Prevalent Synergy and Antagonism Among Antibiotics and Biocides in Pseudomonas aeruginosa

Franziska Pietsch; Gabriele Heidrich; Niclas Nordholt; Frank Schreiber

doi:10.3389/fmicb.2020.615618

Prevalent Synergy and Antagonism Among Antibiotics and Biocides in Pseudomonas aeruginosa

Front Microbiol. 2021 Feb 4:11:615618. doi: 10.3389/fmicb.2020.615618. eCollection 2020.

Authors

Franziska Pietsch¹, Gabriele Heidrich¹, Niclas Nordholt¹, Frank Schreiber¹

Affiliation

¹ Division of Biodeterioration and Reference Organisms (4.1), Department of Materials and the Environment, Federal Institute for Materials Research and Testing (BAM), Berlin, Germany.

Abstract

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).

Keywords: CTAB (cetyltrimethylammonium bromide); Povidone-iodine (PVP-I); antagonism; antibiotics; biocides; pseudomonas aeruginosa; suppression; synergy.