Questions associated with the development of novel drugs intended for the treatment of bacterial infections in veterinary species

• Published in: The veterinary journal (1997) 2019-06, Vol.248, p.79-85
• Main Authors: Martinez, Marilyn N., Watts, Jeffrey L., Gilbert, Jeffrey M.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antivirulence targets; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Bacterial Infections - veterinary; Drug Resistance, Multiple, Bacterial; Drugs, Investigational; Effectiveness assessments; Regulatory challenges; Resistance issues; Safety considerations; Virulence Factors
• ISSN: 1090-0233; 1532-2971
• DOI: 10.1016/j.tvjl.2019.04.009

[Display omitted] •Drugs acting through effects on antivirulence targets present a novel approach for reducing the pathological effects of bacterial infections.•Impacting the development of these drugs for animals are the many uncertainties associated with the questions that need to be addressed.•These questions pertain to assessment of product effectiveness, human food safety, and bacterial resistance selection and its consequences.•It is unclear if these compounds should be evaluated as stand-alone therapy or concomitant or sequential use with traditional antibacterials.•Because these drugs are highly specific for a particular pathogen/disease process, they are likely to be less lucrative than more traditional therapies. The emergence of multi-drug resistant bacteria has limited therapeutic options for the treatment of bacterial diseases in both human and veterinary medicine. This has resulted in an urgent need for novel agents to treat infectious diseases. Veterinary medicine is further constrained by the need to ensure that our emerging therapeutics have minimal or no impact on resistance in human pathogens. Thus, there has recently been increased attention given to the development of alternative treatments for infectious disease in animals. The domain of alternative therapies, which includes antimicrobial peptides, bacteriophages, probiotics, and immunomodulators, provides a means to directly inhibit the ability of a pathogen to damage the host while optimally, not imposing a selective pressure favouring antibiotic resistance. However, it is recognized that bacterial pathogens have the capability of expressing a variety of virulence factors, necessitating a clear understanding of the specific target for that therapeutic intervention. This manuscript explores the various virulence mechanisms, the potential utility of developing novel anti-virulence agents for counteracting the expression of diseases associated with veterinary species, and some of the unique regulatory hurdles to be addressed within the framework of a new animal drug application. We conclude with the public health concerns to be considered as these agents are integrated into the veterinary therapeutic arsenal. Our hope is that this manuscript will provide a platform to stimulate discussions on the critical questions that need to be addressed.