Distribution of Serotypes Causing Invasive Pneumococcal Disease in Children From High-Income Countries and the Impact of Pediatric Pneumococcal Vaccination.

BACKGROUND: The introduction and adoption of pneumococcal conjugate vaccines (PCVs) into pediatric national immunization programs (NIPs) has led to large decreases in invasive pneumococcal disease (IPD) incidence caused by vaccine serotypes. Despite these reductions, the global IPD burden in children remains significant. METHODS: We collected serotype-specific IPD data from surveillance systems or hospital networks of all 30 high-income countries that met inclusion criteria. Data sources included online databases, surveillance system reports, and peer-reviewed literature. Percentage of serotyped cases covered were calculated for all countries combined and by PCV type in the pediatric NIP. RESULTS: We identified 8012 serotyped IPD cases in children <5 or ≤5 years old. PCV13 serotype IPD caused 37.4% of total IPD cases, including 57.1% and 25.2% for countries with PCV10 or PCV13 in the pediatric NIP, respectively, most commonly due to serotypes 3 and 19A (11.4% and 13.3%, respectively, across all countries). In PCV10 countries, PCV15 and PCV20 would cover an additional 45.1% and 55.6% of IPD beyond serotypes contained in PCV10, largely due to coverage of serotype 19A. In PCV13 countries, PCV15 and PCV20 would cover an additional 10.6% and 38.2% of IPD beyond serotypes contained in PCV13. The most common IPD serotypes covered by higher valency PCVs were 10A (5.2%), 12F (5.1%), and 22F and 33F (3.5% each). CONCLUSIONS: Much of the remaining IPD burden is due to serotypes included in PCV15 and PCV20. The inclusion of these next generation PCVs into existing pediatric NIPs may further reduce the incidence of childhood IPD.

Long-Term effects of COVID-19: a review of current perspectives and mechanistic insights.

Although SARS-CoV-2, responsible for COVID-19, is primarily a respiratory infection, a broad spectrum of cardiac, pulmonary, neurologic, and metabolic complications can occur. More than 50 long-term symptoms of COVID-19 have been described, and as many as 80% of patients may develop ≥1 long-term symptom. To summarize current perspectives of long-term sequelae of COVID-19, we conducted a PubMed search describing the long-term cardiovascular, pulmonary, gastrointestinal, and neurologic effects post-SARS-CoV-2 infection and mechanistic insights and risk factors for the above-mentioned sequelae. Emerging risk factors of long-term sequelae include older age (≥65 years), female sex, Black or Asian race, Hispanic ethnicity, and presence of comorbidities. There is an urgent need to better understand ongoing effects of COVID-19. Prospective studies evaluating long-term effects of COVID-19 in all body systems and patient groups will facilitate appropriate management and assess burden of care. Clinicians should ensure patients are followed up and managed appropriately, especially those in at-risk groups. Healthcare systems worldwide need to develop approaches to follow-up and support patients recovering from COVID-19. Surveillance programs can enhance prevention and treatment efforts for those most vulnerable.

Antibiotic susceptibility rates of invasive pneumococci before and after the introduction of pneumococcal conjugate vaccination in Germany.

Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. A total of 22,208 isolates from invasive pneumococcal disease were collected between July 1, 1992 and June 30, 2013. The present study was conducted to analyze changes in antimicrobial susceptibility and pneumococcal vaccine coverage after the introduction of pneumococcal conjugate vaccination in Germany. Most of the isolates originated from adults ≥16 years (82.5%), while 17.5% were obtained from children <16 years. Penicillin resistance was observed in 7.2% of meningitis cases both among children and adults during the entire study period. In the post-PCV13 period, the resistance rate was 11.3% in children and 10.0% in adults, which is higher than in the pre-PCV7 and post-PCV7 periods. In the non-meningitis group, an overall penicillin nonsusceptibility rate (intermediate resistance and resistance) of 0.5% was detected both among children and adults. Nonsusceptibility rates among children were 6.3% (pre-PCV7), 7.6% (post-PCV7) and 9.0% (post-PCV13). The corresponding nonsusceptibility rates among adults were 4.4%, 6.0% and 7.9%, respectively. Concerning cefotaxime, in meningitis cases 0.8% of all isolates were intermediate and 0.5% resistant among children, while among adults, 0.9% were intermediate and 0.2% resistant. In non meningitis cases, cefotaxime nonsusceptibility rates were 0.5% in children and 0.3% in adults. Macrolide nonsusceptibility rates were lower in the post-PCV13 period (children 8.2%; adults 8.8%) than in the post-PCV7 period (children 17.3%; adults 13.0%) and the pre-PCV7 period (children 24.8%; adults 13.3%). In the pre-PCV7 period, macrolide resistance was mainly caused by M-phenotype clones carrying the mefA gene. In the post-PCV7/13 period, ermB (MLSb-phenotype) was the dominant resistance marker. Overall nonsusceptibility rates were 5.5% for clindamycin (intermediate 0.3%, resistant 5.2%), 0.7% for levofloxacin (intermediate 0.4%, resistant 0.3%), 8.5% for tetracycline (intermediate 0.6%, resistant 7.9%) and 11.0% for trimethoprim-sulfamethoxazole (SXT) (intermediate 5.7%, resistant 5.3%). In summary, childhood pneumococcal conjugate vaccination has had a strong effect on the pneumococcal population in Germany, both among vaccinated children as well as among non-vaccinated children and adults. Serotypes included in the pneumococcal conjugate vaccines have strongly diminished, while some non-vaccine serotypes have gained importance, particularly with respect to antibiotic resistance. However, concerning antibiotic non-susceptibility the most outstanding change over the years is the decline in macrolide resistance, especially among children.

Pneumococcal meningitis and vaccine effects in the era of conjugate vaccination: results of 20 years of nationwide surveillance in Germany.

BACKGROUND: Long-term complications and a case mortality rate of 7.5% make meningitis caused by Streptococcus pneumoniae a serious clinical threat. In 2006, a general pneumococcal conjugate vaccination (PCV) recommendation was issued for all children under 2 years in Germany. Here, we investigate serotype changes in meningitis cases after this vaccine recommendation. METHODS: The German National Reference Center for Streptococci (NRCS) has conducted surveillance for invasive pneumococcal disease (IPD) in Germany since 1992. Pneumococcal isolates were serotyped by the Neufeld's Quellung reaction and antibiotic susceptibility was tested using the broth microdilution method. RESULTS: Of 22,204 IPD isolates sent to the NRCS from July 1992 to June 2013, 3,086 were meningitis cases. Microbiological and statistical investigations were performed to characterize and quantify all meningitis cases, focusing on changes reflecting implementation of the national PCV recommendation. 1,766 isolates (57.2% of meningitis cases) were from adults (≥16 years) and 1,320 isolates (42.8%) originated from children (<16 years). Overall, the leading serotypes were 14 (9.7%), 7F (7.8%), 3 (6.9%), 19F (5.7%) and 23F (5.0%). Among children, serotypes 14 (16.2%), 7F (8.9%) and 19F (7.1%) were most common, whereas among adults, serotypes 3 (9.6%), 7F (6.9%), 22F (5.0%), 23F (4.9%) and 14 (4.8%) were most prevalent. After the introduction of general PCV7/10/13 vaccination a significant decrease for most vaccine serotypes was observed. Generally, the differences in antibiotic nonsusceptibility between children <16 years and adults ≥16 were low. For macrolides in the pre-PCV7 period, a significantly higher proportion of resistant isolates was found in children (25.1%), compared to the post-vaccination period (9.7%; p<0.0001). CONCLUSIONS: Implementation of the pneumococcal conjugate vaccines broadly reduced vaccine-type meningitis cases. Changes in serotype prevalence must be continuously monitored to observe future trends concerning pneumococcal meningitis.

Global in vitro activity of tigecycline and comparator agents: Tigecycline Evaluation and Surveillance Trial 2004-2013.

BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (TEST) is a global antimicrobial susceptibility surveillance study which has been ongoing since 2004. This report examines the in vitro activity of tigecycline and comparators against clinically important pathogens collected globally between 2004 and 2013. METHODS: Antimicrobial susceptibility was determined using guidelines published by the Clinical and Laboratory Standards Institute. The Cochran Armitage Trend Test was used to identify statistically significant changes in susceptibility between 2004 and 2013. RESULTS: Among the Enterobacteriaceae susceptibility was highest to the carbapenems [imipenem 97.1% (24,655/25,381), meropenem 97.0% (90,714/93,518)], tigecycline (97.0%, 115,361/118,899) and amikacin (96.9%, 115,200/118,899). Against Acinetobacter baumannii the highest rates of susceptibility were for minocycline (84.5%, 14,178/16,778) and imipenem (80.0%, 3,037/3,795). The MIC90 for tigecycline was 2 mg/L. 40% (6,743/16,778) of A. baumannii isolates were multidrug-resistant. Enterococci were highly susceptible to tigecycline and linezolid (>99%); vancomycin resistance was observed among 2% of Enterococcus faecalis (325/14,615) and 35% of Enterococcus faecium (2,136/6,167) globally. 40% (14,647/36,448) of Staphylococcus aureus were methicillin-resistant while 15% (2,152/14,562) of Streptococcus pneumoniae were penicillin-resistant. Against S. aureus and S. pneumoniae susceptibility to linezolid, vancomycin, and tigecycline was ≥99.9%. Globally, 81% (331/410) of statistically significant susceptibility changes during the study period were decreases in susceptibility. CONCLUSIONS: Amikacin, the carbapenems, and tigecycline were active against most gram-negative pathogens while linezolid, tigecycline, and vancomycin retained activity against most gram-positive pathogens collected in TEST during 2004-2013.

Epidemiology of serotype 19A isolates from invasive pneumococcal disease in German children.

BACKGROUND: This study presents an analysis of 159 serotype 19A isolates from IPD in children before and after the general recommendation for childhood pneumococcal conjugate vaccination in Germany in July 2006. Vaccination formulations used were PCV7, PCV10 (from April 2009) and PCV13 (from Dec. 2009, replacing PCV7). METHODS: Isolates from invasive pneumococcal disease in children were serotyped using the Quellung reaction, tested for antibiotic susceptibility and analysed for their multi locus sequence type. RESULTS: In an analysis of 3328 isolates from invasive pneumococcal disease (IPD) in children that were sent to the German National Reference Center for Streptococci between July 1997 and June 2011, we show that the proportion of 19A isolates ranged between 1.7 and 4.2% in the period 1997 to 2006. After the recommendation for pneumococcal conjugate childhood vaccination, which was issued in July 2006, the proportion of 19A isolates increased significantly to 15.0% in 2010/11. Eight clonal complexes (CC) and groups accounted for 77.2% and 65.3% of all serotype 19A isolates before and after vaccination, respectively. While three CCs and several STs were not detected after vaccine introduction, four CCs and several STs first appeared after vaccination, including three ST320 isolates that could be traced to recent imports from the US, UK and India. The proportion of penicillin-nonsusceptible and of multidrug-resistant 19A isolates moderately increased after vaccine introduction. A significant increase in the use of cephalosporins and azithromycin was noted post-vaccination (p=0.00001 and p=0.0013 respectively). CONCLUSIONS: The prevalence of serotype 19A in Germany has increased significantly between July 2007 and June 2011. Possible reasons for this are the introduction of pneumococcal conjugate vaccination, increased use of cephalosporins and azithromycin, import of multidrug-resistant isolates and increased reporting.

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies.

BACKGROUND: Neither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines. METHODS: We collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated. RESULTS: Among 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes. CONCLUSIONS: Vaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.

A review of evidence for pneumococcal vaccination in adults at increased risk of pneumococcal disease: risk group definitions and optimization of vaccination coverage in the United Kingdom.

