Clinical impact of a gastrointestinal PCR panel in children with infectious diarrhoea

ObjectivesMultiplex gastrointestinal PCR (GI-PCR) allows fast and simultaneous detection of 22 enteric pathogens (including Campylobacter, Salmonella, Shigella/enteroinvasive Escherichia coli (EIEC), among other bacteria, parasites and viruses). However, its impact on the management of children with infectious diarrhoea remains unknown.Patients/DesignAll children eligible for stool culture from May to October 2018 were prospectively included in a monocentric study at Robert-Debré University-Hospital.InterventionA GI-PCR (BioFire FilmArray) was performed on each stool sample.Main measuresData on the children’s healthcare management before and after GI-PCR results were collected. Stool culture results were also reported.Results172 children were included. The main criteria for performing stool analysis were mucous/bloody diarrhoea and/or traveller’s diarrhoea (n=130). GI-PCR’s were positive for 120 patients (70%). The main pathogens were enteroaggregative E. coli (n=39; 23%), enteropathogenic E. coli (n=34; 20%), Shigella/EIEC (n=27; 16%) and Campylobacter (n=21; 12%). Compared with stool cultures, GI-PCR enabled the detection of 21 vs 19 Campylobacter, 12 vs 10 Salmonella, 27 Shigella/EIEC vs 13 Shigella, 2 vs 2 Yersinia enterocolitica, 1 vs 1 Plesiomonas shigelloides, respectively. Considering the GI-PCR results and before stool culture results, the medical management was revised for 40 patients (23%): 28 initiations, 2 changes and 1 discontinuation of antibiotics, 1 hospitalisation, 2 specific room isolations related to Clostridioides difficile infections, 4 additional test prescriptions and 2 test cancellations.ConclusionThe GI-PCR’s results impacted the medical management of gastroenteritis for almostone-fourth of the children, and especially the prescription of appropriate antibiotic treatment before stool culture results.

Review of Rifaximin: A Summary of the Current Evidence and Benefits Beyond Licensed Use

Antibiotic resistance in patients with cirrhosis continues to draw significant attention. With a propensity to frequent hospitalisations, patients with cirrhosis are subject to frequent antibiotic prescription. This increases their risk of developing resistance to one or more antimicrobial agents, making management of their condition particularly challenging. Despite advancements being made in the management of liver disease, mortality rates continue to rise: almost 5-fold in those <65 years of age while remaining the leading cause of death in those 35–49 years of age. Alternative therapeutic options to prevent disease progression and cirrhosis-associated complications are urgently required; rifaximin is one such example. The medication use in patients with cirrhosis demonstrates additional benefits beyond current licensed use in the UK, that being for the prevention of hepatic encephalopathy and traveller’s diarrhoea; rifaximin has especially been explored beyond current licensed use in the context of enteric-driven pathologies. Through the therapy’s key central action as a broad-spectrum antimicrobial, rifaximin has the ability to modulate the gut–liver axis via removal of gut microbial products associated with the progression of cirrhosis and its sequalae. The benefits of rifaximin use continues to gather momentum, given its non-absorbable nature and well-tolerated side-effect profile, and these require consideration. With broad-spectrum antimicrobial properties, its use may assist in overcoming the conundrum posed of antibiotic resistance amongst patients with cirrhosis. This literature review discusses the chemical and antimicrobial properties of rifaximin, its licenced indication for use, and its reported benefits beyond this, as well as concerns regarding rifaximin resistance.

Multidrug-Resistant Lineage of Enterotoxigenic Escherichia coli ST182 With Serotype O169:H41 in Airline Waste

Enterotoxigenic Escherichia coli (ETEC) is the primary aetiologic agent of traveller’s diarrhoea and a significant cause of diarrhoeal disease and death in developing countries. ETEC O169:H41 strains are known to cause both traveller’s diarrhoea and foodborne outbreaks in developed countries and are cause for concern. Here, whole-genome sequencing (WGS) was used to assemble 46 O169:H41 (ST182) E. coli draft genomes derived from two airplane waste samples sourced from a German international airport. The ST182 genomes were compared with all 84 publicly available, geographically diverse ST182 genomes to construct a core genome-based phylogenetic tree. ST182 isolates were all phylogroup E, the majority serotype O169:H41 (n = 121, 93%) and formed five major clades. The airplane waste isolates differed by an average of 15 core SNPs (range 0–45) but their accessory genome content was diverse. While uncommon in other ST182 genomes, all airplane-derived ST182 isolates carried: (i) extended-spectrum β-lactamase gene blaCTX–M–15 notably lacking the typical adjacent ISEcp1; (ii) qnrS1 and the S83L mutation in gyrA, both conferring resistance to fluoroquinolones; and (iii) a class 1 integron structure (IS26-intI1Δ648-dfrA17-aadA5-qacEΔ1-sul1-ORF-srpC-padR-IS6100-mphR-mrx-mphA-IS26) identified previously in major extraintestinal pathogenic E. coli STs but not in ETEC. ST182 isolates carried ETEC-specific virulence factors STp + CS6. Adhesin/invasin tia was identified in 89% of aircraft ST182 isolates (vs 23%) and was located on a putative genomic island within a hotspot region for various insertions including PAI I536 and plasmid-associated transposons. The most common plasmid replicons in this collection were IncFII (100%; F2:A-:B-) and IncB/O/K/Z (89%). Our data suggest that potentially through travel, E. coli ST182 are evolving a multidrug-resistant profile through the acquisition of class 1 integrons and different plasmids.

