COVID-19 and C. difficile

COVID-19 Complications

C. difficile infection (CDI) is a challenge to tackle in a normal year. Unfortunately, the end of 2019 introduced a new pathogen to the block, launching us into the COVID-19 pandemic.This module will briefly cover some challenges and complications to CDI treatment caused by the COVID-19 pandemic.

*Note: research on this topic is still being conducted, so the information may change as more findings are published and as the pandemic situation continues to evolve. Information in this module is current up until April 4th, 2021.

Increased Exposure and Risk

If you recall from our introductory sections, risk factors for acquiring a CDI include old age, prolonged hospital stay, and antibiotic use, among other factors. It certainly does not help that the COVID-19 pandemic more severely affects elderly populations compared to younger populations, resulting in more elderly patients having prolonged hospitalization (1). This places an already high-risk group in the perfect environment for acquiring a CDI.

It has been estimated that about 72% of COVID-19 patients are given broad-spectrum (non-specific) antibiotics to prevent bacterial co-infections and super-infections that may occur on top of the COVID-19 infection (2). We know that use of broad-spectrum antibiotics is a significant risk factor for developing a CDI. In addition, mild COVID-19 patients can be treated with a cocktail of antibiotics such as moxifloxacin, cefoperazone, or azithromycin which are all drugs highly associated with developing a CDI (3). This means that treatment or management strategies for COVID-19 may inadvertently be increasing the risk of acquiring a CDI in populations that are already at high risk.

Finally, as you may have heard on the news already, COVID-19 has particularly impacted long-term care facilities. About 75% of residents in long-term care facilities already receive one course of antibiotics for 6 or more months (4). Thus, if COVID-19 treatment involves further antibiotic use, the risk of getting a CDI increases even more in these patients.

Ultimately, COVID-19 management may be placing patients that are already at high risk of developing a CDI in an even higher-risk situation.

Are there more cases during the pandemic?

There is currently not that much data out right now. However, a group of investigators from the University of Virginia Health System conducted a study to answer this question at a single hospital center from November 2019 to May 2020 and presented their data at the American College of Gastroenterology 2020 Conference. They found that CDI cases decreased both in proportion and number among hospital inpatients during the studied pandemic period compared to pre-COVID numbers. As for CDI cases among outpatient visits, these numbers remained relatively unchanged between the pre- and post-COVID era. The decreasing trend observed in inpatients may be due to the reduction of elective procedures that are high risk for CDI during the pandemic, as well as the hypervigilance and adherence to sanitation, hygiene, and infection control in hospitals during the pandemic (5).

However, keep in mind that this study was only performed at one hospital center and the data included was up until May 2020. Further studies that involve more health centers and more recent and longer periods of study are needed to assess trends in C. difficile infection as the pandemic continues to progress.

Diagnostic challenges caused by COVID-19

The initial symptoms of a CDI and of COVID-19 infection can be similar in some cases. Both infections can present symptoms such as diarrhea, nausea, vomiting, and abdominal pain which can make it difficult to diagnose a CDI while COVID-19 infections are so rampant. This can cause patients to be treated as if they only have COVID-19, which may exacerbate the CDI or leave it untreated. Thus, clinicians must be especially vigilant of a co-infection with C. difficile during the pandemic (6).

Impact on Fecal Microbiota Transplantation (FMT)

Finally, the pandemic is also impacting the ability of patients to receive fecal microbiota transplantation (FMT), a life-saving and cost-effective treatment for recurrent CDI. FMT is when a stool sample from a donor is introduced into the gut of a CDI patient in order to transfer healthy gut bacteria into the patient to help fight off the CDI (see FMT section of our website for more info).

The pandemic has forced hospitals to decrease the performance of certain procedures to reduce the potential transmission of the virus. Hospitals have had to prioritize which procedures they would postpone during the pandemic and which ones they would continue based on weighing risk and need. FMT is considered life-saving and its benefits would outweigh the risks for some patients. Thus, FMT can be considered non-postponable.