INTRODUCTION: Pneumococcal disease (PD) significantly contributes to morbidity and mortality, carrying substantial economic and public health burden. This article is a targeted review of evidence for pneumococcal vaccination in the UK, the definitions of groups at particular risk of PD and vaccine effectiveness. AREAS COVERED: Relevant evidence focusing on UK data from surveillance systems, randomized controlled trials, observational studies and publicly available government documents is collated and reviewed. Selected global data are included where appropriate. EXPERT OPINION: National vaccination programs have reduced the incidence of vaccine-type PD, despite the rising prominence of non-vaccine serotypes in the UK. The introduction of higher-valency conjugate vaccines provides an opportunity to improve protection against PD for adults in risk groups. Several incentives are in place to encourage general practitioners to vaccinate risk groups, but uptake is low-suboptimal particularly among at-risk individuals. Wider awareness and understanding among the public and healthcare professionals may increase vaccination uptake and coverage. National strategies targeting organizational factors are urgently needed to achieve optimal access to vaccines. Finally, identifying new risk factors and approaches to risk assessment for PD are crucial to ensure those at risk of PD can benefit from pneumococcal vaccination.

Superantigen genes are more important than the emm type for the invasiveness of group A Streptococcus infection.

BACKGROUND: In this study, we examined the role of superantigen genes and emm genotypes of clinical Streptococcus pyogenes isolates collected in Germany between 1997 and 2003. METHODS: Multiplex polymerase chain reaction for all 11 currently known superantigen genes and sequencing for emm types were used. RESULTS: Using a 2-step explorative data analysis procedure, we found that after combined analysis of superantigen genes and emm types, only the superantigen genes spea1-spea3, spem, and spea4 have a predictive value for invasiveness, with odds ratios of 7.992, 3.209, and 2.323, respectively. The predictive value for invasiveness of emm1 was lost after combined analysis because of the association between emm type and the highly predictive superantigen genes. On the other hand, presence of the superantigen gene ssa and of emm77 are predictors of noninvasiveness, with odds ratios of 0.370 and 0.271, respectively. CONCLUSIONS: These results indicate that the presence of superantigen genes is more important for the invasiveness of group A Streptococcus infection than emm type and may be the connection between the high-risk HLA type of the host and the pathogen. Furthermore, we found a very clear correlation between the presence of the genes spea1-spea3 and the presence of the gene emm1, which indicates that the relationship between emm1 and invasiveness is based on the superantigen gene profile. Our data suggest that the superantigen gene profile is of high importance for the clinical outcome of group A Streptococcus infections.

A review of current data to support decision making for introduction of next generation higher valency pneumococcal conjugate vaccination of immunocompetent older adults in the UK.

INTRODUCTION: The burden of pneumococcal disease in older UK adults remains substantial. Higher valency pneumococcal conjugate vaccines (PCVs) are currently in development with adult formulations for two of these anticipated to become available in 2022. This article collates and reviews relevant candidate data now available that may be used to support cost effectiveness assessments of vaccinating immunocompetent UK adults aged ≥65-years with PCVs. AREAS COVERED: This article uses published data from surveillance systems, randomized controlled trials and observational studies. It focuses on local data from the UK but where these are either limited or not available relevant global data are considered. EXPERT OPINION: The body of relevant data now available suggests the UK is well placed to assess the cost effectiveness of vaccinating immunocompetent ≥65-year olds with new generation higher valency PCVs. Recent contemporary data provide important new and robust insights into the epidemiology of pneumococcal disease in older UK adults and help to address much of the uncertainty and data gaps associated with previous analyses. Using these data to make informed decisions about use of new higher valency PCVs for routine use in older adults will be important for public health in the UK.

Association of serotypes of Streptococcus pneumoniae with age in invasive pneumococcal disease.

A total of 7,764 isolates from patients with invasive pneumococcal disease (IPD) were collected from 1992 to June 2006. Data on serotypes were available for 5,022 isolates (64.7% of all invasive isolates). Some 54.0% of the isolates originated from adults >or=16 years of age, and 46.0% were from children <16 years of age. The leading serotypes were 14, 23F, 1, 6B, 7F, 3, and 4. The serotypes significantly more common in children were 14, 6B, 19F, and 18C, while among adults, serotypes 3 and 4 were predominant. Serotype 7F was statistically more prevalent among children <4 months old than among the other age groups. Among children aged >or=4 months and <1 year, serotype 19F occurred statistically more frequently; and among children aged >or=1 year to <5 years, serotypes 14, 6B, and 18C were overrepresented. The serotypes predominantly affecting patients younger than the remaining collective of patients were 14, 6B, 19F, and 18C, while patients with IPD caused by serotypes 3, 4, and 9V were older than the collective, on average.

