Zbigniew Ochocki, Andrzej Stańczak

Antybiotyki beta-laktamowe. Część III

Beta-lactam antibiotics. Part 3. The penicillinis and cephalosporins are the family of beta-lactam antibiotics are frequently prescribed antibiotics that share a common structure and mechanism of action-inhibition of the bacterial peptidoglycan cell wall remains an important part of our antimicrobial armamentarium. In general, these agents have bactericidal activity, excellent distribution throughout the body, low toxicity, and efficacy against infections caused by susceptible bacteria. The emergence of penicillinase-producing Staphylococcus aureus prompted the development of the penicillinase-resistant penicillinis, in which an acyl side chain prevented disruption of the beta-lactam ring. Subsequently, the aminopenicillins were developed because of the need for gram-negative antimicrobial activity. The search for a penicillin with additional antimicrobial activity against the Enterobacteriaceae and Pseudomonas aeruginosa led to the development of the carboxypenicillins and the ureidopenicillins. Finally, the combination of a beta-lactamase inhibitor and an aminopenicillin or ticarcillin has further extended their antibacterial spectra. The development of an ideal penicillin that is rapidly bactericidal, nonsensitizing, nontoxic, bioavailable, resistant to beta-lactamase, and without inoculum effect and that has a high affinity for penicillin-binding proteins remains the goal. The second groups of beta-lactam antibiotics are cephalosporins. The cephalosporin ring structure is derived from 7-aminocephalosporanic acid while the penicillins are derived from 6-aminopenicillanic acid. Both structures contain the basic beta-lactam ring but the cephalosporin structure allows for more gram negative activity than the penicillins and aminocillins. Substitution at the different side chains allows for variation in the spectrum of activity and duration of action. Cephalosporins are grouped into generations by their antimicrobial properties. The first cephalosporins were designated first generation while later, more extended spectrum cephalosporins were classified as second generation cephalosporins. Currently, three generations of cephalosporins are recognized and a fourth has been proposed. Significantly, each newer generation of cephalosporins has greater gram negative antimicrobial properties than the preceding generation. Conversely, the older generations of cephalosporins have greater gram-positive coverage than the newer generations.