Penicillins

β-Lactams (Antibiotics)
Time Dependent Bactericidal Agents

Obtained from fungi Penicillium chrysogenum = Penicillium notatum

Structure:
β-Lactams ring + Thiazolidine ring
Hydrophilic

Antibacterial spectrum:

• Narrow Spectrum Penicillins: AMEG D, mainly for Gr+ infections (Streptococcus, Clostridium)
  • Benzylpenicillin-Na+ / K+ (IV, IM)
  • Benzylpenicillin-Procaine (IM, SC)
  • Benzylpenicillin-Benzathine (IM, SC)
  • Phenoxymethyl-Penicillin (PO): ONLY Oral Narrow Spectrum Penicillins
  • Penethamat (IM): ONLY Narrow Spectrum Penicillins that can cross BBB and BMB
  • Combination of Narrow Spectrum Penicillins:
    • Procaine-Penicillin + Benzathine-Penicillin + Dihydrostreptomycin: Synergistic effect
• Penicillinase Stable Penicillins: AMEG D
  • For mastitis (Staphylococcus, Streptococcus)
  • Acid Sensitive: Impractical to use (damaged by gastric acids)
    • Methicillin
  • Acid Resistant (In increasing lipophilicity order): most contain Halogen compounds
    • Oxacillin
    • Cloxacillin
    • Dicloxacillin
    • Flucloxacillin
    • Nafcillin
• Extended Spectrum Penicillins (Aminopenicillins): AMEG D alone, AMEG C if combined with β-Lactamase Inhibitors
  • Good for E. Coli UTI (not for Gastroenteritis)
  • Ampicillin (often combined with with Sulbactam)
    • Ampicillin Sodium
    • Ampicillin Trihydrate
  • Amoxicillin (often combined with with Clavulanic Acid)
    • Amoxicillin Sodium
    • Amoxicillin Trihydrate
• (Penicillins Acting Against Pseudomonas spp): AMEG A Forbidden in veterinary medicine
  • Piperacillin + Tazobactam (β-Lactamase Inhibitors)
  • Ticarcillin
  • Carbenicillin

Mechanism of action:

• The bacterial cell wall (Peptidoglycan) is made of NAG - NAM chains linked together by transpeptide bonds
  • Penicillins inhibit the formation of these transpeptide bonds by inhibiting the Transpeptidase and Carboxypeptidase (known as PBP Penicillins Binding Proteins)
    • This leads to rupture of the bacterial cell wall > Bactericidal Agents
    • Don’t combine with Bacteriostatic Agents as Penicillins only work against dividing bacteria

Mode of action:
Time Dependent Bactericidal Agents (give every 12h)
PAE: 4-8h > BID administration

Resistant Bacteria:

• Ab ovo (=Naturally resistant bacteria): No PBP to act on
  • Mycoplasma: They don’t have a cell wall
  • Chlamydia: They are IC parasites > Penicillins can’t penetrate
  • Acid-fast bacteria (Mycobacterium, Nocardia…): They have a unique type of cell wall made of Mycolic acid
• β-Lactamase production: Enzymatic degradation of the Penicillins
  • Methicillin, Oxacillin and Cephalosporins are resistant against β-Lactamase
  • Amoxicillin with Clavulanic Acid (β-Lactamase Inhibitor) also works
• PBP gene mutation: Target modification, the Penicillins can’t bind the PBP > the bacterial cell wall synthesis isn’t inhibited
  • Frequent Resistance mechanism in the MRSA Methicillin Resistant Staphylococcus Aureus and MRSP Methicillin Resistant Staphylococcus Pseudointermedius. They are resistant to ALL β-Lactams Antibiotics
    • The Antibiotics used in MRSA/MRSP infections are Rifampicin (AMEG A) and Amikacin, Florfenicol (AMEG C)

Adverse effects: Almost non-toxic

• Allergy, Non immunological anaphylactic reactions (Anaphylactoid): Cross allergy with Cephalosporins
  • Hemolytic anemia in Horses
• Dysbacteriosis
  • Herbivorous rodents (Degu, Chinchilla, Hamster, Guinea pig, Rabbits) and Horses are very sensitive to Dysbacteriosis
    • It is not forbidden though, but use with care

Antibacterial Spectrum Table:

Penicillins	Most Gr+	Staphylococcus	Enterococcus	Acid-fast	Most Gr-	Anaerobes, Fastidious, Leptospira, Borrelia	Enterobacteriacea	Pseudomonas	Chlamydia, Mycoplasma, Rickettsia, Brachyspira MRSA, MRSP
Narrow Spectrum Penicillins	Yes			No β-Lactams at all	Few	Yes			No β-Lactams at all
Penicillinase Stable Penicillins	Yes	Yes		No β-Lactams at all	No Gr- at all	No Gr- at all	No Gr- at all	No Gr- at all	No β-Lactams at all
Extended Spectrum Penicillins with β-Lactamase Inhibitors	Yes	Yes	Yes	No β-Lactams at all	Several	Yes	Yes (but resistance for GI infections)		No β-Lactams at all
Penicillins Acting Against Pseudomonas spp	AMEG A Forbidden	AMEG A Forbidden	AMEG A Forbidden	No β-Lactams at all	AMEG A Forbidden	AMEG A Forbidden	AMEG A Forbidden	Yes AMEG A Forbidden	No β-Lactams at all
Frequent indications	Streptococcus: Strangles, Septicaemia, Mastitis, Metritis, Dermatitis, Meningitis, Osteomyelitis Cl. perfringens: Necrotic enteritis of Chicken and Pigs	Mastitis, Metritis, Dermatitis, Osteomyelitis				Anaerobes: Oral cavity infections, bite wounds Fastidious: Respiratory tract infections Leptospira, Borrelia: Vector borne infections	Enterobacteriacea: UTI, GI infections