Exploring Doxycycline’s Impact on C difficile Infections: An In-Depth Interview With Kari A. Mergenhagen, PharmD, BCPS, BCIDP

Navigating the complexities of health care, particularly concerning Clostridioides difficile infections, requires a comprehensive understanding of treatments. Infection Control Today^® (ICT^®) exclusive interview with Kari A. Mergenhagen, PharmD, BCPS, BCIDP, residency director for infectious diseases at the Veterans Affairs (VA) of Western New York Healthcare System, as she unravels the potential of doxycycline in managing C difficile infections among hospitalized pneumonia patients as described in a recent study published in the American Journal of Infection Control. The title of the study is “Impact of Doxycycline on Clostridioides difficile Infection in Patients Hospitalized With Community-Acquired Pneumonia.”

ICT: Your study found that doxycycline might reduce the development of new C difficile infections in hospitalized patients with pneumonia. Could you elaborate on why doxycycline showed a significant difference in patients with a prior history of C difficile and how it might function differently from azithromycin?

Kari A. Mergenhagen, PharmD, BCPS, BCIDP: C difficile is a bacterium that can overgrow in the gut and disrupt the normal gut microbiome. Once patients develop an episode, they are at risk for recurrence. Each recurrence significantly increases the risk for further recurrences. Additionally, antibiotic use is a widely recognized risk factor for CDI as it further alters our gut microbiome. This may be why we saw the best benefit in patients with a history of C difficile who received doxycycline. The potential protective benefit of doxycycline is not completely known, but one idea includes its extensive absorption in the upper GI tract, with minimal impact on our gut microbiome.

ICT: The analysis focused on a specific demographic within VA hospitals, which were predominantly male, older, and Caucasian. How confident are you in generalizing these findings to a broader demographic, especially considering the variation in patient populations across different health care settings?

KAM: I think it would be broadly applicable to most patients. The VA serves a vulnerable population of older patients. Age is a risk factor for C difficile.

ICT: What prompted the decision to exclude patients diagnosed with Legionella pneumonia or viral pneumonia from the study? Could these exclusions influence the broader applicability of your findings in different patient groups?

KAM: We excluded viral pneumonia because it is not treated with antibiotics. If patients were started on antibiotics for possible bacterial pneumonia and then viral pneumonia was diagnosed, the antibiotics would be discontinued. Legionella pneumonia was excluded because azithromycin is favored for this type of pneumonia due to its excellent lung penetration and improved coverage against different Legionella species.

ICT: Among the patients treated with doxycycline, what were the common types of pneumonia that led to this specific treatment choice, and how did these types differ from those treated with azithromycin?

KAM: The only pneumonia we looked at was presumed community-acquired pneumonia. Hospital-acquired pneumonia requires treatment with a broader antibiotic regimen. We decided to look at community-acquired pneumonia because azithromycin or doxycycline are typically added onto a beta-lactam antibiotic for coverage of atypical organisms. This narrow inclusion criterion allowed a pure sample to study the population differences.

ICT: Your study suggests a potential 45% reduction in antibiotic-associated C difficile infection for patients with a history of C difficile receiving doxycycline. Are there any plans or considerations for a prospective study to validate and further investigate these findings, especially concerning the choice of antibiotic for patients at risk of C difficile infections?

KAM: We currently do not have any plans to conduct a prospective study to validate these findings. The C difficile rates for [community-acquired pneumonia] CAP are low, so it would require a very large sample size.

ICT: Given the rising concern of antibiotic resistance, do you foresee any concerns or potential risks associated with the increased use of doxycycline over azithromycin in patients with a prior history of C difficile or other patient groups?

KAM: If antibiotics are being used appropriately, such as the right antibiotic, the correct indication for use, and coverage of the right organism, there is less concern for antibiotic resistance.