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Optimization of Antimicrobial Treatment to Minimize Resistance Selection

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  • Authors: Luca Guardabassi1, Mike Apley2, John Elmerdahl Olsen3, Pierre-Louis Toutain4, Scott Weese5
  • Editors: Frank Møller Aarestrup6, Stefan Schwarz7, Jianzhong Shen8, Lina Cavaco9
    Affiliations: 1: Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark; 2: Kansas State University College of Veterinary Medicine, Manhattan, Kansas, 66506; 3: Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark; 4: INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France; 5: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Canada; 6: Technical University of Denmark, Lyngby, Denmark; 7: Freie Universität Berlin, Berlin, Germany; 8: China Agricultural University, Beijing, China; 9: Statens Serum Institute, Copenhagen, Denmark
  • Source: microbiolspec June 2018 vol. 6 no. 3 doi:10.1128/microbiolspec.ARBA-0018-2017
  • Received 31 March 2017 Accepted 21 February 2018 Published 21 June 2018
  • Luca Guardabassi, [email protected]
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  • Abstract:

    Optimization of antimicrobial treatment is a cornerstone in the fight against antimicrobial resistance. Various national and international authorities and professional veterinary and farming associations have released generic guidelines on prudent antimicrobial use in animals. However, these generic guidelines need to be translated into a set of animal species- and disease-specific practice recommendations. This article focuses on prevention of antimicrobial resistance and its complex relationship with treatment efficacy, highlighting key situations where the current antimicrobial drug products, treatment recommendations, and practices may be insufficient to minimize antimicrobial selection. The authors address this topic using a multidisciplinary approach involving microbiology, pharmacology, clinical medicine, and animal husbandry. In the first part of the article, we define four key targets for implementing the concept of optimal antimicrobial treatment in veterinary practice: (i) reduction of overall antimicrobial consumption, (ii) improved use of diagnostic testing, (iii) prudent use of second-line, critically important antimicrobials, and (iv) optimization of dosage regimens. In the second part, we provided practice recommendations for achieving these four targets, with reference to specific conditions that account for most antimicrobial use in pigs (intestinal and respiratory disease), cattle (respiratory disease and mastitis), dogs and cats (skin, intestinal, genitourinary, and respiratory disease), and horses (upper respiratory disease, neonatal foal care, and surgical infections). Lastly, we present perspectives on the education and research needs for improving antimicrobial use in the future.

  • Citation: Guardabassi L, Apley M, Olsen J, Toutain P, Weese S. 2018. Optimization of Antimicrobial Treatment to Minimize Resistance Selection. Microbiol Spectrum 6(3):ARBA-0018-2017. doi:10.1128/microbiolspec.ARBA-0018-2017.


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Optimization of antimicrobial treatment is a cornerstone in the fight against antimicrobial resistance. Various national and international authorities and professional veterinary and farming associations have released generic guidelines on prudent antimicrobial use in animals. However, these generic guidelines need to be translated into a set of animal species- and disease-specific practice recommendations. This article focuses on prevention of antimicrobial resistance and its complex relationship with treatment efficacy, highlighting key situations where the current antimicrobial drug products, treatment recommendations, and practices may be insufficient to minimize antimicrobial selection. The authors address this topic using a multidisciplinary approach involving microbiology, pharmacology, clinical medicine, and animal husbandry. In the first part of the article, we define four key targets for implementing the concept of optimal antimicrobial treatment in veterinary practice: (i) reduction of overall antimicrobial consumption, (ii) improved use of diagnostic testing, (iii) prudent use of second-line, critically important antimicrobials, and (iv) optimization of dosage regimens. In the second part, we provided practice recommendations for achieving these four targets, with reference to specific conditions that account for most antimicrobial use in pigs (intestinal and respiratory disease), cattle (respiratory disease and mastitis), dogs and cats (skin, intestinal, genitourinary, and respiratory disease), and horses (upper respiratory disease, neonatal foal care, and surgical infections). Lastly, we present perspectives on the education and research needs for improving antimicrobial use in the future.

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A logical thinking process to enable antimicrobial stewardship across all animal species and therapeutic challenges. This logical process requires (1) veterinary guidance in constructing case definitions and validating the definitions through caretaker training and diagnostics, (2) consideration of possible alternatives to prevent, control, or treat the bacterial disease, (3) choice of a first-line agent for empiric treatment if there are no alternatives to antimicrobials, and (4) safe and effective usage of the selected agent. During the time of antimicrobial use, it is appropriate to constantly evaluate if the disease challenge is still present according to the definitions established in step 1 above. If not, stop the antimicrobial use and monitor according to these definitions and diagnostics. If the challenge is still present, constantly evaluate step 2.

Source: microbiolspec June 2018 vol. 6 no. 3 doi:10.1128/microbiolspec.ARBA-0018-2017
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Image of FIGURE 2

Mutant selection window and mutant prevention concentration (MPC). Optimal dosage regimens should maintain as long as possible the drug concentration at or above the MPC (blue area), which reflects the highest possible MIC of the resistant mutants (red bacteria). The minimum amount of time required to prevent selection of the resistant mutants can be estimated for each species by using a specific PK/PD index (T > MPC or AUC/MPC). The mutant selective window delimitates the range of antimicrobial concentrations selecting for the resistant mutants, which range from the MPC (upper horizontal red line) to the MIC (lower horizontal green line) of the initial (wild-type) bacterial population (green bacteria). Drug concentrations below the MIC inhibit neither the mutants nor the wild-type population. Abbreviations: T, drug concentration time; AUC, area under the concentration-time curve, C max, maximum drug concentration; C min, minimum drug concentration.

Source: microbiolspec June 2018 vol. 6 no. 3 doi:10.1128/microbiolspec.ARBA-0018-2017
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