Patients with cancer are at high risk for death from severe sepsis and septic shock (SS/SSh), especially those with disease-related or iatrogenic immunosuppression.1,2 Mortality due to sepsis is poorly studied in patients with cancer in the ambulatory setting, where most cancer care is delivered in the United States. Delay to effective antimicrobial therapy is strongly associated with mortality,3–6 such that a low threshold for intervention is required before a full clinical assessment. Choice of empiric antibiotics must balance the increased toxicity of combination therapy7 with the survival benefit of antibiotics with an appropriate spectrum of activity.4 Multiple national guidelines8,9 strongly recommend monotherapy for uncomplicated neutropenic fever, but differ regarding which antibiotics should be included in combination therapy for initial management of SS/SSh, reflecting sparse and conflicting data in patients with cancer and SS/SSh.
We reasoned that intervening in the disease process of patients with cancer and SS/SSh using an aggressive approach prioritizing completion of broad antibiotics should improve overall mortality. Many antibiotic combinations require long infusion times and are incompatible for coadministration (ie, vancomycin, gentamicin); these logistics of drug delivery lead to delays in completion of effective antimicrobial therapy. The Sepsis STAT Pack (SSP) program simplifies emergent administration of broad-spectrum antibiotics that can be coadministered via rapid infusion. The protocol ensures at least one active agent is delivered in this heavily antibiotics-treated population with a high prevalence of antibiotic resistance.10 We report on the feasibility, mortality, and adverse events associated with the use of this novel care bundle among a unique cohort of ambulatory patients with cancer and suspected SS/SSh.
The authors would like to thank the medical staff, especially the nurses, and the patients and their families. We thank Marco Mielcarek, Steve Fijalka, David Carlbom, and Claudia Stener for helpful discussions, and Christine Fong for supporting electronic database query.
Dr. Boeckh has disclosed that he has received research support and served as a consultant for Merck and GlaxoSmithKline. Dr. Casper has disclosed that he serves on an external advisory board for and receives travel compensation from GlaxoSmithKline and receives research support from Janssen. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
This work was supported by the National Institute of Allergy and Infectious Diseases (T32 AI0740) and National Center for Advancing Translational Sciences (UL1TR000423), both at the National Institutes of Health. This work was also supported by a grant from the Division of Allergy and Infectious Disease at the University of Washington (J.D.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
See JNCCN.org for supplemental online content.
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