Vancomycin Nonsusceptibility Common in CDI Cases

A new report raises an alarm about the prevalence of Clostridioides difficile (C diff) strains that are resistant to one of the most common therapies.

The study found vancomycin-resistant C diff was common in two different regions studied. The authors argue that the findings support the need for routine susceptibility testing.

Writing in the journal Clinical Infectious Diseases, corresponding author Charles Darkoh, PhD, of the University of Texas, and colleagues, explained that C diff infection (CDI) is a major public health problem not only because of its potentially fatal symptoms, but also because as many as one-quarter of CDI cases recur following treatment with antibiotics.

“The number of antibiotics currently available for CDI treatment are dwindling because of the intrinsic ability of C difficile to resist multiple drugs,” the authors wrote. “Oral vancomycin is one of the few drugs currently recommended for CDI treatment.”

They added that vancomycin is one of a small number of therapies that appears to be effective against both severe and nonsevere cases of CDI. Unfortunately, Darkoh and colleagues noted that vancomycin-resistant strains are also becoming more prevalent.

The international team of researchers decided to find out whether vancomycin-resistant strains were circulating in their own patient populations in Houston, Texas, and Nairobi, Kenya. They embarked on a study to collect stool samples of patients with CDI to see if they could identify vancomycin resistance within the strains.

Samples were collected from a total of 438 patients in Houston and 98 patients in Kenya. They were then examined for the presence of vancomycin and metronidazole nonsusceptible C diff using a variety of testing methods.

The analysis identified significant proportions of resistant strains in both locations. In Houston, 26% of samples had vancomycin resistance and 29% were nonsusceptible to metronidazole. In Nairobi, 67% of patients had vancomycin-resistant isolates, and 85% of samples were metronidazole-nonsusceptible.

The investigators noted that metronidazole is poorly bioavailable in the colon, which they said could explain the rates of nonsusceptibility. They added that “exposure to subinhibitory concentrations could have contributed to selection of resistance.”

Fecal concentrations of vancomycin were much higher than that of metronidazole, which the authors said could have major implications for CDI treatment.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in CDI since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” Darkoh and colleagues said.

Though the authors chose to focus on vancomycin because of its status as a highly recommended therapy, they said susceptibility studies should also be done for other therapies, such as fidaxomicin, tigecycline, and ramoplanin.

“The spread of C difficile strains that are not susceptible to vancomycin will produce challenges to therapy for this common infection and has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” the authors concluded.

Furthermore, Darkoh and colleagues said, routine susceptibility testing and clearer, specific definitions of resistance will be important components of fighting CDI, as will the expansion of molecular detection of genes involved in vancomycin nonsusceptibility.