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Otitis externa (OE) is a frequently reported disorder in dogs associated with secondary infections by Staphylococcus, Pseudomonas and yeast pathogens. The presence of biofilms may play an important role in the resistance of otic pathogens to antimicrobial agents. Biofilm production of twenty Staphylococcus pseudintermedius and twenty Pseudomonas aeruginosa canine otic isolates was determined quantitatively using a microtiter plate assay, and each isolate was classified as a strong, moderate, weak or nonbiofilm producer. Minimum biofilm eradication concentration (MBEC) of two ionophores (narasin and monensin) and three adjuvants (N-acetylcysteine (NAC), Tris-EDTA and disodium EDTA) were investigated spectrophotometrically (OD 570nm ) and quantitatively (CFU/ml) against selected Staphylococcus and Pseudomonas biofilm cultures. Concurrently, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of planktonic cultures were assessed. 16/20 of the S. pseudintermedius clinical isolates were weak biofilm producers. 19/20 P. aeruginosa clinical isolates produced biofilms and were distributed almost equally as weak, moderate and strong biofilm producers. While significant antibiofilm activity was observed, no MBEC was achieved with narasin or monensin. The MBEC for NAC ranged from 5,000-10,000 µg/ml and from 20,000-80,000 µg/ml against S. pseudintermedius and P. aeruginosa, respectively. Tris-EDTA eradicated P. aeruginosa biofilms at concentrations ranging from 6,000/1,900 to 12,000/3,800 µg/ml. The MBEC was up to 16-fold and eightfold higher than the MIC/MBC of NAC and Tris-EDTA, respectively. Disodium EDTA reduced biofilm growth of both strains at concentrations of 470 µg/ml and higher. It can be concluded that biofilm production is common in pathogens associated with canine OE. NAC and Tris-EDTA are effective antibiofilm agents in vitro that could be considered for the treatment of biofilm-associated OE in dogs., (© 2019 John Wiley & Sons Ltd.)

Background: An antibiotic adjuvant is a chemical substance used to modify or augment the effectiveness of primary antimicrobial agents against drug-resistant micro-organisms. Its use provides an alternative approach to address the global issue of antimicrobial resistance and enhance antimicrobial stewardship., Hypothesis/objectives: To determine the antimicrobial activity of a panel of potential antimicrobial adjuvants against common pathogens associated with canine otitis externa (OE)., Animals/isolates: A number of type strains and clinical isolates (n = 110) from canine OE were tested including Staphylococcus pseudintermedius, β-haemolytic Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis and Malassezia pachydermatis., Methods and Materials: Antimicrobial activities of monolaurin, monocaprin, N-acetylcysteine (NAC), polymyxin B nonapeptide, Tris-EDTA, Tris-HCL and disodium EDTA were tested using microdilution methodology according to CLSI guidelines., Results: N-acetylcysteine, Tris-EDTA and disodium EDTA had antimicrobial activity against both type strains and otic pathogens. The other adjuvants tested had limited to no efficacy. NAC had a minimal inhibitory concentration (MIC) range of 2,500-10,000 μg/mL for the various organisms. Pseudomonas aeruginosa isolates were eight times more susceptible to disodium EDTA in the presence of Tris-HCL in comparison to disodium EDTA alone. Malassezia pachydermatis isolates were most susceptible to Tris-EDTA (MIC 90  = 190/60 μg/mL) and disodium EDTA (MIC 90  = 120 μg/mL)., Conclusions and Clinical Relevance: N-acetylcysteine, Tris-EDTA and disodium EDTA have intrinsic antimicrobial activity and represent promising adjuvants that could be used to enhance the efficacy of existing antibiotics against Gram-negative and multidrug-resistant bacterial infections. These agents could be combined with other antimicrobial agents in a multimodal approach for mixed ear infections in dogs., (© 2018 ESVD and ACVD.)

