{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:04:33Z","timestamp":1789362273078,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Difficult-to-treat resistant\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      (DTR-PA) represents the most severe antimicrobial resistance phenotype of\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      , with limited therapeutic options and poor clinical outcomes. However, previous studies have largely focused on carbapenem-resistant\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      (CRPA), and the factors associated with resistance acquisition and progression remain insufficiently characterized. This study aimed to investigate the clinical characteristics and risk factors associated with different resistance phenotypes of\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      from the perspectives of both resistance acquisition and resistance escalation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective case-control study was conducted from January 2020 to December 2025 at a tertiary teaching hospital.\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      isolates were classified according to antimicrobial susceptibility profiles. All DTR-PA cases (n = 67) were included, and CRPA and carbapenem-susceptible\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      (CSPA) controls were selected using a time-stratified 1:2:2 sampling strategy. Clinical data were collected, and three comparative models were developed to explore determinants of resistance acquisition and resistance escalation across different\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      phenotypes: resistant\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      (R-PA, defined as CRPA and DTR-PA) versus CSPA, DTR-PA versus CRPA, and DTR-PA versus non-DTR-PA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During the study period, 2,692\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      clinical isolates were included for analysis, including 67 (2.5%) DTR-PA, 407 (15.1%) CRPA, and 2,218 (82.4%) CSPA. A total of 335 patients were included in the risk factor analysis. With increasing antimicrobial resistance severity, inflammatory markers showed a stepwise increase, whereas nutritional status, as reflected by serum albumin levels, demonstrated a progressive decline. In the R-PA versus CSPA model, invasive respiratory procedures, prolonged hospitalization, and polymicrobial co-infection were associated with increased risk, whereas higher BMI and serum albumin levels showed modest inverse associations with resistant\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      infection. In the DTR-PA versus CRPA model, diabetes mellitus, chronic respiratory diseases, and recent ICU admission were associated with DTR-PA infection. In the DTR-PA versus non-DTR-PA model, prior antibiotic exposure, central venous catheterization, and invasive procedures were associated with DTR-PA infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Antimicrobial resistance in\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      follows a dynamic, stage-dependent process with distinct risk profiles. Healthcare exposure primarily contributes to resistance emergence, whereas host comorbidities and intensive care exposure are more closely associated with progression to DTR-PA. This resistance gradient framework may support early identification, risk stratification, and infection control strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1930952","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:32:53Z","timestamp":1789360373000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical gradient and predictors for stepwise resistance escalation of carbapenem-susceptible, carbapenem-resistant, and difficult-to-treat resistant Pseudomonas aeruginosa infections: a 6-year retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Lin","family":"Chen","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbang","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaguli","family":"Rouzimaimaiti","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinju","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruigang","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/s0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","year":"2022","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1016\/s1473-3099(22)00459-5","article-title":"Who's first global infection prevention and control report","volume":"22","author":"Balakrishnan","year":"2022","journal-title":"Lancet Infect. 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