Regional differences in serotype distribution, pneumococcal vaccine coverage, and antimicrobial resistance of invasive pneumococcal disease among German federal states.

Continuous nationwide surveillance of invasive pneumococcal disease has been conducted in Germany for more than 15 years. In this study, 3724 isolates were included. A total of 2065 isolates were obtained from children under 16 years of age from 1997 to 2006, and 1659 isolates were obtained from adults aged 16 years and older between 2002 and 2006. Results were classified to federal states, and supra-regional trends were illustrated by classifying the federal states into the regions 'North-West', 'North-East' and 'South'. Among childhood isolates, the most common serotypes were 14 (26.4%), 6B (7.7%), 23F (7.4%), 19F (7.1%), 1 (7.0%), 18C (6.2%), and 7F (5.6%). Serotype coverage for the 7-valent conjugate vaccine was 62.3%. For the 10-valent and 13-valent vaccines (both in development) the coverage was 75.5% and 84.8%, respectively. The 23-valent polysaccharide vaccine had a coverage of 87.3%. The coverage varies considerably among the federal states. Penicillin G resistance was observed in 7.4% of meningitis cases. In the non-meningitis group, no intermediate resistant or resistant strains were detected. Among adults, the most common serotypes were 14 (16.9%), 3 (9.2%), 4 (7.8%), 7F (7.5%), 1 (6.8%), and 9V (6.1%). Serotype coverage for the 7-valent conjugate vaccine was 46.5%. For the pneumococcal conjugate vaccines in development, the coverage was 61.1% (10-valent) and 76.3% (13-valent). The 23-valent polysaccharide vaccine had a coverage of 88.7%. Penicillin G resistance was observed in 6.4% of meningitis cases. Among these, considerably higher rates of resistance were observed in the North-East region (13.0%) than in the North-West (7.1%) and South (1.8%) regions.

Serotype-specific penicillin resistance of Streptococcus pneumoniae in Germany from 1992 to 2008.

A total of 12,137 isolates from invasive pneumococcal disease was collected between January 1, 1992, and December 31, 2008, by the German National Reference Center for Streptococci (NRCS). Data on penicillin susceptibility were available for 11,814 isolates, whereat 8837 isolates (74.8%) were from adults, and 2977 isolates (25.2%) originated from children. Overall, the leading serotypes were serotypes 14 (16.5% of serotyped isolates), 3 (8.1%), 7F (7.7%), 1 (7.4%), and 23F (6.0%). The overall nonsusceptibility rate of all isolates adds up to 5.5% (intermediate, 4.3%; resistant, 1.2%) when the CLSI 2006 guidelines were applied, and to 1.4% (intermediate, 0.2%; resistant, 1.2%) when using the CLSI 2009 guidelines. Generally, slightly higher resistance rates were observed among children than among adults. Serotypes contributing considerably to pneumococcal penicillin nonsusceptibility by a combination of frequency among invasive isolates and relatively high penicillin nonsusceptibility are 19A, 9V, 6B, 19F, 23F, and 14. While the nonsusceptibility among serotype 19A isolates increased considerably over the years, the development of nonsusceptibility rates among the other serotypes is less and more ambiguous.

Macrolide susceptibility and serotype specific macrolide resistance of invasive isolates of Streptococcus pneumoniae in Germany from 1992 to 2008.

