Achievements and problems from the view of a physician.

Penicillin made possible the cure of many common, and also the most serious, infections, such as meningococcal meningitis and bacterial endocarditis, often with few or no sequelae. Endocarditis had been invariably fatal. Semisynthetic penicillins added new dimensions of convenience of administration and a broader spectrum in the presence of many beta-lactamases. A quantum step forward was permitted by the derivatives of cephalosporin C. Specific clinical advances were (1) the opportunity to use these in some penicillin-allergic patients, (2) activity against wider range of Gram-negative bacilli, (3) activity against Bacteroides fragilis (cefoxitin), (4) more complete renal excretion after oral cephalosporins than with oral penicillins, and (5) delayed renal excretion. Major remaining problems limiting beta-lactam use are (1) allergy, (2) resistant organisms, (3) relatively poor entry into the cerebrospinal fluid (especially of cephalosporins, (4) some nephrotoxicity, (5) local irritation of veins and tissues during administration, and (6) poor results in patients with agranulocytosis.