This Antibiotic May Reduce C. Diff Risk in Pneumonia Patients

Compared with azithromycin, doxycycline was associated with reduced Clostridioides difficile infection (CDI) among hospitalized patients with community-acquired pneumonia (CAP), a retrospective cohort study found.

Used alongside ceftriaxone, the tetracycline antibiotic was associated with a 17% decrease in CDI within 30 days when compared with azithromycin (OR 0.83, 95% CI 0.70-0.99), reported Kari Mergenhagen, PharmD, of the Veterans Affairs of Western New York Healthcare System, Buffalo, and coauthors in the American Journal of Infection Control.

Among patients who had a previous history of a CDI, doxycycline was associated with a 45% reduction in recurrent infection (OR 0.55, 95% CI 0.31-0.91), according to their nationwide analysis of Veterans Affairs (VA) data.

Mergenhagen told MedPage Today that these findings could support doxycycline as a first-line prevention of CDI in CAP patients. “It may prevent them from having a C. diff relapse, which we know is very disruptive to their life and can lead to longer hospital stays.”

She suggested a role for doxycycline as a tool that also helps neighboring patients in the hospital.

“Unfortunately when you have one case of C. difficile on the floor, a lot of times you’re going to get more, because C. diff spreads. We obviously do our best as hospital workers … with good hand hygiene, gowns, and gloves and things like that, but it still doesn’t necessarily prevent patient-to-patient spread,” she said.

“Any time we can reduce C. diff in the healthcare field, you’re not only helping the patient in front of you, but also every patient on that ward, potentially,” Mergenhagen emphasized.

CDI affects approximately 500,000 patients in the U.S. annually and is fatal for 15,000 to 30,000 each year. Following an initial case of CDI, about 35% of patients will go on to experience a second infection.

Mergenhagen’s group cited research showing that doxycycline may attenuate C. difficile toxin production through its mechanism of action as a protein synthesis inhibitor. It is also believed that its lower association with CDI may be partly attributed to its minimal impact on gut flora due to extensive absorption in the upper gastrointestinal tract.

Doxycycline may also share similarities with tigecycline, a derivative of tetracycline that has some evidence of efficacy against C. difficile.

“This does not mean we can use doxycycline to treat C. diff, it is just that time and again we have seen a lower odds of incident C. diff infection with doxycycline and in the case of community-acquired pneumonia it can be ‘protective’ when other antibiotics that do confer a higher risk of C. diff are used, such as cephalosporins,” cautioned Tara Vijayan, MD, of the David Geffen School of Medicine at UCLA Health in Los Angeles.

The retrospective study included 156,107 VA patients who had been diagnosed with pneumonia from 2009 to 2022. Treatment was azithromycin in 86.9% of cases and doxycycline in the remaining 13.1%.

The 96.4% male cohort had an average age of 72 years, and was over 75% white. Prior to the index hospitalization, 0.6% of the azithromycin patients and 1.1% of the doxycycline patients had had a positive PCR test for C. difficile within the previous year.

The incidence of CDI within 30 days of starting antibiotic therapy reached 0.8% of the azithromycin group and 0.7% of the doxycycline group.

Regardless of treatment, a person who had a history of CDI within the past year was 18.5 times more likely to develop CDI during CAP hospitalization.

Other predictors of CDI were a high Charlson Comorbidity Index (OR 1.20, 95% CI 1.08-1.36) and more ceftriaxone doses (OR 1.03, 95% CI 1.01-1.04).

The study’s retrospective design left room for residual confounding. Researchers also acknowledged the study’s potential limited applicability to other populations outside the VA system.

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