Invasive Pneumococci Research Articles

Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial

Vaccine effectiveness of pneumococcal conjugate vaccines against culture-confirmed invasive pneumococcal disease has been well documented. In the Finnish Invasive Pneumococcal disease (FinIP) trial, we reported vaccine effectiveness and absolute rate reduction against laboratory-confirmed invasive pneumococcal disease (confirmation by culture or antigen or DNA detection irrespective of serotype). Here, we assessed vaccine effectiveness of PHiD-CV10 against clinically suspected invasive pneumococcal disease in children by use of diagnoses coded in hospital discharge registers. For this phase 3/4 cluster-randomised, double-blind trial, undertaken between Feb 18, 2009, and Dec 31, 2011, in municipal health-care centres and the Tampere University Vaccine Research Centre (Finland), we randomly assigned (2:2:1:1) 78 clusters into PHiD-CV10 three plus one, PHiD-CV10 two plus one, control three plus one, control two plus one groups (26:26:13:13 clusters) to give PHiD-CV10 in either three plus one or two plus one schedule (if enrolled before 7 months of age; infant schedules), two plus one (if enrolled between 7 and 11 months; catch-up schedules), and two doses at least 6 months apart (if enrolled between 12 and 18 months; catch-up schedules). Children were eligible if they had not received and were not anticipated to receive any of the study vaccines and had no general contraindications to vaccinations. We collected all inpatient and outpatient discharge notifications from the national hospital discharge register with International Classification of Diseases (ICD) 10 diagnoses compatible with invasive pneumococcal disease or unspecified sepsis, and verified data with patient files. We excluded invasive pneumococcal disease cases confirmed by positive culture or DNA/RNA detection from normally sterile body fluid. The primary objective was to estimate vaccine effectiveness against all register-based non-laboratory-confirmed invasive pneumococcal disease or unspecified sepsis and patient-file verified non-laboratory-confirmed invasive pneumococcal disease in infants younger than 7 months at enrolment. Masked follow-up lasted from the date of the first vaccination to Dec 31, 2011. Vaccine effectiveness was calculated against all episodes. This trial is registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254. We enrolled 47,366 children. On the basis of ICD-10 diagnoses, we recorded 264 episodes of register-based non-laboratory-confirmed invasive pneumococcal disease or unspecified sepsis, of which 102 were patient-file verified non-laboratory-confirmed invasive pneumococcal disease. The vaccine effectiveness was 50% (95% CI 32-63) in the 30,527 infants with three plus one and two plus one schedules combined and the absolute incidence rate reduction was 207 episodes per 100,000 person-years (95% CI 127-286). The vaccine effectiveness against the patient-file verified non-laboratory-confirmed invasive pneumococcal disease was 71% (95% CI 52-83) in infant three plus one and two plus one schedules combined. The absolute rate reduction was 142 episodes per 100,000 person-years (95% CI 91-191) in infant cohorts. This vaccine-probe analysis is the first report showing the effect of pneumococcal conjugate vaccines on clinically suspected invasive pneumococcal disease. The absolute rate reduction was markedly higher compared with laboratory-confirmed invasive pneumococcal disease, which implies low sensitivity of the laboratory-based case definitions and subsequently higher public health effect of pneumococcal conjugate vaccines against invasive pneumococcal disease than previously estimated. GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare (THL), Finland.

Invasive pneumococci before the introduction of pneumococcal conjugate vaccine in Turkey: antimicrobial susceptibility, serotype distribution, and molecular identification of macrolide resistance

This study evaluates the antimicrobial susceptibilities and serotype distributions of invasive Streptococcus pneumoniae (SP) isolates identified in a Turkish hospital before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The susceptibilities of all isolates were determined by evaluating six antibiotics: penicillin (PEN), ceftriaxone (CRO), levofloxacin (LEV), erythromycin (ERY), clindamycin (CD), and vancomycin (VAN). Serotyping and amplification of macrolide resistance genes were performed. Sixteen (50%) and four (2%) isolates were resistant to PEN and LEV, respectively. No isolates demonstrated VAN resistance. Intermediate resistance to CRO was found in 4% of all invasive isolates. Twenty-three (12·6%) isolates were resistant to ERY. Four (2%) invasive SP isolates demonstrated multidrug resistance. Serogroups 3, 5, 6, 8, 9, and 23 were the most common in both age groups. The potential coverage rates of PCV7 and PCV13 were 44·1 and 66·1% in children and 39·8 and 71·5% in adults, respectively. Continuous surveillance of antimicrobial resistance is required.

