Toxicologic and pharmacologic considerations in the choice of empiric parenteral antibiotics

The last five years have produced an explosive development of new beta-lactam compounds with extended bacterial spectra to include most of the gram-positive cocci as well as the gram-negative bacilli. With the exception of activity against enterococci, there are now third-generation cephalosporins with a spectrum of activity similar to that of the aminoglycosides. In addition, beta-lactams retain a high level of activity against anaerobes and against aerobes surviving in anaerobic conditions, a capacity that is lacking with the aminoglycoside group of antibiotics. The beta-lactams in general and some specific compounds in particular (moxalactam, ceftriazone) have a good penetration into the cerebrospinal fluid, a capacity that is also lacking with the aminoglycosides. Since there is a wide range of different spectra of activity among penicillins and cephalosporins, it is also possible to choose an antibiotic with a spectrum restricted to the offending microorganisms. Finally, because the potential toxicity of beta-lactams is less than that of the aminoglycosides (with the possible exception of myelotoxicity), the first choice of antibiotic in a patient with suspected severe infection should be a beta-lactam. The addition of an aminoglycoside should be reserved for those situations in which a synergistic action between the beta-lactam and the aminoglycoside antibiotics is expected to increase the efficacy of the beta-lactam alone, e.g., enterococcal infections, Pseudomonas aeruginosa infections, infections in severely neutropenic patients, or bacterial endocarditis.