983. Doing the Same with Less: A Randomized, Multinational, Open-Label, Adjudicator-Blinded Trial of an Algorithm vs. Standard of Care to Determine Treatment Duration for Staphylococcal Bacteremia
Session: Oral Abstract Session: Advances in Management of Bacteremia and Sepsis
Friday, October 6, 2017: 10:30 AM
Room: 07AB


The appropriate duration of antibiotics for staphylococcal bloodstream infection (BSI) is unknown. An algorithm to identify patients with staphylococcal BSI who can be safely treated with shorter courses of therapy would improve care and reduce total antibiotic use.


Adult patients with staphylococcal BSI were randomized to treatment based on Algorithm-Based Therapy (ABT) or to standard of care (SOC). Co-primary outcomes were clinical success, as determined by a blinded Adjudication Committee, and serious adverse event (SAE) rates.  The prespecified secondary outcome measure was antibiotic days by treatment group, among patients without complicated BSI. Prespecified durations of therapy in ABT were:  S. aureus BSI (SAB): uncomplicated: 14d; complicated: 4-6wks. Coagulase-negative staphylococci BSI (CoNSB): simple (1 positive blood culture) (0-3d), uncomplicated (>1 positive blood culture) (5d), complicated (7-28d).  Outcomes were compared using intention-to-treat principles.  The target sample size was 500 patients, to ensure 90% power for establishing noninferiority within a margin of 15%.


Between April 2011 and March 2017, 509 adults with suspected staphylococcal BSI at 16 sites in the US and Spain were randomized to ABT (N=255) or SOC (N=254). There were 116 patients with SAB (23%) and 385 (76%) with CoNSB (Figure 1). Overall success rate in the ABT group was 82.0% vs 81.5% in the SOC group, difference 0.5%, 95% CI -5.2% to 6.1%.  SAEs were reported in 32.9% of ABT vs 28.3% of SOC patients (OR 1.2, 95% CI 0.9 to 1.8). Among evaluable patients without complicated BSI, mean duration of therapy was 4.4 days in the ABT group vs 6.4 days in the SOC group (difference -2.0 days, 95% CI -3.3 to -0.7, p=0.003).  Among patients with uncomplicated SAB, treatment durations were similar (15.3d in ABT vs 16.3d in SOC, difference -1d, 95% CI -3.89 to 1.91, p=0.497), whereas for uncomplicated CoNSB, duration was shorter in the ABT group (5.3d in ABT vs 8.4d in SOC, difference -3d, 95% CI -4.87 to -1.34, p<0.001).


Use of a treatment algorithm for staphylococcal BSI was associated with significant reductions in duration of antibiotic therapy in patients without complicated BSI, without significant differences in overall success or SAEs.

Figure 1: Schematic of Study Design


Thomas L. Holland, MD1, Helen W. Boucher, MD, FIDSA2, Issam Raad, MD3, Deverick J. Anderson, MD, MPH, FIDSA, FSHEA4, Sara E. Cosgrove, MD, MS5, Suzanne Aycock, MSN6, John W. Baddley, MD7, Shein-Chung Chow, PhD1, Vivian H. Chu, MD1, Paul P. Cook, MD8, G. Ralph Corey, MD1, Jennifer S. Daly, MD9, Ray Y. Hachem, MD3, Anne-Marie Chaftari, MD10, James M. Horton, MD11, Timothy C. Jenkins, MD12, Jiezhun Gu, PhD6, Donald P. Levine, MD13, Jose M Miro, MD, PhD14,15, Paul Riska, MD16, Zachary A. Rubin, MD17, Mark E. Rupp, MD18, John Schrank Jr., MD19, Matthew Sims, MD, PhD20, Dannah Wray, MD21, Marcus J. Zervos, MD22 and Vance G. Fowler Jr., MD1, (1)Duke University Medical Center, Durham, NC, (2)Infectious Diseases, Tufts Medical Center, Boston, MA, (3)Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, TX, (4)Division of Infectious Diseases, Duke University Medical Center, Durham, NC, (5)Johns Hopkins Medical Institutions, Baltimore, MD, (6)Duke Clinical Research Institute, Durham, NC, (7)University of Alabama at Birmingham, Birmingham, AL, (8)Infectious Diseases, Brody School of Medicine at East Carolina University, Greenville, NC, (9)University of Massachusetts Medical School, Worcester, MA, (10)University of Texas MD Anderson Cancer Center, Houston, TX, (11)Carolinas Medical Center, Charlotte, NC, (12)Denver Health, Denver, CO, (13)Wayne State University, Detroit, MI, (14)Hospital Clinic-IDIBAPS, Barcelona, Spain, (15)Hospital ClĂ­nic-IDIBAPS. University of Barcelona, Barcelona, Spain, (16)Albert Einstein College of Medicine, Bronx, NY, (17)David Geffen School of Medicine/University of California, Los Angeles, Los Angeles, CA, (18)Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, (19)Greenville Health System, Greenville, SC, (20)Beaumont Health System, Royal Oak, MI, (21)Medical University of South Carolina, Charleston, SC, (22)Infectious Disease, Henry Ford Health System, Detroit, MI


T. L. Holland, None

H. W. Boucher, None

I. Raad, None

D. J. Anderson, None

S. E. Cosgrove, None

S. Aycock, None

J. W. Baddley, None

S. C. Chow, None

V. H. Chu, None

P. P. Cook, None

G. R. Corey, None

J. S. Daly, None

R. Y. Hachem, None

A. M. Chaftari, None

J. M. Horton, None

T. C. Jenkins, None

J. Gu, None

D. P. Levine, None

J. M. Miro, None

P. Riska, None

Z. A. Rubin, None

M. E. Rupp, None

J. Schrank Jr., None

M. Sims, None

D. Wray, None

M. J. Zervos, None

V. G. Fowler Jr., NIH: Investigator , Contract HHSN272200900023C

Previous Abstract | Next Abstract >>

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.