bioRxiv2017
BackgroundThe incidence of Escherichia coli bloodstream infections (EC-BSIs), particularly those caused by antibiotic-resistant strains, is increasing in the UK and internationally. This is a major public health concern but the evidence base to guide interventions is limited.\n\nMethodsIncidence of EC-BSIs and E. coli urinary tract infections (EC-UTIs) in one UK region (Oxfordshire) were estimated from anonymised linked microbiological and hospital electronic health records, and modelled using negative binomial regression based on microbiological, clinical and healthcare exposure risk factors. Infection severity, 30-day allcause mortality, and community and hospital co-amoxiclav use were also investigated.\n\nFindingsFrom 1998-2016, 5706 EC-BSIs occurred in 5215 patients, and 228376 EC-UTIs in 137075 patients. 1365(24%) EC-BSIs were nosocomial (onset >48h post-admission), 1863(33%) were community (>365 days post-discharge), 1346(24%) were quasi-community (31-365 days post-discharge), and 1132(20%) were quasi-nosocomial ([≤]30 days postdischarge). 1413(20%) EC-BSIs and 36270(13%) EC-UTIs were co-amoxiclav-resistant (41% and 30%, respectively, in 2016). Increases in EC-BSIs were driven by increases in community (10%/year (95% CI:7%-13%)) and quasi-community (8%/year (95% CI:7%-10%)) cases. Changes in EC-BSI-associated 30-day mortality were at most modest (p>0{middle dot}03), and mortality was substantial (14-25% across groups). By contrast, co-amoxiclav-resistant EC-BSIs increased in all groups (by 11%-19%/year, significantly faster than susceptible EC-BSIs, pheterogeneity<0{middle dot}001), as did co-amoxiclav-resistant EC-UTIs (by 13%-29%/year, pheterogeneity*0{middle dot}001). Co-amoxiclav use in primary-care facilities was associated with subsequent co-amoxiclav-resistant EC-UTIs (p=0{middle dot}03) and all EC-UTIs (p=0{middle dot}002).\n\nInterpretationCurrent increases in EC-BSIs in Oxfordshire are primarily community-associated, with high rates of co-amoxiclav resistance, nevertheless not impacting mortality. Interventions should target primary-care facilities with high co-amoxiclav usage.\n\nFundingNational Institute for Health Research.\n\nResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for publications from inception up until October 26, 2017, with the terms \"Escherichia coli\", \"E. coli\", \"bacteraemia\", \"bloodstream infection\", restricting the search to English language articles, and also reviewed references from retrieved articles. Escherichia coli (E. coli) is the most common cause of bloodstream infection, and the incidence of E. coli bloodstream infection, and particularly antibiotic-resistant infections, is increasing in the UK and internationally. Although the UK government aims to reduce healthcare-associated E. coli bloodstream infection, there is only limited evidence to inform appropriate interventions.\n\nAdded value of this studyWe investigated potential drivers for these increases in incidence by exploiting available linked electronic health records over 19 years for ~5200 patients with E. coli bloodstream infection and ~140000 with E. coli urinary tract infection, together with community antimicrobial prescribing data for the most recent six years. Our study identified several findings with significant implications for health policy and patient care: O_LIIncreases in the incidence of E. coli bloodstream infections were driven mainly by non-hospital-associated cases; however, neither patients with previous urinary tract infections nor having previously had urine specimens sent from catheters appeared to be driving the increases\nC_LIO_LICo-amoxiclav-resistant bloodstream infections rose significantly faster than co-amoxiclav-susceptible bloodstream infections, with the greatest number of co-amoxiclav-resistant bloodstream infections in 2016 being in patients discharged more than a month previously (i.e. community-associated)\nC_LIO_LIHigher co-amoxiclav use in primary care was associated with higher rates of both co-amoxiclav-resistant E. coli urinary tract infections and E. coli urinary tract infections overall, supporting drives to reduce broad-spectrum and inappropriate antibiotic use in primary care\nC_LIO_LIDespite substantial increases in co-amoxiclav-resistant bloodstream infections there was no evidence that mortality was increasing in these cases; this does not support moving to broader empiric antibiotic prescribing in hospitals (i.e. carbapenems, piperacillin-tazobactam)\nC_LI\n\nImplications of all available adviceThis suggests that government strategies to effectively reduce E. coli bloodstream infections should target community settings, as well as healthcare-associated settings. The absence of an increased mortality signal suggests that co-amoxiclav resistant E. coli infections are either being successfully treated by dual empiric therapy in severe cases (e.g. with concomitant gentamicin), can be \"rescued\" once isolate susceptibilities become available, or currently deployed phenotypic susceptibility testing breakpoints do not adequately correlate with clinical outcome.