Initial Effects of the National PCV7 Childhood Immunization Program on Adult Invasive Pneumococcal Disease in Israel

BackgroundPCV7 was introduced as universal childhood vaccination in Israel in July 2009 and PCV13 in November 2010. Here we report data on adult invasive pneumococcal disease (IPD), two years post PCV7 implementation and before an expected effect of PCV13.MethodsAn ongoing nationwide active-surveillance (all 27 laboratories performing blood cultures in Israel), providing all blood & CSF S. pneumoniae isolates from persons >18 y was initiated in July 2009. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. IPD outcome and medical history were recorded in 90%. Second year post PCV implementation is compared to the first year.ResultsDuring July 2009 to June 2011, 970 IPD cases were reported (annual incidence [/100,000] of 9.17 and 10.16 in the two consecutive years, respectively). Respective case fatality rates (CFRs) were 20% and 19.1%. Incidence of IPD and CFR increased with age and number of comorbidities. Incidence rate was significantly greater during the second winter, 7.79/100,000 vs. 6.14/100,000 in first winter, p = 0.004, with a non-significant decrease during summer months (3.02 to 2.48/100,000). The proportion of IPD cases due to PCV7-serotypes decreased from 27.5% to 13.1% (first to second year) (p<0.001). Yet, non-PCV13-strains increased from 32.7% to 40.2% (p = 0.017). The increase in non-PCV13-strains was highly significant in immunocompromised patients and to a lesser degree in non-immunocompromised at risk or in older patients (>64 y). Among younger/healthier patients serotype 5 was the major increasing serotype. Penicillin and ceftriaxone resistance decreased significantly in the second year.ConclusionsWhile overall annual incidence of IPD did not change, the indirect effect of PCV7 vaccination was evident by the significant decrease in PCV7 serotypes across all age groups. Increase in non-VT13 strains was significant in immunocompromised patients. A longer follow-up is required to appreciate the full effect of infant vaccination on annual IPD.

Genetic diversity of Streptococcus pneumoniae causing meningitis and sepsis in Singapore during the first year of PCV7 implementation

Streptococcus pneumoniae is a major cause of sepsis, meningitis and respiratory disease worldwide. Pneumococcal conjugate vaccines (PCVs) have now been implemented in many countries worldwide, including Singapore. To evaluate the effectiveness of these vaccines, pneumococcal surveillance studies are required. Detailed and unified pneumococcal epidemiology data are currently scarce in South East Asia. Thus, we present data on invasive pneumococcal (IPD) isolates from Singapore that could assist in evaluating the effectiveness of pneumococcal vaccine in Singapore. One hundred and fifty-nine invasive pneumococcal disease isolates were received by the National Public Health Laboratory in Singapore between June 2009 and August 2010. Isolates were characterized using serotyping and multilocus sequence typing. Twenty-four different serotypes were found, the most common of which were 19A, 3, 7F, 23F, 6B, 14, 8 and 19F (in rank order). One hundred and two sequence types were observed, of which 38 were novel due to new alleles or new combinations of already existing alleles. Based on the Simpson’s Index of Diversity, serotypes 3, 6B and 19A were the most genetically diverse. Novel sequence types were more prevalent among conjugate vaccine serotypes 3, 19F and 23F and non-conjugate vaccine serotype 8, serogroup 15 and in non-typable isolates. We have demonstrated considerable genetic diversity among invasive pneumococci before and during the widespread use of conjugate vaccines in Singapore. Approximately half of all novel IPD clones identified in this study were non-conjugate vaccine serotypes. Although PCVs would target the most common serotypes, the high genetic diversity in non-vaccine serotypes would require further surveillance studies.

