985. The Emperor’s New Clothes: Prospective Observational Evaluation of the Association between the Day 2 Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infections (PROVIDE)
Session: Oral Abstract Session: Advances in Management of Bacteremia and Sepsis
Friday, October 6, 2017: 11:00 AM
Room: 07AB

Background: Current guidelines recommend vancomycin (VAN) dosing to achieve AUC/MIC ratio ≥ 400 for patients (pts) with serious MRSA bloodstream infections (BSI), but supporting data were largely derived in single center retrospective studies. A recent study using a Bayesian approach to estimate the VAN AUC found that pts with MRSA BSI who had an AUCDAY2/MICBMD ≥ 650 or an AUCDAY2/MICETEST ≥ 320 had lower incidences of failure (Clin Infect Dis 59:666, 2014).  This study prospectively evaluated if these VAN AUCDAY2/MIC targets were associated with lower incidences of failure (PROVIDE, Award number UM1AI104681- Antibacterial Resistance Leadership Group).

Methods: Prospective, multi-center (n=14), observational study (2014-2106) of hospitalized adults with confirmed MRSA BSI treated with VAN ≥ 72 h. Exclusion: 1) neutropenia; 2) cystic fibrosis; 3) renal replacement therapy; 4) APACHE-II score > 25; 5) previous MRSA BSI within 60 d. VAN exposures were estimated using maximum a posteriori probability procedure in ADAPT 5. MICBMD and MICETEST were performed at a central lab. Outcomes: failure (30-day mortality or MRSA BSI ≥ 7 d); acute kidney injury (AKI), ≥ 1.5 X increase in serum creatinine (Scr) among pts with a baseline SCR < 2.0 mg/dL.  Study was powered at 80% to detect a 17.5% difference in failure between AUCDAY2/MIC groups. 

Results: Among the 265 evaluable pts, mean (SD) age was 61 (17) and APACHE-II was 12 (6). Endocarditis was definite/possible in 29%. The MIC50/90 by BMD and ETEST were 1/1 and 1.5/1.5 mg/L, respectively. Failure occurred in 18%; 26% had AKI. Mean (SD) VAN duration was 18 (14) days. Mean (SD) AUCDAY2 was 586.9 (235.5) and 44% and 73% of pts achieved an AUCDAY2/MICBMD ≥ 650 and AUCDAY2/MICETEST ≥ 320. In the multivariate analyses (Figure 1), failure was not significantly different between AUCDAY2/MIC groups. In contrast, AKI was significantly more common in pts with an AUCDAY2/ MICETEST >= 320.

Conclusion: Achievement of higher VAN AUCDAY2/MIC exposures for pts with MRSA BSIs were not associated with better outcomes and were found to result in increased AKI.  Clinicians should assess the benefits vs. risks of using VAN regimens that confer high AUCDAY2/MIC exposures for pts with MRSA BSIs.

Thomas P. Lodise Jr., PharmD, PhD1, Susan L Rosenkranz, PhD2, Matthew Finnemeyer, MPH3, Jacqueline Huvane, PhD4, Alenda Pereira, BS4, Matthew Sims, MD, PhD5, Marcus J. Zervos, MD6, C Buddy Creech, MD, MPH, FPIDS7, Pratish C. Patel, PharmD, BCPS8, Michael Keefer, MD9, Paul Riska, MD10, Fernanda P. Silveira, MD, MS11, Marc Scheetz, PharmD, MSc12, Richard G. Wunderink, MD13, Martin Rodriguez, MD, FIDSA14, John Schrank, MD15, Susan C. Bleasdale, MD16, Sara Schultz, MD17, Michelle Barron, MD18, Ann Stapleton, MD, FIDSA19, H Chambers, MD20, Vance G. Fowler Jr., MD21 and Thomas L. Holland, MD22, (1)Albany College of Pharmacy and Health Sciences, Albany, NY, (2)Harvard TH Chan School of Public Health, Boston, MA, (3)Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA, (4)Duke Clinical Research Institute, Durham, NC, (5)Beaumont Health System, Royal Oak, MI, (6)Infectious Disease, Henry Ford Health System, Detroit, MI, (7)Vanderbilt University School of Medicine, Nashville, TN, (8)Vanderbilt University Medical Center, Nashville, TN, (9)Medicine, University of Rochester, Rochester, NY, (10)Albert Einstein College of Medicine, Bronx, NY, (11)University of Pittsburgh Medical Center, Pittsburgh, PA, (12)Department of Pharmacy, Northwestern Medicine, Chicago, IL, (13)Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, (14)Medicine, University of Alabama at Birmingham, Birmingham, AL, (15)Infectious Disease, Greenville Health System, Greenville, SC, (16)Division of Infectious Diseases, University of Illinois at Chicago, Chicago, IL, (17)Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, (18)Internal Medicine/Infectious Diseases, University of Colorado Denver, Aurora, CO, (19)Medicine, University of Washington, Seattle, WA, (20)SF General Hosp, San Francisco, CA, (21)Medicine, Duke University, Durham, NC, (22)Duke University Medical Center, Durham, NC

Disclosures:

T. P. Lodise Jr., allergan: Consultant , Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
medicines company: Consultant , Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
melinta: Consultant , Consulting fee
motif: Consultant and Scientific Advisor , Consulting fee
paratek: Consultant and Scientific Advisor , Consulting fee
nabriva: Consultant , Consulting fee

S. L. Rosenkranz, None

M. Finnemeyer, None

J. Huvane, None

A. Pereira, None

M. Sims, None

M. J. Zervos, Merck, Inc.: Investigator , Research grant

C. B. Creech, None

P. C. Patel, None

M. Keefer, None

P. Riska, None

F. P. Silveira, None

M. Scheetz, Bayer: Scientific Advisor , Consulting fee

R. G. Wunderink, None

M. Rodriguez, None

J. Schrank, None

S. C. Bleasdale, None

S. Schultz, None

M. Barron, None

A. Stapleton, None

H. Chambers, None

V. G. Fowler Jr., Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy, Janssen, xBiotech, Contrafect: Consultant , Consulting fee
NIH, Basilea, MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius: Grant Investigator , Research grant
Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm: Consultant , Consulting fee
UpToDate: author on several chapters , Royalties

T. L. Holland, None

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.