Staphylococcus aureus Drug Resistance Project Database
For the past 40 years, vancomycin has been the mainstay of therapy for methicillin-resistant S. aureus (MRSA) infections. Daptomycin is an important new addition to the clinician's arsenal. These antibiotics now play a critical role in the fight against drug-resistant, life-threatening staphylococcal infections. Of great concern, however, is the observation that daptomycin-resistant S. aureus isolates are evolving not only during clinical exposure to daptomycin, but also during exposure solely to vancomycin. Many clinicians are using daptomycin after the patient has failed a course of vancomycin, and thus the risk of one antibiotic failure (vancomycin) affecting the efficacy of a subsequent antibiotic (daptomycin) is unacceptably high. Therefore, it is of extreme importance to understand and characterize the genetic mutations that lead to daptomycin resistance, in isolates from patients previously treated with vancomycin and from patients with no prior exposure to vancomycin (i.e. daptomycin exposure only), in order to assess how they differentially evolve.
The genetic mutations that lead to daptomycin resistance, after vancomycin or daptomycin exposure, are currently unknown. We wish to sequence a carefully selected clinical collection of S. aureus strains that have been isolated both pre-and post-development of daptomycin resistance. This will provide meaningful snapshots of the acquisition of antibiotic resistance in a real life clinical setting. We propose to sequence 11 clinical strain pairs (sensitive and resistant) and 2 clinical strain series (sensitive, intermediate resistant, and resistant) for a total of 32 carefully selected clinical isolates. As an important reference set, we also propose sequencing an analogous set of laboratory generated strain pairs and series, 14 strains in all. The combined total is 46 strains.
Collaborating scientist for this project is:Anton Y. Peleg
Division of Infectious Diseases, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.