Phenotypic and Genotypic Characteristic of Invasive Pneumococcal Isolates from Both Children and Adult Patients from a Multicenter Surveillance in China 2005–2011

Streptococcus pneumoniae is an important pathogen in both children and the elderly, but previous studies in China have provided limited information about invasive pneumococcal disease (IPD). A total of 240 IPD S. pneumoniae strains (from 105 children and 135 adults) were collected from 12 cities in China in 2005–2011. Their phenotypes and genetic characteristics were analyzed. Streptococcus pneumoniae remained highly resistant to macrolides, tetracycline, and cotrimoxazole each year. Serotypes were assigned to the 240 isolates, and 19A (22.1%), 19F (21.7%), 14 (7.5%), 3 (7.1%), and 23F (5.4%) were the most prevalent, accounting for 63.8% of all strains. Serogroup 19 strains were significantly more common among children than among adults (58.7% vs 32.4%, respectively; P < 0.001). Serotypes 19F and 19A demonstrated higher resistance to β-lactams and cephalosporins than the other serotypes. The coverage of PCV13 was superior to that calculated for PCV7 and PCV10 (77.9% vs 40.8% and 47.1%, respectively), and coverage was higher in children than in adults (85.6% vs 72.1%, respectively; P = 0.012). A multilocus sequence typing analysis revealed great diversity, with nine clonal complexes and 83 singletons among all the strains. Specifically, CC271 was more common in children, whereas singletons were more prevalent in adults. Among the serogroup 19 strains, 84.7% were ST271, ST320, or ST236, belonging to CC271. The homogeneous genetic background of 19F and 19A, together with the high resistance of these strains, suggests that clonal spread is responsible for the high prevalence of serogroup 19 in IPD. This is the first large study to investigate IPD strains in both children and adults in China.

Evolution and genetic diversity of the Spain23F-ST81 clone causing adult invasive pneumococcal disease in Barcelona (1990–2012)

ObjectivesWe aimed to analyse the clinical epidemiology and genetic diversity of invasive pneumococcal disease (IPD) episodes attributed to the Spain23F-ST81 (PMEN1) clone.MethodsFifty-eight (2.7%) of 2117 invasive pneumococci isolated from adult patients during the 1990–2012 period shared a PFGE pattern related to the PMEN1 clone. The genotype was confirmed by multilocus sequence typing. The pbp2x, pbp1a, pbp2b and pspA genes were PCR-amplified and sequenced. Polymorphisms in the pspC gene were identified by PCR restriction fragment length polymorphism. The presence of transposons with erythromycin and tetracycline resistance determinants was detected by PCR.ResultsThe prevalence of the PMEN1 clone increased from 0.8% in 1991 to 6.2% in 2001, and decreased to 0% in 2010–12, concomitant with the introduction of the seven-valent pneumococcal conjugate vaccine for children. A total of 93.1% of patients had pneumonia, meningitis or peritonitis; 87.9% of patients had associated underlying diseases, mainly cancer, chronic obstructive pulmonary disease and diabetes. Two closely related sequence types (STs) (ST81, n = 52; ST85, n = 6) were detected, with different serotypes: 23F (n = 42), 19A (n = 9) and 19F (n = 6). All the isolates were resistant to penicillin, co-trimoxazole and chloramphenicol. All the isolates also shared the same pbp1a allele, whereas multiple alleles of pbp2b, pbp2x, pspA and pspC were detected. Of the isolates, 89.7% were tetracycline resistant and 60.3% (n = 35) were macrolide resistant, and resistance was associated with different Tn916-like transposons.ConclusionsAdult IPD caused by this clone was mainly detected in patients with underlying conditions, and genetic variability was observed among PMEN1 isolates collected in our area over the past 20 years.

Population Genetic Structure of Streptococcus pneumoniae in Kilifi, Kenya, Prior to the Introduction of Pneumococcal Conjugate Vaccine

BackgroundThe 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10. Methods and FindingsUsing multilocus sequence typing (MLST), we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC) 217. There were temporal fluctuations in the major circulating sequence types (STs); and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ≤2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates. ConclusionsUnderstanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation.

Piliation of invasive Streptococcus pneumoniae isolates in the era before pneumococcal conjugate vaccine introduction in Malawi.

The pneumococcal pilus has been shown to be an important determinant of adhesion and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus is capable of inducing protective immunity, supporting its inclusion in next-generation pneumococcal protein vaccine formulations. Whether this vaccine target is common among pneumococci in sub-Saharan Africa is uncertain. To define the prevalence and genetic diversity of type I and II pili among invasive pneumococci in Malawi prior to the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into routine childhood immunization, we examined 188 Streptococcus pneumoniae isolates collected between 2002 and 2008 (17% serotype 1). In this region of high disease burden, we found a low frequency of invasive piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen previously in multiple global pneumococcal lineages. All common serotypes with pilus were covered by PCV13 and so we predict that pilus prevalence will be reduced in the Malawian pneumococcal population after PCV13 introduction.

