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Penicillins and cephalosporins are the major antibiotics that inhibit bacterial cell wall synthesis. They are called beta-lactams because of the unusual 4-member ring that is common to all their members. The beta-lactams include some of the most effective, widely used, and well-tolerated agents available for the treatment of microbial infections. Vancomycin, fosfomycin, and bacitracin also inhibit cell wall synthesis but are not nearly as important as the beta-lactam drugs. The selective toxicity of the drugs discussed in this chapter is mainly due to specific actions on the synthesis of a cellular structure that is unique to the microorganism. More than 50 antibiotics that act as cell wall synthesis inhibitors are currently available, with individual spectra of activity that afford a wide range of clinical applications.
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All penicillins are derivatives of 6-aminopenicillanic acid and contain a beta-lactam ring structure that is essential for antibacterial activity. Penicillin subclasses have additional chemical substituents that confer differences in antimicrobial activity, susceptibility to acid and enzymatic hydrolysis, and biodisposition.
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Penicillins vary in their resistance to gastric acid and therefore vary in their oral bioavailability. Parenteral formulations of ampicillin, piperacillin, and ticarcillin are available for injection. Penicillins are polar compounds and are not metabolized extensively. They are usually excreted unchanged in the urine via glomerular filtration and tubular secretion; the latter process is inhibited by probenecid. Nafcillin is excreted mainly in the bile and ampicillin undergoes enterohepatic cycling. The plasma half-lives of most penicillins vary from 30 min to 1 h. Procaine and benzathine forms of penicillin G are administered intramuscularly and have long plasma half-lives because the active drug is released very slowly into the bloodstream. Most penicillins cross the blood-brain barrier only when ...