Statins Show Protection Against Clostridium Difficile, Should Not Be Withheld in At-Risk Patients

Sahil Khanna, MBBS, gastroenterologist at the Mayo Clinic

Sahil Khanna, MBBS

Patients using statin drugs may face lower risk of Clostridium difficile (CDI) infection than those not prescribed such medication, data on almost 35,000 cases of CDI suggest.

Meta-analyses of 8 studies assessing the association between statin use and the bacterial infection found that statins may be associated with a 20% reduction in the risk for CDI. Patients using statins had a 4.3% infection rate compared with a 7.8% rate for those not taking the drugs, the researchers reported.

“Health care providers should continue to encourage and reinforce the use of statins when indicated in patients, not only for their direct cardiovascular benefits but also for indirect benefits such as prevention of CDI,’’ corresponding author Sahil Khanna, MBBS, told MD Magazine.

The recommendations are especially true in settings involving systemic exposure to antibiotics, the researchers wrote in a study published by Dove Medical Press.

“Elective withholding of statin medications in hospitalized patients with multiple risk factors for CDI should be discouraged,” said Khanna, a gastroenterologist at the Mayo Clinic in Rochester, MN.

Khanna noted, however, that the team found no protective effect from statins when reviewing studies that adjusted for confounders such as age, sex and comorbid conditions.

“But this analysis barely missed statistical significance, which could be a sample size issue,” he said. “The difference still remains clinically meaningful, but should be interpreted with caution.”

Exposure to antibiotics alters the intestinal microbiota, making usage of the drugs the most common factor predisposing individuals to CDI.

Despite improved antibiotic stewardship and new treatment strategies, infections are increasing and outcomes for patients are worsening, the researchers wrote. Innovative methods are required to tackle the infection.

While statins are largely prescribed for cardiovascular conditions, these drugs have been shown to improve outcomes in cases of pneumonia, pulmonary hypertension, new-onset inflammatory bowel disease, hepatocellular carcinoma and gastric cancer, among other conditions, previous research suggests.

When it comes to statins and CDI, though, studies have yielded conflicting findings, according to the authors.

To try to pin down a potential preventative link between statin use and CDI, the authors reviewed 6 case-control and 2 cohort studies in which patients had been recruited from 2002 through 2015.

“To our knowledge, this study is the first meta-analysis to explore an association between statins and incident CDI,’’ the authors wrote.

The research included 156,722 patients who were exposed to statins and 356,185 controls. A total of 34,849 cases of CDI were reported in 7 of the studies.

In 5 of the 8 included studies, statins decreased the risk of incident CDI. One study showed an increased risk, however, that investigation was limited to intensive care unit (ICU) patients with sepsis and included very few patients with CDI.

“We conclude that statins may be associated with a decreased risk of CDI, with a 20% risk reduction,’’ the researchers said.

Khanna described several theories to explain why statins might show a protective effect against CDI.

“Statins are known to interfere with molecules involved in endothelial adhesion and trans-endothelial migration of polymorphonuclear cells to sites of inflammation,” he said. "Statins also reduce the activation of the monocyte/macrophage system and reduce the cytotoxicity of T cells, reducing inflammation.’’

It is also possible that the protective effects of statins relate to CDI toxins targeting Rho-GTPase proteins in the host cytosol, which is also a major target for the action of statins.

Another potential mechanism against CDI could be the alteration of microbiota by statins, although the specific effects of statins on the intestinal microbiome are unknown, noted Khanna.

“A large cohort study which follows patients at risk for CDI who are on statins for other indications and comparing them to patients at risk for CDI who are not on statins would be the next logical step,” he concluded.

The study, "Statin use and the risk of Clostridium difficile infection: a systematic review with meta-analysis" was published in Dovepress.