698. Gut Microbiome Changes in Response to Protocolized Antibiotic Administration During Hematopoietic Cell Transplantation
Session: Oral Abstract Session: Microbiome
Friday, October 9, 2015: 8:45 AM
Room: 25--ABC

Background: The healthy human gut contains a complex mix of bacterial species felt to contribute to immunologic health, metabolism of dietary nutrients, and resistance to invasion by pathogens. Patients undergoing hematopoietic stem cell transplantation (HCT) typically receive extensive antibiotics with unclear consequences.

Methods: Within our hospital system, patients undergo protocol-driven antibiotic administration following HCT: Levofloxacin (LV) is given once neutropenia develops. LV is stopped and ceftazidime is started with development of neutropenic fever. Vancomycin is started in patients with severe mucositis, evidence of central line site infection, or microbiologic evidence for gram-positive infection.

A cohort of patients undergoing HCT prospectively self-collected serial weekly serial stool samples, starting pre-transplantation and continuing weekly till 100 days post-transplant. Using 16S rRNA gene PCR with degenerate primers, followed by sequencing via the 454 platform, we identified bacterial community composition in 238 stool samples from 32 patients.

Results: Expected changes were discovered, including the loss of most Enterobacteriaceae species with LV, and many gram positive Firmicutes with vancomycin exposure. LV, vancomycin and ceftazidime all promoted Clostridium species (sp) (Fig 1). The Bacteroides genus had offsetting changes: LV increased B. thetaiotaomicron (61%. 95% CI: 33% to 88%). Ceftazidime reduced B. stercoris (-96%. 95% CI: -100% to -52%) and B. vulgatus (-97%. 95% CI: -100% to -63%) (Fig 2). Unexpectedly, vancomycin decreased most Bacteroides sp., including beneficial B. thetaiotaomicron (-21%. 95% CI: -21% to -21%).

Conclusion: Select antibiotics impart predictable changes in gut bacterial communities in patients undergoing HCT.  The Bacteroides genus is affected in unexpected ways, with vancomycin administration consistently resulting in the loss of beneficial Bacteroides species. The shifts in Firmicutes caused by vancomycin may be disrupting synergistic partners for Bacteroides species, resulting in their depletion.

Jonathan L Golob, MD PhD1,2, Sujatha Srinivasan, PhD1, Steven Pergam, MD, MPH, FIDSA3, Congzhou Liu, MS1, Daisy Ko, BS1, Sarah Aker, BS1 and David N Fredricks, MD1,2, (1)Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, (2)Medicine / Allergy and Infectious Diseases, University of Washington, Seattle, WA, (3)Fred Hutchinson Cancer Research Center, Seattle, WA

Disclosures:

J. L. Golob, None

S. Srinivasan, None

S. Pergam, Merck: Consultant , Consulting fee
Cubist: Consultant , Consulting fee

C. Liu, None

D. Ko, None

S. Aker, None

D. N. Fredricks, None

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