New weapons enter the fray against resistant bugs

But drug resistance a reality’ ICPs must deal with

With resistant pathogens rapidly outstripping available antibiotics, new antimicrobials are entering the fray in an attempt to again level the playing field in the endless struggle between the bugs and the drugs.

Those include Synercid (quinupristin/dalfopristin), which recently was approved by the Food and Drug Administration, and Zyvox (linezolid), the first drug from the new oxazolidinone class of antibiotics. Zyvox is in late-stage clinical trials and is expected to be submitted for a new drug application to the FDA by the end of the year.

While the new weapons are welcome, few clinicians surmise that the wave of resistance is at an end — or that infection control is any less critical. Indeed, one infection control professional says it’s déjà vu all over again.

"We’re almost coming full circle the second time around," says Patti Grant RN, MS, CIC, director of infection control at RHD Memorial Medical Center and Trinity Medical Center, both in Dallas. "If you stop and look at infection control before the advent of antibiotics, hand washing was everything. And then we kind of lapsed because we had miracle drugs. Well, we’re seeing the pattern repeating, but I really don’t think that these new antibiotics supersede the basic need for infection control. The reality is, these organisms are coming, many of them are already here, and the ones that are here are gaining in resistance. We need to continue to have these super-antibiotics,’ but [resistance] is basically a reality we have to deal with."

Efficacy data and clinical trials on the new antibiotics were updated recently in San Francisco at the Interscience Conference on Antimicrobial Agents and Chemotherapy. Synercid, the first injectable antibiotic in a distinct class of antibacterials known as streptogramins, was approved by the FDA to treat bloodstream infections due to vancomycin-resistant Enterococcus faecium (VRE) and skin and skin structure infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes. Synercid is the first antibiotic to be specifically indicated for the treatment of patients with serious or life-threatening infections associated with VRE. The drug is active against the pathogen, although several cases of emerging resistance already have occurred in VRE trials. The two distinct antibiotic agents that form Synercid — quinupristin and dalfopristin — work synergistically to inhibit or destroy susceptible bacteria through a two-pronged attack on protein synthesis in bacterial cells. Without the ability to manufacture new proteins, the bacterial cells are inactivated or die.

An emergency-use program was established in 1993 to give physicians access to Synercid to treat infected patients for whom no other available drug was effective. Among the 1,222 enrolled patients, 27% did not have specific sites of infection but had two or more blood cultures showing VRE. Overall, 90% of those patients had clearance of their bacteremia within the first 48 to 72 hours of administration of the antibiotic. The overall efficacy rate in the patients who met strict clinical criteria (24.4% of overall patients) was 52.3%.

In what is being billed as the first antibiotic with a novel mechanism of action in more than 35 years, Zyvox blocks bacterial protein synthesis from starting, rather than sabotaging it once it has begun. The Zyvox compassionate-use program was started in October 1997 to give physicians access to the drug to treat patients with serious infections caused by VRE or methicillin-resistant S. aureus (MRSA).

In a preliminary analysis of clinical trials involving 397 patients with hospital-acquired pneumonia, IV Zyvox plus aztreonam showed a 66.4% clinical success rate. Results for Zyvox were compared with a regimen of IV vancomycin plus aztreonam, which showed a clinical success rate of 68.1%. In a preliminary analysis of a study of Zyvox for the treatment of infections caused by MRSA, the antibiotic had a clinical success rate of 77%. Those results were compared to IV vancomycin, which had a clinical success rate of 74.4%.

Preliminary results from a clinical trial involving 145 patients with infections caused by VRE compared the efficacy of two dose levels of the antibiotic. Zyvox in a 600 mg dose every 12 hours showed an 88.6% clinical success rate; a 200 mg dose every 12 hours showed a 73.7% success rate.

As new antibiotics are added to hospital formularies, ICPs can play important education roles, emphasizing judicious use in order to preserve drug efficacy as long as possible, Grant notes. For example, infectious disease consults may be appropriate in some cases to avoid situations like using Synercid on patients who are only colonized with VRE, she says. "All of us in our individual institutions are going to have to look at what’s on formulary, what’s not on formulary, and see if there are any controls in place for use of these new antibiotics," she says. "Because we don’t want to teach’ these organisms to become resistant to the new antibiotics. Otherwise, we are going full circle. It’s starts sounding like that Abbot and Costello skit —who’s on first — but it’s not funny."