Background: Large quantities of antimicrobials are given to food animals, particularly in feed, potentially increasing antimicrobial resistance in humans. However, the magnitude of this effect is unclear., Methods: We searched PubMed, Embase and Web of Science for studies on interventions that limited antimicrobial use in food animals, in any setting and context, to reduce antimicrobial resistance 1) in those food animals; and 2) in humans. We validated our strategy by testing whether it identified known relevant studies. Data from included studies were extracted into pre-designed and pilot-tested forms., Results: We included 104 articles containing 93 studies. Heterogeneity (different animal species, environs, antimicrobial classes, interventions, administration routes, sampling, and methods), was considerable, precluding meta-analysis. The evidence was therefore synthesised narratively. A total of 89 studies (3 directly, 86 indirectly) addressed whether limiting antimicrobial exposure in food animals led to decreased antimicrobial resistance in those animals. The evidence was adequate to conclude this, although the magnitude of the effect could not be quantified. Four studies (1 directly, 3 indirectly) examined whether withdrawal of antibiotics changed resistance of potential pathogens in retail food for human consumption, and in bacteria of humans themselves. The direct (observational) study of broiler hatchery in ovo antimicrobial injection found a credible effect in terms of size reduction and time sequences., Interpretation: Limiting antimicrobial use in food animals reduces antimicrobial resistance in food animals, and probably reduces antimicrobial resistance in humans. The magnitude of the effect cannot be quantified., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Antimicrobial resistance and antimicrobial stewardship are of ever-increasing importance in veterinary medicine. Re-purposing of old drugs that are not used in human medicine is one approach that addresses the emergence of multidrug resistance in canine skin and ear infections, and can reduce the use of critically important human antibiotic classes., Hypothesis/objectives: To determine the antimicrobial activity of narasin, a polyether ionophore conventionally used as a rumen modifier and anticoccidial agent in production animals, against common clinical isolates of canine otitis externa (OE)., Animals/isolates: Clinical isolates (n = 110) from canine OE were tested, including 17 meticillin-susceptible Staphylococcus pseudintermedius (MSSP), 13 multidrug-resistant Staphylococcus pseudintermedius (MDRSP), and 20 each of β-haemolytic Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis and Malassezia pachydermatis., Methods: Bacterial and yeast isolates were subcultured, suspended in broth and inoculated into 96-well plates. Organisms were tested against concentrations of narasin ranging from 0.03 to 128 μg/mL. Minimal inhibitory concentrations (MICs) were determined after overnight incubation., Results: Narasin MICs for staphylococcal and streptococcal isolates ranged from 0.06 to 0.25 μg/mL; MIC 50 and MIC 90 values for both organisms were 0.125 μg/mL. No MICs were achieved for Pseudomonas or Proteus isolates. There was a weak antifungal effect against M. pachydermatis isolates (MIC 32 to >128 μg/mL)., Conclusions and Clinical Relevance: Narasin was effective against Gram-positive bacteria and had antifungal activity at higher concentrations against M. pachydermatis. However, the lack of Gram-negative activity would prevent its use as a sole antimicrobial agent in cases of canine OE., (© 2018 ESVD and ACVD.)

There are very few articles in the literature describing continuous models of bacterial infections that mimic disease pathogenesis in humans and animals without using separate cohorts of animals at each stage of disease. In this work, we developed bioluminescent mouse models of partial-thickness scald wound infection and sepsis that mimic disease pathogenesis in humans and animals using a recombinant luciferase-expressing Staphylococcus aureus strain (Xen29). Two days post-scald wound infection, mice were treated twice daily with a 2% topical mupirocin ointment for 7 days. For sepsis experiments, mice were treated intraperitoneally with 6 mg/kg daptomycin 2 h and 6 h post-infection and time to moribund monitored for 72 h. Consistent bacterial burden data were obtained from individual mice by regular photon intensity quantification on a Xenogen IVIS Lumina XRMS Series III biophotonic imaging system, with concomitant significant reduction in photon intensities in drug-treated mice. Post-mortem histopathological examination of wounds and bacterial counts in blood correlated closely with disease severity and total flux obtained from Xen29. The bioluminescent murine models provide a refinement to existing techniques of multiple bacterial enumeration during disease pathogenesis and promote animal usage reduction. The models also provide an efficient and information-rich platform for preclinical efficacy evaluation of new drug classes for treating acute and chronic human and animal bacterial infections. [ABSTRACT FROM AUTHOR]

The spread of multidrug resistance among bacterial pathogens poses a serious threat to public health worldwide. Recent approaches towards combating antimicrobial resistance include repurposing old compounds with known safety and development pathways as new antibacterial classes with novel mechanisms of action. Here we show that an analog of the anticoccidial drug robenidine (4,6-bis(2-((E)-4-methylbenzylidene)hydrazinyl)pyrimidin-2-amine; NCL195) displays potent bactericidal activity against Streptococcus pneumoniae and Staphylococcus aureus by disrupting the cell membrane potential. NCL195 was less cytotoxic to mammalian cell lines than the parent compound, showed low metabolic degradation rates by human and mouse liver microsomes, and exhibited high plasma concentration and low plasma clearance rates in mice. NCL195 was bactericidal against Acinetobacter spp and Neisseria meningitidis and also demonstrated potent activity against A. baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. in the presence of sub-inhibitory concentrations of ethylenediaminetetraacetic acid (EDTA) and polymyxin B. These findings demonstrate that NCL195 represents a new chemical lead for further medicinal chemistry and pharmaceutical development to enhance potency, solubility and selectivity against serious bacterial pathogens. [ABSTRACT FROM AUTHOR]