Flash optimization of drug combinations for Acinetobacter baumannii with IDentif.AI-AMR.

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Tác giả: Nurhidayah Binte Mohamed Yazid, Conrad E Z Chan, Li Ming Chong, Edward Kai-Hua Chow, Stephen Chua, Dean Ho, Lissa Hooi, Alrick Zi Xin Kok, Ethan Lim, Kalisvar Marimuthu, Oon Tek Ng, Shawn Vasoo, Peter Wang, Kui You, Isaiah Zhuang

Ngôn ngữ: eng

Ký hiệu phân loại: 364.177 Illegal sale, possession, use of drugs

Thông tin xuất bản: England : npj antimicrobials and resistance , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 494094

Antimicrobial resistance (AMR) is an emerging threat to global public health. Specifically, Acinetobacter baumannii (A. baumannii), one of the main pathogens driving the rise of nosocomial infections, is a Gram-negative bacillus that displays intrinsic resistance mechanisms and can also develop resistance by acquiring AMR genes from other bacteria. More importantly, it is resistant to nearly 90% of standard of care (SOC) antimicrobial treatments, resulting in unsatisfactory clinical outcomes and a high infection-associated mortality rate of over 30%. Currently, there is a growing challenge to sustainably develop novel antimicrobials in this ever-expanding arms race against AMR. Therefore, a sustainable workflow that properly manages healthcare resources to ultra-rapidly design optimal drug combinations for effective treatment is needed. In this study, the IDentif.AI-AMR platform was harnessed to pinpoint effective regimens against four A. baumannii clinical isolates from a pool of nine US FDA-approved drugs. Notably, IDentif.AI-pinpointed ampicillin-sulbactam/cefiderocol and cefiderocol/polymyxin B/rifampicin combinations were able to achieve 93.89 ± 5.95% and 92.23 ± 11.89% inhibition against the bacteria, respectively, and they may diversify the reservoir of treatment options for the indication. In addition, polymyxin B in combination with rifampicin exhibited broadly applicable efficacy and strong synergy across all tested clinical isolates, representing a potential treatment strategy for A. baumannii. IDentif.AI-pinpointed combinations may potentially serve as alternative treatment strategies for A. baumannii.
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