Penicillin Classification and Mechanism

• Natural Penicillins: Penicillin G, Penicillin V – Effective against Gram-positive bacteria.
• Aminopenicillins: Amoxicillin, Ampicillin – Broader spectrum, including Gram-negative organisms.
• Penicillinase-Resistant Penicillins: Methicillin, Nafcillin, Oxacillin – Resistant to β-lactamase.
• Extended-Spectrum Penicillins: Ticarcillin, Piperacillin – Effective against Pseudomonas spp. and other Gram-negative bacteria.
• Beta-lactamase Inhibitor Combinations: Amoxicillin-clavulanate, Piperacillin-tazobactam – Protects penicillin from degradation.

Penicillins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), disrupting the formation of peptidoglycan cross-links, which results in bacterial cell lysis and death.

• β-lactamase Production: Bacteria produce enzymes that degrade the β-lactam ring of penicillin.
• Alteration of PBPs: Mutations in PBPs reduce penicillin binding affinity.
• Efflux Pumps: Bacteria expel penicillin from their cells.
• Reduced Permeability: Mutations in bacterial membrane reduce drug uptake.

• Respiratory tract infections, skin infections, urinary tract infections.
• Meningitis, endocarditis, and syphilis.

• Allergic reactions (rash, anaphylaxis).
• Gastrointestinal disturbances (nausea, vomiting, diarrhea).
• Hematological issues (hemolytic anemia, thrombocytopenia).
• Neurotoxicity (seizures in high doses).
• Superinfection (e.g., *C. difficile* colitis).

The **Jarisch-Herxheimer reaction** is a reaction that can occur in patients being treated for syphilis, particularly after the administration of penicillin. It is characterized by the acute onset of fever, chills, muscle pain, headache, and exacerbation of the primary syphilis symptoms (such as rash or sores). This reaction is thought to be due to the release of endotoxins from the dying *Treponema pallidum* bacteria, which triggers an inflammatory response.

This reaction is self-limiting and typically resolves within 24–48 hours, but it can be severe in some cases. It is not a sign of treatment failure but rather a response to the rapid killing of bacteria.

• History of severe allergic reactions to penicillins.
• Patients with mononucleosis (risk of rash with amoxicillin).
• Severe renal impairment (requires dosage adjustment).