Determinants of Invasiveness Beneath the Capsule of the Pneumococcus

Interventions provide unique opportunities to learn about the natural history of infectious diseases, and one such intervention is the global rollout of pneumococcal conjugate vaccine. This is a vast experiment in natural selection, during which specific capsular types contained in 10–13-valent vaccines are increasingly being prevented from circulating in the human population. These types were chosen on the basis of their prevalence among invasive pneumococcal disease isolates, so by definition they represent a selection of the dominant invasive pneumococcal serotypes. The remaining ≥80 serotypes are then increasingly free to compete in an environment without their most invasive competitors. We can measure the invasive potential of these “replacement” strains most simply by comparing their prevalence in collections of carriage strains versus invasive strains. This allows the development of an invasiveness index [1–6],which has until now been based entirely on capsular types. Thus, serotypes 1, 5, and 7F, which are rarely detected among carriage isolates and almost exclusively found in collections of invasive disease isolates, have the highestinvasivepotential, whichissimply a ratio of their occurrence in collections ofinvasiveversuscarriagestrains.Acaveat ofthisapproachisthatthesestudiesoncarriage have used culture only, so as molecular or immunologic methods are developed to identify low density carriage, these invasive indices may change. There are some further caveats to these comparisons, such as taking the invasive strains and carriage strains from the same population in time and place, and these fundamentals are met in the article by Browall et al [7], from the Karolinska Institute in Sweden. They examined a collection of 550 carriage strains and 165 invasive strains, all recovered from children <18 years of age in the Stockholm area between 1997 and 2004, presumably before the introduction conjugate vaccine in much of that population. The mean age of 2.5 years among subjects with invasive pneumococci and 3.3 years among those carrying pneumococci meansthat onlyafraction of the subjects in each group were <1 year old, the age when most mortality due to pneumococcal infection occurs in children in developing countries. Nonetheless, these data offer a useful comparison between invasiveandcarriagestrainsinthe samecommunity in a developed country.

Serotype 5 Pneumococci Causing Invasive Pneumococcal Disease Outbreaks in Barcelona, Spain (1997 to 2011)

In this study, we analyzed the clinical and molecular epidemiology of invasive serotype 5 (Ser5) pneumococcal isolates in four teaching hospitals in the Barcelona, Spain, area (from 1997 to 2011). Among 5,093 invasive pneumococcal isolates collected, 134 (2.6%) Ser5 isolates were detected. Although the overall incidence of Ser5-related invasive pneumococcal disease (IPD) was low (0.25 cases/100,000 inhabitants), three incidence peaks were detected: 0.63/100,000 in 1999, 1.15/100,000 in 2005, and 0.37/100,000 in 2009. The rates of Ser5 IPD were higher among young adults (18 to 64 years old) and older adults (>64 years old) in the first two peaks, whereas they were higher among children in 2009. The majority (88.8%) of the patients presented with pneumonia. Comorbid conditions were present in young adults (47.6%) and older adults (78.7%), the most common comorbid conditions being chronic obstructive pulmonary disease (20.6% and 38.3%, respectively) and cardiovascular diseases (11.1% and 38.3%, respectively). The mortality rates were higher among older adults (8.5%). All Ser5 pneumococci tested were fully susceptible to penicillin, cefotaxime, erythromycin, and ciprofloxacin. The resistance rates were 48.5% for co-trimoxazole, 6.7% for chloramphenicol, and 6% for tetracycline. Two major related sequence types (STs), ST1223 (n = 65) and ST289 (n = 61), were detected. The Colombia(5)-ST289 clone was responsible for all the cases in the Ser5 outbreak in 1999, whereas the ST1223 clone accounted for 73.8% and 61.5% of the isolates in 2005 and 2009, respectively. Ser5 pneumococci are a frequent cause of IPD outbreaks in the community and involve children and adults with or without comorbidities. The implementation of the new pneumococcal conjugated vaccines (PCV10 and PCV13) might prevent such outbreaks.

