Positive Impact of [18F]FDG-PET/CT on Mortality in Patients With Staphylococcus aureus Bacteremia Explained by Immortal Time Bias

Abstract

Background: Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias.

Methods: Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB. [18F]FDG-PET/CT was performed on clinical indication as part of usual care. Primary outcome was 90-day all-cause mortality. Effect of [18F]FDG-PET/CT was modeled with a Cox proportional hazards model using [18F]FDG-PET/CT as a time-varying variable and corrected for confounders for mortality (age, Charlson score, positive follow-up cultures, septic shock, and endocarditis). Secondary outcome was 90-day infection-related mortality (assessed by adjudication committee) using the same analysis. In a subgroup-analysis, we determined the effect of [18F]FDG-PET/CT in patients with high risk of metastatic infection.

Results: Of 476 patients, 178 (37%) underwent [18F]FDG-PET/CT. Day-90 all-cause mortality was 31% (147 patients), and infection-related mortality was 17% (83 patients). The confounder adjusted hazard ratio (aHR) for all-cause mortality was 0.50 (95% confidence interval [CI]: .34-.74) in patients that underwent [18F]FDG-PET/CT. Adjustment for immortal time bias changed the aHR to 1.00 (95% CI .68-1.48). Likewise, after correction for immortal time bias, [18F]FDG-PET/CT had no effect on infection-related mortality (cause specific aHR 1.30 [95% CI .77-2.21]), on all-cause mortality in patients with high-risk SAB (aHR 1.07 (95% CI .63-1.83) or on infection-related mortality in high-risk SAB (aHR for 1.24 [95% CI .67-2.28]).

Conclusions: After adjustment for immortal time bias [18F]FDG-PET/CT was not associated with day-90 all-cause or infection-related mortality in patients with SAB.

Keywords: Staphylococcus aureus bacteraemia; [18F]FDG-PET/CT; immortal time bias; mortality.

This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/positive-impact-of-18f-fdg-pet-ct-on-mortality-in-patients-with-staphylococcus-aureus-bacteremia-explained-by-immortal-time-bias-b4db7e26-22b3-4771-bad6-9eba9b0c3dcc/update

Figure 1.

Kaplan-Meier survival curves with PET/CT as a time-fixed effect. A, The Kaplan-Meier curves with PET/CT as a time-fixed effect. B, Magnification of the first 7 days which clearly demonstrate risk of immortal time bias, as no deaths occur in the PET/CT group in the first 7 days, while in the no PET/CT group 24% of total deaths (n = 25) occur in the first 7 days. C, The effect of drawing the Kaplan-Meier curves after 7 days, demonstrating that after this time period the curves are nearly overlapping. Abbreviation: PET/CT, positron emission tomography/computed tomography.