Increase of serotypes 15A and 23B in IPD in Germany in the PCV13 vaccination era

Background: This study presents an analysis of 1,491 serogroup 23 and 762 serogroup 15 isolates from invasive pneumococcal disease (IPD) in children and adults before and after the general recommendation for childhood pneumococcal conjugate vaccination in Germany in July 2006. Vaccination formulations used were PCV7 (from July 2006), PCV10 (from April 2009) and PCV13 (from December 2009, replacing PCV7). Methods: The German National Reference Center for Streptococci (GNRCS) has conducted surveillance of IPD since 1992. Isolates were serotyped and tested for antibiotic susceptibility. Selected isolates were characterized using MLST. Results: In an analysis of 23,957 isolates from IPD in children and adults sent to the GNRCS between July 1992 and June 2014, we found a strongly significant increase of non-PCV13 serotypes in the late vaccination (PCV13) period (2010-2014). Among these, the proportions of serotypes 15A and 23B were the most strongly significantly increasing. After the recommendation for pneumococcal conjugate childhood vaccination in 2006 and the introduction of higher-valent vaccines in 2009, the proportion of 15A increased significantly from 0.5% in the early vaccination period (2007-2010) to 2.4% in the late vaccination period (2010-2014, p=3.14x10(-22)). The proportion of serotype 23B increased from 0.5% to 2.8% in the same period (p=1.55x10(-29)). Penicillin non-susceptibility levels of the serotype 15A (47.4%) and serotype 23B (46.5%) isolates were high, with MIC values ranging from 0.12-2 mu g/ml (15A) and 0.12-0.5 mu g/ml (23B). MLSTs of serotype 23B isolates grouped in two clonal complexes (CC): CC439, with sequence type (ST) 439 as the main representative and CC338 (linked to CC156), with ST1349 as most prevalent clone. Both CCs have been present over almost the whole surveillance period. All penicillin non-susceptible isolates occurred in CC338. Serotype 15A isolates appeared to be more diverse. Six CCs, one group of three STs and two singletons were found among 20 isolates. Most prevalent was CC63, with ST63 as most prominent representative (n=5). Most penicillin non-susceptible isolates were found among CC63 isolates. Conclusions: The prevalence of non-PCV13 serotypes in Germany has increased significantly between July 2007 and June 2014, with 15A and 23B being the most strongly increasing serotypes of all. Both serotypes show a high proportion of penicillin non-susceptibility.