Trends in serotypes and sequence types among cases of invasive pneumococcal disease in Scotland, 1999–2010

IntroductionThe 7-valent pneumococcal conjugate vaccine (Prevenar®, Wyeth; PCV7) was introduced to the UK paediatric immunisation schedule in 2006. This study investigates trends in serotypes and multi locus sequence types (STs) among cases of invasive pneumococcal disease (IPD) in Scotland prior to, and following, the introduction of PCV7. MethodsScottish Invasive Pneumococcal Disease Enhanced Surveillance has records of all cases of IPD in Scotland since 1999. Cases diagnosed from blood or cerebrospinal fluid isolates until 2010 were analysed. Logistic and poisson regression modelling was used to assess trends prior to and following the introduction of PCV7. ResultsPrior to PCV7 use, on average 650 cases of IPD were reported each year; 12% occurred in those aged <5 years and 35% affected those aged over 65 years. Serotypes in PCV7 represented 47% of cases (68% in <5 year olds). The serotype and ST distribution was relatively stable with only serotype 1 and associated ST 306 showing an increasing trend. PCV7 introduction was associated with a 69% (95% CI: 50%, 80%) reduction in the incidence of IPD among those aged <5 years, a 57% (95% CI: 47%, 66%) reduction among those aged 5–64 years but no significant change among those aged 65 years and over where increases in non-PCV7 serotypes were observed. Serotypes which became more prevalent post-PCV7 are those which were associated with STs related to the PCV7 serotypes. ConclusionsRoutine serotyping and sequence typing in Scotland allowed the assessment of the relationship between the capsule and the clones in the post vaccination era. Changes in the distribution of serotypes post PCV7 introduction appear to be driven by associations between serotypes and STs prior to PCV7 introduction. This has implications for the possible effects of the introduction of higher valency vaccines and could aid in predicting replacement serotypes in IPD.

Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial

The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was designed to assess the effectiveness of a pneumococcal vaccine containing ten serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) against invasive pneumococcal disease. In this cluster-randomised, double-blind trial, children aged younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants aged younger than 7 months at the first vaccination received either a 3+1 or a 2+1 vaccination schedule, children aged 7-11 months received a 2+1 schedule, and those 12-18 months of age received a two-dose schedule. The primary and secondary objectives were to assess vaccine effectiveness against culture-confirmed invasive pneumococcal disease due to any of the ten vaccine serotypes for the 3+1 and 2+1 schedules, respectively, in children who received at least one PHiD-CV10 dose before 7 months of age. Masked follow-up of pneumococcal disease lasted from the first vaccination (from February, 2009, to October, 2010) to January 31, 2012. Invasive disease data were retrieved from data accumulated in the national infectious diseases register. This trial and the nested acute otitis media trial are registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254, respectively. 47,369 children were enrolled from February, 2009, to October, 2010. 30,528 participants were assessed for the primary objective. 13 culture-confirmed vaccine-type cases of invasive pneumococcal disease were detected: none in the PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control groups. The estimates for vaccine effectiveness were 100% (95% CI 83-100) for PHiD-CV10 3+1 and 92% (58-100) for PHiD-CV10 2+1 groups. Two cases of any culture-confirmed invasive disease irrespective of serotype were detected in combined PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts (vaccine effectiveness 93%, 75-99). In catch-up cohorts, seven cases of invasive disease were reported, all in the control group: two cases in the children enrolled at 7-11 months of age; and five cases in children enrolled at 12-18 months of age (vaccine effectiveness 100%, 79-100). Non-fatal serious adverse events suspected to be vaccine-related were reported via routine post-immunisation safety surveillance in 18 children. This nationwide trial showed high PHiD-CV10 effectiveness against invasive pneumococcal disease when given in different schedules. For the first time, effectiveness of a 2+1 schedule in infants was confirmed in a clinical trial. GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare, Finland.

268 Serotype and Antimicrobial Susceptibility Distribution of Invasive Streptococcus Pneumoniae Isolated from Children in Turkey

Streptococcus pneumoniae is a major cause of invasive infections. The aim of this study was to evaluate the serotype and antimicrobial susceptibility of invasive pneumococci isolated at 14 different centers...

