Principles of antimicrobial therapy

PRINCIPLES OF ANTIMICROBIAL THERAPY

Penicillins

  • β-Lactams. G+, easy G-, anaerobes. Bactericidal. Inhibit cell wall synthesis. Safe. Elimated via kidney, good for UTIs.
  • Natural penicillins – G+, poor G-, spirochetes, destroyed by penicillinase. PenG and PenV. Penicillinase-resistant penicillins – Penicillinase producing G+ cocci, esp. Staphylococcus.

Drugs

  • Cloxacillin, dicloxacillin. Aminopenicillins – Broad spectrum, ↑ G- activity. Ampicillin, amoxicillin. Extended spectrum penicillins – addl G- activity, Pseudomonas.
  • Carbenicillin, ticarcillin, piperacillin. Potentiated penicillins - Developed to inactivate β-lactamases.
  • Clavomox, timentin. Don’t use penicillins in rodents and lagomorphs; elimination of G+ gut flora can lead to fatal colibacillosis.

Cephalosporins

  • β-Lactams. G+, some G- (more with each generation), anaerobes. Bactericidal. β-lactam antibiotics. Inhibit cell wall synthesis.
  • More effective against actively growing bacteria. Classifications – 1st generation cepholosporins include cephalothin, cefazolin, cephapirin, cephadine, cephalexin, cefadroxil. Activity against most G+, poor G- activity. 2nd generation cepholosporins - not very popular, same G+ activity, expanded G-. 3rd generation cepholosporins – same G+ activity, much expanded G- activity; cefotaxime, moxolactom, cefoperazone, ceftiofur (BRD, no withdrawal time).

Aminoglycosides

  • 1° G- aerobes. Some G+. Pseudomonas, staphylococcus, atypical mycobacterium (nocardia/actinomyces).
  • Irreversibly bind to 30S ribosomal unit and inhibits protein synthesis. Bactericidal.
  • Includes amikacin (SID, parvo pups), gentamicin, neomycin, and spectinomycin.
  • Inactive against fungi, viruses and most anaerobic bacteria. Accumulate in inner ear and kidneys.
  • Elimination via glomerular filtration. Adverse Effects – Nephrotoxic.
  • Casts in urine, increased BUN and Cr. Nephrotoxicity reversible when drug discontinued. Ototoxic. 8th cranial nerve toxicity.
  • Auditory and vestibular symptoms may be irreversible.

Fluoroquinolones

  • Good G- aerobes, facultative anaerobes, atypical mycobacterium, chlamydia, mycoplasma, ehrilichia, BRD.
  • Bactericidal. DNA gyrase inhibitor, prevent DNA synthesis. Enrofloxacin (SID, prostate, RMSF, deethylated to cipro), ciprofloxacin. Variable activity against Streptococci – not recommended. Contraindicated in young animals due to cartilage defects. Baytril associated with blindness in cats.

Sulfonamides

  • G+, easy G-, anaerobes; nocardia and actinomyces. Bacteriostatic.
  • Inhibit folic acid pathway (PABA/pteridine not converted to DHFA). Broad spectrum.
  • Many bacteria have developed resistance. Potentiated sulfonamides – TMPS.
  • Bactericidal, inhibits bacterial thymidine synthesis in folic acid pathway.
  • Excellent tissue distribution. Most drug side effects of all Abs, allergic reactions, hepatotoxic, KCS, hypothroidism, crystalluria, thyrotoxic, anemia, BM toxicity (aplastic anemia, thrombocytopenia hypoprothrombinemia).

Tetracyclines

  • G+, easy G-, Mycoplasma, spirochetes, chlamydia, Rickettsia, Hemobartonella, Brucellosis. Bacteriostatic.
  • Inhibits protein synthesis by binding to the 30S ribosomal unit. Safe.
  • Prostate. Includes doxycycline (biliary excretion), oxytetracycline, tetracycline. Resistance ↑.
  • May cause esophagitis. Chloramphenicol – G+, G-. Bacteriostatic.
  • Binds to the 50S ribosomal subunit preventing protein synthesis.
  • Penetrates everything. Can cause aplastic anemia in humans.

Lincosomides

  • G+ aerobes, anaerobes. No G-. Often combo w/ aminoglycosides. Lincomycin, clindamycin.
  • Bacteriostatic or bactericidal. Bind to the 50S ribosomal subunit.
  • Distribute well, biliary elimination. Contraindicated in rabbits, rodents, horses, ruminants due to serious GI effects.

