News

Antibiotic Awareness Week

Antibiotic ‘control’: a global issue.

Rather like global warming, antibiotic resistance is a global problem that needs a co-ordinated world agreement on antibiotic stewardship.

 Due to extreme selective pressure, bacterial resistance to antibiotics occurs faster than new antibiotics can be developed.

Educating patients that antibiotics do not work for viral upper respiratory tract infections (URTIs) is a major public health issue. A Scottish study revealed a demonstrable difference between socioeconomic deprivation and antibiotic prescribing with the most socially deprived patients receiving 36.5% more antibiotic prescriptions than the most affluent. This relationship is likely to be replicated across the UK. These are complex data with issues of patient expectation, lifestyle, morbidity and mortality, but it highlights groups to be targeted for health promotion.

Primary care accounts for 80-90% of all antibiotic prescriptions in Europe.  Most patients want reassurance that their or their child’s URTI is viral and will get better on its own without antibiotics. Adverse events are high with 1 in 14 children treated with antibiotics for ear infections experiencing vomiting, diarrhoea or a rash,8 and women hate getting thrush after broad spectrum antibiotics. Clinicians have been found to overestimate patient expectations for antibiotics, especially in patients presenting with acute cough.

Incidentally, a Spanish study recently published compared treatments for cough with mucky sputum.  Antibiotic, Ibuprofen and Dummy pill all had similar effects!

 Probiotics

A recently published, evidence-based guide aimed to provide practical guidance on the role of specific probiotics in managing particular gastrointestinal symptoms. In patients receiving antibiotic therapy, probiotics had supportive evidence.  A probiotic drink containing Lactobacillus casei, L. bulgaricus and Streptococcus thermophilus was assessed in a 135 hospital patients aged over 50 who required a course of antibiotics. 12% of the group taking the probiotic drink developed diarrhoea compared with 34% of the placebo group (p=0.007). Nobody in the probiotic group had C. difficile associated diarrhoea versus 17% of the placebo group (p=0.001).

I have always advised travellers to include natural yogurt in their diet – due to long experience of travelling and strong aversion to public ‘WCs’ in strange places!

Here is a complete article which deserves to be read in its entirety.  Remember the words “the gut is like an additional liver and chromosome”.  It is that important.

The collateral damage of antibiotics on gut microbiota

By Dr Richard Stevens, GP and Editor-in-Chief of The Digest

The human body is a structure that is populated by huge numbers of bacteria, yeasts and fungi, viruses and other microorganisms. Every nook, crease and cranny is a perfect environment for some species, or collection of species, and the bowel is a positive metropolis for a great many.

Traditionally the gut microbiota has been rather ignored and traditional culture methods were relied upon for identification. Recently, new techniques, principally involving gene typing, have shown the full extent, range and diversity of the gut microbiota. Increasingly we recognise the role that this biomass has in many biological functions of the host.

An individual’s gut will contain tens of trillions of bacteria and these will contribute three million genes. This means there are ten times more bacterial cells present than in the body and 150 times more genes than in the human genome. Moreover, while more than 1,000 different bacterial species can be found in the human gut, only 150 to 170 predominate in a given individual. The exact composition of gut microbiota is unique to each individual (as defining as a fingerprint) and is stable over time.

The gut is essentially a muscular tube that has a large amount of lymphoid tissue in the wall. The microbiota is constantly interacting with the host and has both a metabolic and genetic function.

Metabolic activity of microbiota

Examples of the metabolic function are the breaking down of some foodstuffs prior to absorption and the synthesis of some vitamins and drugs. For example, sulfasalazin is cleaved by colonic bacterial action into a sulphonamide and 5-ASA, which has a local action on inflamed colonic epithelial cells in inflammatory bowel disease.

Other examples are obesity in discordant twins which is associated with differences in gut microbiota in animals,1 while it has been demonstrated that kwashiorkor susceptibility is affected by the microbiota.2

Genetic and immunological activity of microbiota

The vast amount of genetic material, the “enterotype”, present interacts with that of the host. There have long been theories of gut organism involvement in gastroenterological conditions such as irritable bowel syndrome and inflammatory bowel disease. Recently colorectal cancer has been associated with disturbance of the microbiota.3

Now there is increasing evidence for a range of systemic and distant conditions that are associated with specific patterns of microbiota, including autoimmune conditions such as type 1 diabetes.4 There is an emerging picture of the enterotype actively interacting with the host and being responsible for the immune responses provoked.

In summary, the gut microbiota can no longer be seen as commensals, or at best symbiotically related to the host. Active metabolically and immunologically, the microbiota can be thought of as an additional liver and chromosome.

Antibiotic effects

There is no doubt that antibiotics have done an enormous amount of good. There is an equal lack of doubt that they are, and have been, frequently overprescribed. Animal feeds continue to regularly contain antibiotic supplements and the drugs enter the food chain from them. However, they are blunt instruments and affect the microbiota, the “additional liver and chromosome”.

There is good evidence that antibiotic use strongly affects microbial intestinal metabolism and thereby impacts on human health. This effect could be more sustained and profound than previously realised.5 This can be added to many reasons to be thoughtful and consider the costs and benefits of prescribing antimicrobials.

Restoring the gut microbiota in this situation would seem to make sense, especially if there are symptoms such as antibiotic-associated diarrhoea (AAD). Probiotics – preparations of non-pathogenic bacteria – have been tried in a number of gastrointestinal conditions and the strongest evidence of benefit to date is for AAD. Several good quality trials have demonstrated a prevention or reduction of AAD with probiotics and meta-analysis confirms this.6 There are a number of probiotics marketed which contain different organisms and it is important to remember that their effects are strain specific and cannot be extrapolated from one probiotic to another.7

Clostridium difficile infection is a severe sequelae that sometimes occurs secondary to antibiotic use. There is a paradox that the usual treatment is even more antibiotics, predominantly vancomycin or metronidazole. There are fascinating trials ongoing where instead the faecal bacteria from a healthy donor are “transplanted” into the patient via enema or colonoscope (but via a nasogastric tube has also been used). Results so far are extremely encouraging and further evidence is being collected.

In the near future the microbiota will receive a great deal of attention. There is a body of evidence implying its role in a number of conditions including some as unlikely as anxiety and depression.8 Far from commensuals, the gut bacteria play an active, and indeed inter-active, part in maintaining health.

References

  1. Ridaura V K, Faith J J et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013;341:1241214
  2. Garrett W S. Kwashiorkor and the gut microbiota. N Engl J Med 2013;368:1746-1747
  3. Wu N, Yang X et al. Dysbiosis signature of fecal microbiota in colorectal cancer patients. Microb Ecol 2013;66:462-470
  4. Wen L, Ley R E. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 2008;455:1109-1113
  5. Pérez-Cobas A E, Gosalbes M J et al. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut 2013;62:1591-1601
  6. Hempel S, Newberry S J et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 2012;307:1959-1969
  7. Hungin A P, Mulligan C et al. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice – an evidence-based international guide. Aliment Pharmacol Ther 2013;38:864-886
  8. Foster J A, McVey Neufeld K A. Gut-Brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 2013;36:305-312
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