Vancomycin drug still effective in treating Staphylococcus aureus bloodstream infections

A University of Nebraska Medical Center research team has determined that a longtime antibiotic, vancomycin, is still effective in treating Staphylococcus aureus bloodstream infections and that physicians should continue to use the drug even though several newer antibiotics are now available in the marketplace.

The research was reported in the Oct. 15 issue of The Journal of the American Medical Association (JAMA), one of the leading research journals in the country. The study was released early online to coincide with IDWeek 2014, the annual conference of the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) being held in Philadelphia Oct. 8-12.

The four-person UNMC team was led by Andre Kalil, M.D., professor in the UNMC Department of Internal Medicine and an infectious diseases specialist. He was assisted by two other infectious diseases specialists - Mark Rupp, M.D., professor, and Trevor VanSchooneveld, M.D., assistant professor, and Paul Fey, Ph.D., professor, pathology and microbiology.

Staphylococcus aureus is among the most common causes of health care-associated infection throughout the world. It causes a wide range of infections, with blood¬stream infections - S aureus bacteremia (SAB) - among the most common and lethal.

For more than 50 years, the primary therapy for Staphylococcus aureus infections has been either semisynthetic penicillins or vancomycin.

In recent years, physicians treating staph infections with vancomycin have seen an increase in the minimum inhibitory concentration (MIC), the lowest concentration of an antimicrobial agent that inhibits the growth of a microorganism.

MIC values lower than 4 mg/L indicate that the staphylococcus is susceptible to vancomycin. However, when the MIC value exceeds 1.5 mg/L, some physicians have taken it as an indication that the vancomycin may not be working at maximum effectiveness.

This condition is referred to as vancomycin "MIC creep." It is an indicator that the bacteria might be developing a reduced susceptibility to vancomycin. There also have been reports suggesting that elevations in vancomycin MIC values may be associated with increased treatment failure and death.

To determine the effectiveness of vancomycin and other newer antibiotics used to treat Staphylococcus aureus, the UNMC team analyzed nearly 8,300 episodes of Staphylococcus aureus bloodstream infections from patients around the U.S. and in several other countries.

Over a two-year period, the UNMC team conducted a systematic analysis of the evidence regarding the association of vancomycin MIC elevation with mortality in patients with SAB. Among 8,291 episodes of SAB studied, overall mortality was 26.1 percent.

The adjusted absolute risk of mortality among patients with SAB with high-vancomycin MIC was not statistically different from patients with SAB with low-vancomycin MIC.

In studies that included only methicillin-resistant Staphylococcus aureus (MRSA) infections, the mortality among SAB episodes in patients with high-vancomycin MIC was 27.6 percent, compared with a mortality of 27.4 percent among patients with low-vancomycin MIC.

"The study provides strong evidence that vancomycin remains highly useful," Dr. Kalil said. "Even though vancomycin is an older drug, it is still killing staph very efficiently. There are newer antibiotics available to treat Staphylococcus aureus infections, but this study demonstrates that physicians don't necessarily need to switch to these new drugs when the MIC is increased but still within the susceptible range.

"The prevention of a rapid switch to newer drugs has another great benefit to our patients -- less unnecessary exposure to these drugs, which will translate into less development of antibiotic resistance."

Dr. Kalil said the study may have implications for clinical practice and public health, including:
•that standards for vancomycin MIC most likely do not need to be lowered;
•routine differentiation of MIC values between 1mg/L and 2 mg/L appears unnecessary; and
•the use of alternative antistaphylococcal agents may not be required for Staphylococcus aureus isolates with elevated but susceptible vancomycin MIC values.

"These conclusions are consistent with current IDSA treatment guidelines that recommend use of vancomycin for treatment of MRSA bacteremia with consideration for alternative agents based on the patient's clinical response and not the MIC," he said.

Through world-class research and patient care, UNMC generates breakthroughs that make life better for people throughout Nebraska and beyond. Its education programs train more health professionals than any other institution in the state. Learn more at unmc.edu and follow us on social media.

SOURCE University of Nebraska Medical Center