{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:29:36Z","timestamp":1785403776031,"version":"3.56.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00339, PI21\/01000, INT22\/00096, CIBERES-CB06\/06\/0037"],"award-info":[{"award-number":["PI18\/00339, PI21\/01000, INT22\/00096, CIBERES-CB06\/06\/0037"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CIBERINFEC-CB21\/13\/00009"],"award-info":[{"award-number":["CIBERINFEC-CB21\/13\/00009"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Amoxicillin is one of the most commonly used antibiotics to treat pneumococcal infections. We analyzed the epidemiology and clinical impact of amoxicillin non-susceptibility in invasive pneumococcal pneumonia. This is an observational study based on prospectively collected data at Bellvitge University Hospital (Barcelona, Spain) from 1994 to 2020. Isolates were tested for antibiotic susceptibility, serotyped, and genotyped. Clinical characteristics and 30 day mortality were evaluated using independent Cox proportional hazards models. We analyzed 1,663 episodes. While the proportion of isolates susceptible to amoxicillin increased from 72.9% (1994\u20132001) to 91.4% (2016\u20132020), the proportion of isolates with MIC &gt; 2 mg\/L remained stable (4.8% and 5.3%, respectively). A single lineage (GPSC6; serotypes 9V, 14, and 11A) accounted for 56.5% of non-susceptible strains. High McCabe scores (ultimately fatal: HR 2.87 [2.10\u20133.92] and rapidly fatal: HR 4.98 [3.50\u20137.09]), along with parameters linked to disease severity such as leukopenia (HR 2.14 [1.63\u20132.82]), shock (HR 3.47 [2.63\u20134.57]), respiratory failure (HR 4.26 [2.63\u20136.89]), and bilobar pneumonia (HR 1.44 [1.09\u20131.90]), were associated with 30 day mortality. The risk of mortality was higher in episodes treated with amoxicillin than with third-generation cephalosporins (HR 1.81 [1.28\u20132.56]), especially in episodes with amoxicillin MIC &gt; 2 mg\/L (HR 6.14 [1.65\u201322.80]). Amoxicillin therapy was not associated with increased mortality in patients with a non-fatal McCabe score (HR 1.49 [0.62\u20133.55]), but it was in the ultimately fatal\/rapidly fatal group (HR 1.97 [1.34\u20132.90]). In addition to the crucial importance of host factors in the outcome of invasive pneumococcal pneumonia, our data indicate that amoxicillin yields poorer outcomes compared to third-generation cephalosporins, particularly in patients with a worse prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00237-25","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T09:59:36Z","timestamp":1751968776000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Amoxicillin-non-susceptible\n                    <i>Streptococcus pneumoniae<\/i>\n                    causing invasive pneumonia: serotypes, clones, and clinical impact"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0817-0931","authenticated-orcid":true,"given":"Jordi","family":"C\u00e0mara","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Grau","sequence":"additional","affiliation":[{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]},{"name":"Infectious Diseases Department, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Gonz\u00e1lez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiara","family":"Santos","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Bellvitge Biomedical Research Institute-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fe","family":"Tubau-Quintano","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]},{"id":[{"id":"https:\/\/ror.org\/021018s57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Pe\u00f1afiel","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Bellvitge Biomedical Research Institute-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"\u00c1ngeles Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"id":[{"id":"https:\/\/ror.org\/021018s57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona","place":["Barcelona, Spain"]},{"name":"Research Network for Infectious Diseases (CIBERINFEC-CB21\/13\/00009), ISCIII","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Li\u00f1ares","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]},{"id":[{"id":"https:\/\/ror.org\/021018s57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rom\u00e1n","family":"Pallar\u00e9s","sequence":"additional","affiliation":[{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]},{"name":"Infectious Diseases Department, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"id":[{"id":"https:\/\/ror.org\/021018s57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Sciences, University of Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-607X","authenticated-orcid":true,"given":"Carmen","family":"Ardanuy","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Hospital Universitari de Bellvitge-IDIBELL","place":["L'Hospitalet de Llobregat, Spain"]},{"name":"Research Network for Respiratory Diseases (CIBERES-CB06\/06\/0037), ISCIII","place":["Madrid, Spain"]},{"id":[{"id":"https:\/\/ror.org\/021018s57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00176-2"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201908-1581ST"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198545"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.4.829"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00429-15"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111835"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1329"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010727"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.10.3210-3216.1999"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky305"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2020.25.16.1900457"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508243330802"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9343(02)01162-2"},{"key":"e_1_3_5_15_2","volume-title":"M100-ED32:2022 performance standards for antimicrobial susceptibility testing","author":"CLSI","unstructured":"CLSI. M100-ED32:2022 performance standards for antimicrobial susceptibility testing. 32nd ed","edition":"32"},{"key":"e_1_3_5_16_2","unstructured":"The European Committee on Antimicrobial Susceptibility Testing. 2024. Breakpoint tables for interpretation of MICs and zone diameters. Version 14.0. http:\/\/www.eucast.org."},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac199"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1196"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki442"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.10.4020-4022.2004"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw441"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab482"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa465"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051642"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1470-9465.2004.00862.x"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw226"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00004-06"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2375"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.4.941"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/377534"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.2105\/ajph.90.2.223"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1089\/107662901750152864"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2012-203106"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2016.01.011"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofu024"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-60-5-759"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.044107-0"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00237-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00237-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T21:39:42Z","timestamp":1773178782000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00237-25"}},"subtitle":[],"editor":[{"given":"Cesar A.","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,6]]}},"alternative-id":["10.1128\/aac.00237-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00237-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"2025-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00237-25"}}