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Culture-Negative Septic Shock Compared With Culture-Positive Septic Shock: A Retrospective Cohort Study

Kethireddy, Shravan MD1,2; Bilgili, Beliz MD3; Sees, Amanda MS4; Kirchner, H. Lester PhD4; Ofoma, Uchenna R. MD1; Light, R. Bruce MD5; Mirzanejad, Yazdan MD6; Maki, Dennis MD7; Kumar, Aseem PhD8; Layon, A. Joseph MD1; Parrillo, Joseph E. MD9; Kumar, Anand MD5; for the Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group

doi: 10.1097/CCM.0000000000002924
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Objectives: To determine the clinical characteristics and outcomes of culture-negative septic shock in comparison with culture-positive septic shock.

Design: Retrospective nested cohort study.

Setting: ICUs of 28 academic and community hospitals in three countries between 1997 and 2010.

Subjects: Patients with culture-negative septic shock and culture-positive septic shock derived from a trinational (n = 8,670) database of patients with septic shock.

Interventions: None.

Measurements and Main Results: Patients with culture-negative septic shock (n = 2,651; 30.6%) and culture-positive septic shock (n = 6,019; 69.4%) were identified. Culture-negative septic shock compared with culture-positive septic shock patients experienced similar ICU survival (58.3% vs 59.5%; p = 0.276) and overall hospital survival (47.3% vs 47.1%; p = 0.976). Severity of illness was similar between culture-negative septic shock and culture-positive septic shock groups ([mean and sd Acute Physiology and Chronic Health Evaluation II, 25.7 ± 8.3 vs 25.7 ± 8.1]; p = 0.723) as were serum lactate levels (3.0 [interquartile range, 1.7–6.1] vs 3.2 mmol/L [interquartile range, 1.8–5.9 mmol/L]; p = 0.366). As delays in the administration of appropriate antimicrobial therapy after the onset of hypotension increased, patients in both groups experienced congruent increases in overall hospital mortality: culture-negative septic shock (odds ratio, 1.56; 95% CI [1.47–1.66]; p < 0.0001) and culture-positive septic shock (odds ratio, 1.65; 95% CI [1.59–1.71]; p < 0.0001).

Conclusions: Patients with culture-negative septic shock behave similarly to those with culture-positive septic shock in nearly all respects; early appropriate antimicrobial therapy appears to improve mortality. Early recognition and eradication of infection is the most obvious effective strategy to improve hospital survival.

1The Departments of Critical Care Medicine, Geisinger Medical Center, Danville, PA.

2Section of Infectious Diseases, Geisinger Medical Center, Danville, PA.

3Division of Critical Care Medicine, Department of Anesthesiology, Marmara University, Istanbul, Turkey.

4Department of Biostatistics, Geisinger Medical Center, Danville, PA.

5Sections of Critical Care and Infectious Diseases, Departments of Medicine and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.

6Section of Infectious Diseases, Surrey Memorial Hospital, Surrey, BC, Canada.

7Sections of Infectious Diseases and Critical Care Medicine, University of Wisconsin Hospital and Clinics, Madison, WI.

8Biomolecular Sciences Program, Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, Canada.

9Sections of Cardiology and Critical Care Medicine, Hackensack University Medical Center, Hackensack, NJ.

Supplemental File 1 (Supplemental Digital Content 1, http://links.lww.com/CCM/D104) lists the full list of Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group Members.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Dr. Parrillo’s institution received funding from Beckman Coulter, and he received funding from Asahi Kasai Pharmaceuticals, Beckman Coulter, and the National Heart, Lung, and Blood Institute Heart Failure Network: Protocol Review Committee. Dr. Kumar’s institution received funding from Pfizer and GlaxoSmithKline. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: akumar61@yahoo.com

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