Long term, cryptic, adverse effects of antibiotic therapy
I’m going to be a bit controversial here….My observation is that, despite widespread awareness of the potential undesirable consequences of antibiotic use, they are still commonly prescribed in small animal practice in the UK in circumstances where evidence-based justification is lacking. Furthermore, this practice isn’t restricted to the ‘dinosaurs’ of the profession. ‘Defensive’ use of antibiotics is also common in young, enlightened and knowledgeable vets and in referral practice in circumstances where there is felt to be a need to ‘cover all bases’. Fever in post-op orthopaedic cases; severe acute gastroenteritis; acute URTIs would be good examples.
There is almost universal acceptance that the spread of antibiotic resistance is an important downside. I believe, however, that the risk of adverse consequences for individual patients may be underestimated.
There are, obviously, immediate undesirable effects. To list a few:
- neurological signs associated with metronidazole
- deafness associated with cephalosporins
- idiosyncratic acute renal tubular necrosis due to tetracyclines
- triggering of IMHA or other immune-mediated diseases by various agents
- wide variety of cutaneous adverse drug reactions (TEN, erythema multiforme etc.)
Having been around for a few years and made just about every mistake possible I find it relatively easy to persuade owners that their pet doesn’t need antibiotics by recounting a few stories of this kind of thing. Fortunately, none of these are very common: otherwise we’d stop using them.
What’s more concerning to me is the potential for insidious, delayed sequelae which may not been identified as due to antibiotic use. Primarily, that means disruption of skin and gut flora.
The intestinal microbiota plays beneficial roles in many physiological processes of the host. It extracts energy and nutrition from food but, we increasingly realise, also protects against enteropathogens, and supports development and maintenance of the host immune system.
An illustration of the latter is the emerging (and amazing!) role of specific gut bacteria in the pathogenesis of type 1 (immune mediated) diabetes:
Brugman S, Klatter FA, Visser JT, Wildeboer-Veloo AC, Harmsen HJ, Rozing J, Bos NA: Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat: is the gut flora involved in the development of type 1 diabetes? Diabetologia 49:2105–2108, 2006
https://www.ncbi.nlm.nih.gov/pubmed/16816951
Or how about this:
Clin Psychopharmacol Neurosci. 2016 Aug; 14(3): 231–237.
Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders
Alper Evrensel and Mehmet Emin Ceylan
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977816/
Who knew that gut flora might be important in the pathogenesis of Parkinson’s!!
It’s becoming clear that we have only the slightest inkling of the profound systemic effects of gut bacteria. And thus no real idea what we are doing to long term health of our patients when we prescribe antibiotics.
Dysbiosis, a disruption of microbial composition by various stresses, has been implicated in inflammatory bowel disease (IBD), colon cancer, obesity, asthma, and other diseases.
Nicely reviewed here:
Yonsei Med J. 2018 Jan 1; 59(1): 4–12.
Disruption of the Gut Ecosystem by Antibiotics
Mi Young Yoon1,2 and Sang Sun Yoon
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725362/
Antibiotic-induced changes in gut flora are not fully reversed, even after several months of discontinuation of dosing.
Sekirov I, Tam NM, Jogova M, Robertson ML, Li Y, Lupp C, et al. Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection. Infect Immun. 2008;76:4726–4736.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546810/
Eventually, the antibiotic-induced dysbiosis of the intestinal microbiota affects the immune system and increases the risk of intestine-related diseases, such as IBDs and infectious diseases, in addition to diverse immunity-related disorders, such as allergic or atopic skin diseases and type 1 diabetes.
Antibiotic therapy triggers the proliferation of intestinal pathogenic bacteria due to the ability of infectious bacteria to effectively exploit the disorder that arises when the intestinal microbiota has collapsed.
J Clin Invest. 2014 Oct 1; 124(10): 4212–4218.
Antibiotics and the gut microbiota
Sheetal R. Modi,1,2 James J. Collins,1,2 and David A. Relman
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191029/
…and yet, the use of antibiotics in acute severe gastro-entero-colitis in dogs is almost universal. Despite the fact that we have a nice study demonstrating that co-amoxyclav is not beneficial in non-septic acute haemorrhagic diarrhoea:
J Vet Intern Med. 2011 Sep-Oct;25(5):973-9. doi: 10.1111/j.1939-1676.2011.00765.x. Epub 2011 Jul 22.
Treatment of aseptic dogs with hemorrhagic gastroenteritis with amoxicillin/clavulanic acid: a prospective blinded study.
Unterer S1, Strohmeyer K, Kruse BD, Sauter-Louis C, Hartmann K.
https://www.ncbi.nlm.nih.gov/pubmed/21781168
The issue of whether antibiotics are beneficial even in septic dogs with AHDS was not addressed.
When we prescribe antibiotics to young dogs with diarrhoea (when they haven’t returned to normal faecal consistency after a couple of weeks) are we at risk of inducing long term dysbiosis and perpetuating their problem? Should we warn owners that it’s a possibility?
