By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: In this retrospective study of an elderly male population hospitalized with community-acquired pneumonia, the combination of doxycycline with a beta-lactam was at least as effective as a respiratory fluoroquinolone or a combination of a beta-lactam with azithromycin.
SOURCE: Uddin M, Mohammed T, Metersky M, et al. Effectiveness of beta-lactam plus doxycycline for patients hospitalized with community-acquired pneumonia. Clin Infect Dis 2022;75:118-124.
Uddin and colleagues performed a retrospective cohort study with propensity score matching to examine the efficacy of treatment of patients hospitalized with community-acquired pneumonia (CAP) with doxycycline together with a beta-lactam antibiotic. Using administrative and clinical databases of the Department of Veterans Affairs Health Care System, they identified 70,533 patients hospitalized over an 11-year period ending in 2012. The criteria included age ≥ 65 years, received no intensive care unit (ICU) care, had adequate follow-up, and received guideline-concordant antibiotic therapy within 48 hours after admission. Guideline concordance means that they received a respiratory fluoroquinolone or an appropriate beta-lactam plus either azithromycin or doxycycline.
A total of 5,282 (7.4%) patients among the total eligible cohort received doxycycline as part of their regimen. The mean age of the cohort was 78.1 years and, as expected, 98.2% were male. The groups receiving and not receiving doxycycline were similar at baseline. The unadjusted 30-day mortality among those who received a beta-lactam plus doxycycline was 6.4%, while it was 9.1% in the comparator group; the unadjusted 90-day mortality rates for the groups were 13.8% and 16.8%, respectively. Each comparison had P < 0.0001. The results were similar after propensity score analysis. The unadjusted length of stay was modestly shorter in the doxycycline group (5.5 days vs. 5.84 days, P = 0.01).
COMMENTARY
The 2019 American Thoracic Society/Infectious Diseases Society of America guideline for empiric treatment of inpatients with CAP who do not require intensive care recommend administration of a beta-lactam antibiotic together with either a macrolide antibiotic or a respiratory fluoroquinolone alone. They recommend the use of doxycycline together with a beta-lactam when there are contraindications to these preferred choices.
Doxycycline has a number of beneficial properties, beside activity against most pathogens causing CAP, including atypical etiologies. These include excellent and rapid oral bioavailability, especially important for older populations and, in contrast to macrolides and respiratory fluoroquinolones, it does not prolong the QTc interval. Also, in contrast to fluoroquinolones, doxycycline is less likely to cause delirium in the elderly and, importantly, it has been reported to be less likely to be associated with the development of Clostridioides difficile disease (which was not assessed in this study). In general, doxycycline is less expensive than either macrolides or respiratory fluoroquinolones.
In concordance with several observational studies, this analysis concludes that doxycycline plus a beta-lactam antibiotic appears to be at least as effective as the standard alternatives. What is critically lacking is a randomized, controlled, clinical trial.
REFERENCE
- Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200:e45-e67.
In this retrospective study of an elderly male population hospitalized with community-acquired pneumonia, the combination of doxycycline with a beta-lactam was at least as effective as a respiratory fluoroquinolone or a combination of a beta-lactam with azithromycin.
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