Delay from the Onset of Hypotension to Appropriate Antifungal Therapy Initiation is the Critical Determinant of Outcome in Candida-associated Septic Shock
Bibliographic record
Abstract
Abstract Rationale: Candida-associated septic shock is associated with a very high mortality rate. Initiating early, appropriate antifungal therapy is central to survival. Few studies have assessed the relationship between antifungal treatment delay and mortality rates in this group. This study explores the effect of delay in initiation of antifungal therapy following the onset of persistent/recurrent hypotension on mortality rates in patients with Candida-associated septic shock. Methods: This retrospective cohort study included 850 adults with culture-confirmed Candida-associated septic shock, conducted in 29 hospitals across Canada, the U.S., and Saudi Arabia from July 1989 to June 2018. Univariate analysis assessed delay effects on in hospital survival, while multivariate regression evaluated adjusted odds of mortality per hour of delay, with subgroup analyses by infection type, fungemia status, and APACHE II scores. Results: Among 850 patients, 589 (69.2%) received antifungal therapy after hypotension onset. Each hour of delay increased mortality risk, with an adjusted OR of 1.045 (95% CI: 1.035-1.056, p < 0.0001). Patients treated within 2 hours had an 85.7% hospital survival rate. Beyond this 2-hour window, the survival rate decreased by an average of 3.70% each hour, demonstrating a rapid reduction in survival probability with increasing delays. Delays of 12–24 hours resulted in a 38.5% hospital survival rate, dropping sharply to around 0.1% for delays over 36 hours. Results of multivariate analysis, which included the APACHE II score and epidemiologic/therapeutic variables, demonstrated that the time to initiate appropriate antifungal therapy emerged as the single strongest independent predictor of outcomes. Conclusion: This study highlights the critical impact of early antifungal therapy in Candida-associated septic shock. In our cohort, only 20% of patients received effective antifungal therapy within six hours of hypotension onset. Measures to improve early recognition are needed. Figure 1: Mortality risk (adjusted odds ratio) increases with delays in effective antifungal therapy. Bars show 95% confidence intervals. Elevated death risk is evident by 4-6 hours post-hypotension and continues rising beyond 36 hours.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".