Antimicrobial activity, bacterial resistance, and antimicrobial pharmacology. Is it possible to use new agents...

Perusal of the various journals devoted to antimicrobial agents and to the chemotherapy of infectious diseases reveals an increasing number of articles devoted to the analysis of the pharmacology of antimicrobial agents and the relationships of antimicrobial activity and pharmacologic properties. However, most attention to the pharmacokinetic properties of antimicrobial agents in the past decade has focused on the toxic properties of these agents, and there has been little work devoted to improving methods of administration. The availability of nontoxic antibiotics that are extremely active at low concentrations and of agents with markedly extended half-lives should cause us to reevaluate some of our current dosing practices. In many ways, a major adverse influence on appropriate antimicrobial therapy of ordinary infections has been the febrile neutropenic patient. Lessons learned from the care of these patients are inappropriately applied to the treatment of other patients. The neutropenic patient requires frequent administration of antibiotics at maximally tolerated doses. Many patients at risk for infection do not require antimicrobial therapeutic programs in which the antibiotic always exceeds the minimal inhibitory concentration. Indeed, the concept that the drug must be present in the serum well above the minimal inhibitory concentration for the entire interval of infection is derived from studies of neutropenic patients infected with Pseudomonas aeruginosa. Increasing resistance of hospital-acquired bacteria to older antibacterial agents will alter the initial and subsequent selection of antimicrobial agent. Combination drug therapy, which has a prominent role in the neutropenic patient, frequently results in greater cost to the health care system than is seen with single agents that are active against resistant bacteria. There are clear areas in which new antibacterial agents will be beneficial. We may be at a stage in which use of the older agents can no longer be viewed as the best clinically and economically. Better use of twice- or once-daily dosing programs of new agents coupled with use of intramuscular and oral administration of antibiotics can help reduce nosocomial infections that contribute to rising health costs.