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

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

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study—The ARTHR-IS Study Group

Introduction: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. Methods: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. Results: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson >= 2, haemoglobin 30 kg/m(2) and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. Conclusions: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. [GRAPHICS]

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

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

An epidemiological analysis of the determinants of childhood malnutrition and mortality in southwest Uganda.

4320 children aged, 0-59 months, were measured (Weight, Height and Mid Upper Arm Circumference) in 31 villages in the district of Mbarara (Southwest Uganda) in March and April 1988. Socioeconomic and health characteristics of the families of the children were also collected. The socioeconomic variables were analysed through Multiple Correspondence Analysis which produced 7 socioeconomic classes. These were reduced to 3 socioeconomic groups (SEGs) because of similarities between some of the classes. SEG I was the most advantaged group with a higher level of education, a high prevalence of Government workers and professionals who were able to hire labour. SEG II was mainly composed of cattle keepers and producers of export crops with only primary education, not hiring labour and not working on other people's land. SEG III was the most disadvantaged group with minimal or no education and mainly comprised of subsistence farmers frequently working on other people's land. SEG I was the best off in every socioeconomic, health and nutrition indicator, while SEG III was the worst off. After 12 months, a follow-up survey was carried out in order to assess the number of children who had died. Mortality rates were inversely proportional to anthropometric indices. There was no interaction between mortality associated with different anthropometric cut-off points and SEGs. Malnutrition produced similar mortality across the SEGs. The most sensitive predictor for mortality was Mid Upper Arm Circumference and the weakest was Weight for Height. Malnourished children had a significantly higher risk of death from fever, measles, diarrhoea, acute respiratory infections and malnutrition while there was no evidence of a higher risk of death from other causes. Ownership of cattle, length of stay in the village, birth order, father's education and kind of lighting fuel were significantly associated with child mortality. Nutritional status was influenced by socioeconomic variables directly related to the poverty conditions of the family, to morbidity (especially diarrhoea), and to hygienic conditions in the house. Poverty was the main determinant of mortality and malnutrition, but even in the better off sector of the community, malnutrition per se put children at a higher risk of death

Potential Costs and Effects of the National Service Framework for Coronary Heart Disease in the UK

Objective: To estimate the costs and effect of implementing the National Service Framework for Coronary Heart Disease (CHD) in the UK. Design: Decision trees were built on the results from randomised controlled trials on improving coronary revascularisation. All costs were presented in UK pounds (1997 values). Patients: Each year 6600 new patients with CHD are expected to require revascularisation in the UK. Interventions: The new patients would be equally divided into those undergoing coronary artery bypass grafting (CABG) and those undergoing a percutaneous coronary intervention (PCI) i.e., percutaneous transluminal angioplasty (PCTA). PTCA could be administered with or without abciximab (a glycoprotein IIb/IIIa receptor antagonist), stent, or stent plus abciximab (stent+). Results: CABG/stent alone has an incremental cost of more than Lstg 115 489 per additional quality-adjusted life-year (QALY) gained compared with CABG/ PTCA+. This high incremental cost is not attractive because if CABG/ stent would be added to abciximab (CABG/stent+) its incremental cost-effectiveness ratio would be Lstg 2529 per extra QALY compared with CABG/stent. Therefore, the debate should not be limited to the issue of stents but it should focus on the need for administering abciximab in addition to stent. The 5-year direct costs of implementing such a strategy in the UK is expected to be Lstg 50.6 million (1997 values). Conclusions: Abciximab and probably any glycoprotein IIb/IIIa receptor antagonists should be added to any PCI, especially if stents are used.Abciximab, Coronary disorders, Coronary interventions, Cost utility, GPIIb IIIa antagonists, Pharmacoeconomics

Synthesizing pathogen- and infection-specific estimates of the burden of antimicrobial resistance in Europe for health-technology assessment: gaps, heterogeneity, and bias

No abstract availabl

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies A Multinational Cohort Study—The ARTHR-IS Study Group

Introduction Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. Methods A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. Results One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin  30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. Conclusions TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies