Ralf Rene Reinert

Pneumococcal disease caused by serotype 19A: Review of the literature and implications for future vaccine development

Streptococcus pneumoniae serotype 19A is associated with all forms of pneumococcal disease and was the first reported pneumococcal serotype with high-level penicillin and multidrug resistance. While the seven-valent pneumococcal conjugate vaccine (PCV7), which contains serotype 19F, has reduced rates of disease among children and adults, the incidence of disease due to nonvaccine and increasingly drug-resistant serotypes - predominantly serotype 19A - has increased. This review summarizes the published literature to analyze the factors contributing to the emergence of serotype 19A, the diseases associated with this serotype, and the importance of including this serotype in novel pneumococcal conjugate vaccines. A recently approved 13-valent vaccine includes this serotype, and is likely to significantly reduce the burden of disease due to serotype 19A.

Advances in pneumococcal vaccines: the 13-valent pneumococcal conjugate vaccine received market authorization in Europe

The 13-valent pneumococcal conjugate (PCV13, Prevenar 13, Pfizer Inc., NY, USA) was developed as a successor to the currently registered 7-valent pneumo coccal conjugate vaccine (PCV7, which contains serotypes 4, 6B, 9V, 14, 18C, 19F and 23F; Prevnar/Prevenar, Pfizer Inc.), for use in infants and young children to prevent disease such as invasive pneumococcal disease (IPD), nonbacteremic pneumonia and acute otitis media (AOM), caused by the 13 pneumococcal serotypes contained in the vaccine. In addition to the serotypes in PCV7, PCV13 contains serotypes 1, 3, 5, 6A, 7F and 19A [1]. For PCV13, the global pediatric filings were initiated in late 2008 and, to date, regulatory applications for PCV13 have been submitted in more than 50 countries spanning six continents. The first country to approve PCV13 was Chile on 14th July 2009. PCV13 has been granted priority review in the USA, Canada, Australia and South Africa. In Europe, this vaccine received positive feedback from the Committee for Medicinal Products for Human Use (CHMP) on 24th September 2009 and received market authorization on 11th December 2009. Streptococcus pneumoniae is a major source of morbidity and mortality worldwide. It is estimated by the WHO that approximately one million children die of pneumococcal disease every year, mostly in developing countries [2]. Pneumococcal infections are the leading cause of death from a vaccine-preventable illness in children younger than 5 years of age [3,4]. Invasive diseases caused by pneumococci include meningitis, bacteremia, and pneumonia with bacteremia and/or empyema [5]. PCV7 was licensed in the USA in the year 2000 and in Europe in 2001. By December 2009, PCV7 was licensed in approximately 100 of 193 member states of the WHO. In addition, it had been included in the routine or national immunization programs or was widely used in 42 of these countries. The achievements of the PCV7 vaccination programs were recently reviewed in detail in this journal [6,7], and are therefore only briefly discussed here.

Adult invasive pneumococcal disease between 2003 and 2006 in North‐Rhine Westphalia, Germany: serotype distribution before recommendation for general pneumococcal conjugate vaccination for children <2 years of age

A laboratory-based surveillance study of adult invasive pneumococcal disease was conducted in North-Rhine Westphalia, Germanys most populous federal state, with approximately 18 million inhabitants. Invasive isolates (n = 519) were obtained between 2003 and 2006, before the general recommendation for vaccination of German children <2 years with the pneumococcal conjugate vaccine was issued at the end of July 2006. Penicillin G resistance was observed in 5% of meningitis cases. In the non-meningitis group, only intermediately resistant strains were detected (0.4%). Intermediate resistance to cefotaxime occurred both in meningitis cases (1.7%) and non-meningitis cases (0.4%). Non-susceptibility rates (intermediate resistance and resistance) were 16.2% for macrolides, 10.9% for trimethoprim-sulphamethoxazole, 5.0% for tetracycline, 3.9% for clindamycin, and 0.4% for levofloxacin. All isolates were susceptible to amoxycillin (non-meningitis) and telithromycin. The leading serotypes were serotypes 14 (14.3%), 7F (9.4%), 3 (9.2%), 4 (8.7%) and 1 (8.1%). Serotype coverage for the seven-valent conjugate vaccine was 43.9%. For the ten-valent and 13-valent vaccines (in development), the coverages were 61.8% and 76.7%, respectively. The 23-valent polysaccharide vaccine had a coverage of 91.1%.

Globicatella sanguinis Is an Etiological Agent of Ventriculoperitoneal Shunt-Associated Meningitis

ABSTRACT Globicatella sanguinis is a very rare isolate in clinical samples. We present a case of meningitis in a 69-year-old female patient after implantation of an external left ventricular drainage due to a hydrocephalus. She recovered after antibiotic treatment with ceftriaxone.

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.

Effectiveness of pneumococcal vaccines in preventing pneumonia in adults, a systematic review and meta-analyses of observational studies

Introduction S. pneumoniae can cause a wide spectrum of diseases, including invasive pneumococcal disease and pneumonia. Two types of pneumococcal vaccines are indicated for use in adults: 23-valent pneumococcal polysaccharide vaccines (PPV23) and a 13-valent pneumococcal conjugate vaccine (PCV13). Objective To systematically review the literature assessing pneumococcal vaccine effectiveness (VE) against community-acquired pneumonia (CAP) in adults among the general population, the immunocompromised and subjects with underlying risk factors in real-world settings. Methods We searched for peer-reviewed observational studies published between 1980 and 2015 in Pubmed, SciELO or LILACS, with pneumococcal VE estimates against CAP, pneumococcal CAP or nonbacteremic pneumococcal CAP. Meta-analyses and meta-regression for VE against CAP requiring hospitalization in the general population was performed. Results 1159 unique articles were retrieved of which 33 were included. No studies evaluating PCV13 effectiveness were found. Wide ranges in PPV23 effectiveness estimates for any-CAP were observed among adults ≥65 years (-143% to 60%). The meta-analyzed VE estimate for any-CAP requiring hospitalization in the general population was 10.2% (95%CI: -12.6; 33.0). The meta-regression indicates that VE against any-CAP requiring hospitalization is significantly lower in studies with a maximum time since vaccination ≥60 months vs. <60 months and in countries with the pediatric PCV vaccine available on the private market. However, these results should be interpreted cautiously due to the high influence of two studies. The VE estimates for pneumococcal CAP hospitalization ranged from 32% (95%CI: -18; 61) to 51% (95%CI: 16; 71) in the general population. Conclusions Wide ranges in PPV23 effectiveness estimates for any-CAP were observed, likely due to a great diversity of study populations, circulation of S. pneumoniae serotypes, coverage of pediatric pneumococcal vaccination, case definition and time since vaccination. Despite some evidence for short-term protection, effectiveness of PPV23 against CAP was not consistent in the general population, the immunocompromised and subjects with underlying risk factors.

Erratum to: Pneumococcal vaccination: what have we learnt so far and what can we expect in the future?

Erratum to: Eur J Clin Microbiol Infect Dis DOI 10.1007/s10096-014-2208-6 The original version of this article unfortunately contains an error in Table 2. The pneumococcal vaccination recommendations for Ireland are incorrectly shown in Table 2. These recommendations have been corrected in the table below. The authors wish to apologize for these errors. Table 2 National adult pneumococcal vaccination recommendations in Western Europe (Ireland) aDate of implementation of recommendation CSF, cerebrospinal fluid; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus; IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; PPV, pneumococcal polysaccharide vaccine; SCID, severe combined immunodeficiency

P246: Evolution of S. pneumoniae serotypes in invasive pneumococcal diseases (IPD) in Western Europe: a literature review

Pneumococcal diseases (PDs) are a major cause of morbidity and mortality worldwide. Pneumococcal conjugate 7-valent vaccine (PCV7) was introduced in national immunization programs (NIPs) in 2006 in many European countries; higher valency PCVs became available in 2009-2012.