Fighting Fire With Fire: When an Antibiotic Can Help Fight Antibiotic Resistance

Antimicrobial stewardship and addressing the increasing prevalence of antibiotic-resistant bacteria are major focuses of infection control efforts worldwide. Antibiotics are being over-prescribed, and bacteria are continually evolving into antibiotic-resistant strains.

One antibiotic demonstrates promising results not only for effective infection treatment — including resolving infections that are difficult to treat with more traditional, first-line treatments — but also because clinical trials have shown no evidence of bacteria developing resistance to the drug.

VIBATIV (telavancin) was discovered by Theravance, a biopharmaceutical company. It is currently indicated for use in adult patients in the U.S. with hospital-acquired and ventilator-associated bacterial pneumonia caused by Staphylococcus aureus when other treatments are not suitable, as well as complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria, including MRSA.

This intravenous antibiotic is re-engineered from vancomycin, a common antibiotic to which some bacteria have begun to develop resistance. Researchers have found more than 99.9 percent of the isolates tested against VIBATIV are susceptible to the drug, says Steve Barriere, PharmD, vice president of clinical and medical affairs at Theravance.

"We have a combination of a drug like vancomycin where it took decades for resistance to develop, and published data that suggests it's difficult to induce resistance to VIBATIV," he says. "You can't say resistance will never develop. But we believe the dual mechanisms of actions and the fact it was engineered from a drug that took a long time for resistance to develop [indicate an increased longevity of efficacy.]"

Dr. Barriere says VIBATIV is a bactericidal drug, meaning it kills bacteria instead of just reducing the number present. The bactericidal properties and its relation to vancomycin present an opportunity to positively impact the current trend of antibiotic resistance.

"One of the four cornerstones of management and prevention of antibiotic resistance is development of new drugs that are active against resistant pathogens. We have a drug active against bacteria that are less susceptible to other standard drugs," he says. "Commonly, bacteria are resistant to antibiotics by any one of a number of mechanisms, and those mechanisms can inactivate the drug or prevent it from reaching the target. VIBATIV was engineered to defeat those mechanisms of resistance."

At the European Congress on Clinical Microbiology and Infectious Diseases Meeting in Barcelona this past week, researchers from Theravance presented new and retrospective data on VIBATIV from a number of studies.  Two of the studies were conducted to confirm VIBATIV's in vitro activity against current, changing real-world bacteria. Researchers tested common bacterial samples collected from across Europe and uncommon bacterial samples from around the world to test their susceptibility to VIBATIV.  The latest trial results show prominent in vitro activity of the drug.

"The data demonstrates the incredible potency of [VIBATIV] for Gram-positive bacteria," says Dr. Barriere. "Clinicians like to see potent drugs. If potent drugs are present in infected areas in adequate concentrations, they will kill the bacteria."

In an oral presentation at the ECCMID conference, researchers presented findings from a retrospective analysis of the original Phase III VIBATIV trials in cSSSI.  The retrospective analysis was conducted to examine the drug's efficacy under the U.S. Food and Drug Administration's new guidance on evaluating cSSSI antibiotic drugs. The original Phase III studies of VIBATIV in cSSSI found lower efficacy rates in patients with severe renal impairment compared to patients with milder renal impairment or normal renal function.  Comparing the results in adherence to the new FDA guidance, researchers noted the trend of poorer efficacy in patients with severe renal impairment did not appear and they noted better responses to treatment across the board.

"It gives us a reason to do some additional work to explore whether or not this is in fact something that should be examined or whether there were other reasons amongst those patients who didn't do well in the original analysis," Dr. Barriere says.

As for next steps, Dr. Barriere says Theravance is going to continue researching to ensure VIBATIV is being used as effectively and safely as possible.

"We're in the process of still digesting some of this and internally trying to decide what our next steps will be. We want to make sure we get as much information out as possible to make sure the right patients get telavancin," Dr. Barriere says. "We're not resting on any laurels."

More Articles on Infection Control:

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Sepsis Plays Role in Half of All Hospital Deaths, Study Says

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