Escherichia coli causing bloodstream and other extraintestinal infections: tracking the next pandemic

In The Lancet Infectious Diseases, Michaela J Day and colleagues1Day MJ Hopkins KL Wareham DW et al.Extended-spectrum β-lactamase-producing Escherichia coli in human-derived and foodchain-derived samples from England, Wales, and Scotland: an epidemiological surveillance and typing study.Lancet Infect Dis. 2019; (published online Oct 22)https://doi.org/10.1016/S1473-3099(19)30273-7Scopus (105) Google Scholar present the results of a large genomic epidemiology study that asks whether a food source exists for extended-spectrum β-lactamase-producing Escherichia coli isolates (ESBL-E coli) that cause bloodstream infections in the UK. This question is controversial, with evidence both for and against the food-source hypothesis.2Lazarus B Paterson DL Mollinger JL Rogers BA Do human extraintestinal Escherichia coli infections resistant to expanded-spectrum cephalosporins originate from food-producing animals? A systematic review.Clin Infect Dis. 2015; 60: 439-452Crossref PubMed Scopus (161) Google Scholar, 3Manges AR Johnson JR Food-borne origins of Escherichia coli causing extraintestinal infections.Clin Infect Dis. 2012; 55: 712-719Crossref PubMed Scopus (203) Google Scholar Disagreements tend to revolve around the discriminatory power of genotyping approaches used to characterise E coli and on the scope and appropriateness of E coli sampling from human and non-human sources in past molecular epidemiology studies. Implementation of highly discriminatory genome sequencing, as in the present study, will begin to provide high quality evidence to either refute or support the hypothesis. The study compared the number and type of multilocus sequence types (STs) and β-lactamase genes in ESBL-E coli isolates collected in 2011–14 from human and non-human sources. Human sources of ESBL-producing E coli (n=718) included sewage samples, human faecal samples, and bloodstream infections. Non-human sources (n=218) included veterinary diagnostic specimens, dairy cattle faeces, and food products (beef, pork, chicken, berries, vegetables, and herbs). ST131 and ST10 isolates were identified in bloodstream and non-human samples, but were found to be genetically unrelated. ST69, ST117, and ST23 were also found in bloodstream and food samples, and ST602 in faeces and chicken meat, but genome similarity and evolutionary relationships across sources were not assessed. Three of the most common meat, slurry, and animal-source E coli STs in the study (ST10, ST117, and ST23) have been reported in other studies of human extraintestinal infections and were among the top 20 STs in a systematic review of human extraintestinal pathogenic E coli lineages.4Manges AR Geum HM Guo A Edens TJ Fibke CD Pitout JDD Global extraintestinal pathogenic Escherichia coli (ExPEC) lineages.Clin Microbiol Rev. 2019; 32: 1-25Crossref Scopus (206) Google Scholar CTX-M-1 β-lactamase was present in both human and non-human sources, including a single bloodstream ST117 isolate containing the CTX-M-1 enzyme. Because the STs that were common across sources were relatively rare, Day and colleagues conclude that the ESBL-E coli causing bacteremia do not arise from food animal sources. Two practical public health questions emerge from these results. First, timing. The authors rightly focus on bacteremia, a severe infection with the biggest impact on medical services and costs. E coli ST131 has increased explosively over the past 20 years as a cause of all extraintestinal infections, including bacteremia,5Price LB Johnson JR Aziz M The epidemic of extended-spectrum-β-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx.MBio. 2013; 4: e00377-e00413Crossref PubMed Scopus (298) Google Scholar, 6Stoesser N Sheppard AE Pankhurst L et al.Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131.MBio. 2016; 7: e02162-e02215Crossref PubMed Scopus (207) Google Scholar yet its original source remains unknown. E coli strains that are currently causing bloodstream infections, especially E coli ST131, might be highly host-adapted and human host-restricted, and could be more closely linked to health-care system exposure than to environmental exposures. Contemporaneous sampling of food and environmental isolates is a strength of the paper, but might have missed the period in the past when a link with food sources was measureable. The difference in ST131 clades (B, C1, and C2) by source also suggests past divergence. Similarly, the predominant ESBL genes associated with human-adapted STs probably emerged in parallel with these E coli lineages, with changing antibiotic use patterns and selective pressures over time. Second, sampling. Day and colleagues sampled diverse reservoirs to investigate the source of bacteremia-causing E coli; another strength of the study. Sampling is always challenging. Studies must balance logistical feasibility with selection bias avoidance. Large numbers of E coli were screened to identify the predominant ESBL-producing members within each source population. Still, this finding represents a tiny fraction of the total diversity of circulating E coli, and ignores E coli isolates that are highly genetically similar across sources but have lost (or never had) ESBL-encoding mobile genetic elements. Selection for resistant-only isolates would miss any such link. Finding any genomic match between human and non-human source isolates, even between a pair of singleton STs, could be important to public health, especially in the face of extensive E coli diversity and finite study sample sizes. A single introduction of a highly successful resistant clone might suffice to trigger the next (non-ST131) pandemic. The repeated emergence in E coli and other uropathogens of novel resistance genes, encoding not just ESBLs but also colistin and carbapenem resistance, has been linked genetically to food animal sources.7Lin YC Kuroda M Suzuki S Mu JJ Emergence of an Escherichia coli strain co-harbouring mcr-1 and blaNDM-9 from a urinary tract infection in Taiwan.J Glob Antimicrob Resist. 2019; 16: 286-290Crossref PubMed Scopus (18) Google Scholar Several new lineages are emerging, some of which (eg, ST1193) might ultimately supplant ST131.8Tchesnokova VL Rechkina E Larson L et al.Rapid and extensive expansion in the United States of a new multidrug-resistant Escherichia coli clonal group, sequence type 1193.Clin Infect Dis. 2019; 68: 334-337Crossref PubMed Scopus (51) Google Scholar To detect newly emerging, multidrug-resistant E coli lineages, stand-alone research studies might not be enough. Distributed surveillance systems that involve better integrated human and animal health systems and food inspection agencies, with sharing of carefully curated local and regional epidemiological and E coli genome sequencing data, will be required to counter the public health and medical threats posed by resistant and non-resistant, E coli causing bloodstream and other extraintestinal infections. I declare no competing interests. Extended-spectrum β-lactamase-producing Escherichia coli in human-derived and foodchain-derived samples from England, Wales, and Scotland: an epidemiological surveillance and typing studyMost human bacteraemias with ESBL-E coli in the UK involve internationally prevalent human-associated STs, particularly ST131; non-human reservoirs made little contribution to invasive human disease. Any interventions that seek to target food or livestock can affect the numbers of human infections caused by ESBL-E coli; prevention of the spread of resistant lineages among humans is more vital. Full-Text PDF Open AccessDolutegravir and neural tube defects: a new insightDolutegravir is a highly effective antiretroviral therapy (ART) allowing a fast viral load decrease, which is promising in low-income and middle-income countries.1 However, according to preliminary results from a nationwide birth surveillance programme in Botswana,2 it has been associated with the development of neural tube defects in newborn babies. Incidence of neural tube defects in the newborn babies of women who were taking dolutegravir at the time of conception was estimated to be 0·94% (95% CI 0·37–2·4). Full-Text PDF

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