Excess Burden of Antibiotic-Resistant Bloodstream Infections: Evidence from a Multicentre Retrospective Cohort Study in Chile, 2018-2022

Abstract

Background: Antibiotic-resistant bloodstream infections (ARB BSI) cause an enormous disease and economic burden. We assessed the impact of ARB BSI caused by high- and critical-priority pathogens in hospitalized Chilean patients compared to BSI caused by susceptible bacteria.

Methods: We conducted a retrospective cohort study from 2018 to 2022 in three Chilean hospitals and measured the impact of ARB BSI on in-hospital mortality, length of hospitalisation (LOS), and intensive care unit (ICU) admission. We focused on BSI caused by Acinetobacter baumannii, Enterobacterales, Staphylococcus aureus, Enterococcus species, and Pseudomonas aeruginosa. We addressed confounding using propensity scores, inverse probability weighting, and multivariate regressions. We stratified by community- and hospital-acquired BSI and assessed total hospital and productivity costs.

Findings: We studied 1,218 adult patients experiencing 1,349 BSI episodes, with 47·3% attributed to ARB. Predominant pathogens were Staphylococcus aureus (33% Methicillin-resistant 'MRSA'), Enterobacterales (50% Carbapenem-resistant 'CRE'), and Pseudomonas aeruginosa (65% Carbapenem-resistant 'CRPA'). 80% of BSI were hospital-acquired. ARB was associated with IRR=1·14 (95%CI=1·05-1·24), OR=1·25 (1·07-1·46), and OR=1·42 (1·20-1·68) greater LOS, ICU admission, and mortality after index blood culture among hospital- and community-acquired infected patients. Mortality risk was 1.35-fold higher (1·16-1·58) for ARB patients, notably among hospital-acquired MRSA and CRE (1·37- and 1·48-greater hazards ratios). We found $10,300 excess hospital costs per patient for ARB and estimated a national burden of 2270 DALYs and USD53 million in hospital and productivity losses.

Interpretation: It is urgent to develop and implement interventions to reduce ARB BSIs' burden, particularly from MRSA and CRE.

Funding: This research was supported by the Agencia Nacional de Investigación y Desarrollo ANID through the Fondo Nacional de Desarrollo Científico y Tecnológico FONDECYT Grant 1211933 (to PG, JM, EU), ANID/FONDAP CIGIDEN Grant 1522A0005 (to EU), and Beca de Doctorado en el Extranjero Becas Chile 2020 Grant 72210084 (to KA). EU was supported by The Canadian Institute for Advanced Research CIFAR under the Humans and the Microbiome programme, and KA through the early career grant award of the Royal Society of Tropical Medicine and Hygiene (RSTMH). KP was supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with the UK Health Security Agency (UK HSA) NIHR200915 and the Wellcome Trust 222051/Z/20/Z for the ADILA project.

Declaration of Interest: KP declares to have received grant support from NIHR/HPRU, Wellcome Trust, Ineos Oxford Institute for AMR Research, CEPI, UK Health Security Agency, NIHR, Medical Research Foundation, Waltham Foundation, EU-H2020 IMI-2, and EU-H2020. JM declares to have received research grant support from ANID/FONDECYT, Pfizer, and MSD. EU declares to have received research grant support from ANID/FONDECYT, ANID/FONDAP, CIFAR, and MSD. KA, AP, HP, MS, JC, PG, LY declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical Approval: The study has already been approved by the Pontificia Universidad Catolica Chile Human Research Ethics Committee (Protocol ID: 200706001). All patient data were anonymised.

Keywords: Antibiotic resistance, bloodstream infections, disease burden, mortality, Latin America