Antimicrobial management strategies for Gram-positive bacterial resistance in the intensive care unit

This article summarizes the current situation with Gram-positive infections, including the two primary consequences - failure to cure and resistance - relevant to the intensive care unit. The past few years have seen Enterococcus faecium resistance to vancomycin increase from 10% of strains to approaching 60% of strains in some centers. Failure is now so frequent that vancomycin can no longer be safely used. This has lead to use of two new antibiotics, quinupristin/dalfopristin (Synercid), first marketed in the United States in September 1999, and linezolid (Zyvox), which reached the U.S. market in May 2000. Both of these agents are being used to treat culture-proven vancomycin-resistant E. faecium. The calculated areas under the inhibitory curve (AUIC) values of vancomycin, even when its minimal inhibitory concentration (MIC) is 4.0 μg/mL, show almost all vancomycin-resistant E. faecium have AUICs <125. This explains failure, as well as the further selection of this bacteria into subpopulations with progressively higher MICs. Less well defined, but potentially an even greater problem, is the poor efficacy of vancomycin against multiresistant Staphylococcus aureus. Here, there is evidence of clinical failure in lower respiratory tract infection patients, but in most cases the MIC values of the organism have not risen to the point where AUICs are <125. However, the minimum bactericidal concentration of this organism may be considerably higher than its MIC, and in other cases there may be a high inoculum effect or a protein-binding effect to explain the failure of vancomycin to kill multiresistant S. aureus. Besides the increasing use of the new agents, strategies to manage these two increasingly resistant Gram-positive infections include cephalosporin restriction, switch and streamlining when cultures come back from the lab, combination regimens, and cycling in selected intensive care units.