Epidemiology of Invasive Pneumococcal Disease in Older People in Spain (2007–2009): Implications for Future Vaccination Strategies

BackgroundRecently, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for adults. We analyzed the epidemiology of invasive pneumococcal disease (IPD) in older adults in Spain before PCV13 introduction.Methodology/Principal FindingsIPD episodes, defined as clinical findings together with an invasive pneumococcal isolate, were prospectively collected from patients aged over 65 years in three hospitals in Spain from 2007 to 2009. A total of 335 IPD episodes were collected. Pneumonia was the main clinical syndrome, while chronic obstructive pulmonary disease, diabetes mellitus and cancer were the main underlying diseases. Pneumococcal isolates were serotyped and the molecular typing was performed by PFGE/MLST. PCV13 serotypes accounted for 59.3% of isolates, the most prevalent being serotypes 19A (15.1%), 3 (9.6%), 7F (7.5%), 14 (6.9%) and 1 (5.4%). The most frequent non-PCV13 serotypes were serotypes 16F (4.5%), 22F (3.6%), 24F (3.3%) and 6C (2.1%). The most common genotypes were CC230 (8.5%, serotypes 19A and 24F), CC156 (8.2%, serotypes 9V and 14), ST191 (7.9%, serotype 7F), CC260 (6.6%, serotype 3), ST306 (5.2%, serotype 1), CC30 (4.6%, serotype 16F) and ST433 (3.6%, serotype 22F). Comparing the 335 IPD isolates to 174 invasive pneumococci collected at the same hospitals in 1999–2000, PCV7 serotypes decreased (45.4% vs 18.4%,p<0.001), non-PCV7 serotypes included in PCV13 increased (26.4% vs 41.0%,p = 0.001) and two non-PCV13 serotypes increased (serotype 6C 0% vs 2.1%, p = 0.05; serotype 24F 0.6% vs 3.3%, p = 0.04,).ConclusionIn our older adult population two serotypes (19A and 3) included in PCV13 accounted for about a quarter of IPD episodes in people ≥65 years. Non-PCV13 emerging serotypes should be carefully monitored in future surveillance studies.

Serotype Distribution and Antimicrobial Resistance of Invasive Pneumococcal Disease Strains in the Comunidad Valenciana, Spain, during the Winter of 2009-2010: Low PCV7 Coverage and High Levofloxacin Resistance

Streptococcus pneumoniae can cause serious invasive pneumococcal 1 coccal disease (IPD) such as pneumonia, sepsis and meningitis and is the cause of major morbidity and mortality worldwide.…

Characteristics ofStreptococcus pneumoniaeStrains Colonizing Upper Respiratory Tract of Healthy Preschool Children in Poland

Antibiotic resistant and invasive pneumococci may spread temporally and locally in day care centers (DCCs). We examined 267 children attending four DCCs located in the same city and 70 children staying at home in three seasons (autumn, winter, and spring) to determine prevalence, serotype distribution, antibiotic resistance patterns, and transmission of pneumococcal strains colonizing upper respiratory tract of healthy children without antipneumococcal vaccination. By pheno- and genotyping, we determined clonality of pneumococci, including drug-resistant strains. The average carriage of pneumococci in three seasons was 38.2%. 73.4% and 80.4% of the isolates belonged to serotypes present in 10- and 13-valent conjugate vaccine, respectively. Among the pneumococcal strains, 33.3% were susceptible to all antimicrobial tested and 39.2% had decreased susceptibility to penicillin. Multidrug resistance was common (35.7%); 97.5% of drug-resistant isolates represented serotypes included to 10- and 13-valent conjugate vaccine. According to BOX-PCR, clonality definitely was observed only in case of serotype 14. Multivariate analysis determined DCC attendance as strongly related to pneumococcal colonization in all three seasons, but important seasonal differences were demonstrated. In children attending DCCs, we observed dynamic turnover of pneumococcal strains, especially penicillin nonsusceptible and multidrug resistant, which were mostly distributed among serotypes included to available pneumococcal conjugate vaccines.

