Older Cancer Patients at Higher Risk of
C diff Infection

Ricki Lewis, PhD

August 23, 2019

Older adults with cancer, particularly of the blood or recently-diagnosed metastatic solid tumors, are at higher risk of Clostridiodes difficile infection (CDI) compared with people who do not have cancer, according to findings of a study published online August 21 in Emerging Infectious Diseases.

C diff is the leading cause of healthcare-associated infection in the US. It is more than 26 times as likely to strike patients older than 65 years, in whom symptoms are more severe.

A perfect storm of predisposing factors may make older adults with cancer at elevated risk for CDI. Effects of chemotherapy that disrupt resistance to C diff colonization in the GI tract accompany risk factors such as use of antimicrobials, exposure to bacteria in hospitals, and lowered humoral immunity that comes with age.

Further complicating the clinical picture is that both chemotherapy and CDI can cause severe diarrhea. A report from 1992 identified increased risk of CDI in patients receiving chemotherapy who had not taken antimicrobials. (A rapid test to diagnose CDI has been available for more than a decade.)

Mini Kamboj, MD, chief medical epidemiologist for infection control at Memorial Sloan Kettering Cancer Center in New York City, and colleagues sought to untangle the connection between cancer and elevated risk of CDI, seeking identifying factors that could be used to prevent the infection in patients with certain cancers.

The researchers conducted a population-based retrospective cohort study with a nested case–control analysis to probe whether the risk for CDI is higher among older adults with cancer than among older adults without cancer.

The study compared the Surveillance, Epidemiology, and End Results cancer registry with Medicare enrollment information (the SEER-Medicare dataset) for 2011 to controls who didn't have cancer from the SEER geographic regions. The cancer patients had solid (breast, colon, lung, prostate, and head and neck) tumors or liquid (lymphoma, myeloma, leukemia) tumors, and had been diagnosed between 2006 and 2010.

Five controls were randomly matched to each patient for age and sex. All Medicare recipients considered in the study were at least 66 years old in 2011 and had to have been hospitalized at least once that year.

The investigators assessed infection incidence as the percentage of the cohort in whom CDI developed during the study period. They calculated adjusted and unadjusted odds ratios (ORs) for CDI incidence, considering tumor type, stage at cancer diagnosis, and year of diagnosis.

Of the 93,566 beneficiaries, 2.6% had CDI during the time of the study. In unadjusted analyses, 2.8% of people with cancer had CDI compared with 2.4% for individuals who did not have cancer.

The proportion of people with CDI was higher among beneficiaries who were female, or residing in the Northeast US or in cities. CDI risk assessed for 5-year age intervals revealed an increase from 1.9% for patients aged 66 to 69 to 2.9% for patients 85 years or older.

The nested case–control analysis compared 2421 case-patients with CDI to 12,105 controls. Case-patients were more likely to have cancer (54%) than were controls (49%). Case-patients were also more likely to have been hospitalized more than once or had stayed in a skilled nursing facility.

The odds of CDI developing were higher among cancer patients than non-cancer patients (adjusted OR, 1.15; 95% confidence interval [CI], 1.04 - 1.26; P = .005).

Having a liquid tumor was significantly associated with increased risk for CDI compared with no cancer diagnosis (adjusted OR, 1.74; 95% CI, 1.48 - 2.06; P < .001), but having a solid tumor wasn't (adjusted OR, 1.05; 95% CI, 0.95 - 1.16) unless the diagnosis was since 2009. If that was the case, then the stage of the tumor (in situ or local/regionalized) didn't alter the elevated risk of infection. The researchers hypothesize that the elevated risk derives from more intensive chemotherapy at the time of diagnosis of a solid tumor.

Having more than two hospitalizations or a stay at a skilled nursing facility was each associated with increased odds of CDI occurrence, whether or not a patient had cancer.

"Our findings collectively expand knowledge of how cancer diagnosis affects CDI-associated illness among older adults. This population-based assessment can be used to identify targets for prevention of CDI," the researchers conclude. They cite three studies that discuss such measures: a drug (bezlotoxumab) to prevent CDI recurrence and fecal microbiota transplantation.  

"Our study defines the subset of older adults with cancer who would probably benefit the most from such therapies to minimize the vulnerability to CDI during cancer treatment," the researchers write. 

They also point out that CDI can delay or disqualify a patient from further cancer treatment. "The wide-ranging effects of CDI in this population warrants (sic) assessment of primary prevention strategies," they conclude.

Limitations of the study include inability to distinguish whether the type of cancer treatment or overuse of antimicrobials was associated with increased CDI risk, and the study did not include community-acquired CDI cases that did not result in hospitalization, possibly misidentifying some recurrent cases as incident.

Funding for the study was provided by the National Cancer Institute. The study authors have disclosed no relevant financial relationships.

Emerg Inf Dis. Published online August 21, 2019. Full text

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