Data_Sheet_1_Prevalent Synergy and Antagonism Among Antibiotics and Biocides in Pseudomonas aeruginosa.pdf

Antimicrobials can exert specific physiological effects when used in combination that are different from those when applied alone. While combination effects have been extensively mapped for antibiotic-antibiotic combinations, the combination effects of antibiotics with antimicrobials used as biocides or antiseptics have not been systematically investigated. Here, we investigated the effects of combinations of antibiotics (meropenem, gentamicin, and ciprofloxacin) and substances used as biocides or antiseptics [octenidine, benzalkonium chloride, cetrimonium bromide, chlorhexidine, Povidone-iodine, silver nitrate (AgNO3), and Ag-nanoparticles] on the planktonic growth rate of Pseudomonas aeruginosa. Combination effects were investigated in growth experiments in microtiter plates at different concentrations and the Bliss interaction scores were calculated. Among the 21 screened combinations, we find prevalent combination effects with synergy occurring six times and antagonism occurring 10 times. The effects are specific to the antibiotic-biocide combination with meropenem showing a tendency for antagonism with biocides (6 of 7), while gentamicin has a tendency for synergy (5 of 7). In conclusion, antibiotics and biocides or antiseptics exert physiological combination effects on the pathogen P. aeruginosa. These effects have consequences for the efficacy of both types of substances and potentially for the selection of antimicrobial resistant strains in clinical applications with combined exposure (e.g., wound care and coated biomaterials).

抗菌剂（Antimicrobials）联合使用时，可产生与单独使用时截然不同的特异性生理效应。尽管抗生素-抗生素联合的效应已被广泛阐明，但抗生素与用作杀菌剂或消毒剂的抗菌剂之间的联合效应尚未得到系统性研究。本研究针对三类抗生素（美罗培南、庆大霉素与环丙沙星）与用作杀菌剂或消毒剂的物质[奥替尼啶、苯扎氯铵、十六烷基三甲基溴化铵、氯己定、聚维酮碘、硝酸银（AgNO3）及银纳米颗粒]的联合效应展开研究，考察其对铜绿假单胞菌（Pseudomonas aeruginosa）浮游生长速率的影响。研究通过不同浓度下的微孔板（microtiter plates）生长实验分析联合效应，并计算Bliss交互评分（Bliss interaction scores）。在筛选的21组联合方案中，我们观测到广泛存在的联合效应：其中协同作用出现6次，拮抗作用出现10次。此类效应具有抗生素-杀菌剂组合特异性：美罗培南与7种杀菌剂中的6种均表现出拮抗倾向，而庆大霉素则与5种杀菌剂表现出协同倾向。综上，抗生素与杀菌剂或消毒剂可对致病菌铜绿假单胞菌产生特异性生理联合效应。此类效应会影响两类物质的抗菌效能，且在联合暴露的临床应用场景（如伤口护理与涂层生物材料）中，可能对抗菌耐药菌株的筛选产生潜在影响。