Reduced fidaxomicin susceptibility may emerge during C. difficile treatment
Key takeaways:
- Among 108 patients with fidaxomicin-treated C. difficile, six had reduced fidaxomicin susceptibility.
- Patient-to-patient spread was suspected among three patients with “genomically indistinguishable” isolates.
Clostridioides difficile isolates with reduced fidaxomicin susceptibility may emerge during treatment and could spread to other patients, researchers found.
“I was consulted on a patient with C. difficile infection (CDI) who had no response after 10 days of fidaxomicin but responded well after a switch to oral vancomycin,” Curtis J. Donskey, MD, chair of the infection control committee at the Cleveland VA Medical Center, told Healio. “This raised the question of whether reduced susceptibility might have contributed to treatment failure and led us to do the study.”
Donskey and colleagues conducted a 3-year cohort study of patients with CDI to evaluate the frequency of infection with isolates with reduced fidaxomicin susceptibility.
For the study, stool specimens cultured for C. difficile underwent susceptibility testing followed by whole-genome sequencing to identify mutations associated with reduced fidaxomicin susceptibility and to determine if the isolates were related.
Of 108 patients treated with fidaxomicin, six had isolates with reduced fidaxomicin susceptibility three achieved clinical cure with fidaxomicin, two had clinical failure and one refractory CDI. The researchers noted that none of the isolates with reduced susceptibility had mutations associated with rifamycin resistance and that all were susceptible to vancomycin, rifampin, moxifloxacin and erythromycin.
“There was evidence from lab studies that reduced fidaxomicin susceptibility can emerge due to mutations in RNA polymerase so it was inevitable that this would occur in patients,” Donskey said. “It wasn’t clear if this would be clinically significant because fidaxomicin achieves high concentrations in the intestinal tract and there was some evidence that the mutations might make the C. difficile strains less fit to cause illness.”
Among the six patients, three were infected with “genomically indistinguishable” ribotype 097 isolates. The researchers wrote that this ribotype is “rarely reported” and accounted for only 0.3% of CDI cases between 2012 and 2020, according to CDC surveillance data.
They added that there were no ward-level interactions between the three patients however, the “presumptive index case” had prolonged stays in the hospital and long-term care facility. The other two patients had six or seven outpatient hospital visits each during the first patient’s stay.
“Clinicians should be aware that reduced susceptibility should be considered as a potential contributor to fidaxomicin treatment failure
For ore nformation:
Curtis J. Donskey, MD, can be reached at curtis.donskey@va.gov.