Gram-Positive Resistance: Pathogens, Implications, and Treatment Options

Insights From the Society of Infectious Diseases Pharmacists

Ronda L. Akins, Pharm.D.; Krystal K. Haase, Pharm.D.


Pharmacotherapy. 2005;25(7):1001-1010. 

In This Article

Abstract and Introduction

Despite the advent of new antibiotics, resistance in gram-positive pathogens, including staphylococci and enterococci, continues to increase. This is evident with the recent emergence of vancomycin-resistant Staphylococcus aureus. Newer treatment agents are available, including quinupristin-dalfopristin, linezolid, and daptomycin. In addition, investigational agents are being explored. Clinical trials have been conducted for various infections, such as skin and skin structure infections, pneumonia, and bloodstream infections. Antibacterial activity, site of infection, and potential for adverse effects must be taken into account when making decisions regarding therapy.

Antibiotic resistance is an ongoing problem despite the development of new therapeutic options. Gram-positive pathogens are of particular concern, as resistance is increasing in organisms that have been susceptible to most available antibiotics until the past decade. Vancomycin has remained the gold standard antibiotic for treatment of resistant gram-positive organisms. However, the increased frequency of vancomycin-resistant enterococci (VRE) has necessitated the development of other agents.

Two agents, quinupristin-dalfopristin and linezolid, were previously approved for the treatment of VRE. Simultaneously, a small number of Staphylococcus aureus isolates with intermediate resistance to vancomycin emerged worldwide.[1,2,3] Concern then turned to the issue of whether S. aureus could become fully resistant to vancomycin. This fear was realized in 2002, when two clinical isolates of vancomycin-resistant S. aureus (VRSA) were identified.[4,5,6,7] A third isolate of VRSA was identified in March 2004.[8,9]

At the end of 2003 a third agent, daptomycin, was approved with an indication for complicated skin and skin structure infections due to S. aureus (including isolates with methicillin resistance), streptococci, and vancomycin-susceptible Enterococcus faecalis.[10] However, in vitro data demonstrating activity for daptomycin against multidrug-resistant gram-positive organisms led to use of this agent as a viable treatment alternative to vancomycin, quinupristin-dalfopristin, and linezolid.[11] Other investigational antibiotics are in the pipeline but are not yet available. Unfortunately, despite the development of new antibiotics, organisms continue to demonstrate increasing resistance patterns. Resistance has already been identified in numerous organisms, including staphylococci and enterococci, for two of the three agents targeted for use against resistant gram-positive pathogens.