ISSN 2398-2950      

Therapeutics: antimicrobial drug

ffelis

Synonym(s): Antibiotic


Antimicrobial agents which inhibit bacterial wall synthesis

The beta-lactam family of antibiotics

1.Penicillins
Spectrum of activity

  • Narrow spectrum: natural penicillins (penicillin G Benzylpenicillin, penicillin V   Phenoxymethylpenicillin) and penethamate (diathylaminoethylester of benzylpenicillin, prodrug):
    • Gram-positive bacteria, anaerobes, fastidious Gram-negative bacteria (eg Haemophilus spp, Pasteurella spp  Pasteurella multocida). NOT Enterobacteriaceae.
    • Beta-lactamase susceptible.
  • Anti-staphylococcal: isdazoyl penicillins (cloxacillin, methicillin, oxacillin):
    • Gram-positive bacteria only; less active than penicillin G.
    • Stable to beta-lactamases.
  • Broad spectrum: aminopenicillins (ampicillin  Ampicillin  ('Amfipen'), amoxycillin   Amoxicillin   ('Clamoxyl'), hetacillin, pivampicillin):
    • Gram-positive bacteria (less active than penicillin G), Gram-negative bacteria including E. coli  Escherichia coli  , P. mirabilis  Proteus spp  , Salmonella spp   Salmonella spp  . NOT Klebsiella spp   Klebsiella pneumoniae  and Pseudomonas aeruginosa  Pseudomonas aeruginosa  . Ampicillin is an alternative to penicillin G for streptococcal and clostridial infections, periodontal disease, tooth abscesses, wound infections (eg cat bite abscesses) and pyometra, and has better systemic availability after oral administration than penicillin G.
    • Beta-lactamase susceptible.
  • Extended spectrum: carboxypenicillins (carbenicillin, carfecillin, ticarcillin Ticarcillin, ticarcillin plus clavulanic acid), ureidopenicillins (azlocillin, piperacillin, mezlocillin):
    • Broader spectrum than aminopenicillins for Enterobacteriaceae.
    • Active against P. aeruginosaKlebsiella spp are resistant.
    • Beta-lactamase susceptible     →   developing Gram-positive and negative resistance.
  • Gram-negative: amidinopenicillin:
    • Gram-negative only (binds to penicillin-binding protein PBP2).
    • Unstable to beta-lactamases
    • Also produced as metabolite of pivmecillinam.
    • Rarely used for dogs and cats.

Pharmacokinetics

  • Inorganic acids (pKa 2.7).
  • Unstable in gastric acid - EXCEPT: penicillin V, isoxazoyl penicillins (not methicillin (meticilline)), aminopenicillins, carfecillin.
  • Confined to extracellular fluids and some transcellular fluids (joint, pleural, bile).
  • Cross membranes poorly.
  • Renal elimination; short half-life in cats as in all species (0.5-1.2 hours).
  • Formulations to slow absorption and prolong duration of action   →   reduced peak blood levels obtained.
  • Amoxycillin better absorbed than ampicillin.
  • Hetacillin and pivamicillin broken down in body   →   ampicillin.
  • Carfecillin broken down by gastrointestinal mucosa   →   carbenicillin.

Toxicity

  • Generally very safe.
  • Can see acute anaphylaxis or mild hypersensitivity.
    If contain procaine, do NOT give IV.

2.Cephalosporins
Spectrum of activity

  • Stable to staphylococcal beta-lactamase.
  • Variable instability to Gram-negative beta-lactamases.
  • In general, as activity against Gram-negative spectrum widens, activity against Gram-positive spectrum reduces.
  • Oral cephalosporins: eg cephalexin   Cefalexin    ('Rilexine', 'Ceporex'), cefadroxil   Cefadroxil   ('Cefa-cure'), cephadrine, cefachlor:
    • Gram-positive and many Gram-negative bacteria.
    • NOT indole positive Proteus spp   Proteus spp  and Pseudomonas spp   Pseudomonas spp  . Thus useful in cats for skin and urinary tract infections as well as abscesses and wound infections caused by susceptible organisms.
  • Parenteral cephalosporins: variable activity against Gram-negative bacteria, high activity against Gram-positive bacteria:
    • Group I: eg cefacetrile , cephalonium , cephaloridine, cephalothin, cephazolin   Cefazolin  . Pseudomonas spp   Pseudomonas spp  resistant. Fewer clinical applications now that beta-lactamase-stable cephalosporins available. However, useful in treating penicillinase-resistant S. aureus  Staphylococcus aureus  or gram-positive infections in patients allergic to penicillin. May be useful to produce high tissue levels rapidly before use of an oral cephalosporin. Specific applications as for oral cephalosporins.
    • Group II: eg ceftiofur ('Excenel', 'Naxcel'), cefuroxime   Cefotaxime  , cefamandole, cefotetan, cefovecin ('Convenia')   Cefovecin  . High activity against Enterobacteriaceae.
    • Group III: eg cefoperazone, cefsulodin, ceftazidime, cefquinime ('Cobactan', 'Cephaguard'). High activity against Pseudomonas spp.
    • Group IV (cephamycins): eg cefoxitin   Cefoxitin  , moxolactam, cefmetazole.None licenced for veterinary use. Good for Bacteroides spp   Bacteroides fragilis  ; NOT Pseudomonas spp   Pseudomonas spp except for moxolactam.