Macrolide-resistant phenotypes of invasive streptococcus pneumoniae isolates in Serbia

Macrolide resistance in Streptococcus pneumoniae has emerged as an important worldwide problem over the past decade. The aim of this study was to investigate macrolide-resistant phenotypes and the antimicrobial susceptibility patterns of invasive pneumococci in Serbia. A total of 68 invasive pneumococcal strains, collected from 2009 to 2011, were sent from regional laboratories to the National Reference Laboratory. Susceptibility testing was performed using the VITEK2 system and phenotypes were determined by triple-test. Overall penicillin and erythromycin nonsusceptibility rates were 26% and 43%, respectively. Resistance rates were higher in children than in adults. Co-resistance to penicillin and erythromycin was detected in 18% strains. Resistance rates to the third generation of cephalosporins, TMP-SXT and tetracycline were 16%, 37% and 29%, respectively. All isolates were fully susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and rifampicin. Twenty-two isolates (79%) an expressed macrolide-lincosamide-streptogramin B (MLSB) resistance phenotype and M phenotype was found in 21% of macrolide resistant strains.

In vitro activity of ceftobiprole and seven other antimicrobial agents against invasive Streptococcus pneumoniae isolates in Spain

The in vitro activity of ceftobiprole was compared with that of seven antimicrobial agents against invasive Streptococcus pneumoniae isolated from adult patients (>15years old). Characterization of erythromycin-resistant strains and serotype distribution of all pneumococci were also evaluated. Seventy invasive S. pneumoniae strains were isolated from December 2007 to January 2009. Serotyping was carried out by Quellung reaction. Antibiotic susceptibility was tested by broth microdilution (CLSI guidelines). The comparator agents were penicillin, cefotaxime, erythromycin, clindamycin, telithromycin, tetracycline and moxifloxacin. Phenotypic characterization of macrolide resistance was performed by the double disk method. Macrolide resistance genes [erm(B) and mef(A/E)] and the promoter of erm(B) were detected by PCR. Twenty-five different serotypes were detected of which 87% were non-PCV7 types. The percentages of resistance to erythromycin, clindamycin and tetracycline were 20%, 8.6% and 16%, respectively. A penicillin MIC ≥0.12mg/L was observed in 14 of the 70 invasive pneumococci strains. The cefotaxime and ceftobiprole MIC(50)/MIC(90) of these 14 strains were 1/4 and 0.03/1mg/L, respectively. Ceftobiprole showed higher in vitro activity than penicillin and cefotaxime with all isolates being inhibited by ≤1mg/L. Its high in vitro activity should make ceftobiprole a very promising drug for the treatment of pneumococcal infections.

Multidrug-resistant pneumococci (serotype 8) causing invasive disease in HIV+ patients

From July 2007 to June 2009, all pneumococci causing invasive pneumococcal disease in our hospital were serotyped. Antimicrobial susceptibility was determined by microdilution. Molecular typing was performed by pulsed-field gel electrophoresis and by multilocus sequence typing. Among 251 invasive pneumococci, serotype 8 was the most frequent (13.5%). All serotype 8 strains were susceptible to penicillin; however, 61.8% (21/34) were co-resistant to erythromycin, levofloxacin and tetracycline and identical to the Sweden15A-ST63 clone. Serotype 8 was significantly more frequent among human immunodeficiency virus (HIV)-infected patients (36.5%). The high prevalence of this nonconjugate vaccine multiresistant serotype 8 is a cause for concern mainly in HIV-infected patients.

Molecular analysis of Streptococcus pneumoniae clones causing invasive disease in children in Singapore

Streptococcus pneumoniae remains a leading cause of serious paediatric disease. However, there are few published epidemiological data regarding invasive pneumococcal disease (IPD) in many countries in South East Asia, including Singapore. Baseline data for IPD are essential to inform policy regarding pneumococcal conjugate vaccine (PCV) use in Singapore. To our knowledge, this is the first study to use multilocus sequence typing (MLST) to investigate clonal relationships among Singaporean IPD isolates. We characterized 86 invasive pneumococci isolated from Singaporean children between 2001 and 2006 using serotyping and MLST. The objectives were to compare Singaporean MLST data to worldwide data and to assess serotype distribution in relation to current PCV formulations. We observed 50 sequence types (STs), a high proportion of which (n = 16) were novel STs. Despite the presence of these novel STs, serotype distribution was similar to that observed elsewhere. Serotypes 14, 6B, 19A and 19F accounted for 85 % of IPD cases. PCV7, PCV10 and PCV13 covered 85 %, 86 % and 97 % of IPD isolates, respectively. We have demonstrated a pressing need for larger studies to determine the molecular epidemiology and antibiotic susceptibility of circulating pneumococcal clones from both carriage and disease in Singapore.