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Patients with sickle cell disease may have lower risk for C. difficile

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February 27, 2019

Seah H. Lim, MD, PhD
Seah H. Lim

Findings from a retrospective cohort study conducted at a single hospital suggest that patients with sickle cell disease have a lower — and not higher — risk for Clostridioides difficile infection compared with the hospitalwide patient population, researchers reported in The New England Journal of Medicine.

In introducing their study, Seah H. Lim, MD, PhD, and colleagues from New York Medical College said health care-associated C. difficile infections “might be expected to be more common” in patients with sickle cell disease, and not less common, as the study found.

“Patients with sickle cell disease have defects in immune function; they are frequently hospitalized for painful vaso-occlusive crisis and are often given empirical antibiotic treatment for fever in this setting. They also have intestinal dysbiosis,” they wrote.

Lim and colleagues conducted their study at Westchester Medical Center in Valhalla, New York, between January 2015 and November 2018. They included 106 patients with a median age of 26 years, representing 365 total consecutive hospital admissions.

According to the study, the mean length of hospital stay was 10.2 days and the total number of patient days spent in the hospital was 3,727. During 180 hospitalizations, 454 courses of antibiotics were administered, with the most frequently used agents being ceftriaxone, azithromycin, vancomycin, piperacillin–tazobactam and cefepime, the researchers noted.

For reference, Lim and colleagues highlighted other studies conducted in hospitalwide populations that showed incidence rates of 6.3, 8.5 and 9.3 cases per 10,000 patient-days among adult patients. At their institution, the annual incidence rates hospitalwide were 7 to 10.8 cases per 10,000 patient-days, and the combined incidence rate was 9.1 cases per 10,000 patient-days (95% CI, 7.3-11.1).

However, among patients with sickle cell disease, only one case of C. difficile infection was reported over 3,727 patient-days, for an incidence rate of 2.7 cases per 10,000 patient-days (95% CI, 1.8-3.9) — significantly lower compared with the hospitalwide patient population.

“Despite the very many risk factors, such as intestinal dysbiosis, repeated hospitalizations, and frequent use of antibiotics, the intestine in sickle cell patients confers a protective effect against C. difficile infection,” Lim told Infectious Disease News. “Further knowledge into the mechanisms may provide important translational information to devise novel approaches to reducing the risks for C. difficile infections in other high-risk patient groups.” – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.

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Sickle cell is a complex disease, and we know that patients with sickle cell have alterations in their microbiome. It is also true that C. difficile is a microbiome disease. Based on this study, there is some evidence that perhaps the microbiome of patients with sickle cell disease contains bacteria that are protective against C. difficile. Following up on this lead, may be something that is an avenue for further research, to understand what it is in the microbiome of a patient with sickle cell disease that allows them to have this resistance to C. difficile. Microbiome-based therapies against C. difficile are an active area of research and this phenomenon may be a productive lead and one clue that can be studied.

Clinicians often think of any kind of chronic illness as a risk factor for C. difficile, but it may not be completely that homogenous. There could be certain chronic illnesses that are higher risk for C. difficile and others do not carry a higher risk for the bacterial infection.

However, this is an observational study, and it is hard to completely discern any causal mechanisms to understand what is happening in this type of a study. What it looks like in this study, though, is that sickle cell does not have as a high a risk for C. difficile infections as other chronic illnesses. Thus, not all chronic illnesses should be treated the same in terms of C. difficile risk.

It will be really important to understand the mechanism for this resistance to C. difficile in patients with sickle cell disease. The authors of the article discuss some of the components of the microbiome of a patient with sickle cell disease and how that differs from a someone without sickle cell disease. The biggest research question is trying to untangle the effects of the patient’s microbiome on C. difficile and determining whether that information can be harnessed for other C. difficile microbiome-based treatments that are currently being developed in an attempt to figure out the exact mix of the C. difficile-resistant microbiome. I think this study provides some clues to that.

Amesh A. Adalja, MD

Spokesperson, Infectious Diseases Society of America
Senior scholar, Johns Hopkins Center for Health Security

Disclosure: Adalja reports no relevant financial disclosures.