First in New Class of Antibacterials Demonstrates Promising Activity Against Pathogens Commonly Found in Skin Infections

WASHINGTON, D.C. -- Studies presented today demonstrated that GlaxoSmithKline's investigational antibacterial retapamulin showed an excellent microbiology profile and a high degree of in vitro potency in laboratory studies against key pathogens commonly associated with skin and soft tissue infections (SSTI), consistently showing potent activity when compared to other commonly-prescribed topical and oral antimicrobial agents.  Furthermore, retapamulin showed a low propensity for development of resistance in target pathogens.  These data were presented today in Washington, D.C., at the 45th Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC).

Retapamulin belongs to a new class of antibiotics called pleuromutilins and is being developed for the topical treatment of uncomplicated skin and skin structure infections due to susceptible strains of Staphylococcus aureus or Streptococcus pyogenes.

"A growing cause of many community and hospital-acquired infections are gram-positive bacteria, such as streptococci and staphylococci, and their resistance to antibiotics is on the rise," said Clarence Young, MD, vice president of the Infectious Diseases Medicines Development Centre for GlaxoSmithKline. "These studies showed that retapamulin not only demonstrated promising in vitro activity against these specific types of bacteria, it also may have a low propensity to generate drug resistance."

Streptococcus pyogenes is a gram-positive bacterium, which is surrounded by a carbohydrate capsule that protects it from being destroyed by the immune system.  Embedded within the capsule are proteins that also make it more virulent.  Through the release of toxins, S. pyogenes can lead to many diseases including skin infections such as cellulitis and erysipelas, and other diseases such as scarlet fever and streptococcal toxic shock syndrome. Staphylococcus aureus is a bacterium, often found living in the nose or on the skin of a healthy person, which can lead to illnesses ranging from uncomplicated skin infections to more serious, life-threatening diseases such as bloodstream infections and pneumonia.

In one laboratory study (Abstract F2050), researchers from International Health Management Associates and GlaxoSmithKline determined the minimum inhibitory concentration (MIC) of retapamulin against more than 3,700 clinical isolates of staphylococci, beta-hemolytic (BHS) and viridans streptococci (VSP), collected from patients at 17 sites across North America.  The results demonstrated that retapamulin has excellent in vitro antibacterial activity against the organisms tested.  The concentration of antibacterial required to inhibit the growth of 90 percent of bacteria tested was lowest for retapamulin when compared to 13 other agents tested, including mupirocin, amoxicillin/clavulanic acid, erythromycin and fusidic acid.

Another laboratory study (Abstract F2068), led by researchers from Hershey Medical Center, looked at the potential for S. aureus to develop resistance to retapamulin and seven other commonly-used antibacterials, including mupirocin, cephalexin, vancomycin and fusidic acid.   Researchers tested the ability of antibacterials to select the drug resistant clones among 12 S. aureus strains. The results showed that retapamulin demonstrated excellent activity against the 12 S. aureus isolates tested and had a low frequency of spontaneous mutations affecting the activity of the compound against S. aureus.  The development of S. aureus resistance following daily passage in the presence of sub-inhibitory antibiotic concentrations occurred faster for mupirocin and fusidic acid than for retapamulin.  Overall, these data demonstrate that retapamulin has a low propensity to generate resistance in S. aureus.

These data, along with data from further in vitro work, suggest that retapamulin could offer a new treatment option against S. aureus and S. pyogenes in skin and skin structure infections. Retapamulin has a unique mechanism of action.  By binding to a distinct

site on the 50s sub-unit of the bacterial ribosome, retapamulin inhibits protein synthesis.  In addition, retapamulin has shown no target-specific cross-resistance to other established classes of antibiotics.

Source: GlaxoSmithKline