Coronavirus disease (COVID-19), which is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), predominantly includes pulmonary symptoms; however, <10% of cases also include gastrointestinal events, including abdominal pain, diarrhea, and vomiting (1–4). During the COVID-19 pandemic, clinicians must be vigilant of co-infections in patients with COVID-19.

Several studies have collected data on concomitant antibiotic use in patients with COVID-19. A single-center study of 52 critically ill patients cited hospital-acquired infection in only 7 (13.5%) patients, yet 49 (94%) patients received antibiotic therapy (5). Another study, which analyzed 113 deceased patients from a cohort of 799 moderate-to-severely ill COVID-19 patients during January 13–February 12, 2020, reported that 105 (93%) deceased patients and 144 (89%) survivors had received empiric antibacterial therapy with either moxifloxacin, cefoperazone, or azithromycin (6). These antibiotics are strongly associated with Clostridioides difficile infection (CDI) (7). We report an observation of CDI as a co-occurrence or sequalae of overuse of antibiotics in COVID-19 patients.

We conducted a clinical surveillance review of CDI for all laboratory-confirmed COVID-19 patients treated at any of the hospitals belonging to Detroit Medical Center (Detroit, Michigan, USA). We screened patients by using TheraDoc software (https://www.theradoc.com) during March 11–April 22, 2020. We abstracted data regarding baseline demographics, medical history, symptoms, laboratory values, microbiologic findings, concomitant antibiotic use, and treatment for CDI. We obtained institutional review board approval for this study.

We identified 9 cases of co-infection with SARS-CoV-2 and C. difficile. This cohort mainly included elderly patients who were predominantly female (Table). The rate of CDI at the center was 3.32/10,000 patient-days during January–February 2020 and increased to 3.6/10,000 patient-days during March–April 2020.

We noted prior CDI in 3 patients; these infections occurred 1–4 months before admission. All patients were confirmed to be positive for C. difficile by PCR and showed symptoms of diarrhea in addition to other characteristic signs and symptoms, such as abdominal pain, nausea, and vomiting. Two patients had diarrhea and were found to be positive for C. difficile at admission, whereas the remaining 7 had onset of diarrhea only after COVID-19 diagnosis; median duration from CDI diagnosis to COVID-19 diagnosis in these 7 patients was 6 days. This group of patients were severely ill, having high ATLAS scores (https://www.mdcalc.com/atlas-score-clostridium-difficile-infection) and multiple underlying conditions; hypertension (n = 8) and diabetes (n = 5) were the most frequent of these conditions.

Three patients received antibiotics in the month before admission; 8 received antibiotics at admission. One patient was initiated on antibiotics on day 15; this patient was also receiving antibiotics the month before admission. The most commonly administered antibiotics were cefepime (n = 5), ceftriaxone (n = 3), meropenem (n = 2), and azithromycin (n = 2). Specific CDI therapies were oral vancomycin (n = 6); vancomycin and intravenous metronidazole (n = 1); no treatment (n = 1); and a combination of oral vancomycin, intravenous metronidazole, rectal vancomycin, fidaxomicin, and fecal microbiota transplantation (n = 1). One patient who did not receive antibiotics was considered to be colonized with C. difficile. Four (44.4%) patients died during hospital admission, 1 (11.1%) was discharged to hospice, 1 (11.1%) is still hospitalized, and 3 (33.3%) were discharged to a long-term care facility.

CDI is a challenging disease, with a recurrence rate of 15%–20% and a mortality rate of 5% (8). When CDI is present as a co-infection with COVID-19, CDI therapy can be difficult to monitor if diarrhea persists because of COVID-19.

These cases highlight the importance of judicious use of antibiotics for potential secondary bacterial infection in patients with COVID-19. Antibiotics are known to have unintended consequences, such as C. difficile infection. All 9 patients received antibiotics; the median duration of antibiotic use before PCR-positive CDI was 5 days. All patients in our cohort were elderly, an age group at higher risk for complications from overuse of antibiotics, such as adverse events, antibiotic resistance, and concomitant infections like CDI (9). Secondary infections on top of CDI can increase the risk for death in patients with severe COVID-19; in this cohort, 4 patients died and 1 was discharged to hospice. To prevent CDI co-infections during the COVID-19 pandemic, integrated use of antimicrobial stewardship is needed to monitor appropriate antibiotic use.

Symptoms of CDI can complicate diagnosis of COVID-19 because both conditions can have similar manifestations; in a study of 206 COVID-19 patients, 19.4% had diarrhea as the first symptom onset (10). Of the 2 patients who had CDI diagnosed at admission, 1 patient solely had gastrointestinal symptoms, which possibly led to delayed diagnosis of COVID-19. Both COVID-19 and CDI should be considered when evaluating patients with diarrhea during the COVID-19 pandemic. Distinguishing between actual CDI versus colonization also is vital; 1 patient in our cohort was colonized. A limitation of this study is the small number of cases. However, in the face of the COVID-19 pandemic and the extensive use of antibiotics, clinicians should remain aware of possible CDI and SARS-CoV-2 co-infection.

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