The Penicillins

Abstract

The penicillin family of antibiotics is ever expanding and remains an important part of our antimicrobial armamentarium. These medications generally have bactericidal activity, excellent distribution throughout the body, low toxicity, and efficacy against infections due to susceptible organisms. The clinical introduction of aqueous penicillin G for treatment of streptococcal and staphylococcal infections was an important pharmacologic landmark. The emergence of penicillinase-producing staphylococci prompted the development of the penicillinase-resistant penicillins (methicillin, oxacillin, nafcillin, and others), in which the acyl side chain prevented disruption of the beta-lactamase ring. The aminopenicillins (ampicillin, amoxicillin, and others) were later developed because of the need for gram-negative antimicrobial activity. Their spectrum included Escherichia coli, Proteus mirabilis, Shigella, Salmonella, Listeria, and Haemophilus. The search for a penicillin with even further antimicrobial activity against the Enterobacteriaceae and Pseudomonas aeruginosa led to the development of the carboxypenicillins, ureidopenicillins, and piperazine penicillins. Recently, the combination of a beta-lactamase inhibitor (clavulanic acid or sulbactam) and an amino-penicillin or ticarcillin has resulted in further extension of their antibacterial spectra. The development of an ideal penicillin that is nonsensitizing, bioavailable, beta-lactamase-resistant, rapidly bactericidal, nontoxic, and inexpensive and that has high affinity to penicillin-binding proteins and no inoculum effect remains the goal.