BACKGROUND: Macrolide resistant Streptococcus pneumoniae has been on a gradual increase in Germany for over a decade. The current study was undertaken against the background of the recent observation of declining macrolide resistance rates especially among German children. Nationwide surveillance of invasive pneumococcal disease has been conducted in Germany since 1992. A population- and laboratory-based approach was used to collect data on invasive pneumococcal disease, and isolates sent to the National Reference Center for Streptococci by diagnostic microbiological laboratories from 1992 to 2008 were included in this study. RESULTS: From 1992 to 2008, data on macrolide susceptibility were available for 11,807 invasive isolates. 8,834 isolates (74.8%) were from adults (≥ 16 years), and 2,973 isolates (25.2%) from children (< 16 years). The overall nonsusceptibility rate of all isolates was 16.2% (intermediate, 0.2%; resistant, 16.0%). Higher resistance rates were observed among children (intermediate, 0.2%; resistant, 23.8%) than among adults (intermediate, 0.3%; resistant 13.4%). Maximum nonsusceptibility rates during the period under study were observed in 2005 (children: intermediate, 0.3%; resistant, 32.3%; adults: intermediate, 0.0%; resistant, 18.6%), while nonsusceptibility rates in 2008 were considerably lower, especially for children (children: intermediate, 0.0%; resistant, 15.2%; adults: intermediate, 0.1%; resistant, 12.9%). The rate of resistance was higher among the vaccine serotypes (7-valent, 36.6%; 10-valent, 28.2%; 13-valent, 24.3%) than among the non vaccine serotypes (non 7-valent, 6.5%; non 10-valent, 7.4%; non 13-valent, 6.3%). Serotype 14 (69.6% nonsusceptibility) proved to be the most resistant serotype. CONCLUSIONS: There has been a considerable and statistically significant decrease in macrolide nonsusceptibility in Germany since 2005, especially among children.

Streptococcus pneumoniae serotype distribution and antimicrobial nonsusceptibility trends among adults with pneumonia in the United States, 2009‒2017.

Background In the United States, the 13-valent pneumococcal conjugate vaccine has been recommended for children since 2010 and for adults aged ≥65 years since 2014. We assessed S. pneumoniae antimicrobial nonsusceptibility among adults with suspected pneumonia from hospital settings. Methods Isolates were collected from 105 US sites between 2009 and 2017 in the SENTRY Antimicrobial Surveillance Program. Clinical and Laboratory Standards Institute methods were used for susceptibility testing. Serotypes were determined by cpsB sequence obtained by PCR or whole genome sequencing, plus multiplex PCR and/or Neufeld Quellung reactions as needed. Findings Of 7254 S. pneumoniae isolates analyzed, 63.6% and 36.4% were from patients aged 18‒64 and ≥65 years, respectively. Among all isolates, penicillin and ceftriaxone nonsusceptibility declined by 72.3% and 73.8%, respectively, with smaller changes observed for other antibiotics. Nonsusceptibility patterns were serotype-specific; for example, nonsusceptibility was relatively stable for serotype 19A but declined for 19F. Simultaneously, the percentage of serotype 19A isolates decreased from 17.4% to 3.9%, whereas for serotype 19F this percentage increased from 2.8% to 5.0%. The percentage of serotype 3 isolates that were nonsusceptible increased for select antibiotic classes, and the percentage of serotype 3 among all isolates increased minimally from 10.2% to 11.8%. Interpretation Overall pneumococcal nonsusceptibility patterns were influenced by distinct patterns within serotypes, indicating the likelihood of serotype-specific resistance mechanisms. Serotype 19A observations were consistent with vaccine-induced reductions in circulation with no change in the organism susceptibility, whereas the nonsusceptibility increases for serotypes 3 and 19F may indicate circulation of more antibiotic-resistant clones.

Cost effectiveness analysis of heptavalent pneumococcal conjugate vaccine in Germany considering herd immunity effects.

