Prevalência de sorotipos e resistência antimicrobiana de cepas invasivas do pneumococo em crianças: análise de 9 anos

Objective: To determine the prevalence of serotypes and antimicrobial susceptibility of strains of pneumococcus in children and to evaluate the implications for vaccine formulation.Methods: Strains of pneumococcus obtained from children admitted with invasive diseases were isolated at Hospital de Clinicas of Universidade Federal de Uberlandia, Uberlandia, Brazil, and sent to Instituto Adolfo Lutz, São Paulo, Brazil, for further identification, serotyping, and determination of antimicrobial susceptibility.Results: From April 1999 to December 2008, 142 strains of pneumococcus, obtained from children under 5 years of age, were analyzed. Seventy-five (52.8%) patients were male, and the age ranged from 1 to 60 months (mean age = 19 +/- 15.4 months; median = 15 months). the most common diagnoses were pneumonia [92 cases (64.8%)] and meningitis [33 cases (23.2%)]. the strains were mostly isolated from blood [61 samples (43%)], pleural fluid [52 samples (36.6%)], and cerebrospinal fluid [28 samples (19.7%)]. the most common serotypes were 14, 5, 6B, 1, 6A, 18C, 19A, 3, 9V, 19F, 23F, 9N, and 10A. There were 14 [9.9%] penicillin-resistant strains, which was detected only in the following serotypes: 14, 6B, 19F, 19A, and 23F, being predominant from 2004 to 2008 (p = 0.000). There was reduced susceptibility to co-trimoxazole (79.5%), erythromycin and clindamycin (11.3% each), and ceftriaxone (5.6%).Conclusions: Penicillin resistance was detected in 9.9% of the strains, being predominant from 2004 to 2008. Twenty different pneumococcal serotypes were identified, and 71.9% of the serotypes were represented in the 7-valent conjugate vaccine (PN CRM7) currently available.Univ Fed Uberlandia, Fac Med, Programa Posgrad Ciencias Saude, BR-38400 Uberlandia, MG, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilUniv Fed Uberlandia, Lab Hosp Clin Uberlandia, Uberlandia, MG, BrazilUniv São Paulo, Microbiol Clin, São Paulo, BrazilIAL, Secao Bacteriol, Projeto Sistema Reg Vacinas SIREVA, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

A Streptococcus pneumoniae lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV.

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005-2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005-2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for comparison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci

Geographical migration and fitness dynamics of Streptococcus pneumoniae

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient

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.

BackgroundIn 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.MethodsWe 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 ResultsAmong 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 ConclusionWe 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

Distribution of Streptococcus pneumoniae serotypes in the northeast macro-region of São Paulo state/Brazil after the introduction of conjugate vaccine

Abstract Background Infections caused by Streptococcus pneumoniae (Spn) still challenge health systems around the world, even with advances in vaccination programs. The present study evaluated the frequency of various Spn serotypes isolated in Regional Health Care Network 13 (RRAS 13), which includes the regional health departments (RHDs) of Araraquara, Barretos, Franca and Ribeirão Preto, especially after the introduction of 10-valent pneumococcal conjugate vaccine (PCV10) in 2010. Methods The analyzed Spn strains were isolated from patients with invasive pneumococcal diseases (IPDs) and then sent to Adolfo Lutz Institute (ALI) for further confirmative identification tests during the period from 1998 to 2013. The samples were from the cities in RRAS13, which is located in the Northeast region of São Paulo State, and totals 90 municipalities. Results We analyzed strains isolated from 796 patients. They were predominantly: men (58.9%); 20 to 60 years old (32.2%); evaluated from 2003 to 2010 (60.2%); and diagnosed with meningitis (45.7%) and pneumonia (45.0%), the most common invasive pneumococcal diseases. In 2010, serotypes 3, 19F, 1, 23F, 6A and 6B were among the most frequent, while serotypes 3, 12F, 14, 6A, 18C, 8 and 6B were more common after the introduction of PCV10. Serotypes 14, 19F and 3 were more frequent in meningitis, while serotypes 14, 3 and 1 prevailed in pneumonia. After 2010, there was a decrease in serotypes 14, 1, 23F and 5 and an increase in serotypes 3, 12F, 11A and 8, which were not present in the vaccine. Conclusions The present study noted the increase in serotypes 3, 12F, 11A and 8 after vaccination. None of those serotypes are included in the available conjugate vaccines, which highlights the importance of continued monitoring of IPDs in order to measure the disease burden in the population in the long term and provide new epidemiological information to determine the impact of PCV10 in Brazil

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

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

Novos pontos de corte de sensibilidade nas taxas de resistência antimicrobiana de cepas invasivas de pneumococo New susceptibility breakpoints in antimicrobial resistance rates of invasive pneumococcal strains

