrophils and efferocytosis of these cells by alveolar macrophages, but had no direct effect on IAV replication in vitro. MasR-deficient (MasR-/-) mice were highly susceptible to IAV infection, displaying uncontrolled inflammation, increased viral load and greater lethality rate, as compared to WT animals. Ang-(1-7) was not protective in MasR-/- mice. Interestingly, Ang-(1-7) given during a sublethal dose of IAV infection greatly reduced morbidity associated with a subsequent S. pneumoniae infection, as seen by decrease in the magnitude of neutrophil influx, number of bacteria in the blood leading to a lower lethality. Altogether, these results show that Ang-(1-7) is highly protective against severe primary IAV infection and protects against secondary bacterial infection of the lung. These effects are MasR-dependent. Mediators of resolution of inflammation, such as Ang-(1-7), should be considered for the treatment of pulmonary viral infections.

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.

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.

Invasive infections by non-vaccine serotypes of Streptococcus pneumoniae: a growing threat.

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.

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.

Antibacterial mechanism of gold nanoparticles on Streptococcus pneumoniae.

Streptococcus pneumoniae is a causal agent of otitis media, pneumonia, meningitis and severe cases of septicemia. This human pathogen infects elderly people and children with a high mortality rate of approximately one million deaths per year worldwide. Antibiotic-resistance of S. pneumoniae strains is an increasingly serious health problem; therefore, new therapies capable of combating pneumococcal infections are indispensable. The application of gold nanoparticles has emerged as an option in the control of bacterial infections; however, the mechanism responsible for bacterial cell lysis remains unclear. Specifically, it has been observed that gold nanoparticles are capable of crossing different structures of the S. pneumoniae cells, reaching the cytosol where inclusion bodies of gold nanoparticles are noticed. In this work, a novel process for the separation of such inclusion bodies that allowed the analysis of the biomolecules such as carbohydrates, lipids and proteins associated with the gold nanoparticles was developed. Then, it was possible to separate and identify proteins associated with the gold nanoparticles, which were suggested as possible candidates that facilitate the interaction and entry of gold nanoparticles into S. pneumoniae cells.

Morbidity, mortality and antimicrobial resistance of pneumococcal infections in the Jamaican paediatric and adult populations.

BACKGROUND: Pneumococcal infections are a leading global cause of morbidity and mortality, complicated by the increasing antimicrobial resistance of pneumococcal isolates. OBJECTIVE: To evaluate morbidity and mortality associated with both invasive pneumococcal disease (IPD) and non-IPD in Jamaica in both the paediatric and adult population. Pneumococcal isolates (n= 94) were collected over a 2-year period (2008-2009). METHODS: Risk factors for poor clinical outcomes: death, complicated disease and length of hospitalization (LOH) were evaluated and antimicrobial resistance patterns were determined by Kirby-Bauer disc diffusion. RESULTS: The case fatality rate was 6.8%. Independent mortality risk factors included complicated disease [OR 30.9 (3.4-276.6)] and diabetes mellitus [OR 8.3 (1.4-48.8)]. Independent risk factors for the development of complicated disease included sickle cell disease [OR 36.5 (4.2-320.3)] and sepsis [OR 3.5 (1.2-10.4)]. The LOH was increased most in patients with invasive disease (4.6-fold) and resistance to ceftriaxone (4.3-fold). Penicillin (16.0%) and erythromycin (14.9%) resistance was most prevalent, while ceftriaxone (4.3%) resistance was least prevalent. CONCLUSIONS: The high burden of IPD in at-risk groups in our population and the associated increase in morbidity and mortality underlie the need for improved preventive and therapeutic management strategies in these patients.

Expansion of the multidrug-resistant clonal complex 320 among invasive Streptococcus pneumoniae serotype 19A after the introduction of a ten-valent pneumococcal conjugate vaccine in Brazil.