BACKGROUND: In Germany the heptavalent pneumococcal conjugate vaccine (PCV7) has been recommended as a general infant vaccination since 2006. Data from similar programmes in the USA have reported a reduction of pneumococcal diseases in both vaccinated and unvaccinated populations, suggesting herd immunity effects. This study analyses the cost-effectiveness of a general vaccination with PCV7 in Germany based on these findings. METHODS: A Markov model adapts efficacy and herd immunity data to the German population. Further main model inputs are incidence, vaccination uptake, serotype distribution, case fatality rates, and vaccination and health-care costs. RESULTS: A general vaccination with PCV7 would avoid about 232,000 pneumococcal infections and 1,879 premature deaths per year in Germany. From the health-care payer's perspective, direct cost savings would outweigh vaccination expenditures by a ratio of 1:1.16. The sensitivity analysis shows that these estimates are quite conservative. CONCLUSION: Based on the health-economic evaluation, the authors recommend the continuation of the general recommendation of PCV7 according to the 3 + 1 schedule within the German Statutory Health Insurance.

Polyclonal population structure of Streptococcus pneumoniae isolates in Spain carrying mef and mef plus erm(B).

The population structure (serotypes, pulsed-field gel electrophoresis [PFGE] types, and multilocus sequencing types) of 45 mef-positive Streptococcus pneumoniae isolates [carrying mef alone (n = 17) or with the erm(B) gene n = 28)] were studied. They were selected from among all erythromycin-resistant isolates (n = 244) obtained from a collection of 712 isolates recovered from different Spanish geographic locations in the prevaccination period from 1999 to 2003. The overall rates of resistance (according to the criteria of the CLSI) among the 45 mef-positive isolates were as follows: penicillin G, 82.2%; cefotaxime, 22.2%; clindamycin, 62.2%; and tetracycline, 68.8% [mainly in isolates carrying erm(B) plus mef(E); P < 0.001]. No levofloxacin or telithromycin resistance was found. Macrolide resistance phenotypes (as determined by the disk diffusion approximation test) were 37.7% for macrolide resistance [with all but one due to mef(E)] and 62.2% for constitutive macrolide-lincosamide-streptogramin B resistance [cMLS(B); with all due to mef(E) plus erm(B)]. Serotypes 14 (22.2%), 6B (17.7%), 19A (13.3%), and 19F (11.1%) were predominant. Twenty-five different DNA patterns (PFGE types) were observed. Our mef-positive isolates were grouped (by eBURST analysis) into four clonal complexes (n = 18) and 19 singleton clones (n = 27). With the exception of clone Spain(9V)-3, all clonal complexes (clonal complexes 6B, Spain(6B)-2, and Sweden(15A)-25) and 73.6% of singleton clones carried both the erm(B) and the mef(E) genes. The international multiresistant clones Spain(23F)-1 and Poland(6B)-20 were represented as singleton clones. A high proportion of mef-positive S. pneumoniae isolates presented the erm(B) gene, with all isolates expressing the cMLS(B) phenotype. A polyclonal population structure was demonstrated within our Spanish mef-positive S. pneumoniae isolates, with few clonal complexes overrepresented within this collection.

Epidemiology of severe Streptococcus pyogenes disease in Europe.

The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe.

Time-kill kinetics of Streptococcus pneumoniae with reduced susceptibility to telithromycin.

BACKGROUND: Telithromycin is a new ketolide increasingly used in Europe and the United States. Only very few telithromycin-resistant isolates have been described to date. METHODS: The anti-pneumococcal activity of telithromycin was determined against four clinical isolates of Streptococcus pneumoniae with reduced susceptibility to telithromycin by time-kill methodology. RESULTS: All four telithromycin non-susceptible strains had the constitutive macrolide-lincosamide-streptogramin B phenotype and the ermB genotype. Pneumococcal strains had telithromycin minimum inhibitory concentrations (MICs) ranging between 2 and 8 microg/ml. Mulitlocus sequence typing and serotyping showed three isolates to harbour the identical serotype (serotype 14) and sequence type (sequence type 143) indicating a genetic relatedness of strains. Telithromycin was only bactericidal against the isolates with telithromycin resistance, with 4-8 times the MIC after 24 h. CONCLUSION: The killing by telithromycin of S. pneumoniae isolates having an ermB resistance determinant and a telithromycin MIC of > or =2 microg/ml is slow. Achievable concentrations in serum, alveolar macrophages and epithelial lining fluid are below the concentrations which are necessary for bactericidal killing of highly telithromycin-resistant strains.