Comparative in-vitro activity of MK0787 (N-formimidoyl thienamycin) against 540 blood culture isolates

MK0787 is a stable N-formimidoyl derivative of thienamycin, a new β-lactam antimicrobial with potent and broad-spectrum activity. With standard microtitre broth dilution techniques for determination of minimal inhibitory and bactericidal concentrations, the in-vitro activity of MK0787 was compared with cephalothin, piperacillin, moxalactam, and tobramycin against 540 blood culture isolates. All bacteria were from patients with sepsis and were tested in the same proportion as their occurrence in clinical practice. MK0787 was more active against Staphylococcus aureus than the other antimicrobials tested and was the only agent that was consistently bactericidal against enterococci. Moxalactam was slightly more active than MK0787 or tobramycin against most Enierobacteriaceae; however, MK0787 was the most potent antimicrobial agent against Acinetobacier and Serratia spp. Tobramycin and MK0787 showed similar activity against Pseudomonas aeruginosa, and were more active than moxalactam or piperacillin. MK0787 was also the most active agent against anaerobes, including Bacteroides fragilis. Comparative killing curves showed that tobramycin was usually more rapidly bactericidal than the cell-wall active agents. MK0787 inhibited and killed a greater percentage of blood culture isolates than the other drugs tested. If supported by future clinical trials, MK0787 may have a role as a single agent in empiric treatment of sepsis.