Pharmacokinetics

  • Similar to penicillins except cefovecin (effective for up to 14 days, depending on the pathogen).

Toxicity

  • Generally very safe.
  • Can have acute anaphylaxis or mild hypersensitivity.
  • Painful on IM injection.
  • Nephrotoxicity at high doses, especially cephaloridine.
  • Some cause bleeding problems due to interference with vitamin K in gut, especially moxalactam.

Beta-lactamase inhibitors
1. Clavulanic acid

  • With amoxycillin to give 'Synulox' or 'Clavamox'.
  • Inhibits all beta-lactamases except cephalosporinases.
  • Little antibacterial activity alone, but broadens spectrum of other penicillins.
  • Pharmacokinetics - match penicillin family.

2. Sulbactam

  • Synthetic enzyme inhibitor.
  • Broader spectrum than clavulanic acid. Less potent.

3. Carbapenems

  • Human medicine, eg imipenem.
  • Not approved for veterinary use.

Spectrum of activity

  • Almost all clinically important aerobes and anaerobes (Gram-positive and Gram-negative).
  • Some resistance starting to develop.

Pharmacokinetics

  • Injectable only.
  • Wider distribution in body than penicillins.
  • Renal elimination - hydrolyzed by tubular brush border enzyme.
  • Given with inhibitor of renal enzyme (cilastatin)   →   high urine concentrations of active drug.

Other cell wall antibacterials

1. Glycopeptides

  • Vancomycin, teicoplanin.
  • Bactericidal.
  • Human medicine.
  • Not approved for veterinary use. Use, if at all, should be restricted to life-threatening infections where no other agent is available.

Spectrum of activity

  • Gram-positive bacteria only.
  • Excellent against staphylococci.
  • Resistance rare.

Pharmakokinetics

  • No oral absorption.
  • Poor tissue penetration.
  • Half-life in dog: vancomycin - 2 hours; teicoplanin - much longer.
  • Renal excretion.

Toxicity

  • Highly irritant to tissues, (give vancomycin by IV administration only).
  • Ototoxic in man.
  • Nephrotoxic.
  • Teicoplanin given IM.

2. Bacitracin

  • Bactericidal.
  • Indication: topical treatment of superficial skin and mucosal infections, (with polymixin B to give broad spectrum); growth promoter in cattle and pigs; Clostridium perfringens  enteritis.

Spectrum of activity

  • Gram-positive bacteria only.
  • Resistance is rare.

Pharmacokinetics

  • Not absorbed orally.

Toxicity

  • Highly toxic parenterally - nephrotoxic.

Antimicrobial agents which target the cell membrane

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Nucleic acid synthesis and repair inhibitors

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Drugs which inhibit protein synthesis

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Antifungal drugs

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Further Reading

Publications

Refereed papers

  • Recent references from VetMed Resource and PubMed.
  • Adams V J, Campbell J R, Waldner C L, Dowling P M & Shmon C L (2005) Evaluation of client compliance with short-term administration of antimicrobials to dogs. JAVMA 226, 567-574 PubMed.
  • Grave K & Tanem H (1999) Compliance with short-term oral antibacterial drug treatment in dogs. JSAP 40(4), 158-162.
  • Barter L S, Watson A D & Maddison J E (1996) Owner compliance with short term antimicrobial medication in dogs. Aust Vet J 74, 227-280 PubMed.
  • Moriello K A and DeBoer D J (1995) Feline dermatophytosis:recent advances and recommendations for therapy. In: Veterinary Clinics of North AmericaSmall Animal Practice 25 (4), 901-921.

Other sources of information

  • Prescott J F and Baggot J D (1993) Eds Antimicrobial Therapy in Veterinary Medicine. Ames: Iowa State University Press. ISBN 0 8138 0889 8.

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