(487) Evaluating the use of doxycycline versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus-associated acute pulmonary exacerbations in patients with cystic fibrosis

Thursday, November 3, 2022

12:45 PM – 1:25 PM ET

Presenting Author(s)

Kendall H. Brickel, PharmD

PGY2 Internal Medicine Pharmacy Resident
Ascension Seton
Austin, Texas, United States

Co-Author(s)

DK

Denise Kelley, PharmD, BCPS

Clinical Pharmacy Specialist - Internal Medicine/Transitions of Care
Ascension Seton, United States
TJ

Theresa Jaso, PharmD, BCPS (AQ-ID)

Market Clinical Pharmacy Specialist - Infectious Diseases
Ascension Seton, United States
HT

Hai Quyen Tran, PharmD, BCPPS

Pediatric Clinical Pharmacist
Dell Children's Medical Center, United States
JF

Jason Fullmer, MD

Adult CF Program Director
Ascension Seton
Austin, Texas, United States
DB

Danielle Beachler, MD

Pediatric CF Center Director
Dell Children's Medical Center
Austin, Texas, United States

Background: Among patients with cystic fibrosis (CF), methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) are increasing in prevalence and can cause rapid declines in lung function and mortality. Limited data exist on the preferred treatment of MRSA-associated APEs, with vancomycin often considered first-line. Given the potential toxicities and intolerances associated with vancomycin, evaluating alternative therapies such as doxycycline is warranted. This study aims to add to the paucity of data by evaluating if doxycycline is an effective and safe option in the management of MRSA-associated APEs in patients with CF.

Methods: This evaluation is a multicenter retrospective cohort study of adult and pediatric patients with a CF diagnosis who received greater than 48 hours of either vancomycin or doxycycline to treat MRSA-associated APEs within the Ascension Seton network from May 1st, 2013, to August 31st, 2021. Patients were excluded if they were less than eight years of age, were readmitted within 30 days after a prior MRSA-associated APE, or were missing baseline, admission, or follow-up pulmonary function tests (PFTs). The primary endpoint of this study was the incidence of patients with a return to ≥90% of baseline forced expiratory volume in the first second (FEV1). Secondary endpoints of this study included the mean percent change in FEV1 during hospitalization, the incidence of readmissions within 30 days following treatment for prior MRSA-associated APEs, antibiotic duration, the incidence of co-infections, and the change in both weight and body mass index (BMI) from baseline to follow-up. Safety outcomes included the incidence of acute kidney injury (AKI), concomitant nephrotoxins, and adverse drug events.

Results: Out of 229 patient encounters screened, 89 met inclusion criteria (n = 26, vancomycin; n = 63, doxycycline). There were no significant differences between vancomycin and doxycycline for the primary outcome of incidence of patients with a return to ≥90% of baseline FEV1 (18/26, 77.5% vs. 51/63, 81.0%; p = 0.23). No significant differences were seen in the mean change in FEV1 from admission to discharge, the incidence of 30-day readmissions, the mean duration of antibiotic therapy, or the incidence of co-infections between groups, including Pseudomonas aeruginosa co-infections. The incidence of AKI was similar between groups, however the doxycycline group received significantly more nephrotoxins (12/26, 46.2% vs. 52/63, 82.5%, p = 0.001), namely intravenous aminoglycosides (4/26, 15.4% vs. 42/63, 66.7%; p < 0.0001). Significantly more treatment-associated adverse drug events were reported in the vancomycin group (4/26, 15.4% vs. 1/63, 1.6%, p = 0.024) due to the occurrence of vancomycin infusion reaction during hospitalization. Subgroup analyses of the primary outcome revealed no significant differences based on concomitant CFTR modulator use, the presence of P. aeruginosa, or the vancomycin trough at steady state.

Conclusions: Doxycycline was comparable to vancomycin in the rate of return to ≥90% of baseline FEV1 and for all secondary efficacy outcomes. While the results of this study are limited by the small sample size, retrospective design, and lack of power, the findings suggest doxycycline may be a reasonable alternative to vancomycin for MRSA-associated APEs, particularly in patients who may not tolerate vancomycin or who require concomitant nephrotoxins such as intravenous aminoglycosides.

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