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Culture-Negative Septic Shock: Equally Deadly

Amesh A. Adalja, MD, FACP, FACEP, FIDSA, January 5, 2018

Septic shock and severe sepsis are a final common pathway to ICU admission and death from various infectious diseases. The mortality rates of these conditions range from 20% to 40% and are major targets for quality improvement. While many cases of septic shock are able to be attributed to a specific microbiologic etiology, at least one-third have no identifiable cause. A new study, published in Critical Care Medicine, attempts to determine the differences that exist between culture-negative and culture-positive cases of septic shock.


30% of Cases Without Etiology; Survival Rates Similar

In this retrospective study, Kethireddy et al reviewed 8,670 cases of septic shock over a 14-year period from 28 medical centers in Saudi Arabia, Canada, and the United States. Culture-negative cases amounted to 30.6%.

Important epidemiologic findings included:

  • No difference in severity was noted as measured by APACHE II scoring.
  • Culture-negative cases were more likely to present from the emergency department and be community-associated.
  • Nosocomial onset was more common in culture-positive cases.

Clinical differences included:

  • Culture-negative patients were more likely to be hypothermic, less tachycardic, and less tachypneic.
  • No difference in lactate level or leukocyte count was noted.
  • Thrombocytopenia was more common in the culture-positive group, while diminished cortisol was more common in the culture-negative group.
  • Gastrointestinal and respiratory sites of infection were more common in the culture-negative group.
  • More respiratory failure was found in the culture-negative group (who were also more likely to have congestive heart failure and COPD as comorbidities).

Survival was similar between groups and was associated with appropriate empirical antimicrobial therapy, though culture-negative cases tended to have shorter hospital lengths of stay. In the subgroup of patients with respiratory tract infections, mortality was lower in those with respiratory sites of infection.


Benefits of Closing Diagnostic Gaps

Culture-negative septic shock is just as deadly as culture-positive septic shock. The fact that nearly one-third of cases failed to yield a microbiologic diagnosis provides an opportunity for improvement. It is possible that a specific microbiologic diagnosis would yield improvements in survival as well as better antimicrobial stewardship.

Additionally, understanding which pathogens lurk behind these cases could provide important epidemiologic information as to what new emerging pathogens are circulating. As diagnostic testing becomes more sophisticated and mortality rates from septic shock remain high, reaching an etiologic diagnosis in all cases should be imperative.



Kethireddy S, Bilgili B, Sees A, et al. Culture-negative septic shock compared to culture-positive septic shock: a retrospective cohort study. Crit Care Med 2017. Accessed January 3, 2018.