Proguanil and chlorhexidine augment the antibacterial activities of clarithromycin and rifampicin against Acinetobacter baumannii

• Published in: International journal of antimicrobial agents Vol. 63; no. 2; p. 107065
• Main Authors: Wang, Chuandong, Zhang, Tingting, Wang, Yan, Wang, Yipeng, Pan, Hongwei, Dong, Xinyu, Liu, Siyu, Cao, Meng, Wang, Shuhua, Wang, Mingyu, Li, Yuezhong, Zhang, Jian, Hu, Wei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2024
• Subjects: Acinetobacter baumannii; Chlorhexidine; Clarithromycin; Combination therapy; Proguanil; Rifampicin; Acinetobacter baumannii; Clarithromycin; Chlorhexidine; Rifampicin; Combination therapy; Proguanil
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2023.107065

•PRG and CHX combined with CLR or RIF are effective against A. baumannii.•Combination therapy prevents the formation of antibiotic resistance in A. baumannii.•Combination therapy improves survival and speeds wound healing in infected mouse.•PRG and CHX enhance intracellular accumulation of CLR and RIF. The emergence of Acinetobacter baumannii infections as a significant healthcare concern in hospital settings, coupled with their association with poorer clinical outcomes, has prompted extensive investigation into novel therapeutic agents and innovative treatment strategies. Proguanil and chlorhexidine, both categorized as biguanide compounds, have displayed clinical efficacy as antimalarial and topical antibacterial agents, respectively. In this study, we conducted an investigation to assess the effectiveness of combining proguanil and chlorhexidine with clarithromycin or rifampicin against both laboratory strains and clinical isolates of A. baumannii. The combination therapy demonstrated rapid bactericidal activity against planktonic multidrug-resistant A. baumannii, exhibiting efficacy in eradicating mature biofilms and impeding the development of antibiotic resistance in vitro. Additionally, when administered in conjunction with clarithromycin or rifampicin, proguanil enhanced the survival rate of mice afflicted with intraperitoneal A. baumannii infections, and chlorhexidine expedited wound healing in mice with skin infections. These findings are likely attributable to the disruption of A. baumannii cell membrane integrity by proguanil and chlorhexidine, resulting in heightened membrane permeability and enhanced intracellular accumulation of clarithromycin and rifampicin. Overall, this study underscores the potential of employing proguanil and chlorhexidine in combination with specific antibiotics to effectively combat A. baumannii infections and improve treatment outcomes in clinically challenging scenarios. [Display omitted]