OBJETIVO: Avaliar impacto dos novos pontos de corte de sensibilidade à penicilina nas taxas de resistência de cepas de pneumococo obtidas de crianças com pneumonia. MÉTODOS: Cepas de pneumococo isoladas no laboratório de análises clínicas do Hospital de Clínicas de Uberlândia, Uberlândia (MG), a partir de amostras de pacientes internados foram enviadas ao Instituto Adolfo Lutz, Sao Paulo (SP), para confirmação da identificação, sorotipagem e determinação da sensibilidade aos antimicrobianos. RESULTADOS: De abril de 1999 a dezembro de 2008 foram enviadas ao Instituto Adolfo Lutz 330 cepas de pneumococo, sendo 195 (59%) provenientes de pacientes com diagnóstico de pneumonia. Destas, foram analisadas 100 cepas de pacientes com idade &#8804; 12 anos; a idade dos pacientes variou de 1 a 12,6 anos, com média de 2,4 e mediana de 1,7 anos; 47 pacientes eram do sexo masculino; as fontes de recuperação foram sangue (42%) e líquido pleural (58%). Foram detectadas 35 cepas oxacilina-resistentes: segundo os critérios do Clinical and Laboratory Standards Institute (CLSI) de 2007 [concentração inibitória mínima (CIM) &#8804; 0,06 µg/mL para sensibilidade (S), 0,12 a 1 µg/mL para resistência intermediária (RI) e &#8805; 2 µg/mL para resistência plena (RP)], 22 cepas apresentaram RI e 11, RP para penicilina. De acordo com os critérios atuais do CLSI de 2008 (&#8804; 2 µg/mL para S, 4 µg/mL para RI e &#8805; 8 µg/mL para RP) apenas uma cepa confirmou RI à penicilina. Detectou-se resistência a cotrimoxazol (80%), tetraciclina (21%), eritromicina (13%), clindamicina (13%) e ceftriaxona (uma cepa, simultaneamente resistente a penicilina). CONCLUSÕES: Com a aplicação dos novos pontos de corte para sensibilidade in vitro, as taxas de resistência a penicilina caíram 97%, de 33 para 1%.<br>OBJECTIVE: To evaluate the impact of new penicillin susceptibility breakpoints on resistance rates of pneumococcal strains collected from children with pneumonia. METHODS: Pneumococcal strains collected from patients admitted with pneumonia were isolated at the clinical analysis lab of Hospital de Clínicas de Uberlândia, Uberlândia, Brazil, and sent to Instituto Adolfo Lutz, São Paulo, Brazil, for further identification, serotyping and determination of antimicrobial susceptibility. RESULTS: From April 1999 to December 2008, 330 strains of pneumococcus were sent to Instituto Adolfo Lutz; of these, 195 (59%) were collected from patients with pneumonia. One hundred strains collected from patients &#8804; 12 years old were analyzed. The patients' age ranged from 1 to 12.6 years old (with mean age of 2.4 and median of 1.7 years). Forty-seven patients were male. The strains were isolated from blood (42%) and pleural fluid (58%). There were 35 oxacillin-resistant strains: according to the criteria defined by the Clinical and Laboratory Standards Institute (CLSI) in 2007 [minimum inhibitory concentration (MIC) &#8804; 0.06 µg/mL for susceptibility (S), 0.12 to 1 µg/mL for intermediate resistance (IR), and &#8805; 2 µg/mL for full resistance (FR)], 22 strains had IR and 11 strains had FR. According to the current breakpoints defined by the CLSI in 2008 (&#8804; 2 µg/mL for S, 4 µg/mL for IR and &#8805; 8 µg/mL for FR), only one strain had IR to penicillin. There was resistance to co-trimoxazole (80%), tetracycline (21%), erythromycin (13%), clindamycin (13%), and ceftriaxone (one strain simultaneously resistant to penicillin). CONCLUSIONS: When the new breakpoints for in vitro susceptibility were applied, penicillin resistance rates dropped 97%, from 33 to 1%

Prevalence of pneumococcal serotypes and resistance to antimicrobial agents in patients with meningitis: ten-year analysis

OBJECTIVES: To determine the prevalence of pneumococcal serotypes and antimicrobial susceptibility in patients with meningitis, and to evaluate the implications for vaccine coverage. METHODS: Pneumococcal strains obtained from normally sterile fluids from patients admitted with meningitis were isolated at the Hospital de Clínicas of the Universidade Federal de Uberlândia, Minas Gerais State, and sent to the Instituto Adolfo Lutz, city of São Paulo, São Paulo State, for further identification, serotyping, and antimicrobial susceptibility determination. RESULTS: From April 1999 to April 2009, 338 pneumococcal strains were isolated, and 72 obtained from patients with meningitis, were analyzed. Patients' ages varied from one month to 82.2 years (mean of 18.4 ± 22.9 years; median of 5.2 years) and 46 (63.9%) patients were male. Strains were isolated from cerebrospinal fluid [66 occasions (91.7%)] and blood [6 occasions (8.3%)]. The most commonly identified serotypes were 14, 19F, 3, 7F, 6A, 6B, 10A, 18C, 23F, 5, and 34. Of the 20 [27.8%] oxacillin-resistant strains, 17 [23.6%] were resistant to penicillin and nine [12.5%] to ceftriaxone, both resistance patterns being more common in children aged two years or less and during the 2005-2009 period. CONCLUSIONS: Resistance to penicillin and ceftriaxone was detected in 23.6% and 12.5% of the strains, respectively, and predominated in children aged two years or less and during the 2005-2009 period. There were 24 different serotypes of pneumococcus and 79.8% of the serotypes were represented in the 7-valent conjugated vaccine [PVC7]