{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T08:22:07Z","timestamp":1772180527321,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"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>Purpose<\/jats:title>\n                    <jats:p>\n                      Extensively drug-resistant\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      (XDR-PA) has posed a great threat to public health due to their rising incidence and complicated resistance mechanisms and limited treatment options. XDR-PA has demonstrated high resistance rate to new antibiotic ceftazidime-avibactam (CZA). Therefore, this study was conducted to describe the resistance mechanisms, molecular epidemiology, and type III secretion system (T3SS) of XDR-PA, as well as to evaluate the synergistic antibacterial activity of CZA combined with aztreonam (ATM) against XDR-PA via\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments, aiming at providing insights for the prevention, control and treatment strategies of XDR-PA infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The carbapenemase resistance genes (VIM, IMP, NDM, KPC, GES, OXA-40) and T3SS virulence genes of XDR-PA isolates were identified using polymerase chain reaction (PCR) and sequencing. The expression levels of efflux pump systems (\n                      <jats:italic>mexA and mexC<\/jats:italic>\n                      ),\n                      <jats:italic>oprD2<\/jats:italic>\n                      porin and\n                      <jats:italic>ampC<\/jats:italic>\n                      were detected by the real-time fluorescent quantitative PCR (qPCR). The homology analysis of XDR-PA isolates was performed using multilocus sequence typing (MLST). Combined antimicrobial susceptibility testing of CZA and ATM were performed for XDR-PA isolates through\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 32 XDR-PA strains were isolated from clinical specimens from a tertiary teaching hospital in Southwest China between October 2022 to October 2023. Among the carbapenemase detected, metallo-\u03b2-lactamase (MBL) NDM-1 and VIM-2 were detected in 26 strains (81.25%, 26\/32) and 1 strain (3.13%, 1\/32) respectively. The efflux pump\n                      <jats:italic>mexA<\/jats:italic>\n                      had a higher expression in the XDR-PA group than that in the sensitive-PA (S-PA) group (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.015). The T3SS virulence genes carried by XDR-PA strains mainly were\n                      <jats:italic>exoY+\/exoT+\/exoU+\/exoS-<\/jats:italic>\n                      (87.50%, 28\/32). The 32 XDR-PA isolates belonged to 8 different ST types, mainly including ST1971 and ST308, and the predominant ST type was ST1971 (71.88%, 23\/32), with carrying both NDM-1 and\n                      <jats:italic>exoY+\/exoT+\/exoU+\/exoS-<\/jats:italic>\n                      . Combined antimicrobial susceptibility testing revealed that among the 27 CZA-resistant XDR-PA strains, CZA and ATM combination showed a synergistic effect on 21 CZA-resistant XDR-PA strains (77.78%, 21\/27), of which 20 strains carrying both MBL (95.24%, 20\/21) and\n                      <jats:italic>exoY+\/exoT+\/exoU+\/exoS-<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The underlying resistance mechanisms of XDR-PA isolates involve the overexpression of efflux pump\n                      <jats:italic>mexA<\/jats:italic>\n                      and the existence of MBL. In addition, ST1971 was the predominant ST type in our study, with carrying both NDM-1 and\n                      <jats:italic>exoY+\/exoT+\/exoU+\/exoS-<\/jats:italic>\n                      . Furthermore, combined antimicrobial susceptibility testing suggested that CZA and ATM combination has potential against MBL-producing\n                      <jats:italic>exoY+\/exoT+\/exoU+\/exoS-<\/jats:italic>\n                      XDR-PA. These findings may provide clues for the prevention, control and treatment strategies of XDR-PA infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1737414","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:51:33Z","timestamp":1772175093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic activity of ceftazidime\/avibactam combined with aztreonam against MBL-producing exoY+\/exoT+\/exoU+\/exoS- extensively drug-resistant Pseudomonas aeruginosa"],"prefix":"10.3389","volume":"16","author":[{"given":"Xianzhen","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The First People\u2019s Hospital of Qinzhou","place":["Qinzhou, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingbo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First People\u2019s Hospital of Qinzhou","place":["Qinzhou, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runxian","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First People\u2019s Hospital of Qinzhou","place":["Qinzhou, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First People\u2019s Hospital of Qinzhou","place":["Qinzhou, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First People\u2019s Hospital of Qinzhou","place":["Qinzhou, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]},{"name":"Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education","place":["Nanning, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.2174\/1386207324666210419112210","article-title":"Association Between Biofilm Formation Gene Bla exoU and Metallo and Extend Spectrum Beta-lactamase Production of Multidrug Resistance Pseudomonas aeruginosa in Clinical Samples","volume":"25","author":"Ali","year":"2022","journal-title":"Comb. 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