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Chapter 30 : Optimization of Antimicrobial Treatment to Minimize Resistance Selection

Authors: Luca Guardabassi1, Mike Apley2, John Elmerdahl Olsen3, Pierre-Louis Toutain4, Scott Weese5
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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
Content Type: Monograph
Publication Year: 2018

Category: Clinical Microbiology; Environmental Microbiology

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Abstract:

Optimization of antimicrobial use is a cornerstone in the fight against antimicrobial resistance (AMR) and one of the five objectives of the WHO global action plan on AMR ( ). The growing evidence that antimicrobial use in animals may contribute to some multidrug-resistant (MDR) bacterial infections in humans has increased consumer demand and governmental pressure to optimize antimicrobial use in the veterinary sector ( ). Promoting appropriate use of antimicrobials in veterinary medicine and strengthening of the regulatory framework on veterinary medicines and medicated feed are key actions in the European Union One Health action plan against AMR ( ). Following a request from the EU Commission, the European Food Safety Authority and the European Medicines Agency (EMA) published a joint scientific opinion on how to reduce the need for antimicrobial use in food-producing animals ( ). In 2015, the EU Commission provided the member states with a set of guidelines for prudent antimicrobial use in veterinary medicine ( ), which covers the main animal production types (pigs, cattle, poultry, aquaculture, and rabbits) as well as other species (pets, fur animals, and other non-food-producing species). In the same year, the USA government released a national action plan for combating antimicrobial-resistant bacteria, which includes a plan to eliminate the use of medically important antimicrobials for growth promotion and to foster antimicrobial stewardship in animals ( ).

Citation: Guardabassi L, Apley M, Olsen J, Toutain P, Weese S. 2018. Optimization of Antimicrobial Treatment to Minimize Resistance Selection, p 637-673. In Schwarz S, Cavaco L, Shen J (ed), Antimicrobial Resistance in Bacteria from Livestock and Companion Animals. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.ARBA-0018-2017
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Optimization of Antimicrobial Treatment to Minimize Resistance Selection
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Citation: Guardabassi L, Apley M, Olsen J, Toutain P, Weese S. 2018. Optimization of Antimicrobial Treatment to Minimize Resistance Selection, p 637-673. In Schwarz S, Cavaco L, Shen J (ed), Antimicrobial Resistance in Bacteria from Livestock and Companion Animals. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.ARBA-0018-2017
/content/10.1128/9781555819804.chap30.fig30-1
Figure 1
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.
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10.1128/9781555819804/fig30-1.gif
Image of Figure 1
Figure 1

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.

Citation: Guardabassi L, Apley M, Olsen J, Toutain P, Weese S. 2018. Optimization of Antimicrobial Treatment to Minimize Resistance Selection, p 637-673. In Schwarz S, Cavaco L, Shen J (ed), Antimicrobial Resistance in Bacteria from Livestock and Companion Animals. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.ARBA-0018-2017
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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.
10.1128/9781555819804/fig30-2_thmb.gif
10.1128/9781555819804/fig30-2.gif
Image of Figure 2
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.

Citation: Guardabassi L, Apley M, Olsen J, Toutain P, Weese S. 2018. Optimization of Antimicrobial Treatment to Minimize Resistance Selection, p 637-673. In Schwarz S, Cavaco L, Shen J (ed), Antimicrobial Resistance in Bacteria from Livestock and Companion Animals. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.ARBA-0018-2017
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