Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates among Croatian adults during a fifteen-year period (2005-2019)

AimTo assess serotype distribution, antibiotic resistance, and vaccine coverage against Streptococcus pneumoniae causing invasive infections in Croatian adults from 2005 to 2019.MethodsIn this retrospective study, invasive pneumococcal strains were collected through a microbiological laboratory network with country coverage >95%. Capsular typing was performed with the Quellung reaction. In vitro susceptibility testing was carried out according to the European Committee on Antimicrobial Susceptibility Testing guidelines. In macrolide-resistant isolates, the presence of ermB and mefA genes was evaluated.ResultsDuring the fifteen-year study period, 1123 invasive pneumococcal isolates were obtained. The most prevalent serotypes were 3, 14, 19A, 9V, 7F, and 23F, comprising 60% of all invasive pneumococcal isolates. Serotype 3 was the dominant serotype, with the highest prevalence in patients ≥65 years of age. Penicillin susceptibility, increased exposure was 18.6%, mostly associated with serotypes 14 and 19A. Resistance to penicillin was low (<1%). Macrolide resistance was 23%, mostly associated with serotypes 14, 19A, and 19F. The coverage with 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPV23) was 80.2% and 93.6%, respectively.ConclusionsThe incidence of invasive pneumococcal disease in adults is highest in patients ≥65 years of age. Penicillin susceptibility, increased exposure and macrolide resistance were mostly associated with serotypes 14 and 19A. PCV13 and PPV23 provide very high serotype coverage. Future studies should evaluate the effects of the 10-valent vaccine, introduced in the Croatian National Immunization Program in June 2019, on serotype distribution and antibiotic resistance rates.

Streptococcus pneumoniae is among the most concerning human pathogens, with high morbidity and mortality rates worldwide. Pneumococcal infections range from non-invasive mucosal diseases (including acute otitis media, acute sinusitis, and pneumonia) to invasive, life-threatening infections (such as meningitis, sepsis, and bacteremic pneumonia) (1). Invasive pneumococcal disease (IPD) mostly affects children younger than 5 years and patients ≥65 years old (2). Every year, 500 000 children under 5 years of age die of IPD (3). Both morbidity and mortality rates are higher in developing countries (3). Community-acquired pneumonia is the most common pneumococcal disease worldwide, being responsible for more than 1.5 million of deaths annually. A significant fraction of these deaths are caused by Streptococcus pneumoniae (4,5).Antimicrobial resistance of Streptococcus pneumoniae is a growing global health problem, mostly affecting penicillin and macrolides. The patterns of antimicrobial susceptibility differ among serotypes and geographic regions (6). Penicillin resistance has emerged within a few decades after penicillin introduction and has spread worldwide (7). The prevalence of antibiotic-resistant Streptococcus pneumoniae has been increasing (8,9). In Europe, the resistance rate in France, Spain, and Eastern European countries is concerning (10). Worldwide, some regions, such as South Africa, have antibiotic non-susceptibility rates of up to 79% (11). However, in the past several years some countries have reported decreased resistance rates (12-15).Macrolide resistance is commonly present among invasive and non-invasive Streptococcus pneumoniae isolates. The main mechanisms are drug efflux system encoded by mef genes (M phenotype) and target modification mainly due to ermB genes, (MLS_B phenotype) (16,17).The new fluoroquinolones or respiratory quinolones (levofloxacin, gatifloxacin, and moxifloxacin) have enhanced in vitro activity against Streptococcus pneumoniae and are used to treat respiratory tract infections in adults. Increasing resistance to fluoroquinolones has been reported in Asia and Africa (18,19). In addition, ineffectiveness of fluoroquinolones in the treatment of pneumococcal infections is associated with acquired resistance of Streptococcus pneumoniae to this group of antibiotics (20,21).Increased resistance of Streptococcus pneumoniae to routinely used antibiotics warrants pneumococcal vaccine introduction as a tool for IPD prevention. In Europe, two pneumococcal vaccines are registered for use in adults: a 13-valent pneumococcal conjugate vaccine (PCV13, including serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, and 19A) and a 23-valent pneumococcal polysaccharide vaccine (PPV23, including PCV13 serotypes plus 1, 2, 5, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F) (22,23). In June 2019, a 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Croatian National Immunization Program (NIP) for children only (scheme: 8 weeks – 16 weeks – 12 months) (24). In January 2021, the Croatian Public Health Institute revised its recommendations for pneumococcal vaccination of adults. Immunocompetent adults are now advised to be vaccinated with PPV23 only, while immunocompromised and asplenic patients are recommended to receive both vaccines, starting with PCV13 as the first dose (25). The aim of this study was to analyze the serotype distribution and antibiotic resistance of invasive Streptococcus pneumoniae isolates before the introduction of PCV10 in the childhood vaccination schedule, together with the coverage of currently available vaccines (PCV13 and PPV23). This study is the first and the most comprehensive so far in Croatia, analyzing invasive pneumococcal isolates collected during 15 consecutive years. These data will help us assess the impact of different vaccines in the IPD prevention among adults, especially those ≥65 years old.