BACKGROUND: In 2010, a ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in the routine infant national immunization program in Brazil. Invasive pneumococcal disease (IPD) caused by serotype 19A (Spn19A) increased after the introduction of PCVs in several countries. We compared the frequency, antimicrobial resistance and molecular patterns of invasive Spn19A strains before and after PCV10 introduction in Brazil using data from the national laboratory-based surveillance. METHODS: We analyzed invasive Spn19A strains isolated from 2005-2009 (pre-PCV10 period), 2011-2015 and 2016-2017 (post-PCV10 periods). Antimicrobial susceptibility was performed for all Spn19A strains, and multilocus sequence typing (MLST) was performed for strains isolated in the age groups <5 years and ≥50 years. RESULTS: Among the study period, a total of 9,852 invasive Spn strains were analyzed, and 673 (6.8%) belonged to serotype 19A. Overall, the proportion of Spn19A among the total number of IPD strains increased from 2.8% in 2005-2009 to 7.0% and 16.4% in 2011-2015 and 2016-2017, respectively. The relative increase in Spn19A was observed especially in children <5 years old (2005-2009: 3.2%; 2011-2015: 15.5%; 2016-2017: 31.2%). The percentage of penicillin resistance (MIC 2.0-4.0 µg/mL), erythromycin resistance and multidrug resistance (MDR) increased after PCV10 introduction due to the expansion of the MDR clonal complex CC320 (2005-2009: 8.6%; 2011-2015: 56.1%; 2016-2017: 66.5%). CONCLUSION: We observed an expansion of MDR-CC320 among invasive Spn19A strains after PCV10 introduction in Brazil, probably related to a combination of factors, such as vaccination and antimicrobial pressure. Continued surveillance of Spn19A strains is necessary to monitor the sustainability of this clonal complex in the Brazilian population.

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean 2010-2015: A systematic review and a time series analysis.

BACKGROUND: This systematic review aims to describe the prevalence, trends, and antibiotic resistance of Streptococcus pneumoniae serotype 19A (Spn19A) that causes invasive and non-invasive diseases in children <5 years in Latin-American and Caribbean countries. METHODS: We searched for published (between January 2010 and February 2016) observational and clinical studies within the region including effectiveness and impact on Spn19A after pneumococcal conjugate vaccine (PCV) introduction. We calculated prevalence estimates by country and standardized the frequency of isolates to conduct an interrupted time series analysis for selected countries and to assess the potential changes in disease trends, overall and for Spn19A. RESULTS: We identified and reviewed full-text of 89 publications and included 59 in the analysis. Data from the laboratory surveillance network, SIREVA, were included in 43 (74%) of the invasive pneumococcal disease reports. There are differences in the sensitivity, representativeness, and heterogeneity of laboratory surveillance. There has been and overall reduction in the trend and number of invasive S. pneumoniae isolates in children <5 years after PCVs introduction. To date, the prevalence of Spn19A has increased, however, there has been no observed change in the trend. CONCLUSIONS: This updated systematic review provides evidence of a reduction in the total number of invasive pneumococcal disease isolates after the introduction of PCVs in the region but cannot yet conclude a change in the trend of Spn19A disease.

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.

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

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.

Serotypes, antimicrobial resistance and genotypes of Streptococcus pneumoniae associated with infections in cancer patients in Brazil.

We sought to characterize pneumococcal isolates associated with bacteremia, pneumonia and meningitis in cancer patients and to estimate the coverage of the available pneumococcal vaccines. Fifty isolates recovered from 49 patients attending a cancer reference center over a 1-year period were analyzed. The prevalent serotypes were: 23F (12%), 6A (8%), 3, 4, 20, and 23A (6% each). All isolates were susceptible to chloramphenicol, levofloxacin, rifampicin, and vancomycin. Resistance or reduced susceptibility to penicillin made up 14%, and one isolate was also intermediately resistant to ceftriaxone. The three (6%) erythromycin-resistant isolates presented the M or cMLSB phenotypes and harbored the mef(A/E) gene exclusively or along with the erm(B) gene. Twenty-two (44%) isolates were closely related to 11 international clones, being strongly associated with penicillin non-susceptibility. Combined immunization with the 13-valent conjugate and the 23-valent polysaccharide vaccines might contribute to reduce (76%) the burden of the pneumococcal infections in the population investigated.