Gastrointestinal infections
Herbert Tilg Lecture – Gastro Update Europe 2016, Prague

Some recent developments in gastrointestinal infections were summarized by Prof. Herbert Tilg from Austria. First discussed was the importance of the rising outbreaks of norovirus infection, the most frequent cause of foodborn illness together with Campylobacter infection. Norovirus, a calicivirus, has a worldwide distribution (incubation period is from 24 to 48 hours), with symptoms lasting from ~48 to 72 hours and viral shedding in stool continuing for 2–3 weeks. Viral identification is mandatory especially in an outbreak setting with nucleic acid based testing (RT-PCR – reverset ranscription polymerase chain reaction) or immuno-assay. Vomiting is a key clinical symptom. Particular attention is required when alarm symptoms develop, such as dehydration, enteralbleeding, weight loss, severe abdominal pain, and if symptoms last longer than a week, especially in the elderly or in immunosuppressed people. At the end of 2014, a more virulent genotype variant appeared, which is more capable of immune evasion, causing severe gastroenteritis and often necessitating hospitalisation. It is unfortunate that no antiviral therapy is available; vaccines are under development. Hand wash with soap and water for 30 seconds removes the virus from finger pads in contrast to washing with propanol-based hand desinfectant, which shows little viral reduction.

Campylobacter infection, the mostcommon cause of bacterial diarrhea is largely a foodborn disease. Campylobacter inhabits the intestinal tract of many animals, most notably poultry. The incubation period lasts ~3 days. The disease presents with fever, followed by abdominal cramps and diarrhea. Late complications are reactive arthritis and Guillain-Barre syndrome. Therapy focuses on rehydration; antibiotics should be limited to severe disease (ciprofloxacin, azithromycin). Most intriguing, based on a meta-analysis, is the finding that Campylobacter infection increases the risk of IBD, in contrast to H. pylori infection which seems negatively associated with IBD. This observation begs for understanding.

Clostridium difficile colonizes the human intestinal tract after the normal gut flora has been altered by antimicrobial therapy. The spectrum of clinical presentation is highly variable. Life threatening disease, including fulminant colitis, is possible. Testing for toxin is recommended for symptomatic patients with nosocomial infection. In a large European multicenter (482 hospitals), prospective bi-annual point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhea, it was shown that – absence of clinical suspicion and suboptimal laboratory diagnostic methods were responsible – 40,000 European inpatients per year with Clostridium difficile infection were not diagnosed properly. Note that PCR testing will lead to overdiagnosis of Clostridium difficile infection; measuring the presence of toxin is essential for adequate diagnosis. All Clostridium difficile infection-related complications and deaths occur only in toxin-positive patients. Patients with a positive PCR, but with a negative toxin assay, had similar outcomes as patients without Clostridium difficile infection. It is also wise to remember that there is a high rate of alternative diagnoses in patients referred for presumed Clostridium difficile infection; indeed up to 25% of such patients have a non-Clostridium difficile diagnosis, mainly IBD and IBS (irritable bowel syndrome). Morbidity and mortality of Clostridium difficile infection in postoperative patients is alarmingly high. Almost 500,000 post-sugical patients in well over 100 American hospitals were analysed. The Clostridium difficile infection rate was 0.4% per year. Risk factors were age, frequently hospitalisation, complex surgery, and increased antimicrobial use. Postoperative morbidity was higher and 30-day mortality was 5.3% compared to 1.0% in non-infected patients.

Therapeutic recommendations may be summarized as follows:

• moderately severe disease – oral metronidazole (3 × 500 mg ) or vancomycin (4 × 125 mg ) for 2 weeks
• severe disease – i.v. metronidazole: oral/ nasogastric vancomycin (4 × 500 mg) or fidaxomicin (2 × 200 mg) for 2 weeks
• complicated disease – see above, plus faecal microbiota transplantation (FMT)

The initial spectacular results of TMT, at first infused via the proximal intestine, have been confirmed – also infused via the colon, and in patients with very severe and complicated infection, and further in patients with toxic megacolon. The FMT technology is constantly evolving; frozen microbiota seems equally efficacious as fresh stool enemas. Microbiota suspension as enema in ready-to-use format seems also safe and effective. Finally, studies are ongoing to find out if a small molecule ebselen (an anti-oxidant and antivirulence agent), targeting the cystein protein domain of toxin B, can be used clinically to control the disease. The deleterious effects of continuous proton pump inhibitors (PPI) therapy in recurrent Clostridium difficile infection is well established. In a recent retrospective cohort study involving some 750 patients with Clostridium difficile infection, PPIs were used in 61% (of whom only about half had an evidence based indication). Almost none of the PPI users stopped the drug despite the proven risk. PPI use decreases the bacterial richness and results in profound microbiome changes, affecting 20% of the bacteria. Oral/ pharyngeal bacteria and potential pathogenic bacteria (enterococ, streptococ, staphylococ, micrococ etc.) increase. Some investigators even claim that PPI induce more bacterial alterations than use of antimicrobials.

Exploring the role of the gut microbiome in many diverse diseases continues, also with respect to the gut-braininteraction. As an example: evidence is increasing supporting the role of the indiginous bacteria from the gut microbioma in the regulation of serotonin biosynthesis and metabolism, impacting on gastrointestinal motility, secretion, and hemostasis. Altering the microbiota may well improve 5-hydroxy triptamine-related disease symptoms such as IBS, but also other conditions. Obviously, there is more to come.

Prof. Guido Tytgat, MD, PhD

Department of Gastroenterology and Hepatology

Academic Medical Center

Meibergdreef 9

1105 AZ Amsterdam

The Netherlands

g.n.tytgat@amc.uva.nl