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Researchers recommend new approach to combat drug-resistant staph infections

24.06.2004


Discovery aims to protect hospitalized patients

A team of international researchers has shown that coating implanted medical devices with a key peptide known as RIP can prevent the occurrence of bacterial colonization, biofilm formation and consequent drug-resistant Staphylococcus aureus infection - a leading cause of illness and death among hospitalized patients. RIP acts by preventing bacterial cell-to-cell communication, a process known as ’quorum sensing’. This is the first direct demonstration that inhibiting cell-to-cell communication can prevent staphylococcal infections. The discovery is reported in the June 24 on-line version of the Journal of Infectious Diseases, and will be reprinted in the journal’s July 15 hard-copy edition.

Staphylococcus aureus causes infections ranging from minor skin abscesses to life-threatening conditions, including pneumonia, meningitis, bone and joint infections (arthritis) and infections of the heart and bloodstream (endocarditis, septicemia, and toxic shock syndrome). Staph. infections are often associated with commonly used implanted medical devices, such as prostheses, catheters and artificial heart valves. Such infections can become tenacious because they are increasingly resistant to antibiotics, rendering them potent causes of illness and death.



"It is critical to find new alternative therapies to antibiotics," said Naomi Balaban, PhD, an author of the study and assistant professor at Tufts University School of Veterinary Medicine. "Our findings are significant because about 2 million hospital patients acquire infections each year in the US, including infections associated with implanted medical devices. Of those hospital-acquired infections, 500,000 are caused by Staphylococci, resulting in an annual death rate of approximately 90,000 patients."

Noting, there are currently no new effective treatment plans on the market, Giorgio Dell’Acqua, PhD, an author of the study and scientist from BalaPharm International, said: "Prevention rather than treatment is crucial in combating staph. infections, and we suggest that RIP may be used to coat medical devices to prevent bacterial coloni-zation and consequent infection."

RIP has been shown to inhibit any strain or species of staphylococci so far tested, including antibiotic-resistant strains, and no resistance to RIP has so far been observed. RIP has also been shown to be synergistic with antibiotics, so it can be used in combination therapy.

RIP prevents the bacteria from being virulent by inhibiting a target protein (TRAP). All rats included in the group with RIP-soaked grafts and also systemically administered RIP showed no evidence of graft infection, indicating 100 percent protection. In addition, none of the animals had clinical evidence of drug-related adverse effects.

This is the first breakthrough in preventing staph-induced infections since 1998, when Balaban discovered that a critical concentration of a key protein dubbed RAP (RNAIII activating protein) triggers the production of toxins by Staphylococcus aureus bacteria through a complicated cell-to-cell communications process. Taking this knowledge to the next level, Balaban and her colleagues sought to determine if preventing such cellular communication would preclude the bacteria from becoming virulent and releasing large quantities of infection-causing toxins. The discovery of RIP has done that. "We believe we can give humans RIP with no side effects, and we intend to conduct human clinical trials next," Dell’Acqua said.

The Department of General Surgery and the Institute of Infectious Diseases and Public Health at the University of Ancona, Italy, also participated in this study, which was funded by the Italian Ministry of Education and the American National Institute of Health (NIH).

Barbara Donato | EurekAlert!
Further information:
http://www.tufts.edu

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