Macrolides

  • G+, selected G-. Bacteriostatic. Bind 50S ribosomal subunit. [ ] in alveolar macrophages, great for pulmonary infections.
  • Erythromycin, tylosin, tilmicosin. Erythromycin is used in the treatment of Rhodococcus equi in combo w/ rifampin.
  • Can cause increase in GI motility. Tilmicosin – used in BRD; CV toxicity in primates, horses, swine.

Metronidazole

  • Bactericidal and antiprotozoal. Obligate anaerobes.
  • Disrupts DNA and nucleic acid synthesis. Immunolmodulator in IBD.

Rifampin

  • Bactericidal or bacteriostatic. Inhibits DNA-dependent RNA polymerase.
  • Used for treatment of Rhodococcus equi in combo w/ erythromycin.

Antifungal Agents

Amphotericin B

  • Polyene macrolide. Binds to fungal sterols, altering permeability of membrane.
  • Fungistatic. Dimorphic fungi (histo, blasto, crypto, coccidio).
  • Because of the risk of severe toxicity reserved for disseminated, progressive, potentially fatal fungal infections. Nephrotoxic, anaphylactoid.

Imidazoles

  • Fungistatic. Inhibit ergosterol/steroid synthesis (blocks cytochrome p450), ↑ cell membrane permeability, ↓ cell membrane fluidity.
  • Use for dermatophytes, yeast, dimorphic fungi. Impairs steroid sythesis, so sometimes used in hyperadrenocorticism and prostate diz.
  • Ketaconazole – Fairly safe (hepatotoxicity), give w/ food. Short t½. Not got w/ dimorphic fungi, esp. blasto.
  • Itraconazole – more effective spectrum. Fluconazole – Crosses BBB.

Flucytosine

  • Ancoban. Inhibits DNA synthesis (antimetabolite, competes with uracil, interfering with pyrimidine metabolism and protein synthesis).
  • Limited spectrum - Cryptococcus, Candida. Rapid absorption, excellent distribution. Synergistic effect with amphotericin B.
  • Adverse effects include BM depression (pancytopenia), GI disturbances, rashes, oral ulceration, increased liver enzymes.

Griseofulvin

  • Inhibits fungal mitosis by disrupting mitotic spindle, inhibit nucleic acid and fungal wall sythesis.
  • Limited to dermatophytes only. Give w/ fatty food to ↑ absorption. [ ] in keratin. Side effects include GI, teratogenic and carcinogenic at ↑ doses, bone marrow dyscrasias.
  • Do not give to pregnant animals.

Antiseptic Agents

  • Agents applied to the body vs. disinfectants which are used on inanimate objects.

Alcohol

  • Protein denaturation. 70% is effective against G+ and G- bacteria.
  • Good bactericidal, fungicidal, virucidal. Most rapid acting but least residual action.
  • Fast kill, defatting agent. Evaporates quickly. 2 min for max effect. May be drying or irritating.
  • May cause cytotoxicity. Often used in combo w/ povidone iodine.

Chlorhexidine

  • Cytoplasmic membrane disruption. 0.05% soln effective against Gram+ and Gram-.
  • Persists on skin to give cumulative antibacterial effect. Less irritating.
  • Not inactivated by organic matter. 0.05% is 1:40 dilution, most bactericidal and least toxic to tissues.

Hydrogen peroxide

  • Poor antiseptic. Short-acting germicidal effect through release of nascent O2, irreversibly alters proteins.
  • Effective sporicide. Effervescent action mechanically removes pus and bacteria.

Iodine

  • One of most potent antiseptics. Bactericidal, virucidal, fungicidal. Takes 15 min for sporicidal action.
  • Organic matter inactivates free I in PI. Iodine Soln USP has little to no stinging on broken skin.
  • Iodine tincture USP (I in alcohol) is even more effective, but stings and irritates skin.
  • Rare HPS rxns. Povidone iodine often used in conjunction w/ alcohol. Use PI in 0.1 to 1% [ ]; more dilure solns have ↑ free I and faster, potent bactericidal activity.
  • Dilute stock solution 1:100 or 1:10. Don’t use I scrub on open wounds –damage tissue and ↑ infection.

Iodophors

  • Betadine. Aqueous complex of iodine, less bactericidal but also less irritating. Gram-, gram+.
  • Do not require repeated application for optimal antimicrobial effect.
  • Contact time 10 min for max effect.

Hexachlorophene

  • Gram+ bacteria. Only effective after days of use once film deposition on skin, long contact time.
  • CNS toxin if absorbed, esp in young. Not used much anymore.

Quaternary ammonium compounds

  • Changes in cell membrane permeability. G+.
  • Inactivated by organic debris and soaps. Not recommended.
Last modified: Monday, 28 May 2012, 6:30 AM