However, one major challenge brought on by the pandemic is that there is a potential risk that the virus may be transmitted through feces and thus, the stool sample needed for transplantation. As a consequence, updates to FMT protocols at all levels have had to be “re-vamped” during the pandemic. The Food and Drug Administration (FDA) in the United States had even recommended that only stool samples generated before December 1st, 2019 should be used for FMT until pandemic protocols could be developed, COVID-19 testing of donors and stool samples could be made feasible, and screening protocols made available. Thus, there was a temporary halt in FMT procedures being performed at the beginning of the pandemic. Some FMT centres even had to suspend the active recruitment of new donors due to the pandemic until proper screening tools were developed and made available.

Furthermore, as physicians try to prioritize which patients need FMT the most, some “typical” recurrent CDI patients that normally would have received an FMT before the pandemic, may instead receive other approved therapies if the physician determines them to be appropriate given the pandemic. These alternative therapies include vancomycin, fidaxomicin, and/or bezlotoxumab. This strategy is beneficial as it can effectively treat some recurrent CDI patients while also creating a window of time for the reorganization of FMT protocols during the pandemic to catch up. However, patients for which alternative therapies have already not worked and for which FMT seems to be the only appropriate option will be the highest priority to receive non-postponable FMT (7).

FMT Protocol Adjustments

According to published guidelines for FMT protocols during the pandemic developed by an Italian group (8), if patients require FMT, but are hospitalized due to COVID-19 infection, then they must be treated in a dedicated room with its own equipment, separate from the rooms that non-COVID-19 patients receiving FMT would be treated. This may present resource allocation challenges for some health centers.

One FMT center in Italy developed a working FMT protocol to prevent transmission of the COVID-19 virus that has allowed their center to maintain pre-COVID era standard volumes, efficacy, and safety of FMT for CDI patients during the pandemic. They have reorganized all aspects of the procedure which include, patient selection, donor screening, stool storage and quarantine, the FMT procedure itself, and follow-up evaluation. Some of the changes made to their protocols include extensive use of personal protective equipment, available screening tools, quarantine of stool sample and secondary follow-up with the donor after quarantine, and having a separate building and room for COVID-19 infected patients needing FMT. If you’d like to see their detailed workflow and methods, please click here.

Note, as the authors of the guidelines mentioned, although this model is promising and has worked for their center with their resources, this workflow model may not work for every FMT center. Other FMT centers may currently face challenges that prevent them from maintaining the same volume, safety, and efficacy of FMT procedures that they used to be able to perform before the pandemic (8).

Did this help you learn about C. difficile and COVID-19?

References

1.    Leung C. Clinical features of deaths in the novel coronavirus epidemic in China. Rev Med Virol. 2020;30(3):e2103.
2.    Huttner BD, Catho G, Pano-Pardo JR, Pulcini C, Schouten J. COVID-19: don't neglect antimicrobial stewardship principles! Clin Microbiol Infect. 2020;26(7):808-10.
3.    Chen J, Qi T, Liu L, Ling Y, Qian Z, Li T, et al. Clinical progression of patients with COVID-19 in Shanghai, China. J Infect. 2020;80(5):e1-e6.
4.    Jump RLP, Crnich CJ, Mody L, Bradley SF, Nicolle LE, Yoshikawa TT. Infectious Diseases in Older Adults of Long-Term Care Facilities: Update on Approach to Diagnosis and Management. J Am Geriatr Soc. 2018;66(4):789-803.
5.    Lutz R. Comparing C. Diff Infection Rates Before and During COVID-19 Pandemic [Online]. HCP Live; 2020 [updated November 19, 2020.
6.    Sandhu A. Clostridioides difficile in COVID-19 Patients, Detroit, Michigan, USA, March–April 2020. Emerging Infectious Diseases by Centeres for Disease Control and Prevention. 2020;26(9).
7.    Ianiro G, Mullish BH, Kelly CR, Kassam Z, Kuijper EJ, Ng SC, et al. Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic. Gut. 2020;69(9):1555-63.
8.    Ianiro G, Bibbò S, Masucci L, Quaranta G, Porcari S, Settanni CR, et al. Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study. Dig Liver Dis. 2020;52(12):1390-5.