β-lactam antibiotics

Key points


General

Pharmacodynamics

Beneficial actions and effects

Resistance (by bacteria)

Adverse effects

Pharmacokinetics

Penicillin subclasses


Penicillin G (benzyl penicillin G)

  • Very susceptible to beta-lactamase and penicillinase
  • Limited lipid solubility (limited gram (-) action)
  • Difficult to maintain effective concentrations
    • Acid labile
    • Hydrolyzes in water
    • Rapid elimination
    • Dose forms STRONGLY influence pharmacokinetics and likely efficacy.
      • procaine, benzathine very slowly absorbed
      • Sodium salts rapidly absorbed IM, used almost exclusively IV
ProPenG NaPenG
USP/AAVPT monograph for systemic (injectable) penicillin G
USP/AAVPT monograph for intramammary/local penicillin G

Broad Spectrum Aminobenzyl Penicillins(ampicillin, amoxicillin )

  • More lipid soluble than pen G so more active against Gram (-)
  • Better oral absorption (more stable in acid)
  • Just as susceptibile to penicillinase
  • Hydrolyze in water.
  • Amoxicillin more lipid soluble than ampicillin
    • Kills bacteria slightly faster
    • Slightly better absorption
    • Slightly better "tissue penetration"
amoxicillin ampicillin capsules

USP/AAVPT monograph for systemic (oral and injectable) aminopenicillins

USP/AAVPT monograph for intrammamary / local aminopenicillins

Carboxypenicillins (carbenicillin, ticarcillin)


Penicillinase-resistant Penicillins (methicillin, oxacillin, cloxacillin, nafcillin)

  • Resistant to penicillinase
  • Low lipid solubility, not good for gram (-)
  • Methicillin is the M in MRSA (Staphylococci) and appears on susceptibility profiles
  • Dicloxacillin is the veterinary drug that is used orally
  • Oxacillin is the only commonly used injectable.
Oxacillin for Injection

Acylaminopenicillins - Ureidopenicillins (piperacillin)


Penicillin/beta-lactamase Combinations

  • Counter resistance with a second drug
    • Independent pharmacokinetics
    • Clinical performance may not match susceptibility
  • Individual combinations oral or injectable but not both.
Clavamox Timentin

Carbapenems (imipenem)

  • Broad spectrum
  • Expensive
  • Penicillinase resistant but not effective against (human) MRSA
  • Intravenous only
  • Administered with cilastin. Cilastin inhibits degredation by the renal enzyme dehydropeptidase.
imipenem

Monbactams (aztreonam)

  • A drug with (only) gram negative activity that is NOT in common veterinary use
  • Might pop up when you ask for "extended" susceptibility testing
Aztreonam

Cephalosporin subclasses


Oral, 1st generation (cefadroxil, cephalexin, cephradine)

  • Rapid elimination, must be given frequently.
  • Original replacements for penicillin vs Staphylococci.
  • Better gram negative activity than penicillin G. Resistance is common.
  • Often represented by cephalothin on susceptibility reports.
Keflex
USP/AAVPT Monograph for cephalosporins (oral and parenteral)

Oral, 2nd Generation (Cefachlor, Cefuroxime)
Oral, 3rd generation (cefpodoxime)
  • These were the first cephalosporins noted for gram - activity.
  • NOT as good as first generation against Staphylococci
  • Second generation drugs are rapidly eliminated. Third generation have extended dose interval.

cefpodoxime

1st Generation Parenteral (cefazolin, cephapirin, cephalothin)

  • Similar to orally administered 1st generation cephalosporins
  • Good gram positive, fair gram negative activities.
  • May be more active against bacteria in VARIABLE and MODERATE categories because they reach better plasma/tissue concentrations.
cefazolin
USP/AAVPT Monograph for (Cephapirin Intramammary)

Parenteral general purpose, 3rd generation (ceftiofur, cefotaxime, ceftriaxone, cefovicin)

  • Grouped by duration of action in people (not necessarily in animals). These share similar activity profiles.
  • Ceftiofur and cefovicin are approved for veterinary. Consider the rest when interpreting susceptibility reports.
ceftiofurcefovicin

Parenteral antipseudomonal, 3rd generation (cefoperazone, ceftazidime)

ceftazidime