ABSTRACT Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others Results: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly. Background . (IPD) populations Brazil (PNI) PCV PCV1 yearsold, yearsold old, years-old PPV PPV2 riskpatients patients 6 Methods 201 antimicrobialnonsusceptibility antimicrobial non susceptibility pneumococcus Vaccineserotypecoverage coverage estimated comorbidities atrisk, atrisk at risk, highrisk, highrisk Results 40 evaluated 32 55.9%, 559 55.9% , 55 9 (55.9%) 1 > ( 82.0%. 820 82.0% 82 0 82.0%) 348 34 34.8 Highrisk High groups n 211, 211 211) 28%, 28 28% (28%) HIVAIDS HIV AIDS 25.7% 257 25 7 (25.7% 24.5% 245 24 (24.5% 89, 89 89) 16.5% 165 16 (16.5% 8.1% 81 (8.1% isolates 429 42 42.9 14.1%, 141 14.1% 14 (14.1%) 8.7%, 87 8.7% (8.7%) C 7.7%, 77 7.7% (7.7%) 6.2% 62 (6.2 each each) antimicrobialnonsusceptibility. susceptibility. vaccineserotypecoverage vaccine 191 19 19.1% 43.8% 438 43 PCV15 47.8% 478 47 PCV20 62.9% 629 PCV21 658 65 65.8% 673 67 67.3% 286 28.6 died 542 54 54.2 meningitis Conclusion elderly (IPD (PNI 20 55.9 (55.9% 82.0 34. 21 (28% 25.7 (25.7 24.5 (24.5 16.5 (16.5 8.1 (8.1 42. 14.1 (14.1% 8.7 (8.7% 7.7 (7.7% 6.2 (6. 19.1 43.8 47.8 PCV2 62.9 65.8 67.3 28. 54. 55. (55.9 82. (28 25. (25. 24. (24. 16. (16. 8. (8. 14. (14.1 (8.7 7. (7.7 6. (6 19. 43. 47. 62. 65. 67. (55. (2 (25 (24 (16 (8 (14. (7. (55 (1 (14 (7 (5

OBJETIVO: Avaliar o perfil de sorotipos e a susceptibilidade aos antimicrobianos de cepas de Streptococcus pneumoniae obtidas em espécimes clínicos de pacientes com doença invasiva, bem como suas implicações na formulação de vacinas pneumocócicas. MÉTODOS: Cepas de pneumococo isoladas no Laboratório de Análises Clínicas do Hospital de Clínicas da Universidade Federal de Uberlândia a partir de amostras clínicas de pacientes com doença invasiva foram identificadas e enviadas ao Instituto Adolfo Lutz em São Paulo para confirmação da identificação, sorotipagem e determinação da susceptibilidade aos antimicrobianos. RESULTADOS: De abril de 1999 a março de 2003, foram isoladas 148 cepas invasivas de pneumococo, sendo 84 (56,7%) provenientes de pacientes do sexo masculino. A idade variou de um dia a 88,83 anos, com média de 21,33+25,82 anos e mediana de 4,42 anos. Os diagnósticos clínicos mais comuns foram pneumonia (91 casos; 61,4%), meningite (32 casos; 21,6%) e bacteremia sem foco evidente (15 casos; 10,1%). As principais fontes de recuperação foram sangue (76 amostras; 51,3%), líquido pleural (39; 26,3%) e liquor (30; 20,2%). No total, foram identificados 23 diferentes sorotipos entre 143 amostras testadas, sendo os mais comuns os seguintes: 14, 3, 1, 5, 6A, 6B e 18C. Dentre 30 (20,2%) cepas oxacilina-resistentes, 23 (15,5%) confirmaram a resistência à penicilina (12,8% com nível intermediário e 2,7%, com nível pleno), que esteve restrita aos sorotipos 14, 23F, 19A e 6B, predominando em indivíduos com até dois anos de idade (p = 0,0008). Foi detectada susceptibilidade diminuída ao cotrimoxazol (63,4%), à eritromicina (8,3%), à clindamicina (8,7%) e à ofloxacina (0,8%). A resistência à cefotaxima foi detectada em três das 30 cepas testadas (2% das 148), todas elas com resistência confirmada à penicilina. Não foi observada resistência a cloranfenicol, rifampicina ou vancomicina. CONCLUSÕES: A resistência à penicilina foi detectada em 15,5% das cepas e predominou em crianças abaixo de dois anos de idade. Foram identificados 23 diferentes sorotipos de Streptococcus pneumoniae em pacientes internados com doença invasiva, e a maioria dos sorotipos (82,6%) e das cepas (90,2%) está incluída na vacina polissacarídica 23-valente. As cifras para a vacina 7-valente, atualmente disponível (PN CRM7), são de 46,7% dos sorotipos e 63,6% das cepas, obtidos de crianças com até cinco anos de idade.

