T2. Studies of empiric and pre-emptive therapy
Oral Abstract Submission
Palash Samanta, MBBS, MD
Clinical Assistant Professor
University of Pittsburgh
Pittsburgh, PA
Disclosure: Nothing to disclose
Rachel V. Marini, PharmD
Clinical Pharmacist
UPMC Presbyterian Hospital
Pittsburgh, PA
Disclosure: Nothing to disclose
Erin K. McCreary, PharmD, BCPS, BCIDP
Clinical Assistant Professor, Infectious Diseases Pharmacist
University of Pittsburgh, UPMC
Pittsburgh, PA
Disclosure: Nothing to disclose
Ryan K. Shields, PharmD, MS
Associate Professor of Medicine
University of Pittsburgh
Pittsburgh, PA
Disclosure: Allergan: Consultant, Grant/Research Support
Melinta Therapeutics: Grant/Research Support
Merck, Sharpe, and Dohme: Consultant, Grant/Research Support
Pfizer, Inc: Consultant
Shionogi: Consultant, Grant/Research Support
Tetraphase Pharmaceuticals: Grant/Research Support
VenatoRx: Grant/Research Support
Bonnie A. Falcione, PharmD, BCPS-AQ ID
Associate Professor
University of Pittsburgh
Pittsburgh, PA
Disclosure: Nothing to disclose
J. Alex Viehman, MD
Clinical Assistant Professor
University of Pittsburgh
Pittsburgh, Pennsylvania
Disclosure: Nothing to disclose
Lauren Sacha, PharmD, BCPS
Transplant Unit-Based Clinical Pharmacist
University of Pittsburgh
Pittsburgh, PA
Disclosure: Nothing to disclose
Ryan Rivosecchi, PharmD, BCCCP
Clinical Pharmacist
UPMC Presbyterian Hospital
Pittsburgh, PA
Disclosure: Nothing to disclose
Eun Jeong Kwak, MD
Associate Professor of Medicine
University of Pittsburgh
Pittsburgh, PA
Disclosure: Nothing to disclose
Fernanda P. Silveira, MD, MS, FIDSA
Associate Professor of Medicine
University of Pittsburgh
Pittsburgh, PA
Disclosure: Ansun: Grant/Research Support
Qiagen: Grant/Research Support
Shire: Grant/Research Support
Whiscon: Grant/Research Support
Lloyd Clarke, BSc
Senior System Analyst
University of Pittsburgh
Pittsburgh, PA
Disclosure: Nothing to disclose
Cornelius J. Clancy, MD
Associate Professor of Medicine
University of Pittsburgh
Pittsburgh, PA
Disclosure: Astellas: Consultant, Grant/Research Support
Cidara: Consultant, Research Grant or Support
Melinta: Grant/Research Support
Merck: Consultant, Grant/Research Support
Needham Associates: Consultant
Qpex: Consultant
Scynexis: Consultant
Shionogi: Consultant
Minh-Hong Nguyen, MD
Professor of Medicine
University of Pittsburgh
Pittsburgh, PA
Disclosure: Astellas: Consultant, Grant/Research Support
Cidara: Consultant, Grant/Research Support
Melinta: Grant/Research Support
Merck: Consultant, Grant/Research Support
Scynexis: Consultant
Background : IFI is a significant complication following lung transplant (LT). VOR was universal antifungal px in our LT program from 2004-10/2015, at which time px was changed to ISA. We compared efficacy and tolerability of VOR vs ISA px in LTR.
Methods :
We reviewed all LTR from 9/2013-2/2018 who received VOR or ISA Px. Standard duration of px was 3 or 4 months following basiliximab and alemtuzumab induction, respectively. All patients (pts) were followed for ≥ 1 yr post-Tx. IFI was defined by revised EORTC/MSG criteria.
310 LTR were included, 149 and 161 of whom received ISA and VOR px, respectively. There was no difference in demographics, underlying diseases, single vs double LT, or induction therapy (alemtuzumab vs basiliximab) between the 2 groups. At 1-year after LT, 9% (14) and 8% (13) of pts in ISA and VOR groups developed IFI, respectively (p= 0.5). 5% (7) and 3% (5) of pts developed breakthrough (BT) IFI during ISA and VOR px, respectively (p=0.6; Fig 1, p=0.4, Kaplan-Meier). ISA BT included pneumonia (PNA, 2), endobronchial IFI (2), mediastinitis (1), chest wall IFI (1), and candidemia (1). ISA BT pts were infected with Aspergillus fumigatus (3; 2 with ISA MIC = 0.5 µg/mL, 1 MIC = 1 µg/ml), black mould (1), and yeasts (3; 2 C. glabrata, 1 C. albicans). VOR BT IFI included PNA (2), endobronchial IFI (1), empyema (1), and chest wall IFI (1). VOR BT IFIs were due to A. ustus, A. niger, A. lentulus, black mould, and Rhizopus spp (1 each). All Aspergillus VOR BT isolates exhibited VOR MIC ≥2 µg/mL. Pts with IFI were more likely to have positive pre-LT respiratory fungal culture (p=0.01) and grade ≥ 3 ischemic reperfusion injury (IRI) post-LT (p=0.01). VOR and ISA were prematurely discontinued in 53% (85) and 14% (21) of pts due to adverse events, respectively (p < 0.0001). Hepatotoxicity was more common with VOR (22%, 35) than ISA (5%, 7) (p < 0.0001). IFI was an independent risk factor for death at 1 yr (Fig 2, p < 0.0001, Kaplan Meier)
ISA was as effective as VOR in preventing IFI in LTR, and significantly better tolerated. Pre-LT fungal culture positivity and grade ≥3 IRI post-LT were risk factors for development of IFI. IFI within 1-year post-LT had significant impact on mortality
