What Are the Effects of Culture-Negative vs Culture-Positive Sepsis?

People with culture-negative and culture-positive sepsis had similar characteristics and, after adjusting for illness severity, similar mortality.

People with culture-negative and those with culture-positive sepsis demonstrated similar characteristics and, after adjusting for illness severity, similar mortality rates, according to research in Anesthesia and Analgesics.

Using patient records from intensive care units, emergency departments, and general care wards in a large academic medical center, 9288 patients with a negative blood culture and 1105 patients with a positive blood culture were identified. The primary objective of the study was to compare characteristics of patients with sepsis based on culture. Further, the study investigators sought to determine whether culture status is associated with mortality and whether unique variables were associated with mortality in patients with culture-positive vs culture-negative sepsis.

The findings demonstrated that with the exception of these patients being more likely to receive antibiotics within the 48 hours preceding diagnosis, patients with culture-negative sepsis had similar characteristics to patients with positive blood cultures. After adjusting for illness severity, the presence of a positive culture was not independently associated with mortality (odds ratio 1.01; 95% CI, 0.81-1.26; P =.945). In addition, the models used to predict mortality separately in the negative and positive culture groups showed good and excellent discrimination (C-statistic ± standard deviation, 0.87 ± 0.01 and 0.92 ± 0.01, respectively).

Further, sepsis was evaluated using Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria, and a sensitivity analysis adjusted for illness severity found that positive cultures were 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). Physiologic derangements were associated with mortality in every model tested.

The study investigators noted that because patient and culture data were collected retrospectively, the findings represent associations only and, “prospective studies are needed to infer causality.” Researchers also recognized that retrospective data collection can be subject to missing data and therefore may be less accurate than other forms of collection. Another limitation was that a systemic inflammatory response syndrome-based definition of sepsis was used to identify the initial patient population, after which the Sequential Organ Failure Assessment score or quick Sequential Organ Failure Assessment was applied for sensitivity analyses. This may have led to the exclusion of patients with sepsis. In addition, although the study was the largest study comparing differences between patients with culture-negative vs those with culture-positive sepsis using clinical variables, the results may not be generalizable because the study was conducted at a single center.

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According to the study investigators, blood culture status is an important factor for tailoring antibiotics but, “[patients with] culture-negative and culture-positive sepsis demonstrate similar characteristics and, after adjusting for severity of illness, similar mortality.” They further concluded that the risk for death in patients with suspected infection is mostly associated with severity of illness and that this aligns 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.”


Sigakis MJG, Jewell E, Maile MD, Cinti SK, Bateman BT, Engoren M. Culture-negative and culture-positive sepsis: a comparison of characteristics and outcomes [published online February 27, 2019]. Anesth Analg. doi: 10.1213/ANE.0000000000004072