A comparison of two multiplex-PCR assays for the diagnosis of traveller’s diarrhoea

Background Numerous multiplex-PCR assays are now available in routine diagnostics but their clinical value is controversial if a clear association between clinical symptoms and the detection of a particular pathogen is missing. The objective of this work was to evaluate a multiplex-PCR assay for the diagnosis of traveller’s diarrhoea (TD) in a case-control study and to assess the concordance with the BioFire® FilmArray® Gastrointestinal Panel. Methods Stool samples from cases (n = 61) and controls (n = 30) were collected during travel and analysed by the GI-EB Screening assay (Seegene) in a case-control study. The concordance with the BioFire® FilmArray® Gastrointestinal Panel was expressed as the proportion of participants in which both tests agreed in the category “detected” and “not detected”. Results None of the test-target organisms (Campylobacter spp., Clostridioides difficile toxin A/B, Salmonella spp., Shigella spp./enteroinvasive Escherichia coli, E. coli O157, Shiga toxin-producing E. coli, Yersinia enterocolitica) was significantly associated with TD GI-EB Screening assay. The GI-EB Screening assay had an agreement with the BioFire® FilmArray® of 86.8–100%. Conclusion The selection of test-target organisms included in the GI-EB Screening assay appears inappropriate for the diagnostic work-up of TD as none of the detected pathogens was associated with TD. The GI-EB Screening assay had a good concordance with BioFire® FilmArray®.

Case 18

Traveller’s diarrhoea is among the commonest health problems to afflict travellers to resource-poor countries. It is most commonly caused by E. coli, either enterotoxigenic or enteroaggregative, although there is geographic variation. Most cases are self-limiting but can be debilitating and maintaining hydration is important. Antibiotics are sometimes recommended for travellers to carry as standby treatment, particularly if they are going to be in remote areas or are immunocompromised. Prophylaxis is not recommended for the majority of situations.

Epidemiology of Enterotoxigenic Escherichia coli infection in Minnesota, 2016–2017

Enterotoxigenic Escherichia coli (ETEC) is a well-established cause of traveller's diarrhoea and occasional domestic foodborne illness outbreaks in the USA. Although ETEC are not detected by conventional stool culture methods used in clinical laboratories, syndromic culture-independent diagnostic tests (CIDTs) capable of detecting ETEC have become increasingly prevalent in the last decade. This study describes the epidemiology of ETEC infections reported to the Minnesota Department of Health (MDH) during 2016–2017. ETEC-positive stool specimens were submitted to MDH to confirm the presence of ETEC DNA by polymerase chain reaction (PCR). Cases were interviewed to ascertain illness and exposures. Contemporaneous Salmonella cases were used as a comparison group in a case-case comparison analysis of risk factors. Of 222 ETEC-positive specimens received by MDH, 108 (49%) were concordant by PCR. ETEC was the sixth most frequently reported bacterial enteric pathogen among a subset of CIDT-positive specimens. Sixty-nine (64%) laboratory-confirmed cases had an additional pathogen codetected with ETEC, including enteroaggregative E. coli (n = 40) and enteropathogenic E. coli (n = 39). Although travel is a risk factor for ETEC infection, only 43% of cases travelled internationally, providing evidence for ETEC as an underestimated source of domestically acquired enteric illness in the USA.

Gastrointestinal infections

Gastrointestinal infections, especially diarrhoea and vomiting, are responsible for substantial morbidity, mortality, and socioeconomic penalties worldwide. Poor sanitation, inadequate water supplies, and globalization of food production, processing, and retailing increase the risk of large epidemics of food- and waterborne outbreaks of gastrointestinal disease. Acute diarrhoea can be caused by a range of pathogens. Gastrointestinal pathogens usually cause three principal syndromes: acute watery diarrhoea, acute bloody diarrhoea (inflammatory diarrhoea or dysentery), and persistent diarrhoea. They can also cause systemic disease. Patients who do not have high fever (>38.5°C), systemic illness, tenesmus, bloody diarrhoea, a prolonged course (>2 weeks), or dehydration require neither investigation nor treatment. Investigation is required in patients with any of these features, with faecal specimens examined by culture (bacterial pathogens and some protozoa), microscopy (ova, cysts, and parasites), immunoassays (some protozoa and viruses), and molecular methods, usually polymerase chain reaction (PCR) or reverse transcriptase PCR (bacterial toxin genes and viruses). A specific laboratory diagnosis is useful epidemiologically and therapeutically. Oral rehydration therapy is the priority for patients with mild to moderate diarrhoea as long as vomiting is not a major feature. Antimicrobial therapy is not recommended or usually required for uncomplicated diarrhoea, but antibiotic treatment is beneficial for cholera, giardiasis, cyclosporiasis, shigellosis, symptomatic traveller’s diarrhoea, Clostridium difficile diarrhoea, and typhoid. Antimotility drugs are useful in controlling moderate to severe diarrhoea in adults but they are not generally recommended for infants and young children under the age of 4 years. Strict attention to food and water precautions and hand washing helps reduce the risk of gastrointestinal infections. Immunization has not yet proved successful for combating many gastrointestinal pathogens, with the notable exception of rotavirus.