OBJECTIVE: To determine the prevalence of serotypes and antimicrobial susceptibility of invasive strains of Streptococcus pneumoniae and to discuss the implications of these findings for vaccine formulation. METHODS: Strains of Streptococcus pneumoniae obtained from normally sterile fluids from patients admitted with invasive diseases were isolated and identified at the Hospital de Clínicas, Universidade Federal de Uberlândia, state of Minas Gerais, and forwarded to Instituto Adolfo Lutz, state of São Paulo, for further identification, serotyping and determination of antimicrobial susceptibility. RESULTS: From April 1999 to March 2003, 148 invasive strains of Streptococcus pneumoniae were obtained. The age of patients ranged from 1 day to 88.83 years (mean: 21.33+25.82 years; median: 4.42 years). Eighty-four (56.7%) patients were male. The most common diagnoses were pneumonia (91 cases; 61.4%), meningitis (32 cases; 21.6%) and occult bacteremia (15 cases; 10.1%). Strains were isolated mostly from blood (76 occasions; 51.3%), pleural fluid (39 occasions; 26.3%) and cerebrospinal fluid (30 occasions; 20.2%). There were 23 different serotypes, and the most common were 14, 3, 1, 5, 6A, 6B and 18C. Among 30 (20.2%) oxacillin-resistant strains, 23 (15.5%) were confirmed as resistant to penicillin (12.8% intermediate resistance and 2.7% full resistance). Oxacillin-resistant strains were restricted to serotypes 14, 23F, 19A and 6B. Resistance to penicillin varied with age, being more common in children under two years of age (p=0.0008). We observed decreased sensibility to sulfamethoxazole-trimethoprim (92 isolates; 63.4%), to erythromycin (12 isolates; 8.3%), to clindamycin (12 isolates ;8.7%), to ofloxacin (one strain; 0.8%) and to cefotaxime (three strains; 2%; also resistant to penicillin). All isolates were susceptible to chloramphenicol, rifampin and vancomycin. CONCLUSIONS: The decreased susceptibility to penicillin, detected in 15.5% of the strains was predominant in children under two years of age. There were 23 different Streptococcus pneumoniae serotypes. The 23-valent polysaccharide vaccine covers 82.6% of the serotypes and 90.2% of the invasive strains isolated in this population. In addition, 46.7% of the serotypes and 63.6% of the strains isolated from children until five years of age are covered in the currently available 7-valent conjugated vaccine (PN CRM7).

Objetivo: avaliar letalidade, morbidade, resistência bacteriana e sorotipos mais freqüentes em crianças internadas por meningite bacteriana.Métodos: selecionamos crianças com meningite bacteriana com cultura positiva para S. pneumoniae, entre 1 mês e 15 anos, internadas em dois hospitais em São Paulo, e analisamos dados clínicos e microbiológicos. A identificação do S. pneumoniae foi realizada através do teste de optoquina e solubilidade em bile. Todas as cepas foram testadas com disco de oxacilina 1 µg e, nas cepas que apresentaram alo de inibição <20 mm, foi avaliada a concentração inibitória mínima para penicilina, cloranfenicol, eritromicina, ceftriaxona, vancomicina e trimetoprim/sulfametoxazole pelo método do E-teste. As cepas de pneumococo foram sorotipadas através da reação de Quellung. A evolução clínica dos pacientes foi analisada através de revisão retrospectiva dos prontuários, com uso de um protocolo uniforme de avaliação.Resultados: incluímos 55 pacientes com meningite pneumocócica, sendo que 52,5% delas apresentava idade menor de 6 meses. Das cepas isoladas, 36% apresentava infecção por cepa com resistência intermediaria à penicilina (0,1µg/ ml < CIM < 1,0 µg/ ml). Das cepas com susceptibilidade diminuída à penicilina, 35% era resistente à trimetoprim/sulfametoxazole. Não houve resistência aos outros antibióticos testados. A letalidade foi de 20%, e houve seqüelas neurológicas em 40% das crianças avaliadas. Em relação à perda auditiva, a mesma ocorreu em 60% das crianças avaliadas. Houve correlação estatisticamente significante entre letalidade e alteração neurológica com idade abaixo de 6 meses. Os sorotipos do pneumococo mais freqüentemente encontrados foram 1, 5, 6B, 14, 19A e 23F, sendo que 70% dos sorotipos encontrados estão presentes na vacina heptavalente, recentemente liberada.Conclusão: meningite pneumocócica apresenta alta letalidade e alta morbidade, e a vacina heptavalente tem utilidade potencial na sua prevenção.

