Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study

Background Epidemiological studies are necessary to explore the effect of current pneumococcal conjugate vaccines (PCVs) against antibiotic resistance, including the rise of non-vaccine serotypes that are resistant to antibiotics. Hence, epidemiological changes in the antimicrobial pattern of Streptococcus pneumoniae before and during the first year of the COVID-19 pandemic were studied.Methods In this national surveillance study, we characterised the antimicrobial susceptibility to a panel of antibiotics in 3017 pneumococcal clinical isolates with reduced susceptibility to penicillin during 2004-20 in Spain. This study covered the early and late PCV7 periods; the early, middle, and late PCV13 periods; and the first year of the COVID-19 pandemic, to evaluate the contribution of PCVs and the pandemic to the emergence of non-vaccine serotypes associated with antibiotic resistance.Findings Serotypes included in PCV7 and PCV13 showed a decline after the introduction of PCVs in Spain. However, an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that were not susceptible to penicillin promptly appeared. A rise in the proportion of pneumococcal strains with reduced susceptibility to 13-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2. Cefditoren was the 13-lactam with the lowest minimum inhibitory concentration (MIC)50 or MIC90 values, and had the highest proportion of susceptible strains throughout 2004-20.Interpretation The increase in non-PCV13 serotypes associated with antibiotic resistance is concerning, especially the increase of penicillin resistance linked to serotypes 11A and 24F. The future use of PCVs with an increasingly broad spectrum (such as PCV20, which includes serotype 11A) could reduce the impact of antibiotic resistance for non-PCV13 serotypes. The use of antibiotics to prevent co-infections in patients with COVID-19 might have affected the increased proportion of pneumococcal-resistant strains. Cefotaxime as a parenteral option, and cefditoren as an oral choice, were the antibiotics with the highest activity against non-PCV20 serotypes.Funding The Spanish Ministry of Science and Innovation and Meiji-Pharma Spain.Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Automated summary

The study reveals a decline in serotypes included in PCV7 and PCV13 after their introduction in Spain, but an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that are not susceptible to PCV13, posing a threat to antibiotic resistance. An increase in pneumococcal strains with reduced susceptibility to 13-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2.