Antimicrobials 2 Veterinary Pharmacology And Therapeutics PDF

Antimicrobials 2 Dr Martin Hawes Senior Lecturer Veterinary Pharmacology and Therapeutics 1  Learning Outcomes 1. Describe the pharmacological and therapeutic ch...

Antimicrobials 2 Dr Martin Hawes Senior Lecturer Veterinary Pharmacology and Therapeutics 1  Learning Outcomes 1. Describe the pharmacological and therapeutic characteristics of the main classes of antimicrobials used in veterinary medicine 2. Give common examples of veterinary antimicrobials from each class 3. Demonstrate a logical approach to empirical prescribing using common examples Tuesday, 24 September 2024 2  Pre-read – Key points Empirical prescribing is the practice of prescribing a medicine based on clinical judgement and the best available information in the absence of results from diagnostic tests. Tuesday, 24 September 2024 3  Pre-read – Key points 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. For patients with non-serious infections, consider taking microbiological samples before making a decision about prescribing 6. What is the narrowest spectrum of antibacterial likely to be effective? 7. Take into account the benefits and harms for an individual patient 8. Consider other factors (e.g. licence for use in the patient’s species, administration route, withdrawal times) 9. Present options to the client Tuesday, 24 September 2024 4  Responsible use - EMA Tuesday, 24 September 2024 5  Responsible use - EMA Tuesday, 24 September 2024 6  Responsible use - EMA Consider when there are no antibiotics in Category D that could be clinically effective Tuesday, 24 September 2024 7  Responsible use - EMA 3rd and 4th Generation Cephalosporins Polymyxins Quinolones Tuesday, 24 September 2024 8  Responsible use - EMA Tuesday, 24 September 2024 9  Clinically significant pathogenic bacteria include ….. Taken from Rang and Dale’s Pharmacology Tuesday, 24 September 2024 10  Mechanisms of actions of antibacterials Differences in the biology Eukaryote of bacteria (prokaryotes) and veterinary species (eukaryotes) can be exploited to inhibit or destroy bacteria Prokaryote Tuesday, 24 September 2024 11  Mechanisms of actions of antibacterials There are four main mechanisms of actions of antibacterials: 1. Inhibit bacterial cell wall synthesis 2. Damage bacterial cell wall integrity / function 3. Inhibit nucleic acid synthesis or function 4. Inhibit protein synthesis Inhibit cell wall synthesis Inhibit protein synthesis Damage cell wall Inhibit nucleic acid synthesis Tuesday, 24 September 2024 12  Gram positive and Gram negative bacteria Taken from Nature reviews microbiology: https://www.nature.com/articles/nrmicro3480 Tuesday, 24 September 2024 13  β-lactam antibiotics β-lactam antibiotics (penicillins, cephalosporins) inhibit bacterial growth by interfering with the transpeptidation of bacterial wall synthesis Bactericidal (cell wall lysis) Time-dependent Effective against Gram +ve and Gram -ve bacteria, but spectrum ranges from narrow to broad dependent on particular drug Generally very well tolerated. Associates with hypersensitivity reactions (parenteral > oral), anaphylaxis rare in veterinary species Bacterial resistance – bacterial β-lactamases breakdown the β-lactam ring (also other resistance mechanisms). Tuesday, 24 September 2024 14  β-lactam antibiotics Penicillins Tuesday, 24 September 2024 15  β-lactam antibiotics Cephalosporins Tuesday, 24 September 2024 16  β-lactam antibiotics Class D Natural penicillins e.g. procaine benzylpenicillin Aminopenicillins e.g. amoxicillin, ampicillin Anti-staphylococcal penicillins e.g. cloxacillin Class C Aminopenicillins in combination with β-lactamase inhibitors e.g. amoxicillin + clavulanic acid 1st or 2nd generation cephalosporins e.g. cefalexin, cefapirin Tuesday, 24 September 2024 17  Penicillin antibiotics - example Amoxicillin is licenced for treatment of primary infections of the urogenital tract, e.g. pyelonephritis and infections of the lower urinary tract, endometritis and vaginitis Urinary tract infections Class D Amoxicillin Tuesday, 24 September 2024 18  Protein synthesis Taken