Antimicrobials Lecture 1 Slides PDF

Antimicrobials 1 Dr Martin Hawes Senior Lecturer Veterinary Pharmacology and Therapeutics 1  Learning Outcomes 1. Explain the terms antimicrobial and antibiotic 2....

Antimicrobials 1 Dr Martin Hawes Senior Lecturer Veterinary Pharmacology and Therapeutics 1  Learning Outcomes 1. Explain the terms antimicrobial and antibiotic 2. Define the concepts of minimum inhibitory concentration (MIC) and spectrum of activity with respect to antimicrobials 3. Explain the difference between time-dependant and concentration-dependant modes of action 4. Explain the concept of empirical prescribing within the context of veterinary medicine 5. Explain the concepts of antimicrobial resistance and responsible antimicrobial use with regard to human health, zoonoses and cross-species AMR-gene transfer Tuesday, 24 September 2024 2  Learning Objectives 1 - 2 Explain the terms antimicrobial and antibiotic Define the concepts of minimum inhibitory concentration (MIC) and spectrum of activity with respect to antimicrobials 3  Pre-read – Key points Antimicrobial - A substance that destroys or inhibits micro- organisms (e.g. bacteria, viruses, protozoa) Antibacterial - A substance that destroys or inhibits bacteria Antibiotic - A substance produced by one organism that selectively destroys/inhibits the growth of another Tuesday, 24 September 2024 4  Pre-read – Key points Minimum inhibitory concentration (MIC) The lowest concentration of an antimicrobial that will inhibit the visible growth of a micro- organism after overnight incubation in vitro Clinical breakpoints Clinical breakpoints take account of clinical data to overcome some of the limitations of in vitro MIC data: Species; condition (e.g. systemic vs local); route of administration; dosing regimen; antimicrobial MoA Tuesday, 24 September 2024 5  Pre-read – Key points Spectrum of activity Antimicrobial drugs are typically described as broad or narrow spectrum. Whilst this can mean the type of susceptible organism (e.g. bacteria, protozoa, virus), this more commonly refers to spectrum versus Gram +ve and/or Gram –ve bacteria.… and sometimes aerobic vs anaerobic bacteria Gram +ve: bacteria surrounded by thick peptidoglycan cell wall but no outer membrane Gram –ve: bacteria surrounded by thin peptidoglycan cell wall and outer membrane containing lipopolysaccharide Tuesday, 24 September 2024 6  Additional properties of antimicrobials Bactericidal vs bacteriostatic antimicrobials Bactericidal antibacterials – kill bacteria Bacteriostatic antibacterials – stop bacteria dividing Tuesday, 24 September 2024 7  Additional properties of antimicrobials Bactericidal vs bacteriostatic antimicrobials Tuesday, 24 September 2024 8  Learning Objective 3 Explain the difference between time-dependant and concentration- dependant modes of action 9  Properties of antimicrobials Time-dependent antimicrobials Efficacy is dependent on the time the antimicrobial is above the MIC. Increasing the dose will not enhance the effect. Time-dependent at MIC Time-dependent at 5 x MIC Tuesday, 24 September 2024 10  Properties of antimicrobials Concentration-dependent antimicrobials Efficacy is dependent on the drug concentration above the MIC. Increasing the dose reduces the bacterial count more rapidly. Concentration-dependent at MIC Concentration-dependent at 5 x MIC Tuesday, 24 September 2024 11  Properties of antimicrobials Time-dependent vs concentration-dependent antimicrobials Time –dependent: Dose at MIC and maintain for a prolonged period (typically 5-7 days) Concentration-dependent: Dose to achieve highest tolerable dose for a short period (potentially one or two doses) Tuesday, 24 September 2024 12  Properties of antimicrobials Time-dependent vs concentration-dependent antimicrobials Tuesday, 24 September 2024 13  Learning Objectives 4 and 5 Explain the concept of empirical prescribing within the context of veterinary medicine Explain the concepts of antimicrobial resistance and responsible antimicrobial use with regard to human health, zoonoses and cross-species AMR-gene transfer 14  Antimicrobial resistance Tuesday, 24 September 2024 15  Prescribing antibacterials – what’s the big deal? Antibiotic resistance is one of the biggest threats to global health, food security, and development today’ World Health Organization Critically Important Antimicrobials: The antimicrobial class is the sole, or one of limited available therapies, to treat serious bacterial infections in people. The antimicrobial class is used to treat infections in people caused by either: (1) bacteria that may be transmitted to humans from non-human sources, or (2) bacteria that may acquire resistance genes from non-human sources. Tuesday, 24 September 2024 16  Prescribing antibacterials – what’s the big deal? Tuesday, 24 September 2024 17  Empirical prescribing Empirical prescribing means treating on the basis of the most likely cause of a disease, in the absence of definitive tests Tuesday, 24 September 2024 18  Empirical prescribing 1. Does the patient need an antimicrobial? 