CHICAGO -- Data presented today at the 40th Annual Meeting of the Infectious Diseases Society of America (IDSA) showed evidence that Ramoplanin demonstrates potent in vitro bactericidal activity against vancomycin-resistant enterococci (VRE), even linezolid- and quinupristin/dalfopristin-resistant strains of the bacteria. Linezolid (LZ) and quinupristin/dalfopristin (Q/D) are two recently approved agents used for the treatment of VRE bloodstream infections. Ramoplanin is a novel antibiotic in Phase III clinical testing for the prevention of bloodstream infections caused by VRE.
The in vitro study documented Ramoplanin's ability to kill bacteria, specifically LZ- and Q/D-resistant VRE, by inhibiting an essential component of the bacterial cell wall via a novel mechanism of action. The data further demonstrated that Ramoplanin inhibited these bacteria at very low concentrations (minimum inhibitory concentrations (MIC): 0.125 - 0.25 ug/ml). In addition, time-kill studies showed that Ramoplanin was bactericidal against LZ- and Q/D-resistant VRE. At four-times the MIC, Ramoplanin caused a greater than five log10 reduction in bacterial counts at 24 hours.
"The medical community is encountering an increasing number of antibiotic resistant pathogens and still lacks effective therapies to control the infections they cause," said Robert C. Moellering, MD, chairman of medicine at the Beth Israel Deaconess Medical Center and a member of the Data Safety Monitoring Board that reviewed the Phase II clinical results for Ramoplanin. "Ramoplanin's unique mechanism of action and demonstrated in vitro activity against enterococci that have developed resistance to two recently approved VRE therapies, provides clinicians with additional evidence of the potential utility of this novel antibiotic."
VRE bloodstream infections are among the fastest growing nosocomial infections in the United States. They pose a risk to many patients in the hospital, especially to those with compromised immune systems. At risk populations include patients undergoing chemotherapy, organ transplantation or any immunosuppressive regimen. Patients in hospital intensive care units are also at risk of developing this life-threatening bloodstream infection. According to the CDC, data from the National Nosocomial Infection Surveillance System show that enterococci are now the second most common cause of bloodstream infections acquired in intensive care units in U.S. hospitals, and that the bacteria are increasingly resistant to vancomycin.
"We remain committed to investigating Ramoplanin's clinical utility and activity against resistant strains of enterococci and other Gram-positive organisms," stated Timothy Leach, MD, MPH, vice president of clinical and medical affairs for Genome Therapeutics. "With a growing body of evidence that VRE are further developing resistance to recently approved therapies, it is critical that we advance Ramoplanin's Phase III program for the prevention of VRE bloodstream infections."
Scientists from Genome Therapeutics also presented data on the use of microarrays in measuring Ramoplanin's impact on gene expression in the bacteria Staphylococcus epidermidis. Researchers measured the gene expression profiles of S. epidermidis exposed to increasing concentrations of Ramoplanin and revealed a consistent set of up-and down-regulated genes of unknown function when compared to growth in the absence of Ramoplanin. Future experiments to compare the gene expression profiles with those of known antibiotics are in progress.