Teo Jocelyn Qimin, Toh Jing Heng, Chang Hong Yi, Tan Si Hui, Ho Jayden Jun-Yuan, Ong Zhi Wei, Lee Winnie, Tan Yen Ee, Wong Tse Hua Nicholas, Chung Shimin Jasmine, Tan Thuan Tong, Lim Tze Peng, Kwa Andrea Lay-Hoon
Division of Pharmacy, Singapore General Hospital, Singapore, Singapore.
SingHealth Duke-NUS Pathology Academic Clinical Programme, Singapore, Singapore.
Commun Med (Lond). 2025 Aug 5;5(1):334. doi: 10.1038/s43856-025-01022-2.
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.
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.
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.
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.
对于耐碳青霉烯类铜绿假单胞菌（CRPA），尤其是那些携带碳青霉烯酶的菌株，可用的治疗选择有限。鉴于抗生素联合使用的有效性存在差异，有人建议采用体外试验指导的抗生素治疗方法来改善接受联合治疗患者的治疗效果。我们研究了各种联合用药对CRPA的体外杀菌活性，并描述了我们使用个性化试验指导方法治疗这些难治性感染的经验。
对2017年至2022年进行的一项单中心前瞻性队列研究收集的CRPA分离株进行体外抗生素联合试验（iACT），试验包含临床相关游离浓度下多达180种独特的联合用药。
抗生素联合用药的体外活性具有高度菌株特异性。含多粘菌素的联合用药对66株受试分离株表现出最高的杀菌活性[454/497（91%）的菌株-联合用药对]。大多数CRPA产生碳青霉烯酶（73%）。杀菌活性>60%的不含多粘菌素的联合用药包括磷霉素+氨曲南（40/58）和磷霉素+头孢吡肟（37/58）。我们发现，42例最终接受至少72小时个性化iACT指导治疗患者的治疗效果良好[治疗结束时的临床缓解率：93%；30天全因死亡率：2%]。我们观察到所有血流感染的微生物均被清除，但13%的患者随后再次感染CRPA。
含多粘菌素的联合用药对CRPA表现出最高的杀菌活性，而磷霉素+氨曲南或磷霉素+头孢吡肟是有前景的不含多粘菌素的选择。个性化的体外试验指导治疗方法对于治疗铜绿假单胞菌感染可能是可行的，尤其是那些涉及碳青霉烯酶产生和/或难治性表型的感染。
