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

Background

Inadequate antibiotic therapy predicts poor outcome from sepsis, but there is no simple test of adequacy. We suggested that a time-to-positivity assay (T_pos) 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.

Methods

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.

Results

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 T_pos (n = 11) were associated with a stay in the ICU of less than 6.5 days (P = 0.052). See 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.

Conclusion

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