Data Collected Finding Clostridioides difficile in COVID-19 Patients, Detroit, Michigan, USA

Clostridioides difficile in COVID-19 Patients, Detroit, Michigan, USA, March–April 2020

Avnish Sandhu, Glenn Tillotson, Jordan Polistico, Hossein Salimnia, Mara Cranis, Judy Moshos, Lori Cullen, Lavina Jabbo, Lawrence Diebel, and Teena Chopra
Author affiliations: Detroit Medical Center, Detroit, Michigan, USA (A. Sandhu, J. Polistico, H. Salimnia, M. Cranis, J. Moshos, L. Cullen, L. Jabbo, T. Chopra)Wayne State University School of Medicine, Detroit (A. Sandhu, J. Polistico, H. Salimnia, L. Diebel, T. Chopra)GST Micro LLC, Henrico, Virginia, USA (G. Tillotson)



We describe 9 patients at a medical center in Detroit, Michigan, USA, with severe acute respiratory syndrome coronavirus 2 and Clostridioides difficile. Both infections can manifest as digestive symptoms and merit screening when assessing patients with diarrhea during the coronavirus disease pandemic. These co-infections also highlight the continued importance of antimicrobial stewardship.

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 (14). 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 C. 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.comExternal Link) 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 ( Link) 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 awaren of possible CDI and SARS-CoV-2 co-infection.

Dr. Sandhu is an infectious diseases–epidemiology fellow at Detroit Medical Center, Wayne State University School of Medicine. Her current research interest is in multidrug-resistant hospital-acquired infections.


G.T. is a consultant to Melinta, Crestone, Ferring, AirMmax, and Shionogi. Other authors in the manuscript have no relevant conflict of interest or financial disclosure. No funding was needed for this manuscript.


  1. US Centers for Disease Control and Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19) [cited 2020 May 1].
  2. Guan  WJNi  ZYHu  YLiang  WHOu  CQHe  JXet al.China Medical Treatment Expert Group for Covid-19Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med2020;382:170820DOIExternal LinkPubMedExternal Link
  3. Chen  NZhou  MDong  XQu  JGong  FHan  Yet al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet2020;395:50713DOIExternal LinkPubMedExternal Link
  4. Wang  DHu  BHu  CZhu  FLiu  XZhang  Jet al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA2020;323:10619DOIExternal LinkPubMedExternal Link
  5. Yang  XYu  YXu  JShu  HXia  JLiu  Het al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med2020;8:47581DOIExternal LinkPubMedExternal Link
  6. Chen  TWu  DChen  HYan  WYang  DChen  Get al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ2020;368:m1091DOIExternal LinkPubMedExternal Link
  7. Brown  KAKhanafer  NDaneman  NFisman  DNMeta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother2013;57:232632DOIExternal LinkPubMedExternal Link
  8. Guh  AYMu  YWinston  LGJohnston  HOlson  DFarley  MMet al. Emerging Infections Program Clostridioides difficile Infection Working Group. Trends in US burden of Clostridium difficile infection and outcomes. N Engl J Med2020;382:132030DOIExternal LinkPubMedExternal Link
  9. Biedron  CChopra  TIssues surrounding antibiotic use in older adults. Curr Transl Geriatr Exp Gerontol Rep2013;2:1518DOIExternal Link
  10. Han  CDuan  CZhang  SSpiegel  BShi  HWang  Wet al. Digestive symptoms in COVID-19 patients with mild disease severity: clinical presentation, stool viral RNA testing, and outcomes. Am J Gastroenterol2020;1Epub ahead of printDOIExternal LinkPubMedExternal Link