The beta-lactam antibiotics: past, present, and future

The discovery and development of the beta-lactam antibiotics are among the most powerful and successful achievements of modern science and technology. Since Fleming's accidental discovery of the penicillin-producing mold, sev enty years of steady progress has followed, and today the beta-lactam group of compounds are the most successful example of natural product applicatio n and chemotherapy. Following on the heels of penicillin production by Peni cillium chrysogenum came the discoveries of cephalosporin formation by Ceph alosporium acremonium, cephamycin, clavam and carbapenem production by acti nomycetes, and monocyclic beta-lactam production by actinomycetes and unice llular bacteria. Each one of these groups has yielded medically-useful prod ucts and has contributed to the reduction of pain and suffering of people t hroughout the world. Research on the microbiology, biochemistry, genetics a nd chemistry of these compounds have continued up to the present with major contributions being made by both individual and collaborative groups from industry and academia. The discovery of penicillin not only led to the era of the wonder drugs but provided the most important antibiotics available t o medicine. Continued efforts have resulted in the improvement of these com pounds with respect to potency, breadth of spectrum, activity against resis tant pathogens, stability and pharmacokinetic properties. On the research f ront, major advances are being made on structural and regulatory biosynthet ic genes and metabolic engineering of the pathways involved. New semisynthe tic compounds especially those designed to combat resistance development ar e being examined in the clinic, and unusual non-antibiotic activities of th ese compounds are being pursued. Although seventy years of age, the beta-la ctams are not yet ready for retirement.