Antimicrobial activity of β-lactam antibiotics against pneumococcal isolates causing pneumococcal disease in adults immediately before and after the COVID-19 pandemic in Spain (2019-2020)

Mirella Llamosí¹Covadonga Pérez-García¹Aída Úbeda¹ERICK VIDAL ALCANTARA¹Inés Pareja-Cerbán¹Elena Gómez-Rubio²Pilar Coronel²Juan Carlos Sanz³Mirian Domenech¹Julio Sempere^1*JOSE YUSTE^1*

• ¹Carlos III Health Institute (ISCIII), Madrid, Spain
• ²Meiji Pharma Spain SA, Alcala de Henares, Spain
• ³Comunidad de Madrid Servicio Madrileno de Salud, Madrid, Spain

Background: Streptococcus pneumoniae remains a major respiratory pathogen. Although pneumococcal conjugate vaccines (PCVs) have reduced the burden of resistant vaccine-covered serotypes, serotype replacement has led to the emergence of non-vaccine types. Methods: This study assessed the activity of β-lactam antibiotics against 1,018 clinical isolates of S. pneumoniae with reduced penicillin susceptibility collected across Spain in 2019–2020. Minimum inhibitory concentrations (MICs) were determined for oral cephalosporins (cefditoren, cefuroxime, cefixime, cefpodoxime), intravenous cephalosporins (cefotaxime, cefuroxime), and penicillins (penicillin, amoxicillin). MIC₅₀ and MIC₉₀ values were analyzed by year, serotype (PCV20-vs. PCV21-specific), and clinical presentation. Results: Cefditoren showed the lowest MIC₅₀/₉₀ values among oral β-lactams, and cefotaxime was the most active intravenous cephalosporin. Most isolates were resistant to cefuroxime (oral and intravenous) based on EUCAST breakpoints. While penicillin derivatives showed susceptibility with increased exposure at MIC₅₀, MIC₉₀ values indicated resistance to oral amoxicillin. A rise in antibiotic use during the COVID-19 pandemic's first year was associated with an increased proportion of resistant isolates, particularly among non-invasive respiratory infections. Serotype analysis revealed that PCV20-specific types (9V, 14 and 19A) and shared PCV20 and PCV21 serotypes (11A and 19A) had higher MIC₉₀ values and bigger proportion of resistant strains to β-lactams than PCV21-unique ones (15A, 23B and 24F). Conclusions: Despite the overall increase in resistance, cefditoren and cefotaxime retained favorable in vitro activity, while cefuroxime, cefixime, and cefpodoxime exhibited poor efficacy. Newer PCVs may broaden protection against emerging resistant serotypes, yet continued antimicrobial resistance surveillance is essential, especially regarding non-vaccine serotypes. These findings support cefditoren and cefotaxime as viable therapeutic options against non-susceptible S. pneumoniae isolates.