Studies of cephalothin: aminoglycoside synergism against enterococci

Combinations of cephalothin and aminoglycoside antibiotics are not currently used in the therapy of serious enterococcal infections, because clinical trials of these combinations have been unsuccessful. Studies of 28 enterococci isolated from patients with enterococcal bacteremia suggested three possible mechanisms for this in vivo antibiotic failure: (i) a relatively high level of resistance to cephalothin among all enterococci and especially those characterized as Streptococcus faecium, (ii) a significant incidence of high-level resistance to the aminoglycosides among certain strains of enterococci, and (iii) a failure of synergism to occur when cephalothin concentrations fall below the minimal inhibitory concentration of the enterococcus, as occurs during the in vivo metabolism and excretion of this antibiotic when given in standard doses for endocarditis.