{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:46:01Z","timestamp":1790639161610,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004169","name":"Meiji Seika Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004169","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Streptococcus pneumoniae<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study assessed the activity of \u03b2-lactam antibiotics against 1,018 clinical isolates of <jats:italic>S. pneumoniae<\/jats:italic> with reduced penicillin susceptibility collected across Spain in 2019\u20132020. Minimum inhibitory concentrations (MICs) were determined for oral cephalosporins (cefditoren, cefuroxime, cefixime, cefpodoxime), intravenous cephalosporins (cefotaxime, cefuroxime), and penicillins (penicillin, amoxicillin). MIC<jats:sub>50<\/jats:sub> and MIC<jats:sub>90<\/jats:sub> values were analyzed by year, serotype (PCV20- vs. PCV21-specific), and clinical presentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cefditoren showed the lowest MIC<jats:sub>50<\/jats:sub>\/<jats:sub>90<\/jats:sub> values among oral \u03b2-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 MIC<jats:sub>50<\/jats:sub>, MIC<jats:sub>90<\/jats:sub> values indicated resistance to oral amoxicillin. A rise in antibiotic use during the COVID-19 pandemic\u2019s 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 MIC<jats:sub>90<\/jats:sub> values and bigger proportion of resistant strains to \u03b2-lactams than PCV21-unique ones (15A, 23B and 24F).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite the overall increase in resistance, cefditoren and cefotaxime retained favorable <jats:italic>in vitro<\/jats:italic> 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 <jats:italic>S. pneumoniae<\/jats:italic> isolates.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1658431","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T05:32:46Z","timestamp":1759210366000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Antimicrobial activity of \u03b2-lactam antibiotics against pneumococcal isolates causing pneumococcal disease in adults immediately before and after the COVID-19 pandemic in Spain (2019\u20132020)"],"prefix":"10.3389","volume":"16","author":[{"given":"Mirella","family":"Llamos\u00ed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Covadonga","family":"P\u00e9rez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A\u00edda","family":"\u00dabeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick J.","family":"Vidal-Alc\u00e1ntara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Pareja-Cerb\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"G\u00f3mez-Rubio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Coronel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirian","family":"Domenech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Sempere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Yuste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0137565","DOI":"10.1371\/journal.pone.0137565","article-title":"Emergence of amoxicillin-resistant variants of Spain9V-ST156 pneumococci expressing serotype 11A correlates with their ability to evade the host immune response","volume":"10","author":"Aguinagalde","year":"2015","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e204","DOI":"10.1016\/s1473-3099(17)30478-4","article-title":"Use of mathematical modelling to assess the impact of vaccines on antibiotic resistance","volume":"18","author":"Atkins","year":"2018","journal-title":"Lancet Infect. 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