Culture-Negative and Culture-Positive Sepsis: A Comparison of Characteristics and Outcomes

Abstract

Background: The primary objective of this study was to compare the characteristics of culture-positive and culture-negative status in septic patients. We also determined whether culture status is associated with mortality and whether unique variables are associated with mortality in culture-positive and culture-negative patients separately.

Methods: Utilizing patient records from intensive care units, emergency department, and general care wards in a large academic medical center, we identified adult patients with suspected infection and ≥2 systemic inflammatory response syndrome criteria between January 1, 2007, and May 31, 2014. We compared the characteristics between culture-positive and culture-negative patients and used binary logistic regression to identify variables independently associated with culture status and mortality. We also did sensitivity analyses using patients with Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria for sepsis.

Results: The study population included 9288 culture-negative patients (89%) and 1105 culture-positive patients (11%). Culture-negative patients received more antibiotics during the 48 hours preceding diagnosis but otherwise demonstrated similar characteristics as culture-positive patients. After adjusting for illness severity, a positive culture was not independently associated with mortality (odds ratio = 1.01 [95% CI, 0.81-1.26]; P = .945). The models predicting mortality separately in culture-negative and culture-positive patients demonstrated very good and excellent discrimination (C-statistic ± SD, 0.87 ± 0.01 and 0.92 ± 0.01), respectively. In the sensitivity analyses using patients with sepsis by Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria, after adjustments for illness severity, positive cultures were still not associated with mortality (odds ratio = 1.13 [95% CI, 0.86-1.43]; P = .303; and odds ratio = 1.05 [95% CI, 0.83-1.33]; P = .665), respectively. In all models, physiological derangements were associated with mortality.

Conclusions: While culture status is important for tailoring antibiotics, culture-negative and culture-positive patients with sepsis demonstrate similar characteristics and, after adjusting for severity of illness, similar mortality. The most important factor associated with negative cultures is receipt of antibiotics during the preceding 48 hours. The risk of death in patients suspected of having an infection is most associated with severity of illness. This is aligned with the Sepsis-3 definition using Sequential Organ Failure Assessment score to better identify those suspected of infection at highest risk of a poor outcome.

Figure 1:

A total of 20,522 patients with 2 or more SIRS criteria were identified. Patients younger than 18 years of age (3,878) and subsequent sepsis episodes during hospitalization (1,500) were excluded, resulting in 15,144 patients. Then, patents were further excluded if they had grown positive cultures from samples taken 0 to 48 hours prior to presentation (2,888) or beyond 24 hours after presentation (1,863) resulting in 10,393 patients of whom 9,288 were culture negative and 1,105 were culture positive. SIRS = Systemic Inflammatory Response Syndrome; Culture negative = patients who had samples taken during the first 24 hours of presentation that did not grow a pathogen; Culture positive = patients who had samples taken during the first 24 hours of presentation that did grow a pathogen.