In vitroantimicrobial activity of narasin and monensin in combination with adjuvants against pathogens associated with canine otitis externa

Abstract

Background The emergence of antimicrobial resistance represents a serious human and animal health risk. Good antimicrobial stewardship is essential to prolong the lifespan of existing antibiotics, and new strategies are required to combat infections in man and animals. Hypothesis/Objectives To determine the in vitro interaction of ionophores (narasin or monensin) with antimicrobial adjuvants (N‐acetylcysteine (NAC), Tris‐EDTA or disodium EDTA) against bacterial strains representing pathogens associated with canine otitis externa (OE). Animal/Isolates American Type Culture Collection (ATCC) strains Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853 and P. aeruginosa biofilm producer PAO1, and a clinical isolate of Proteus mirabilis from a case of canine OE were tested. Methods and materials A 2D microdilution checkerboard method was used, allowing calculation of fractional inhibitory concentration index (FICI), dose reduction index (DRI) and plotting of isobolograms. Results The combination of narasin with either Tris‐EDTA or disodium EDTA produced additive effects (FICI = 0.75) against P. aeruginosa ATCC 27853 and P. aeruginosa biofilm producer ATCC PAO1. An additive effect (FICI = 0.53–0.75) was found against S. aureus ATCC 29213 when narasin or monensin were combined with NAC. The highest DRI (32‐fold) was found with monensin/NAC where the MIC of monensin was reduced from 4 to 0.125 μg/mL. Conclusions and clinical importance The combination of narasin with Tris‐EDTA or disodium EDTA is a promising strategy to inhibit the intrinsic resistance elements of Gram‐negative bacteria. These novel combinations potentially could be useful as a multimodal approach to treat mixed infections in canine OE.

Exploring Klebsiella pneumoniae in Healthy Poultry Reveals High Genetic Diversity, Good Biofilm-Forming Abilities and Higher Prevalence in Turkeys Than Broilers

“…Currently, turkey flocks are still given monensin, while narasin has been phased out since 2016 in Norwegian broiler production. Ionophores may affect the gut microbiota, as both narasin and monensin have been found to have an antimicrobial effect on gram-positive bacteria ( Chan et al, 2020 ). A reduction of the gram-positive fraction of the gut microbiota may result in higher abundance of Gram-negative bacteria, such as K. pneumoniae.…”

Biofilm production by pathogens associated with canine otitis externa, and the antibiofilm activity of ionophores and antimicrobial adjuvants

“…Further studies of the antimicrobial adjuvants N‐acetylcysteine (NAC), Tris‐EDTA and disodium EDTA revealed activity against both Gram‐positive and Gram‐negative bacteria (Chan, Khazandi, Hickey, Page, Trott, et al, ). A synergistic effect was seen against P. aeruginosa when narasin was combined with either Tris‐EDTA or disodium EDTA (Chan et al, , submitted). As chronic OE in dogs can be complicated by the presence of biofilms, this study aimed to determine the ability of S. pseudintermedius and P. aeruginosa isolates from cases of canine OE to form biofilm, and to explore the antibiofilm activity of ionophores and adjuvants against these pathogens.…”

A bis(pyrazolyl)methane derivative against clinical Staphylococcus aureus strains isolated from otitis externa

“…There are many reports about compounds with effects against the human bacterial pathogens involved in OE, [22][23][24][25] while research into new molecules that may be effective against infectious agents continues worldwide. 26,27 Thus p-Cymene [1-methyl-4-(1-methylethyl)-benzene] is an alkyl-substituted aromatic hydrocarbon found in nature whose benzene ring features the substitution of a methyl and an isopropyl group.…”