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Background <p>Limited treatment options are available for carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA), especially those harbouring carbapenemases. Given the variability in effectiveness of antibiotic combinations, in vitro test-guided antibiotic therapies have been suggested to improve the outcomes of patients receiving combination therapy. We investigated the in vitro bactericidal activities of various combinations against CRPA and described our experience of using a personalised test-guided approach in managing these difficult-to-treat infections.</p> Methods <p>In vitro antibiotic combination tests (<i>i</i>ACTs) comprising up to 180 unique combinations at clinically relevant unbound concentrations were performed for CRPA isolates collected for a monocentric prospective cohort study conducted between 2017 and 2022.</p> Results <p>In vitro activities of antibiotic combinations are highly strain-specific. Polymyxin-containing combinations exhibit the highest bactericidal activity [454/497 (91%) isolate-combination pairs] against 66 isolates tested. Most of the CRPA produce carbapenemases (73%). Polymyxin-sparing combinations exhibiting &gt;60% bactericidal activity include fosfomycin + aztreonam (40/58) and fosfomycin + cefepime (37/58). We show good outcomes in the 42 patients who eventually received at least 72 h of personalised <i>i</i>ACT-guided therapy [end-of-treatment clinical response rate: 93%; 30-day all-cause mortality: 2%]. We observe microbiological eradication for all bloodstream infections, but 13% of patients get reinfected with CRPA subsequently.</p> Conclusions <p>Polymyxin-containing combinations exhibit the highest bactericidal activity against CRPA, while fosfomycin +  aztreonam or fosfomycin + cefepime represent promising polymyxin-sparing options. A personalised in vitro test-guided treatment approach may be feasible for managing <i>P. aeruginosa</i> infections, particularly those involving carbapenemase production and/or difficult-to-treat phenotypes.</p>

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Personalised bactericidal combination regimens against carbapenem-resistant Pseudomonas aeruginosa

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月5日

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  • Jocelyn Qimin Teo,
  • Jing Heng Toh,
  • Hong Yi Chang,
  • Si Hui Tan,
  • Jayden Jun-Yuan Ho,
  • Zhi Wei Ong,
  • Winnie Lee,
  • Yen Ee Tan,
  • Tse Hua Nicholas Wong,
  • Shimin Jasmine Chung,
  • Thuan Tong Tan,
  • Tze Peng Lim,
  • Andrea Lay-Hoon Kwa

摘要

Background

Limited treatment options are available for carbapenem-resistant Pseudomonas aeruginosa (CRPA), especially those harbouring carbapenemases. Given the variability in effectiveness of antibiotic combinations, in vitro test-guided antibiotic therapies have been suggested to improve the outcomes of patients receiving combination therapy. We investigated the in vitro bactericidal activities of various combinations against CRPA and described our experience of using a personalised test-guided approach in managing these difficult-to-treat infections.

Methods

In vitro antibiotic combination tests (iACTs) comprising up to 180 unique combinations at clinically relevant unbound concentrations were performed for CRPA isolates collected for a monocentric prospective cohort study conducted between 2017 and 2022.

Results

In vitro activities of antibiotic combinations are highly strain-specific. Polymyxin-containing combinations exhibit the highest bactericidal activity [454/497 (91%) isolate-combination pairs] against 66 isolates tested. Most of the CRPA produce carbapenemases (73%). Polymyxin-sparing combinations exhibiting >60% bactericidal activity include fosfomycin + aztreonam (40/58) and fosfomycin + cefepime (37/58). We show good outcomes in the 42 patients who eventually received at least 72 h of personalised iACT-guided therapy [end-of-treatment clinical response rate: 93%; 30-day all-cause mortality: 2%]. We observe microbiological eradication for all bloodstream infections, but 13% of patients get reinfected with CRPA subsequently.

Conclusions

Polymyxin-containing combinations exhibit the highest bactericidal activity against CRPA, while fosfomycin +  aztreonam or fosfomycin + cefepime represent promising polymyxin-sparing options. A personalised in vitro test-guided treatment approach may be feasible for managing P. aeruginosa infections, particularly those involving carbapenemase production and/or difficult-to-treat phenotypes.