822. Evaluation of Empiric Therapy with Third-Generation Cephalosporins for Bloodstream Infections Secondary to Chromosomally-Mediated AmpC-Producing Enterobacteriaceae
Session: Poster Abstract Session: Bacteremia and Endocarditis
Friday, October 9, 2015
Room: Poster Hall
Background: Exposure to third-generation cephalosporins (3GC) may increase the risk of clinical failure in chromosomally-mediated AmpC-producing Enterobacteriaceae (CAE). This study evaluated the effect of empiric 3GC therapy on clinical outcomes for bloodstream infections (BSI) due to Enterobacter, Serratia, and Citrobacter spp. 

Methods: This multicenter, retrospective cohort study evaluated hospitalized adult subjects diagnosed with BSI secondary to CAE from January 1, 2006 to September 1, 2014. Empiric 3GC exposure was defined as any use within the first 72 hours from index blood culture collection. The comparator group was all other empiric antibiotics (OEA). The primary outcome, early treatment failure (ETF), was a composite of persistently positive blood cultures > 72 h, persistent fever > 96 h, or escalation in antibiotic therapy due to presumed/documented therapeutic failure.  The secondary composite endpoint of overall treatment failure (OTF), i.e. in-hospital mortality, 30-day hospital readmission, or 90-day reinfection, was also analyzed.

Results: A total of 243 patients from 11 institutions within the Southeastern Research Group Endeavor (SERGE-45) network were enrolled. The mean age was 58 years, 144 (59%) were men, and 81 (34%) were admitted to the intensive care unit (ICU). The most common sources of infection were the urinary tract 50 (21%) and central venous catheter 45 (19%). Site of acquisition was predominantly hospital-acquired 96 (40%) or healthcare-associated 91 (38%). Empiric 3GC were utilized in 48 (20%) of patients. Compared to the OEA group, the empiric 3GC group was significantly more likely to have a urinary source (33% vs. 17%, P=0.02) or community-acquired site of infection (40% vs. 19%, P<0.01) and less likely to have concomitant exposure to penicillins (35% vs. 55%, P=0.01). ETF occurred in 6/48 (13%) in the empiric 3GC group vs. 33/195 (17%) in the OEA group (P=0.45). OTF was also comparable between groups (33% vs. 28% respectively, P=0.48). 

Conclusion: These data preliminarily suggest empiric 3GC therapy does not significantly affect the risk of early poor clinical outcomes in the treatment of BSI secondary to CAE compared to other empiric antibiotic therapy.

Caroline Derrick, PharmD, BCPS1, Zhiqiang K. Lu, PhD1, P. Brandon Bookstaver, PharmD, FCCP, BCPS (AQ-ID), AAHIVP1, Majdi Al-Hasan, MD2, Christopher M. Bland, PharmD, BCPS3, Bruce Jones, PharmD, BCPS4, Kayla R. Stover, PharmD, BCPS5, S. Travis King, PharmD, BCPS5, Virginia Fleming, PharmD, BCPS6, Trisha N. Branan, PharmD, BCPS6, David Cluck, PharmD7, Brian Odle, PharmD7, V. Paul Dimondi, PharmD, BCPS8, Sandy Estrada, Pharm.D., BCPS (AQ-ID)9, Julie Ann Justo, PharmD, MS, BCPS, AAHIVP1 and Southeastern Research Group Endeavor (SERGE-45) Network, (1)Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, (2)Department of Medicine, Division of Infectious Diseases, University of South Carolina School of Medicine, Columbia, SC, (3)Dwight D. Eisenhower Army Medical Center, Evans, GA, (4)Pharmacy, St. Joseph's/Candler Health System, Savannah, GA, (5)Department of Pharmacy Practice, University of Mississippi Medical Center, Jackson, MS, (6)Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Athens, GA, (7)Pharmacy, East Tennessee State University Gatton College of Pharmacy, Johnson City, TN, (8)Campbell University College of Pharmacy & Health Sciences, Buies Creek, NC, (9)Department of Pharmacy, Lee Memorial Health System, Fort Myers, FL

Disclosures:

C. Derrick, None

Z. K. Lu, None

P. B. Bookstaver, Forest Labs: Grant Investigator and Scientific Advisor , Consulting fee

M. Al-Hasan, None

C. M. Bland, Cubist: Speaker's Bureau , Consulting fee
Theravance: Scientific Advisor , Consulting fee

B. Jones, None

K. R. Stover, Astellas Pharma, Inc.: Grant Investigator , Grant recipient and Research grant

S. T. King, None

V. Fleming, None

T. N. Branan, None

D. Cluck, None

B. Odle, None

V. P. Dimondi, None

S. Estrada, None

J. A. Justo, Cempra Pharmaceuticals: Scientific Advisor , Consulting fee

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