Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; National Institute for Health Research (NIHR) Health Protection Research Unit on Healthcare Associated Infections and Antimicrobial Resistance, Oxford, UK.
Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Lancet Infect Dis. 2018 Oct;18(10):1138-1149. doi: 10.1016/S1473-3099(18)30353-0. Epub 2018 Aug 17.
Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidence base to guide interventions against this major public health concern is small. We aimed to investigate possible drivers of changes in the incidence of E coli bloodstream infection and antibiotic susceptibilities in Oxfordshire, UK, over the past two decades, while stratifying for time since hospital exposure.
In this observational study, we used all available data on E coli bloodstream infections and E coli urinary tract infections (UTIs) from one UK region (Oxfordshire) using anonymised linked microbiological data and hospital electronic health records from the Infections in Oxfordshire Research Database (IORD). We estimated the incidence of infections across a two decade period and the annual incidence rate ratio (aIRR) in 2016. We modelled the data using negative binomial regression on the basis of microbiological, clinical, and health-care-exposure risk factors. We investigated infection severity, 30-day all-cause mortality, and community and hospital amoxicillin plus clavulanic acid (co-amoxiclav) use to estimate changes in bacterial virulence and the effect of antimicrobial resistance on incidence.
From Jan 1, 1998, to Dec 31, 2016, 5706 E coli bloodstream infections occurred in 5215 patients, and 228 376 E coli UTIs occurred in 137 075 patients. 1365 (24%) E coli bloodstream infections were nosocomial (onset >48 h after hospital admission), 1132 (20%) were quasi-nosocomial (≤30 days after discharge), 1346 (24%) were quasi-community (31-365 days after discharge), and 1863 (33%) were community (>365 days after hospital discharge). The overall incidence increased year on year (aIRR 1·06, 95% CI 1·05-1·06). In 2016, 212 (41%) of 515 E coli bloodstream infections and 3921 (28%) of 13 792 E coli UTIs were co-amoxiclav resistant. Increases in E coli bloodstream infections were driven by increases in community (aIRR 1·10, 95% CI 1·07-1·13; p<0·0001) and quasi-community (aIRR 1·08, 1·07-1·10; p<0·0001) cases. 30-day mortality associated with E coli bloodstream infection decreased over time in the nosocomial (adjusted rate ratio [RR] 0·98, 95% CI 0·96-1·00; p=0·03) group, and remained stable in the quasi-nosocomial (adjusted RR 0·98, 0·95-1·00; p=0·06), quasi-community (adjusted RR 0·99, 0·96-1·01; p=0·32), and community (adjusted RR 0·99, 0·96-1·01; p=0·21) groups. Mortality was, however, substantial at 14-25% across all hospital-exposure groups. Co-amoxiclav-resistant E coli bloodstream infections increased in all groups across the study period (by 11-18% per year, significantly faster than co-amoxiclav-susceptible E coli bloodstream infections; p<0·0001), as did co-amoxiclav-resistant E coli UTIs (by 14-29% per year; p<0·0001). Previous year co-amoxiclav use in primary-care facilities was associated with increased subsequent year community co-amoxiclav-resistant E coli UTIs (p=0·003).
Increases in E coli bloodstream infections in Oxfordshire are primarily community associated, with substantial co-amoxiclav resistance; nevertheless, we found little or no change in mortality. Focusing interventions on primary care facilities, particularly those with high co-amoxiclav use, could be effective in reducing the incidence of co-amoxiclav-resistant E coli bloodstream infections, in this region and more generally.
National Institute for Health Research.
大肠埃希菌血流感染在英国和国际上呈上升趋势。指导针对这一主要公共卫生问题的干预措施的证据基础很小。我们旨在调查过去二十年牛津郡(英国)大肠埃希菌血流感染和大肠埃希菌尿路感染(UTI)发病率变化的可能驱动因素,并对住院暴露后的时间进行分层。
在这项观察性研究中,我们使用了来自英国一个地区(牛津郡)的匿名链接微生物学数据和医院电子健康记录,从感染牛津郡研究数据库(IORD)中获取了所有可用的大肠埃希菌血流感染和大肠埃希菌 UTI 数据。我们在二十年期间估计了感染的发病率和 2016 年的年发病率比值(aIRR)。我们根据微生物学、临床和医疗保健暴露风险因素,使用负二项式回归对数据进行建模。我们调查了感染的严重程度、30 天全因死亡率以及社区和医院阿莫西林克拉维酸(co-amoxiclav)的使用情况,以估计细菌毒力的变化以及抗微生物药物耐药性对发病率的影响。
从 1998 年 1 月 1 日至 2016 年 12 月 31 日,5215 名患者发生了 5706 例大肠埃希菌血流感染,137075 名患者发生了 228376 例大肠埃希菌 UTI。1365 例(24%)大肠埃希菌血流感染为医院获得性(发病后>48 小时),1132 例(20%)为准医院获得性(出院后≤30 天),1346 例(24%)为准社区性(出院后 31-365 天),1863 例(33%)为社区性(出院后>365 天)。整体发病率逐年上升(aIRR1.06,95%CI1.05-1.06)。2016 年,515 例大肠埃希菌血流感染中 212 例(41%)和 13792 例大肠埃希菌 UTI 中 3921 例(28%)对 co-amoxiclav 耐药。社区(aIRR1.10,95%CI1.07-1.13;p<0.0001)和准社区(aIRR1.08,1.07-1.10;p<0.0001)病例中大肠埃希菌血流感染的增加是导致发病率上升的主要原因。在医院获得性组中,大肠埃希菌血流感染 30 天死亡率随着时间的推移呈下降趋势(调整后的比率比[RR]0.98,95%CI0.96-1.00;p=0.03),而在准医院获得性(调整后的 RR 0.98,95%CI0.95-1.00;p=0.06)、准社区(调整后的 RR 0.99,95%CI0.96-1.01;p=0.32)和社区(调整后的 RR 0.99,95%CI0.96-1.01;p=0.21)组中保持稳定。然而,所有医院暴露组的死亡率仍然相当高(14-25%)。所有研究期间,co-amoxiclav 耐药性大肠埃希菌血流感染在所有组中均呈上升趋势(每年增加 11-18%,明显快于 co-amoxiclav 敏感性大肠埃希菌血流感染;p<0.0001),co-amoxiclav 耐药性大肠埃希菌 UTI 也呈上升趋势(每年增加 14-29%;p<0.0001)。前一年在初级保健机构中使用 co-amoxiclav 与随后一年社区 co-amoxiclav 耐药性大肠埃希菌 UTI 的发生显著相关(p=0.003)。
牛津郡大肠埃希菌血流感染的增加主要与社区相关,且具有相当大的 co-amoxiclav 耐药性;然而,我们发现死亡率几乎没有变化。将干预措施重点放在初级保健机构上,特别是那些 co-amoxiclav 使用量较高的机构,可能会在该地区乃至更广泛的范围内有效降低 co-amoxiclav 耐药性大肠埃希菌血流感染的发病率。
国家卫生研究院。