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A systematic review on the excess health risk of antibiotic-resistant bloodstream infections for six key pathogens in Europe

Hassoun-Kheir N, Guedes M, Ngo Nsoga MT, Argante L, Arieti F, Gladstone BP, Kingston R, Naylor NR, Pezzani MD, Pouwels KB, Robotham JV, Rodríguez-Baño J, Tacconelli E, Vella V, Harbarth S, de Kraker MEA; PrIMAVeRa Workpackage 1.

Background: Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined.

Objectives: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe.

Methods: A systematic review and meta-analysis.

Data sources: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022.

Study eligibility criteria: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries.

Participants: Paediatric and adult patients diagnosed with drug-resistant BSI.

Interventions: Not applicable.

Assessment of risk of bias: An adapted version of the Joanna-Briggs Institute assessment tool.

Methods of data synthesis: Random-effect models were used to pool pathogen-specific burden estimates.

Results: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively).

Conclusions: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions.

Keywords: Antimicrobial resistance; Bloodstream infections; Burden; Health outcomes; Health technology; Mortality.

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