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Characteristics and outcomes of culture-negative versus culture-positive severe sepsis

Jason Phua12*, Wang Jee Ngerng12, Kay Choong See12, Chee Kiang Tay12, Timothy Kiong3, Hui Fang Lim12, Mei Ying Chew12, Hwee Seng Yip12, Adeline Tan4, Haji Jamil Khalizah5, Rolando Capistrano12, Kang Hoe Lee6 and Amartya Mukhopadhyay12

Author Affiliations

1 Division of Respiratory and Critical Care Medicine, University Medicine Cluster, National University Hospital, National University Health System Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228

2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228

3 Faculty of Medicine, Suite H 2743, 300 Prince Philip Drive, Memorial University of Newfoundland, St. John's NL, A1B 3V6, Canada

4 Department of Medicine, Alexandra Hospital (Jurong Health Services), 378 Alexandra Road, Singapore 159964

5 RIPAS Hospital, Jalan Putera Al-Muhtadee Billah, Bandar Seri Begawan, BA 1710, Brunei Darussalam

6 Asian Centre for Liver Diseases and Transplantation, Gleneagles Hospital, Annexe Block, 02-37, 6A Napier Road, Singapore 258500

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Critical Care 2013, 17:R202  doi:10.1186/cc12896

Published: 12 September 2013



Culture-negative sepsis is a common but relatively understudied condition. The aim of this study was to compare the characteristics and outcomes of culture-negative versus culture-positive severe sepsis.


This was a prospective observational cohort study of 1001 patients who were admitted to the medical intensive care unit (ICU) of a university hospital from 2004 to 2009 with severe sepsis. Patients with documented fungal, viral, and parasitic infections were excluded.


There were 415 culture-negative patients (41.5%) and 586 culture-positive patients (58.5%). Gram-positive bacteria were isolated in 257 patients, and gram-negative bacteria in 390 patients. Culture-negative patients were more often women and had fewer comorbidities, less tachycardia, higher blood pressure, lower procalcitonin levels, lower Acute Physiology and Chronic Health Evaluation II (median 25.0 (interquartile range 19.0 to 32.0) versus 27.0 (21.0 to 33.0), P = 0.001) and Sequential Organ Failure Assessment scores, less cardiovascular, central nervous system, and coagulation failures, and less need for vasoactive agents than culture-positive patients. The lungs were a more common site of infection, while urinary tract, soft tissue and skin infections, infective endocarditis and primary bacteremia were less common in culture-negative than in culture-positive patients. Culture-negative patients had a shorter duration of hospital stay (12 days (7.0 to 21.0) versus 15.0 (7.0 to27.0), P = 0.02) and lower ICU mortality than culture-positive patients. Hospital mortality was lower in the culture-negative group (35.9%) than in the culture-positive group (44.0%, P = 0.01), the culture-positive subgroup, which received early appropriate antibiotics (41.9%, P = 0.11), and the culture-positive subgroup, which did not (55.5%, P < 0.001). After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis.


Significant differences between culture-negative and culture-positive sepsis are identified, with the former group having fewer comorbidities, milder severity of illness, shorter hospitalizations, and lower mortality.