Objective: to determine mortality, morbidity, antimicrobial susceptibility and the most frequent serotypes in children admitted to hospital due to pneumococcal meningitis Methods: patients with meningitis caused by Streptococcus pneumoniae detected by culture in cerebrospinal fluid or blood, aged between 1 month and 15 years old, admitted to two hospitals in the city of São Paulo, were included in the study. Susceptibility to penicillin was determined by the disk diffusion test using oxacillin 1 µg disk. If the inhibition area with oxacillin disk was less than 20mm, the strains were tested for penicillin, chloramphenicol, ceftriaxone, vancomycin and sulfamethoxazole /trimethoprim using the E test.Results: we identified 55 patients, 52.5% of which were younger than 6 months. The prevalence of penicillin-nonsusceptible strains was 36%. All the strains were intermediately resistant (0.1mg/ ml <FONT FACE=Symbol>£</FONT> MIC<FONT FACE=Symbol>£</FONT> 1.0 mg/ ml) and 35% of the penicillin intermediate resistant strains were resistant to sulfamethoxazole/trimethoprim. The mortality rate was 20% and impaired neurological outcome was present in 40% of the children. The audiometric test revealed alteration in 60% of the children tested. Age less than 6 months was associated with poor outcome. The most frequent serotypes were 1, 5, 6B, 14, 19A and 23F, and 70% of the serotypes were included in the new 7-valent vaccine.Conclusions: these findings suggest that pneumococcal meningitis presents high mortality and morbidity and that the 7-valent conjugate vaccine would be potentially useful in preventing serious pneumococcal infections.

Pneumonia is one of the leading causes of hospitalization and death among children in developing countries, and mortality due to pneumonia has been associated with S. pneumoniae infection. This investigation was designed to describe the antimicrobial susceptibility and serotype patterns of pneumococcal strains recovered from the blood of children with community-acquired pneumonia (CAP) and to assess the clinical findings of pneumococcal bacteremic patients with pneumonia. In a 26 month prospective study, blood cultures were obtained as often as possible from children (<16 years of age) diagnosed with CAP in two emergency rooms. Antimicrobial drug susceptibility tests and serotyping were performed when pneumococcus was identified. We studied 3,431 cases and cultured blood samples from 65.5% of those. Pneumococcus was recovered from 0.8% of the blood samples. The differences in age, somnolence, wheezing and hospitalization among children with and without pneumococcal bacteremia were statistically significant. Pneumococcal bacteremia was age-related (mean 1.63 ± 1.55; median 0.92) and associated with somnolence and hospitalization among children with CAP. One strain was recovered from pleural fluid. Penicillin resistance was detected in 21.0% (4/19) of the strains at an intermediate level, whereas 63.0% of the strains were resistant to trimethoprim-sulfamethoxazole. The most common serotypes were 14 and 6B, and these serotypes included the resistant strains. Eight of our 18 isolates from blood were of types included in the heptavalent conjugate pneumococcal vaccine, recently licensed in the USA.

Criança de sete anos, previamente hígida, foi admitida na unidade de terapia intensiva por quadro de toxemia associado à varicela. Evoluiu rapidamente para choque e insuficiência de multiplos órgãos e sistemas e, apesar do tratamento intensivo, morreu no 4o dia após a admissão. A cultura de secreção colhida por punção profunda de partes moles em região torácica foi positiva para Streptococcus pyogenes, proteina-M não tipável e carreador dos genes codificadores da produção de exotoxinas pirogênicas estreptocócicas A e B, preenchendo os critérios para definição de Síndrome do choque tóxico estreptocócico. Os autores discutem aspectos clínicos e fisiopatológicos desta síndrome, bem como alguns aspectos incomuns relacionados a este caso.

A previously healthy seven-year-old boy was admitted to the intensive care unit because of toxaemia associated with varicella. He rapidly developed shock and multisystem organ failure associated with the appearance of a deep-seated soft tissue infection and, despite aggressive treatment, died on hospital day 4. An M-non-typable, spe A and spe B positive Group A Streptococcus was cultured from a deep soft tissue aspirate. The criteria for defining Streptococcal toxic shock-like syndrome were fulfilled. The authors discuss the clinical and pathophysiological aspects of this disease as well as some unusual clinical findings related to this case.