Excess resource use and cost of drug-resistant infections for six key pathogens in Europe: a systematic review and Bayesian meta-analysis

Background: Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action. Objectives: Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe. Methods: A systematic review and Bayesian meta-analysis. Data sources: MEDLINE® (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1st January 1990 to 21st June 2022. Study eligibility criteria: Resource use and cost outcomes (including excess length of stay, overall costs and other excess in/outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, CR or third generation cephalosporin Escherichia coli (3GCREC) and Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecium and patients with drug-susceptible or no infection. Participants: All patients diagnosed with drug-resistant bloodstream infections (BSIs). Interventions: NA. Assessment of risk of bias: An adapted version of the Joanna-Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks. Methods of data synthesis: Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates. Results: Of 5,969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated attributable burden, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalisation attributable to 3GCREC bloodstream infections (BSIs), ranging from -€ 2,465.50 to € 6,402.81. Eight studies presented adjusted excess length of hospital stay estimates for MRSA and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval (CrI): -0.72 - 4.17) and 1.78 (95% CrI: -0.02 - 3.38) days, respectively. Conclusions: Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed.