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

Thomas W van der Vaart; Jan M Prins; Cornelis H van Werkhoven; Thijs Ten Doesschate; Robin Soetekouw; Gitte van Twillert; Jan Veenstra; Bjorn L Herpers; Wouter Rozemeijer; Rogier R Jansen; Marc J M Bonten; Jan T M van der Meer

doi:10.1093/cid/ciad112

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

Clin Infect Dis. 2023 Jul 5;77(1):9-15. doi: 10.1093/cid/ciad112.

Affiliations

¹ Julius Center for Health Sciences and Primary Care, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands.
² Department of Internal Medicine, Division of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
³ Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands.
⁴ Department of Internal Medicine, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands.
⁵ Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands.
⁶ Regional Public Health Laboratory Kennemerland, Haarlem, The Netherlands.
⁷ Department of Medical Microbiology, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands.
⁸ Department of Medical Microbiology, OLVG, Amsterdam, The Netherlands.

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.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Bacteremia*
Cohort Studies
Fluorodeoxyglucose F18
Humans
Prospective Studies
Staphylococcal Infections* / diagnostic imaging
Staphylococcus aureus

Substances

Fluorodeoxyglucose F18