Antimicrobials. Antimicrobials
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1 Antimicrobials For more than 50 years, antibiotics have come to the rescue by routinely producing rapid and long-lasting miracle cures. However, from the beginning antibiotics have selected for resistance in the bacterial populations that they attack resistance that can be easily transferred sometimes been overused or misused use of related classes or antibiotics as growth promoters in agriculture.. The consequence has been a gradual rise in antibiotic resistance.... antibiotic resistance is not a problem we can afford to ignore. Excerpts from CIHR (Canadian Institute of Health Research) Report on, Novel Alternatives to Antibiotics Workshop. March, Vancouver, Canada. Antimicrobials Antimicrobial Drugs (Antibiotics and Antibacterials) General information and Major Groups Mechanisms of action and resistance Applications, brand names, contraindications Alternatives Vaccines Bacteriophage Probiotics, Prebiotics (Synbiotics) 1
2 Antimicrobial Drugs Classification Bactericidal (Pen s) vs Bacteriostatic (Tet s) : dose determines Narrow Spectrum: Penicillin G, Bacitracin Broad Spectrum: Tetracyclines Grouping based: Chemical structure Mechanism of action Cell wall inhibitors (β lactams) Penicillins and Cephalosporins Damage to cell membrane function Polymyxins and antifungals Inhibition of nucleic acid synthesis or function Quinolones Inhibition of protein synthesis Chloramphenicol, Aminoglycosides, Macrolides Antimicrobial Drugs Principles of Therapy Aim: maintain effective concentration Choice: Diagnosis Susceptibility of bug (Constitutive vs. Acquired Resistance) Mutation (Quinolones, Rifampin; Streptomycin, Erythromycin, Streptomycin) Nature of infection (local, systemic etc.) Pharmacokinetics Host species (toxicity), age, pregnancy, etc. Dosage: 3-5 x MIC required at site Routes: P.O., Parenteral (I.V., I.M.,S.Q.), Topical/local- skin, eye, ear, intramammary 2
3 Antimicrobial Drugs: -lactams Inhibitors of cell wall synthesis β-lactams : Bactericidal β-lactam Penicillins and Cephalosporins Resistance due to: β-lactamases/penicillinases Outer envelope exclusion Gram Negatives PBP s (meca- PBP2a) Efflux pumps Antimicrobial Drugs: Penicillins Six Groups of Penicillins (Penicillium ssp.) Narrow Spectrum, β-lactamase susceptible: Penicillin G, Pen V: β-streps, Actinomyces spp., Corynebacteria, Erysipelothrix, Clostridium, Bacillus anthracis, Fusobacterium Narrow Spectrum, β-lactamase resistant : Antistaph Pen s Cloxacillin, Methicillin, Oxacillin (Staph in humans) Broad Spectrum, β-lactamase susceptible: d G ve activity Aminopenicillins Ampicillin, Amoxicillin not PSA Carboxypenicillins - Carbenicillin, Ticarcillin including PSA 3
4 Antimicrobial Drugs: Penicillins + Broad Spectrum, β-lactamase resistant (potentiated penicillins) Clavamox Amoxicillin + Clavulanic acid (dogs, cats p.o. only) Synergistin Ampicillin + Sulbactam cats, dogs, horses, ruminants parenteral Other -lactams (excluding the Cephalosporins) Clavulanic acid, Sulbactam, Tazobactam - lactamase inhibitors Carbapenems atypical β-lactams (Imipenem + Cilastatin) Broad spectrum + anaerobes, human medicine (nosocomial MDR s) Also licensed for dogs, cats, horses (S.Q., I.M., I.V.) PSA, E. coli, K. pneumoniae, Not MRSA or VRE Carbapenemases (from both G+ves and Enterobacteriaceae) Antimicrobial Drugs: Cephalosporins Semi-synthetic derivatives of 7 aminocephalosporanic acid Cephalosporium acremonium Dihydrothiazine ring Three Generations in Vet Med. d activity against G-ves Resistance as per Penicillin: G-ve envelope, -lactamases β-lactam ring Cephalosporinases broad spectrum described in E. coli, Salmonella not affected by Clavulanic or Sulbactam MRSA s resistant to Cephalosporins 4
5 Antimicrobial Drugs: Cephalosporins UTI, SSTI (Skin and Soft Tissue Infections), mastitis, pneumonia First generation Cephalosporins G+ves and G-ves : similar to Ampicillin (Not PSA) Includes: β-lactam resistant Staph, Streps, Corynebacteria, Clostridia, Haemophilus, Pasteurella, +/- Enterobacteria (E. coli, Kleb., Proteus, Salmonella) Cephalothin (Keflin) : parenteral dogs/cats, horses (Cefazolin) Cephalexin (Keflex) : p.o. dogs/cats, foals Cephapirin parenteral: dogs/cats, horses mastitis cattle (intramammary) Antimicrobial Drugs : Cephalosporins Third Generation Cephalosporins (orals and parenterals) d G+ve, best G-ve activity (Enterobacteria, anaerobes, +/- PSA) Ceftriaxone chronic Borreliosis (meningitis, arthritis) Cefovecin (ConveniaJ Pfizer) long acting cephalosporin (S.Q.) SSTI s (Staph., Strep., Pasteurella, Bacteroides) UTI s (including E. coli and Proteus) infections in Cats/Dogs not active against Bordetella, PSA, Enterococci, or MRSA Ceftazidime, Cefoperazone: dogs/cats, horses (good PSA activity) Ceftiofur (Excenel) BRDC, dogs (UTI s), swine (PRDC), horses with Strep infections (i.m., S.Q) Spectramast (Pfizer) i.m.m. (jntramammary ); Staph., Strep., E. coli 5
6 Antimicrobial Drugs : Cephalosporins Second Generation Cephalosporins (parenteral) d activity G-ves (Enterobacteria including Enterobacter), anaerobes (Not PSA ) Cefoxitin (parenteral) dogs/cats, horses and calves Fourth Generation Cephalosporins Cefquinome BRDC, coliform mastitis 6
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