DOI: 10.1097/ccm.0000000000007395 ISSN: 0090-3493

Delay From Hypotension Onset to Appropriate Antifungal Therapy Initiation Is the Critical Determinant of Outcome in Candida Septic Shock

Abhinav Abhishek, Ghazal Mashhadiagha, Azita Ramezani, Chao-Ping Wu, Xiaofeng Wang, Yiying Fan, Marin Kollef, Jorge Guzman, Aseem Kumar, Yoanna Skrobik, Joseph E. Parrillo, Shravan Kethireddy, Anand Kumar,
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Objectives:

To determine the effect of delays in initiation of appropriate antifungal therapy from the initial onset of persistent hypotension to the outcome of Candida septic shock.

Design:

Retrospective cohort study.

Setting:

A total of 32 academic and community hospitals in Canada, the United States, and Saudi Arabia (July 1989 to June 2018).

Patients:

A total of 850 adult patients with culture-positive Candida septic shock.

Interventions:

None.

Measurements and Main Results:

Out of 850 patients with Candida septic shock, 69.2% patients (589) received appropriate antifungal therapy after the onset of persistent hypotension. A strong relationship was observed between the delay in initiation of pathogen-appropriate antifungal (PAA) therapy and hospital survival. The adjusted odds ratio of death was 1.045 per hour of delay (95% CI, 1.035–1.056; p < 0.0001). The survival rate was 86% when an appropriate antifungal for the isolated pathogen was administered within 2 hours of the initial documentation of persistent hypotension. Thereafter, hospital survival decreased an average of 5.0% per hour for each hour of delay to 10–12 hours of delay. In a multivariate analysis, which included the Acute Physiology and Chronic Health Evaluation II score and epidemiologic/therapeutic variables, the time to initiation of appropriate antifungal therapy emerged as the single strongest predictor of outcome. Sensitivity analysis further demonstrated that the adverse effects of delayed antifungal treatment were consistent across various subgroups, including different types of infections, pathogens, and antifungal drug classes. Median time to appropriate antifungal therapy was 32.3 hours (interquartile range, 11.2–66.0 hr), with only 16.9% receiving therapy within 6 hours of hypotension onset.

Conclusions:

Administration of PAAs within the first hours of documented hypotension significantly improved hospital survival. Less than 20% of patients received appropriate antifungals within 6 hours of documented hypotension.

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