Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria

Abstract

The 10-valent pneumococcal conjugate vaccine (PCV10) has been included in Bulgarian Childhood Immunization Program since 2010. This study aimed to assess serotype distribution and antimicrobial resistance of 198 invasive and non-invasive Streptococcus pneumoniae strains that had been isolated in Bulgaria during 2011-2016 from patients with invasive (IPD) and non-invasive (NIPD) pneumococcal diseases. The most common invasive serotypes were 3 (10.1%), 19F (4.0%), and 7F (3.0%). A significant decrease in the proportion of invasive vaccine types (VTs) from 64.2% to 35.2% was found in comparison with pre-vaccine era. The most common serotypes among middle ear fluids were 3, 19A and 19F (5.6% each), and VTs fell down from 66.4% to 40.0% in post-PCV10 period. Among respiratory isolates, the most prevalent serotypes were some emergent serotypes such as 15A/B/C (5.0%), 19A, and 6C (4.0% each). VTs decreased significantly (16.3%) among vaccinated children compared to unvaccinated children and adults (44.0%). Two non-VTs (19A and 6C) have increased significantly more (p<0.05) in vaccinated children than in unvaccinated patients. The rates of antibiotic nonsusceptible S. pneumoniae in Bulgaria remained high in post-PCV10 era. Among all source of isolates, antimicrobial nonsusceptibility rates were: oral penicillin - 46.5%, trimethoprim-sulfamethoxazole - 45.4%, erythromycin - 43.9%, tetracycline - 37.4%, and multidrug-resistance (MDR) was 44%. The most common MDR serotypes were 19F, 19A, 6A/C, 15A/B/C and 23A. Our results proved that PCV10 vaccination substantially reduced VTs pneumococcal IPD and NIPD. There has been a shift in the distribution of S. pneumoniae serotypes mostly in vaccinated children but also in the whole population and strong serotype-specific antibiotic resistance was observed after vaccine implementation. Therefore, it is important to continue monitoring serotype changes and pneumococcal resistance among all patient ages in addition to aid in determining the long-term effectiveness of PCV10 interventions.

Bacterial Spectrum of Acute Otitis Media in Bulgarian Children during the 10-Valent Pneumococcal Conjugate Vaccine Era

“…5 We did not observe a considerable changes in rates of antimicrobialnonsusceptibility in S. pneumoniae in this study compared with studies conducted before PCV10 introduction. 4,5 As previously reported, 21 the rates of antimicrobial-nonsusceptibility in pneumococci in Bulgaria have remained high in the post-PCV10 era because of the wide prevalence of some multidrug-resistant NVTs, which were also found in this study. The prevalence of ampicillin nonsusceptible H. influenzae isolates (25%) among children with AOM was comparable to rates observed before universal administration of PCV10.…”

“…Serotyping of S. pneumoniae was performed according to the "Neufeld Quellung" reaction using commercial antisera (Statens Serum Institute, Copenhagen, Denmark) as described previously. 21 Haemophilus influenzae isolates were serotyped with slide agglutination method using specific antisera (Phadebact; Boule Diagnostics, Huddinge, Sweden). Streptococcus pneumoniae and H. influenzae isolates for which any serotype was not determined with methods used were considered as NT.…”

Effect of Vaccination on Pneumococci Isolated from the Nasopharynx of Healthy Children and the Middle Ear of Children with Otitis Media in Iceland

“…Other researchers have also described an increase in serotype 6C following the introduction of PCV7, especially in non-IPD among children ( 67 ). We rarely detected isolates of serotype 6C PreVac; however, in a recent study, serotype 6C was only detected among vaccinated children with non-IPD after PHiD-CV implementation ( 68 ). Serotype 6C isolates detected PostVac most often belonged to CC315 6B and ST386 6C (a double locus variant [DLV] of PMEN Poland 6B -20).…”

Vaccination of Icelandic Children with the 10-Valent Pneumococcal Vaccine Leads to a Significant Herd Effect among Adults in Iceland

“…Serotypes 6C and 15A have been reported as upcoming PNSP and MDR serotypes following PCV introduction (13, 40, 41), but among adults in Iceland, these serotypes were detected only in low numbers in the PostVac periods of the study. Our group has also detected MDR isolates of serotype 6C that were members of CC315 6B/6C and ST386 6C (a double locus variant of PMEN Poland 6B -20) among children (22, 39), but it remains to be seen whether CC315 6C will replace CC236/271/320 19F as a major MDR lineage in Iceland.…”