Combining Antibiotics May Boost Their Bacteria-Killing Ability

May 06, 1997

MIAMI --- The growing prevalence of antibiotic-resistant bacterial infections has spurred infectious disease specialists at Northwestern University Medical School to find a "better mousetrap" to combat drug-resistant microbes.

They are currently investigating whether combining certain antibiotics, each with different mechanisms of action, might boost the bacteria-killing power of antibiotics that are less effective when used individually. This chemical effect is known as synergy.

For example, infections with the bacteria enterococci are on the rise, primarily due to the emergence of strains resistant to vancomycin, a potent, broad-spectrum antibiotic. Vancomycin-resistant enterococci have been implicated as a leading cause of hospital-acquired, or nosocomial, infections. Enterococci are bacteria that are normally found in the intestines.

In addition, many vancomycin-resistant enterococci, such as Enterococcus faecium, are highly resistant to other antibiotics, leaving few, if any, effective therapeutic options. Patients with vancomycin-resistant enterococcal bloodstream infections have a death rate of 37 percent -- significantly higher than the 16 percent mortality in patients whose infection responds to vancomycin.

In a recent study, Cynthia Boschman, M.D., and the other members of the Northwestern group studied whether there would be synergy against various strains of antibiotic-resistant enterococci using high-dose ampicillin or ampicillin/sulbactam and a newer drug, trovafloxacin, a fluoroquinolone. Ampicillin and ampicillin/sulbactam are cell-wall-active antibiotics, i.e., they work by "punching a hole" in the cell wall of bacteria and killing it.

They performed synergy testing using the three drugs alone and in combination against 24 unrelated strains of vancomycin-resistant enterococci.

The combination of trovafloxacin and ampicillin/sulbactam showed synergy in two of 10 strains of Enterococcus faecalis, while no synergy was seen in any of the 14 strains of E. faecium. Using the combination of trovafloxacin and ampicillin, no synergy was seen in any strain of VRE.

While the combination of trovafloxacin with these two drugs was less successful than the researchers had hoped, Boschman believes that combination antibiotic treatment is the only means currently available to eliminate these dangerous bacterial infections.

"The pressing clinical need to identify any possibly effective antimicrobial agent therapy for these organisms underscores the urgency for continued research into the effectiveness of not only new agents but also combinations of currently available antibiotics," she said.

Boschman is a clinical microbiology fellow at Northwestern University Medical School. Her colleagues on this research study were Gary Noskin, M.D., assistant professor of medicine; Lance R. Peterson, M.D., professor of pathology; and Michelle A. Tornatore, research technologist.

Northwestern University

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