Studies of beta-lactam antibiotics in systemic infections: some personal observations over 25 years

In this paper the problems associated with clinical trials of beta-lactam antibiotics based on 25 years of personal experience are discussed. Clinical trials in patients with uncomplicated urinary tract infections are relatively simple to conduct, but the interpretation of trials in patients with life-threatening infections such as endocarditis can be extremely difficult. Open, noncontrolled studies are necessary for the initial evaluation of an antibiotic, but comparative trials with other agents are essential for determining the indications for the use of new chemotherapeutic agents in the treatment of specific infections. Clinical evaluation of new antimicrobial agents must include pharmacologic and toxicologic studies, and trial protocols should be designed so as to obtain as much information as is practical about the absorption, distribution, and excretion of antibiotics in patients and also to determine the incidence and nature of adverse reactions. The problems associated with undertaking clinical trials in specific infections are discussed.