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

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 1 January 1990, to 21 June 2022. Study eligibility criteria: Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or 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, 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 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant S. aureus and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], −0.72 to 4.17) and 1.78 (95% CrI, −0.02 to 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

Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

BACKGROUND: Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified. METHODS: We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in Escherichia coli and Klebsiella pneumoniae BSI. We matched each bacteraemic patient to two uninfected patients. We compared outcomes between 3GC-susceptible and 3GC-resistant BSI and their respective uninfected controls using Cox regression models. RESULTS: For 1431 E. coli BSI patients, we matched 1152 (81%) 3GC-susceptible and 279 (19%) 3GC-resistant cases to 2263 and 546 uninfected inpatient controls. For 1368 K. pneumoniae BSI patients, we matched 502 (37%) 3GC-susceptible and 866 (63%) 3GC-resistant cases to 982 and 1656 uninfected inpatient controls. We found that 3GC-resistant E. coli had similar hazard ratios (HRs) for in-hospital mortality over their matched controls as compared to susceptible infections over their controls (ratio of HRs 1.03, 95% CI 0.73-1.46). Similarly, 3GC-resistance in K. pneumoniae BSI was not associated with mortality (ratio of HR 1.10, 95% CI 0.80-1.52). Estimates of mortality impact varied by site without a consistent pattern. CONCLUSIONS: In a retrospective analysis, including the use of matched uninfected patients, there did not appear to be an impact of 3GC-resistance on mortality in E. coli or K. pneumoniae BSI in African hospitals, as compared with susceptible BSI with equivalent species. Better information on the actual use of antibiotics in treating infections in African hospitals would improve these impact estimates

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

Mortality associated with third-generation cephalosporin resistance in Enterobacteriaceae bloodstream infections at one South African hospital.

OBJECTIVES: Enterobacteriaceae are common pathogens causing bloodstream infection (BSI) in sub-Saharan Africa and frequently express third-generation cephalosporin (3GC) resistance; however, the impact of 3GC resistance on clinical outcomes is rarely studied. METHODS: We conducted a single-site prospective cohort study at Tygerberg Hospital, Cape Town, South Africa to examine the feasibility of measuring impacts of 3GC resistance in Enterobacteriaceae BSI. We included patients with 3GC-susceptible and 3GC-resistant BSIs and matched each BSI patient to two uninfected patients. We determined the concordance of initial antibiotic treatment with the corresponding isolate's susceptibility profile. We performed exploratory impact analysis using multivariable regression models. RESULTS: Between 1 June 2017 and 31 January 2018, we matched 177 Enterobacteriaceae BSI patients to 347 uninfected patients. Among these BSIs, 35% were phenotypically 3GC resistant. Parameters describing clinical comorbidity showed strong associations with mortality. We found that 18% of 3GC-R and 3% of 3GC-S BSI patient received non-concordant initial therapy. In multivariable Cox regression, we found a mortality impact over their matched patients for both 3GC-R (cause-specific hazard ratio 23.77; 95% CI 5.12-110.3) and 3GC-S (HR 7.49; 95%CI 3.08-18.19) BSI. There was a nonsignificant ratio of these ratios (HR 3.18; 95% CI 0.54-18.70), limited by the small sample size. CONCLUSION: This form of impact estimation was feasible in one hospital in South Africa where 3GC-R status was associated with non-concordant initial antibiotic treatment. There was a possible increase in mortality among individuals with 3GC-resistant Enterobacteriaceae, but with broad confidence intervals. These analytical approaches could be applied to larger datasets to improve precision of estimates

Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study

Background Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified. Methods We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in Escherichia coli and Klebsiella pneumoniae BSI. We matched each bacteraemic patient to two uninfected patients. We compared outcomes between 3GC-susceptible and 3GC-resistant BSI and their respective uninfected controls using Cox regression models. Results For 1431 E. coli BSI patients, we matched 1152 (81%) 3GC-susceptible and 279 (19%) 3GC-resistant cases to 2263 and 546 uninfected inpatient controls. For 1368 K. pneumoniae BSI patients, we matched 502 (37%) 3GC-susceptible and 866 (63%) 3GC-resistant cases to 982 and 1656 uninfected inpatient controls. We found that 3GC-resistant E. coli had similar hazard ratios (HRs) for in-hospital mortality over their matched controls as compared to susceptible infections over their controls (ratio of HRs 1.03, 95% CI 0.73–1.46). Similarly, 3GC-resistance in K. pneumoniae BSI was not associated with mortality (ratio of HR 1.10, 95% CI 0.80–1.52). Estimates of mortality impact varied by site without a consistent pattern. Conclusions In a retrospective analysis, including the use of matched uninfected patients, there did not appear to be an impact of 3GC-resistance on mortality in E. coli or K. pneumoniae BSI in African hospitals, as compared with susceptible BSI with equivalent species. Better information on the actual use of antibiotics in treating infections in African hospitals would improve these impact estimates

Using Interactive Family Science Shows to Improve Public Knowledge on Antibiotic Resistance: Does It Work?

The public plays an important role in controlling the emergence and spread of antibiotic resistance. A large British survey showed that there is still public misunderstanding about microbes and antibiotics. e-Bug, a European DG Sanco sponsored project, aims to disseminate a school antibiotic and hygiene educational pack and website across Europe. Interactive science shows based on the e-Bug educational packs were developed to take the key health and hygiene messages from the e-Bug school resources to families. The science show was evaluated to assess public knowledge and understanding of antibiotics and antibiotic resistance pre and post intervention. An interactive stall comprised of a 362 m backing stand with background information, an interactive activity and discussions with a trained demonstrator was on display at a family holiday resort. Pre-piloted knowledge questionnaires were completed by parents and children pre and post intervention. Adult ($19 years) baseline knowledge regarding antibiotics and antibiotic resistance was high although significant knowledge improvement was observed where baseline knowledge was low. Children’s (5–11 years) knowledge around antibiotics and antibiotic resistance was significantly improved for all questions. The science show can be viewed as a success in improving parents ’ and children’s knowledge of antibiotic use thereby highlighting the importance of educating the public through interaction