from: https://socratic.org/questions/580e5702b72cff43cca22ec6 Tuesday, 24 September 2024 19  Tetracycline antibiotics Tetracyclines inhibit protein synthesis in susceptible bacteria Bacteriostatic Time-dependent Broad spectrum of activity, effective against Gram +ve and Gram -ve bacteria and mycoplasma and protozoa. Generally well-tolerated. Associated with oesophageal erosion. Can interfere with gut flora (use in horses largely abandoned). Use with caution in young animals (binds to calcium). Widespread resistance, but still first-line treatment Class D Doxycycline, oxytetracycline, chlortetracycline Tuesday, 24 September 2024 20  Tetracycline antibiotics - example Doxycycline is licenced for treatment of rhinitis and bronchopneumonia in cats and dogs caused by Bordetella spp. and Pasteurella spp. Kennel cough Class D Doxycycline Tuesday, 24 September 2024 21  Responsible use - EMA Tuesday, 24 September 2024 22  Responsible use - EMA Tuesday, 24 September 2024 23  Sulfonamides, DRIs and combination antibiotics Sulfonamides and dihydrofolate reductase inhibitors interfere with the production of folic acid and thereby purine synthesis - usually combined (TMPS) Bactericidal Time-dependent Broad spectrum of activity, effective against Gram +ve and Gram -ve bacteria and antiprotozoal Serious side effects are uncommon with TMPS Wide variety of adverse events, including hypersensitivity, inappetence, gi disturbance Widespread resistance, still first-line treatment Class D Trimethoprim-sulfadiazine Tuesday, 24 September 2024 24  TMPS - example TMPS is relatively cheap and easy to administered to horses, used to treat infections of the upper respiratory tract, the urogenital system and wound infections Wound infections Class D Trimethoprim-sulfadiazine Tuesday, 24 September 2024 25  Nitroimidazoles Inhibit nucleic acid function by preventing DNA repair Bactericidal Concentration-dependent Active against Gram +ve and Gram –ve anaerobes and protozoa Antiinflammatory effect (see GI therapeutics lecture) N.B. not licenced for use in food producing animals (metabolites in ruminants shown to be carcinogenic in humans) Class D metronidazole Tuesday, 24 September 2024 26  Metronidazole - example Metronidazole is licenced to treat gastrointestinal tract infections caused by Giardia spp. and Clostridium spp. (i.e. C. perfringens or C. difficile) GI infections Class D Metronidazole Tuesday, 24 September 2024 27  Aminoglycosides Aminoglycosides inhibit protein synthesis Bactericidal Concentration-dependent Narrow spectrum - Gram -ve aerobic bacteria Poorly absorbed from gi tract Associated with nephrotoxicity and ototoxicity – plasma levels may require monitoring Some resistance Combined with penicillins to broaden spectrum but …. Class C gentamicin, streptomycin, amikacin Tuesday, 24 September 2024 28  Aminoglycosides - example Gentamicin is included in combination with other antimicrobials and a steroid in some ear drops – used to treat otitis externa Ear infections Class C Gentamicin (in combination with a steroid and an antifungal) Tuesday, 24 September 2024 29  Macrolides & lincosamides Macrolides and lincosamides inhibit protein synthesis Bacteriostatic (later generations bactericidal) Time-dependent Gram +ve bacteria and Mycoplasma, though later generations have activity against Gram -ve Generally well tolerated but can be painful on injection. Avoid in horses (irreversible diarrhoea) Resistance is common Class C Macrolides: erythromycin, tylosin, tilmicosin Lincosamides: clindamycin Tuesday, 24 September 2024 30  Macrolides and lincosamides - example Clindamycin is licenced for the treatment of infected wounds and abscesses and infected mouth cavity and dental infections in cats and dogs Cat bite Advanced abscess peridontitis Class C Clindamycin Tuesday, 24 September 2024 31  Amphenicols Amphenicols inhibit protein synthesis Bacteriostatic Time-dependent Broad spectrum – Gram +ve and Gram –ve and some mycoplasmas Large animal – may cause transient reduction in food intake. Small animal – use limited to topical treatment eye infections Class C florfenicol (mainly LA), chloramphenicol (topical) Tuesday, 24 September 2024 32  Amphenicols - example Florfenicaol is licenced for the treatment of respiratory tract infections in cattle caused by florfenicol susceptible Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. Respiratory tract infections Class C Florfenicol Tuesday, 24 September 2024 33  Fluoroquinolones Inhibit DNA synthesis Bactericidal Concentration-dependent Narrow spectrum – active for Gram –ve and good penetration for otherwise difficult to treat infections Few classes licenced for exotics – fluoroquinolones are, but N.B. Class B antibiotics – treatment of last resort. VMD consider it is justified to prescribe an antibiotic on the cascade in the interests of minimising development of resistance Class B Enrofloxacin, marbofloxacin, danofloxacin Tuesday, 24 September 2024 34  Fluoroquinolones - example Enrofloxacin is licenced for use in pet rabbits, rodents, birds and reptiles e.g. for the treatment of Pasteurella multocida in rabbits. Infections of respiratory and gastrointestinal tract infections Class B Enrofloxacin Tuesday, 24 September 2024 35  Responsible use of antimicrobials Tuesday, 24 September 2024 36  Key Points LO - Describe the pharmacological and therapeutic characteristics of the main classes of antimicrobials used in veterinary medicine – Give common examples from each class β-lactam antibiotics (penicillins and cephalosporins) – interfere with transpeptidation of bacterial wall synthesis - effective against Gram +ve and Gram -ve bacteria, but spectrum ranges from narrow to broad dependent on particular drug amoxicillin, ampicillin, procaine benzylpenicillin, cloxacillin amoxicillin + clavulanic acid, cefalexin, cefapirin Tetracyclines inhibit protein synthesis in susceptible bacteria - broad spectrum of activity, effective against Gram +ve and Gram -ve bacteria and mycoplasma and protozoa doxycycline, oxytetracycline, chlortetracycline Tuesday, 24 September 2024 37  Key Points LO - Describe the pharmacological and therapeutic characteristics of the main classes of antimicrobials used in veterinary medicine – Give common examples from each class Sulfonamides and dihydrofolate reductase inhibitors interfere with the production of folic acid and thereby purine synthesis - usually combined (TMPS) - Broad spectrum of activity, effective against Gram +ve and Gram -ve bacteria and protozoa trimethoprim-sulfadiazine Nitroimidazoles - inhibit nucleic acid function by preventing DNA repair - active against Gram +ve and Gram –ve anaerobes and protozoa metronidazole Tuesday, 24 September 2024 38  Key Points LO - Describe the pharmacological and therapeutic characteristics of the main classes of antimicrobials used in veterinary medicine – Give common examples from each class Aminoglycosides inhibit protein synthesis - narrow spectrum - Gram -ve aerobic bacteria gentamicin, streptomycin, amikacin Macrolides and lincosamides inhibit protein synthesis - Gram +ve bacteria and Mycoplasma, though later generations have activity against Gram –ve Macrolides: erythromycin, tylosin, tilmicosin Lincosamides: clindamycin Tuesday, 24 September 2024 39  Key Points LO - Describe the pharmacological and therapeutic characteristics of the main classes of antimicrobials used in veterinary medicine – Give common examples from each class Amphenicols inhibit protein synthesis - broad spectrum – Gram +ve and Gram –ve and some mycoplasmas florfenicol (mainly LA), chloramphenicol (topical) Fluoroquinolones - inhibit DNA synthesis - Narrow spectrum – active for Gram –ve and good penetration for otherwise difficult to treat infections enrofloxacin, marbofloxacin, danofloxacin Tuesday, 24 September 2024 40  Key Points LO - Demonstrate a logical approach to empirical prescribing using common examples BVA 7-point plan for responsible antibiotic use: 1. Work with clients to avoid the need for antimicrobials 2. Avoid inappropriate use 3. Choose the right drug for the right bug 4. Monitor antimicrobial sensitivity 5. Minimize use 6. Record and justify deviations from protocols 7. Report suspected treatment failure to the VMD Tuesday, 24 September 2024 41