Study: Vancomycin More Effective Than Metronidazole for Severe C. Difficile Infections

Most-prescribed antibiotic may not be the best choice, authors say

Scientists at the University of Utah and the Veterans Affairs Salt Lake City Health Care System have reported that patients with severe Clostridium difficile infections (CDIs) were less likely to die when treated with vancomycin compared with the standard treatment of metronidazole. The findings were published online in JAMA Internal Medicine.

C. difficile does not cause illness outright. Rather, the bacterium produces two chemicals that are toxic to the human body. These toxins work in concert to irritate the cells of the intestinal lining, thereby producing the symptoms associated CDI. These symptoms include watery diarrhea, fever, loss of appetite, nausea, and abdominal pain and tenderness. Severe cases are associated with inflammation of the colon.

Current treatment guidelines primarily recommend two antibiotics––metronidazole and vancomycin––to treat patients with CDI. While vancomycin was the original treatment, the medical community has favored metronidazole for the past few decades because it is less expensive and can limit vancomycin resistance in other hospital-acquired infections. The current guidelines, however, are based on data from small clinical trials conducted approximately 30 years ago.

“For many years the two antibiotics were considered to be equivalent in their ability to cure C. diff and prevent recurrent disease,” said lead author Vanessa Stevens, PhD. “Our work and several other studies show that this isn’t always the case.”

Stevens and her colleagues examined data from more than 10,000 patients treated for CDI through the U.S. Department of Veterans Affairs health care system from 2005 to 2012. A severe case of CDI was defined as a patient with an elevated white blood cell count or elevated serum creatinine level within four days after the CDI diagnosis. Mild-to-moderate cases of CDI were defined as a patient with normal white blood cell counts and creatinine levels. Approximately 35% of the CDI cases in this study were considered to be severe.

Patients with a severe case of CDI had lower mortality rates when treated with vancomycin compared with metronidazole (15.3% vs. 19.8%, respectively). The researchers calculated that only 25 patients with severe CDIs would need to be treated with vancomycin to prevent one death. “That is a powerful, positive outcome for our patients’ well-being,” Stevens said. She cautioned that the researchers still do not understand how the choice of an antibiotic affects mortality rates.

“Although antibiotics are one of the greatest miracles of modern medicine, there are still tremendous gaps in our knowledge about when and how to use them to give our patients the best health outcomes,” said investigator Michael Rubin, MD, PhD.

“This research shows that if providers choose vancomycin over metronidazole to treat patients with severe CDI, it should result in a lower risk of death for those critically ill patients,” Rubin commented.

In the study, less than 15% of CDI patients, including severe cases, received vancomycin.

The study results did not show a significant difference in the CDI recurrence rate after either antibiotic treatment, nor did it show a significant difference in the rates of death after either antibiotic treatment for mild-to-moderate cases of CDI.

Stevens cautioned that the study was observational and did not prove “cause and effect” of the drug. In addition, the study focused primarily on men, although the CDI treatment outcomes were similar for men and women.

According to Stevens, future investigations should balance the targeted application of vancomycin treatment, especially for cases of severe CDI, with economic considerations and the consequences of antibiotic resistance.

Source: Medical Xpress; February 6, 2017.