Pharmacology

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No-no drugs for FA

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-Chloramphenicol
-Clenbuterol
-Diethylstilbestrol
-Dimetridazole
-Ipronidazole
-Other nitroimidazoles
-Furazolidone (except for approved topical use)
-Nitrofurazone (except for approved topical use)
-Sulfanamide drugs in lactating cattle
-Fluoroquinolones
-Glycopeptides

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Anaerobes

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Clostridium
Peptostreptococcus
Bacterioides
Fusobacterium

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Gram (+)

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Streptococcus
Staphylococcus
Enterococcus

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Wimpy Gram (-)

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Bordetella
Pasteurella
Salmonella

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Enteric Gram (-)

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E coli
Klebsiella
Proteus
Enterobacter
Salmonella

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Pseudomonas

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Enteric Gram (-)

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Mechanisms of microbial resistance

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-Intrinsic (anaerobes -> aminoglycosides due to no entry)
-Acquired
-Vertical transfer
-Horizontal transfer (transformation, transduction, CONJUGATION)

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Failure to reach target

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B-lactams
Chloramphenicol
Fluoroquinolones
Macrolides
Tetracyclines

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Inactivation of drug

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Aminoglycosides
B-lactams
Chloramphenicol
Macrolides

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Altered target

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Macrolides
Fluoroquinolones
Sulfonamides
Tetracyclines
Trimethoprim

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Cell wall synthesis inhibitors

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-Beta lactams (penicillins, cephalosporins)
-Glycopeptides (vancomycin)

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Spectrum of natural penicillins (penicillin G, V)

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Anaerobes, some gram + aerobes (streptococcus, NOT staph.), some gram - aerobes (pasteurella).

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Spectrum of aminopenicillins (ampicillin, amoxicillin)

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Less active vs anaerobes, some gram +, better vs gram - (E coli, pasteurella, klebsiella, proteus); NOT pseudomonas.

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Spectrum of anti-staph penicillins (cloxacillin, methicillin)

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Staph (lactamase resistant)

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Spectrum of anti-pseudomonal penicillins (ticarcillin, piperacillin, carbenicillin)

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Gram -, specifically pseudomonas (resistant -); some + but can be inactivated

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Spectrum of beta lactamase inhibitor combinations (amoxicillin clavulanate)

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Used as combination to destroy clavulanate and beta lactamase (suicide substrate)

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Spectrum of 1. cephalosporin (cephalexin, cefazolin)

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+++ gram + (except enterococcus), + gram -, fair anaerobic activity

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Spectrum of 2. cephalosporin (cefoxitin)

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weak/fair anaerobic activity, ++ gram +/-

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Spectrum of 3. cephalosporin (ceftiofur, Simplicef/cefpodoxime)

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variable anaerobic, +++ gram - (pseudomonas)

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Spectrum of other beta lactams (imipenem)

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broad spectrum, reserved for very resistant (rarely used)

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Spectrum of glycopeptides (vancomycin)

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gram +; reserved for resistant Staph/Enterococcus (never used)

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Toxicity of beta lactams

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Very safe; rarely hypersensitivity, renal failure, GI. Procaine penicillin G rxn in horses.

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Pharmacokinetic considerations for beta lactams

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Time-dependent (cephalosporins > penicillins); keep above MIC with increased dosing intervals

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Protein synthesis inhibitors

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-Tetracyclines
-Aminoglycosides
-Amphenicols
-Macrolides
-Lincosamides

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Mechanism of resistance: penicillin and cephalosporin

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Inactivation (by beta lactamases); altered target

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Mechanism of resistance: vancomycin

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Alteration of target

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Mechanism of resistance: tetracyclines

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Failure to reach site (also inactivation, altered target)

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Mechanism of resistance: aminoglycosides

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Inactivation

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Mechanism of resistance: ampenicols

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Inactivation

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Mechanism of resistance: macrolides

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Inactivation

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Mechanism of resistance: lincosamides

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Inactivation

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Spectrum: tetracyclines (tetracycline, doxycycline)

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Broad spectrum, resistance is common - best for mycoplasma, Rickettsia, anaplasma

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Spectrum: aminoglycosides (gentamicin, amikacin)

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Gram +, Gram -, NOT anaerobes

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Spectrum: ampenicols (chloramphenicol)

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Broad spectrum; anaerobes?; bordetella, strep, pasteurella; other resistance is common

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Spectrum: macrolides (erythromycin)

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Gram +, wimpy gram - (clarithromycin greater vs gram -, anaerobes)

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Spectrum: lincosamides (clindamycin)

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+++ Gram +, anaerobes (except clostridium)

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Toxicity: tetracyclines

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GI, discoloration of teeth, renal/hepatic/allergic, esophageal stricture in cats; doxycycline fatal if IV in horses

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Toxicity: aminoglycosides

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*nephrotoxicity, *ototoxicity, *neuromuscular blockade (not in service animals!)

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Toxicity: amphenicols

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rare fatal aplastic anemia, bone marrow suppression, CYP 450 inhibition, GI in horses

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Toxicity: macrolides

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GI, colitis in adult horses, CV in cattle/pigs

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Toxicity: lincosamides

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Horses: clostridial overgrowth

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Clinical use: tetracyclines

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LA: oxytetracycline (respiratory, mastitis, anaplasmosis); SA: doxycycline (intracellular pathogens, respiratory; not for UTI, as other tetracyclines)

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Clinical use: aminoglycosides

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Foals (sepsis), intrauterine, bone/joint infections in horses; neomycin topically