The burden of nosocomial superinfections in a retrospective cohort study of critically ill COVID-19 patients

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OBJECTIVES: Viral respiratory infections can be complicated by bacterial superinfections. SARS-CoV-2 patients may suffer from superinfections, and negative effects of additional infections have been identified. When analysing hospital data, patients typically leave the facility of observation, due to discharge or death, which leads to changes in the study cohort over time. This may distort the estimate of the impact of superinfection. Therefore, it is essential for the statistical analysis of hospital data to acknowledge this change of the risk set over time. We analysed superinfections in a retrospective cohort study with 268 critically ill patients, taking into account discharge and death as competing risks in the statistical analysis. METHODS: We evaluated bacterial respiratory infections and bloodstream infections and used multi-state statistical modelling to account for the different patient states. We calculated risks of superinfection, probability of discharge or death over time and analysed subgroups according to age and sex. RESULTS: The observed pathogen spectrum was mainly composed of Enterobacterales, Nonfermenters but also Staphylococcus aureus. We identified an elevated mortality due to bacterial infection of the respiratory tract or bloodstream infection (adj. cause-specific HR 1.7, CI 1.15-2.52) as well as a reduced discharge rate (adj. cause-specific HR 0.51, CI 0.36-0.73). Female patients showed a tendency to have a reduced risk of acquiring a superinfection (adj. subdistribution HR 0.71, CI 0.48-1.04), and in case of infection a higher mortality compared to male patients (interaction effect HR 1.49, CI 0.67-3.30). CONCLUSIONS: The study accounts for competing risks and quantifies the risk of death associated with bacterial superinfection in critically ill COVID-19 patients. We observed an increased risk of death for patients who developed a superinfection, with Enterobacterales being the predominant agent. The results emphasize the need for microbiological sampling in SARS-CoV-2-infected patients. CLINICAL TRIAL NUMBER: German Clinical Trials Register number: DRKS00031367, registration date: 01.03.2023 ( https://drks.de/search/de/trial/DRKS00031367 ).

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