Antibacterial effect of N‐acetylcysteine in combination with antimicrobials on common canine otitis externa bacterial isolates

Abstract

Background -Approved treatments for canine otitis externa are limited in variety and may contain ototoxic ingredients. With bacterial resistance an ongoing concern, it would be ideal if non-ototoxic agents combined with antibiotics resulted in a synergistic effect, requiring lower antibiotic concentrations to treat infections. Evidence of synergism and antagonism between N-acetylcysteine (NAC) and various antibiotic classes has been reported; the present research group was interested in examining these interactions.Hypothesis/Objectives -To determine if NAC, an otoprotective and antimicrobial compound, has synergistic activity when combined with enrofloxacin or gentamicin in vitro against bacterial isolates causing canine otitis externa.Animals -Twenty-two isolates from canine clinical cases of otitis externa were identified and tested, including seven Staphylococcus pseudintermedius, 12 Pseudomonas aeruginosa and three Corynebacterium spp. isolates.Methods and materials -Each isolate was grown on blood agar for 24 h and transferred to Mueller-Hinton broth (MHB), with a final concentration of 5 9 10 5 cfu/mL. Each well was inoculated with 50 lL of bacterial suspension. N-acetylcysteine was diluted in MHB to a starting concentration of 160 mg/mL. Enrofloxacin and gentamicin were diluted to 64 lg/mL. Individual and checkerboard serial microdilution assays were performed in triplicate with negative controls for all isolates tested.Results -Interactions observed for NAC and enrofloxacin were synergistic (4.5%), indifferent (77.3%) or antagonistic (18.2%). Interactions observed for NAC and gentamicin were synergistic (4.5%), indifferent (45.5%) or antagonistic (50%).Conclusions and Clinical relevance -Most interactions between NAC and enrofloxacin or gentamicin were indifferent or antagonistic at the concentrations tested in vitro.

In vitro efficacy of N-acetylcysteine in combination with antimicrobial agents against Pseudomonas aeruginosa in canine otitis externa

“…Most combinations of NAC with antibiotics displayed different interactions against P. aeruginosa except for four isolates. The rate of synergistic interactions was similar to a previous study, but the rate of antagonistic interactions was lower [20]. Almost all combinations against P. aeruginosa were similar.…”

“…The antimicrobial and antibiofilm activities of NAC in combination with antimicrobials against P. aeruginosa have been studied [16,17,20]. The present study assessed the in vitro efficacy of NAC combined with enrofloxacin, polymyxin B, and gentamicin against P. aeruginosa isolated from dogs with OE.…”

“…Glutathione is an important modulator for the activity of an-tibiotics in microorganisms. Hence, NAC has been investigated for its capabilities in inhibiting bacterial biofilms and promoting the antimicrobial activity of known antibiotics [15][16][17][18][19][20].…”

Managing recurrent otitis externa in dogs: what have we learned and what can we do better?

“…It therefore possible that NAC and similar anti-biofilm compounds may aid treatment of biofilm-associated infections in animals 2 . A commercially available trisEDTA-NAC solution may facilitate removal and treatment of biofilms in ear canals, although time should be left between this and topical antibiotics as an in vitro study found most interactions between NAC and enrofloxacin or gentamicin were indifferent to antagonistic 49 . Other compounds with potential anti-biofilm and antimicrobial activity include chlorhexidine, polihexanide, hypochlorous acid 44,50 and trisEDTA 2 .…”

Pseudomonas spp. in Canine Otitis Externa

“…N-acetylcysteine (NAC) is another candidate being explored as an adjuvant for use in canine OE. Similarly to Tris-EDTA, it has been shown to inhibit the growth of P. aeruginosa, including in canine otitis clinical isolates [97,137,138]. Synergistic interactions between NAC and enrofloxacin or gentamicin have been observed for one P. aeruginosa isolate, but were indifferent or antagonistic at the concentrations tested in vitro for most isolates [137].…”