Viral Co-Infections With C. Diff Add Insult to Injury

Gastrointestinal viruses often come along with community-acquired Clostridioides difficile infection (CA-CDI), CDC researchers said.

Adult and pediatric patients with CA-CDI showed 12% prevalence of viral GI pathogens, norovirus being the most common, reported Alice Y. Guh, MD, MPH, of the CDC in Atlanta, reporting in PLoS One.

Assessing 155 patients with stool-confirmed CA-CDI at five cross-country U.S. sites from December 2012 to February 2013, the investigators identified 18 CDI patients with such viruses: 10 norovirus, four adenovirus, three rotavirus, and one sapovirus.

Co-infected patients were more likely than non-co-infected to have nausea or vomiting – 56% versus 31% (P=0.04) – suggesting viral co-pathogens contributed to these symptoms in some.

Paralleling earlier research, no significant differences emerged between the two groups in previous healthcare, medication exposures, or CDI outcomes complications.

An earlier U.S. study of viral co-infections in pediatric patients reported a higher prevalence of 24% and an association with a greater CDI bacterial burden. Again, norovirus was the most common viral pathogen detected. Other countries have reported even higher viral co-infection rates, approaching 70% in some cases.

A 2016 study assessing for additional symptoms such as abdominal pain and gas found CDI patients co-infected with norovirus had more severe gastrointestinal symptoms.

The current study was undertaken by the CDC’s Emerging Infections Program (EIP), which conducts population- and laboratory-based CDI surveillance. The five participating EIP sites were in Georgia, Maryland, Minnesota, New York, and Oregon.

Although primarily healthcare-associated, CDI has been increasingly reported in the community among people with no traditional CDI risk factors. In previous studies, more than 35% of CA-CDI patients reported no recent antibiotic use, while more than 50% reported nausea or vomiting, neither of which is traditionally associated with CDI. These findings raised concerns that other pathogens may be involved.

They speculated that some CA-CDI cases testing positive for a viral pathogen may have been truly co-infected, with the viral pathogen causing nausea or vomiting and CDI causing diarrhea. Alternatively, some of the co-infected cases could have been merely colonized with C. difficile and actively infected solely with a viral pathogen; in many cases identified as co-infections, C. difficile could not be cultured.

“As the use of multiplex molecular panels increases, a greater frequency of co-pathogens might be identified among patients with CDI,” Guh and colleagues wrote, calling for a better understanding of the clinical significance of such findings in order to guide patient management and infection prevention.

Thaddeus Stappenbeck, MD, PhD, of the Cleveland Clinic’s Lerner Research Institute in Ohio, commented to MedPage Today that polymicrobial infection of the intestine is a well-established paradigm in clinical medicine. It affects a small but significant percentage of patients infected with one gut viral or bacterial pathogen who show co-infection with a pathogen from the other class, he said.

“The co-infection seems to create worse symptoms in a subset of these patients but not all,” he told MedPage Today.

“This report provides evidence that C. diff infection shows co-infection with common viral infections at a rate similar to other bacterial pathogens. This fits the current paradigm well. Thus for patients with severe C. diff, it may be helpful to evaluate for the presence of viral pathogens in those patients.”

Steppenbeck added that the mechanisms of the interactions are mostly unclear. “One informative example is uncontrolled simian immunodeficiency virus in infected monkeys that show multiple bacterial and viral gut pathogens simultaneously due to reduced adaptive immunity/gut barrier function,” he said.

Guh and colleagues cautioned that they tested only for viral co-pathogens but other organisms may be at play (in one case, the patient was also positive for Campylobacter). In addition, since the evaluation was performed on specimens collected during 2012-13, prevalence of viral co-infections among patients with CA-CDI could since have changed.

The researchers also acknowledged that patients’ records could have been incomplete, restricting the study’s ability to assess relevant risk factors and additional clinical characteristics, and the study was based on a convenience sample that might not be representative of all CA-CDI patients.