Doxycycline Versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus Aureus-Associated Acute Pulmonary Exacerbations in People With Cystic Fibrosis

Background: Among people with cystic fibrosis (PwCF), methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) have been increasing in prevalence and can cause rapid declines in lung function and increased mortality. Fortunately, since 2019, incidence has started to decline. Objective: The purpose of this study was to evaluate if doxycycline has comparable efficacy to vancomycin for the treatment of APEs in PwCF. Given the potential toxicities and intolerances associated with vancomycin, evaluating alternative therapies such as doxycycline is warranted. Methods: A multicenter retrospective cohort study was conducted in adult and pediatric PwCF who received greater than 48 hours of either vancomycin or doxycycline to treat MRSA-associated APEs between May 1, 2014, and August 31, 2021. The primary outcome was the number of PwCF with a return to ≥90% of baseline forced expiratory volume in the first second (FEV 1 ). Results: There were 229 PwCF encounters screened, of which 89 met inclusion criteria (n = 26, vancomycin; n = 63, doxycycline). There were no differences between vancomycin and doxycycline for the primary outcome: 18/26 (69.2%) in the vancomycin group vs 51/63 (81.0%) in the doxycycline group ( P = 0.23). Secondary outcomes were similar between groups, including no difference in incidence of acute kidney injury (AKI), although a significantly higher incidence of adverse events occurred in the vancomycin arm. Conclusion and Relevance: The findings of this study suggest doxycycline may be a reasonable alternative to vancomycin for MRSA-associated APEs, particularly in PwCF who may not tolerate vancomycin or who require concomitant nephrotoxins such as intravenous (IV) aminoglycosides.