By Richard R. Watkins, MD, MS, FACP, FIDSA

Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH

Dr. Watkins reports no financial relationships relevant to this field of study.

SYNOPSIS: A prospective cohort study from a single institution found 27% of patients diagnosed with healthcare-associated C. difficile infection were colonized with the same isolate on admission.

SOURCE: Gonzalez-Orta M, Saldana C, Ng-Wong Y, et al. Are many patients diagnosed with healthcare-associated Clostridioides difficile infections colonized with the infecting strain on admission? Clin Infect Dis 2019;69:1801-1804.

The diagnosis of Clostridioides difficile infection (CDI) has important consequences for both patients and healthcare institutions. Emerging evidence suggests many cases of CDI currently classified as healthcare-associated are actually colonized with C. difficile on admission. However, previous studies have not used molecular typing to compare relatedness between admission and infecting strains. Therefore, Gonzalez-Orta and colleagues used whole-genome sequencing (WGS) analysis to compare strains of C. difficile taken on admission to those from patients diagnosed with CDI.

The study was conducted at the Veterans Administration Medical Center in Cleveland. Inclusion criteria were an anticipated length of stay of at least two days, no diagnosis of CDI in the preceding eight months, and no diarrhea at the time of enrollment. Patients who consented had perirectal swabs collected at the time of admission, which were plated on selective media. Stools that tested positive for C. difficile toxin genes by polymerase chain reaction (PCR) were collected from the microbiology laboratory and then cultured for toxigenic C. difficile using a sensitive broth enrichment method. An enzyme immunoassay (EIA) for toxin also was performed. The researchers defined healthcare-associated CDI as the presence of diarrhea (three or more unformed stools in 24 hours) and a positive PCR assay. For patients who had positive perirectal cultures on admission and a diagnosis of CDI, WGS was performed to ascertain the relatedness of the admission and CDI isolates. The investigators recognized the possibility that colonized patients might have been diagnosed with CDI even if they developed diarrhea from noninfectious causes, so they reviewed the medical records to find out if there were other explanations for the diarrhea.

There were 480 patients who enrolled in the study. Of these, 68 (14%) had a positive perirectal swab for toxigenic C. difficile on admission, of which 25 (37%) were detected by the broth enrichment method. During the follow-up period, eight of the 68 (12%) with positive admission rectal swab cultures were diagnosed with CDI, compared to five of 412 (1%) with negative admission cultures (P = 0.0001). Of the eight positive patients, six met the investigational criteria for healthcare-associated CDI (HA-CDI). Three out of the 11 episodes (27%) of HA-CDI occurred in patients who had a positive admission perirectal swab culture for a genetically related strain. Furthermore, four of the eight patients diagnosed with CDI who had a positive admission perirectal swab culture also had a positive EIA for stool toxin.


This is an interesting, although small, study that found a significant proportion (27%) of patients diagnosed with CDI were colonized with the infecting strain on admission. Thus, standard infection control practices (e.g., contact isolation) will not be effective in reducing infections in these patients. This supports the notion that better CDI testing stewardship is needed so that patients with colonization are not falsely diagnosed as having HA-CDI, which carries important ramifications for both the patient and healthcare institutions. For example, patients may receive unnecessary treatment for an infection they do not have, and the diagnosis of CDI will become a permanent part of their medical record, while the healthcare institution suffers due to a publicly reported inaccurate quality measure. Moreover, the study by Gonzalez-Orta and colleagues reminds clinicians that not all nosocomial diarrhea is due to CDI, and providers should carefully consider other potential etiologies (e.g., medications, including antidepressants, antihypertensives, antibiotics, and stool softeners; enteral feedings; and underlying illness).1

The study has some limitations. First, the number of CDI cases was small. Second, the study was conducted at a single institution with a population that was primarily male (95%), had a high rate of hospitalization in the preceding year (44%), and had a high frequency of recent antibiotic use (63%). These characteristics limit the generalizability of the findings to other settings and patient populations. Third, because only one C. difficile isolate was cultured from each perirectal swab, it is possible that additional patients carried the same admission and CDI strains. Similarly, the possibility exists that the infecting strain was present on admission but not detected at that time. Finally, the authors did not provide details about how they ascertained whether a patient with C. difficile colonization had true CDI.

Another take-home point from the study is that it reinforces the usefulness of WGS in helping to solve contemporary clinical dilemmas. Further applications of WGS undoubtedly will be found that will aid in antibiotic stewardship and infection-control efforts. A recent report of WGS used in a cluster of linezolid- and vancomycin-resistant enterococcal infections in transplant recipients when standard microbiology practices proved unreliable highlights the usefulness of this emerging technology.2


  1. Polage CR, Solnick JV, Cohen SH. Nosocomial diarrhea: Evaluation and treatment of causes other than Clostridium difficile. Clin Infect Dis 2012;55:982-989.
  2. Abbo L, Shukla BS, Giles A, et al. Linezolid- and vancomycin-resistant Enterococcus faecium in solid organ transplant recipients: Infection control and antimicrobial stewardship using whole genome sequencing. Clin Infect Dis 2019;69:259-265.