2. Will prescribing an antimicrobial drug improve the prognosis? 3. What are the likely causative organisms? 4. Is there a risk of antimicrobial resistance (AMR) 5. Consider taking microbiological samples before prescribing (non-serious) 6. What is the narrowest spectrum of antibacterial likely to be effective? 7. Benefits and harms for an individual patient? 8. Consider other factors 9. Present options to the client Tuesday, 24 September 2024 19  Responsible use of antimicrobials Tuesday, 24 September 2024 20  Responsible use of antimicrobials Step 2 – Avoid inappropriate use Are bacteria present? Will an antibacterial improve prognosis? Tuesday, 24 September 2024 21  Responsible use of antimicrobials Step 3 – Choose the right drug for the right bug Identify the likely causative organisms Are they Gram +ve /Gram –ve; aerobic or anaerobic; is it likely a mixed infection? Tuesday, 24 September 2024 22  Responsible use of antimicrobials Step 4 – Monitor antimicrobial sensitivity Likely to start empirically, but take a sample if possible, send for culture and check sensitivity Monitor trends in sensitivity locally Tuesday, 24 September 2024 23  Responsible use of antimicrobials Step 5 – Only use when necessary Is there evidence it will reduce morbidity or mortality? Develop practice protocols Tuesday, 24 September 2024 24  Responsible use of antimicrobials Step 6 – Record and justify protocol deviations Keep good clinical records that explain and justify chosen course of action Tuesday, 24 September 2024 25  Responsible use of antimicrobials Step 7 – Report suspected treatment failures May be an early sign of development of antimicrobial resistance Tuesday, 24 September 2024 26  Responsible use of antimicrobials Step 1 – Work to avoid need for antimicrobials Work with clients to convey benefits of regular health checks / herd health plans Tuesday, 24 September 2024 27  Key Points LO - Explain the terms antimicrobial and antibiotic Antimicrobial agents are substances that destroy or inhibit microorganisms (e.g. bacteria, viruses, protozoa). Antibiotics are substances produced by one organism that selectively destroy or inhibit the growth of another. Antibacterial agents are substances that destroy or inhibit bacteria. Tuesday, 24 September 2024 28  Key Points LO - Define the concepts of minimum inhibitory concentration (MIC) and spectrum of activity with respect to antimicrobials The minimum inhibitory concentration (MIC) for an antimicrobial is the lowest concentration that will inhibit the visible growth of a microorganism after overnight incubation. MICs can help inform dosing, however the dose required clinically will dependent on the antimicrobial MoA, species, condition, route of administration, dosing regimen Antimicrobial drugs are typically described as broad or narrow spectrum. Whilst this can mean the type of susceptible organism (e.g. bacteria, protozoa, virus), this more commonly refers to spectrum versus Gram +ve and/or Gram –ve bacteria Antimicrobials can be described as bactericidal (i.e. they kill bacteria) or bacteriostatic (i.e. they prevent bacterial growth) Tuesday, 24 September 2024 29  Key Points LO - Explain the difference between time-dependant and concentration-dependant modes of action The efficacy a time-dependent antimicrobial is dependent on the exposure time above the MIC. A 5-7 day course is typically required. Increasing the dose to achieve concentrations well above the MIC will not enhance the effect. In contrast, bacterial cure can be achieved more rapidly with a concentration-dependent antimicrobial if the drug concentrations well above the MIC are achieved. Tuesday, 24 September 2024 30  Key Points LO - Explain the concept of empirical prescribing within the context of veterinary medicine Empirical prescribing means treating on the basis of the most likely cause of the disease in the absence of definitive tests. In the case of antimicrobials, it means choosing an antibacterial drug on the basis of the most likely causative bacterial species Tuesday, 24 September 2024 31  Key Points LO - Explain the concepts of antimicrobial resistance and responsible antimicrobial use with regard to human health, zoonoses and cross-species AMR-gene transfer Development of antimicrobial resistance (AMR) is one of the greatest threats to medicine. Vets must prescribe antimicrobial drugs responsibly Critically Important Antimicrobials (identified by the WHO) should be avoided as far as possible A stepwise approach helps responsible antimicrobial use – avoid the use of antibiotics where possible, choose the right antimicrobial for the infectious agent, develop local protocols and monitor local sensitivity, justify deviations from protocols, report suspected treatment failures Tuesday, 24 September 2024 32