Zeraatpisheh Anis, Moradi Melika, Arshadi Maniya, Taheri Behrouz, Zahmatkeshan Massomeh, Dehbashi Fereshteh Nezhad, Esmaeili Fariba, Amanzadi Bentolhoda, Farshadzadeh Zahra
Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
BMC Microbiol. 2025 Aug 7;25(1):487. doi: 10.1186/s12866-025-04223-w.
Pseudomonas aeruginosa is a major cause of severe infections, leading to significant morbidity and mortality rates due to its ability of biofilm formation and antibiotic resistance. This study evaluates the in vitro antimicrobial and antibiofilm effects of ciprofloxacin and berberine hydrochloride, alone and in combination, against clinical and standard strains of P. aeruginosa.
Clinical isolates of carbapenem-susceptible P. aeruginosa (CSPA), carbapenem-resistant P. aeruginosa (CRPA), and the standard P. aeruginosa PAO strain were examined. Antimicrobial activity (MIC/MBC) and biofilm inhibition (MBIC/MBEC) were assessed using the microdilution method, checkerboard assay (FICI), and time-kill kinetics.
The minimum inhibitory concentrations (MICs) of ciprofloxacin and berberine hydrochloride ranged from 0.5 to 64 µg/mL and 593 to 1187 µg/mL, respectively. The minimum bactericidal concentrations (MBCs) for both agents were ≥ 2× MIC. Neither ciprofloxacin nor berberine hydrochloride was able to eradicate 24-hour preformed biofilms (MBEC). However, biofilm prevention (MBIC) occurred at sub-MIC levels (0.5-1× MIC). The combination of ciprofloxacin and berberine hydrochloride demonstrated synergistic activity against PAO (FICI ≤ 0.5). The time-kill assay confirmed the bactericidal effect of this combination against PAO and CSPA isolates.
Berberine hydrochloride may serve as a promising synergistic agent to enhance the antimicrobial and antibiofilm activity of ciprofloxacin in vitro. This combination warrants further exploration as a therapeutic strategy against resistant infections.
铜绿假单胞菌是严重感染的主要病因，因其具有形成生物膜和抗生素耐药性的能力，导致显著的发病率和死亡率。本研究评估环丙沙星和盐酸小檗碱单独及联合使用对铜绿假单胞菌临床菌株和标准菌株的体外抗菌及抗生物膜作用。
检测了对碳青霉烯敏感的铜绿假单胞菌（CSPA）、对碳青霉烯耐药的铜绿假单胞菌（CRPA）的临床分离株以及标准铜绿假单胞菌PAO菌株。采用微量稀释法、棋盘法（FICI）和时间杀菌动力学评估抗菌活性（MIC/MBC）和生物膜抑制（MBIC/MBEC）。
环丙沙星和盐酸小檗碱的最低抑菌浓度（MIC）分别为0.5至64μg/mL和593至1187μg/mL。两种药物的最低杀菌浓度（MBC）均≥2×MIC。环丙沙星和盐酸小檗碱均不能根除24小时形成的生物膜（MBEC）。然而，在亚MIC水平（0.5 - 1×MIC）出现了生物膜预防（MBIC）。环丙沙星和盐酸小檗碱的联合使用对PAO显示出协同活性（FICI≤0.5）。时间杀菌试验证实了该联合用药对PAO和CSPA分离株的杀菌作用。
盐酸小檗碱可能是一种有前景的协同剂，可增强环丙沙星在体外的抗菌及抗生物膜活性。作为一种抗耐药感染的治疗策略，该联合用药值得进一步探索。
