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Volume 11 Supplement 4

Sepsis 2007

Time to positivity as a novel predictor of outcome in intensive care unit patients with sepsis


Inadequate antibiotic therapy predicts poor outcome from sepsis, but there is no simple test of adequacy. We suggested that a time-to-positivity assay (Tpos) might act as a surrogate for antimicrobial activity and predict outcome from sepsis in the intensive care unit (ICU) [1]. We are conducting a prospective clinical trial to test this hypothesis.


We studied 35 sequential ICU patients with onset of sepsis who had not had antibiotics for at least 3 days. Sepsis was defined as clinical evidence of infection plus at least three criteria for systemic inflammatory response syndrome. All patients received standard empiric therapy. Sera taken at 24 hours post antibiotics were inoculated into blood culture bottles containing standardised bacteria, incubated in an automated microbial detection system and the time to positivity noted. The primary clinical endpoint was days in the ICU.


Cultures that are negative after 5 days of incubation indicate adequate antimicrobial therapy; cultures that become positive in <5 days indicate inadequate antimicrobial therapy. Patients with negative Tpos (n = 11) were associated with a stay in the ICU of less than 6.5 days (P = 0.052). See Figure 1.

Figure 1
figure 1

Average length of stay for patients with negative and positive time-to-positivity 1 (taken at 24 hours after first dose of antibiotics) with 95% confidence intervals.


These data show that some septic patients on standard antimicrobial regimens are receiving inadequate therapy. The Tpos is a new, simple assay that might be used effectively to monitor antibiotic use.


  1. Kaltsas P, Want S, Cohen J: Development of a time-to-positivity assay as a tool in the antibiotic management of septic patients. Clin Microbiol Infect 2005, 11: 109-114. 10.1111/j.1469-0691.2004.01054.x

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Jerwood, S., Hudson, S., Hankins, M. et al. Time to positivity as a novel predictor of outcome in intensive care unit patients with sepsis. Crit Care 11 (Suppl 4), P54 (2007).

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  • Intensive Care Unit
  • Systemic Inflammatory Response Syndrome
  • Antimicrobial Therapy
  • Intensive Care Unit Patient
  • Septic Patient