{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:03:47Z","timestamp":1784527427356,"version":"3.55.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023674","name":"Deanship of Scientific Research, King Khalid University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Antimicrobial resistance in respiratory gram-negative bacilli (GNB) is rising in Saudi Arabia, yet the clinical impact of difficult-to-treat resistance (DTR) remains poorly defined. We characterized temporal trends in organism distribution, non-susceptibility phenotypes, and their association with 30-day in-hospital mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective cohort of hospitalized patients aged \u226512 years with culture-positive respiratory GNB at a referral hospital in southern Saudi Arabia (January 2013\u2013August 2024). Non-susceptibility phenotypes were fluoroquinolone (FQ-NS), extended-spectrum cephalosporin (ESC-NS), carbapenem non-susceptibility, and DTR. Trends were assessed with segmented binomial regression, mortality with modified Poisson regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 6,999 isolate-episodes from 3,808 patients, Enterobacterales (57.2%) increased while non-fermenting GNB declined (AAPC, \u22122.5%). Carbapenem non-susceptibility rose among Enterobacterales (AAPC,\u00a0+\u00a05.4%), driven by\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      . DTR was 37.6%, rising in Enterobacterales (AAPC,\u00a0+\u00a012.1%) but declining in\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      . Thirty-day mortality was 27.9%. DTR was associated with mortality in Enterobacterales (aRR, 1.34; 95% CI, 1.16\u20131.55) and non-fermenting GNB (aRR, 1.28; 95% CI, 1.12\u20131.46); carbapenem non-susceptibility without DTR was not. Mortality rose as active first-line agents decreased (\n                      <jats:italic>P<\/jats:italic>\n                      -trend&amp;lt;.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Respiratory GNB epidemiology is shifting toward Enterobacterales with rising resistance. DTR, not carbapenem non-susceptibility alone, was consistently associated with 30-day mortality and provides a meaningful framework for risk stratification and resistance-centered surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1871310","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:35:46Z","timestamp":1784525746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Difficult-to-treat resistance, not carbapenem non-susceptibility, is associated with 30-day mortality in respiratory gram-negative bacilli: a 12-year surveillance cohort"],"prefix":"10.3389","volume":"16","author":[{"given":"Yahya","family":"Shabi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Clinical Parasitology, College of Medicine, King Khalid University","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawal","family":"Alwadei","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Alshahrani","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, King Khalid University","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"Somily","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, King Saud University and King Saud University Medical City","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalifa","family":"Binkhamis","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Asiri","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soliuman","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Haematology and Immunohaematology, Faculty of Medical Laboratory Sciences, University of Khartoum","place":["Khartoum, Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulah O. S.","family":"Bawazeer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud Mushabbab","family":"Al Oudhah","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan Abdullah","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Alhamlan","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Salem","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma","family":"Al Ghamdi","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, King Khalid University","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghadah","family":"Habtar","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, King Khalid University","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatimah","family":"Asiri","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Jali","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Almahdi","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program, Aseer Central Hospital","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Alahmari","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, King Khalid University","place":["Abha, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B4","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1007\/s40121-023-00834-w","article-title":"Narrative review of the epidemiology of hospital-acquired pneumonia and ventilator-associated pneumonia in Gulf Cooperation Council countries","volume":"12","author":"Abdalla","year":"2023","journal-title":"Infect. Dis. Ther."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms14020333","article-title":"Resistance, virulence, and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae causing bloodstream infections in Saudi Arabia","volume":"14","author":"Alkhelaiwi","year":"2026","journal-title":"Microorganisms"},{"key":"B3","volume-title":"National Healthcare Safety Network (NHSN) Patient Safety Component Manual","year":"2026"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3670","DOI":"10.1002\/sim.3733","article-title":"Estimating average annual per cent change in trend analysis","volume":"28","author":"Clegg","year":"2009","journal-title":"Stat. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1097\/00005650-199801000-00004","article-title":"Comorbidity measures for use with administrative data","volume":"36","author":"Elixhauser","year":"1998","journal-title":"Med. Care"},{"key":"B12","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.ajic.2016.01.042","article-title":"Ventilator-associated pneumonia rates in critical care units in 3 Arabian Gulf countries: a 6-year surveillance study","volume":"44","author":"El-Saed","year":"2016","journal-title":"Am. J. Infect. Control"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1093\/cid\/ciy378","article-title":"Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents","volume":"67","author":"Kadri","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1080\/02664763.2022.2063265","article-title":"Data-driven choice of a model selection method in joinpoint regression","volume":"50","author":"Kim","year":"2023","journal-title":"J. Appl. Stat."},{"key":"B14","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/(SICI)1097-0258(20000215)19:3<335::AID-SIM336>3.0.CO;2-Z","article-title":"Permutation tests for joinpoint regression with applications to cancer rates","volume":"19","author":"Kim","year":"2000","journal-title":"Stat. Med."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S554543","article-title":"Hospital-based surveillance of Klebsiella pneumoniae and other Klebsiella species in southern Saudi Arabia (2012\u20132024): escalating carbapenem and DTR resistance with species-specific phenotypes and genotypes","volume":"19","author":"Shabi","year":"2026","journal-title":"Infect. Drug Resist."},{"key":"B18","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/cid\/ciac268","article-title":"Infectious Diseases Society of America 2022 guidance on the treatment of extended-spectrum \u03b2-lactamase\u2013producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa)","volume":"75","author":"Tamma","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1097\/MLR.0b013e31819432e5","article-title":"A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data","volume":"47","author":"van Walraven","year":"2009","journal-title":"Med. Care"},{"key":"B13","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"61","author":"von Elm","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"B5","volume-title":"Global Action Plan on Antimicrobial Resistance","year":"2015"},{"key":"B1","volume-title":"Antimicrobial Resistance","year":"2023"},{"key":"B8","volume-title":"Antimicrobial Resistance in the Region","year":"2020"},{"key":"B9","doi-asserted-by":"publisher","first-page":"935","DOI":"10.15537\/smj.2016.9.16139","article-title":"Antimicrobial resistance in Saudi Arabia: an urgent call for an immediate action","volume":"37","author":"Zowawi","year":"2016","journal-title":"Saudi Med. J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1128\/CMR.00096-12","article-title":"\u03b2-lactamase production in key gram-negative pathogen isolates from the Arabian Peninsula","volume":"26","author":"Zowawi","year":"2013","journal-title":"Clin. Microbiol. Rev."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1871310\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:35:48Z","timestamp":1784525748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1871310\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":18,"alternative-id":["10.3389\/fcimb.2026.1871310"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1871310","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"article-number":"1871310"}}