Description

Antibiotics play a key role in the therapeutic management of horses with primary or secondary bacterial infections.  They may kill bacteria (bactericidal antibiotics) or impede their metabolism or multiplication (bacteriostatic antibiotics), and thereby permit the host’s immune response to overcome the infection and regain control.  Antibiotics may be active against specific families of bacteria (narrow-spectrum antibiotics) or against a wide range of bacteria (broad-spectrum antibiotics).

Use

While the importance of antibiotic therapy in the treatment of horses with bacterial infections is clear, it is imperative that these agents be used judiciously and that the role of supportive therapies in promoting a positive outcome be recognised.  The administration of antibiotics is safest and most likely to be effective when a complete physical examination of the patient is first conducted, the bacterium involved is isolated and a sensitivity test performed, and a dosage regimen and method of delivery appropriate to the patient is selected.  However, identification of the infecting agent in a timely manner is not always possible, and in such cases the use of broad-spectrum antibiotics may be necessary.  Moreover, the in vitro efficacy of antibiotics is not always reflected in vivo.  Compounding this is the need to recognise that in some situations, the antibiotic that might be most effective based on probable efficacy may not be the most appropriate in terms of the responsible use of antibiotics, and that a horse may have an allergy or underlying condition that would render the treatment risk unacceptable.

Association with the GI microbiome

In addition to killing or inhibiting the growth of pathogenic bacteria, antibiotics can also kill or inhibit the growth of bacteria that are normal inhabitants of the GI tract.  Those normal inhabitants play important roles, supplying energy to the horse through cellulose fermentation and short chain fatty acid production, and protecting the horse from pathogenic bacteria by lining the intestinal walls and producing substances that are toxic to pathogenic bacteria.  Recent studies using both cultural and high-throughput sequencing techniques have shown that the administration of antibiotics is commonly associated with the development of a microbial imbalance (dysbiosis) within the GI tract of the horse.  Harlow and her colleagues¹ observed a significant decrease in the abundance cellulolytic bacteria, and cellulolytic bacteria and lactobacilli, in horses treated with trimethoprim-sulfadiazine and ceftiofur, respectively.  Moreover, they observed the coincident proliferation of pathogens including Salmonella spp. and Clostridium difficile, noting that the observed state of dysbiosis persisted for some time after the antibiotic treatments ceased.  Costa and his colleagues² also reported significant changes in the population structure and community membership of the GI microbiota associated with the administration of procaine penicillin, ceftiofur sodium and trimethoprim sulfadiazine (TMS).  TMS caused the most marked changes including a significant decrease in the relative abundance of Verrucomicrobia and bacteria that were unclassified at the phylum level, a decrease in the abundance of Proteobacteria, and an increase in the abundance of Firmicutes.  Grønvold and her colleagues³ observed not only that penicillin treatment causes a change in the predominant bacterial populations of the GI tract, but also that bacteria of the GI tract (in their case Escherichia coli) can develop resistance to multiple unrelated antibiotics as a consequence of penicillin exposure.  Together, those studies clearly demonstrate that the use of both broad- and narrow-spectrum antibiotics can cause an imbalance of the microbiota naturally present in the GI tract and that that can set the stage for the proliferation of GI pathogens and the development of antibiotic resistance.

References

¹ Harlow, B.E., Lawrence, L.M. and Flythe, M.D., 2013.  Diarrhea-associated pathogens, lactobacilli and cellulolytic bacteria in equine feces: Responses to antibiotic challenge.  Veterinary Microbiology 166(1-2):  225-232.

² Costa, M.C., Stampfli, H.R., Arroyo, L.G., Allen-Vercoe, E., Gomes, R.G. and Weese, J.S., 2015.  Changes in the equine fecal microbiota associated with the use of systemic antimicrobial drugs.  BMC Veterinary Research  1:  Art 19.

³ Grønvold, A.M.R., L'Abee-Lund, T.M., Strand, E., Sorum, H., Yannarell, A.C., Mackie, R. I., 2010.  Fecal microbiota of horses in the clinical setting: Potential effects of penicillin and general anesthesia.  Veterinary Microbiology 145(3-4):  366-372.

Description

Colitis is defined as inflammation of the colon.  It may be acute and self-limiting or chronic, i.e. persistent.  Causes may be infectious, with common agents including Salmonella, Clostridium difficile, clostridium perfringens, Neorickettsia risticii, rotavirus and parasites such as small strongyles, or non-infectious.  Examples of the latter include antibiotic-associated diarrhoea, sand impaction, dietary imbalances, inflammatory bowel disease, stress, plant toxicities and drug toxicities.  Each etiology leads to inflammation of the wall of the colon.  The inflamed wall of the colon secretes large amounts of fluid and proteins and reduces absorption of water, electrolytes and nutrients from the intestinal content.  Diarrhoea is the primary clinical symptom, with others including fever, tachycardia, tachypnea and abdominal distension.  If diarrhoea is severe enough, signs of dehydration may also be evident.  As the intestinal wall becomes permeable to bacteria normally confined to the intestinal lumen, signs of endotoxemia may also occur.  In many cases the etiologic agent(s) remain(s) undetermined.

Treatment

In most cases treatment is initially directed at rehydration, and electrolyte and plasma protein replacement, by means of intravenous fluid therapy.  Antibiotic therapy is initiated when indicated, or when circulation of bacteria to other organs is suspected.  Anti-endotoxin therapy may also be employed, and absorbents such as Biosponge or activated charcoal are occasionally administered.  Anti-inflammatory and pain medications may be used, and probiotics or filtered manure from a healthy horse may be administered in an attempt to re-establish GI balance.  Additional therapy depends on the inciting cause.

Association with the GI microbiome

While infectious agents including C. difficile, enterotoxigenic C. perfringens and Salmonella spp. have been incriminated as important etiological agents of diarrhoea in horses, most cases of equine colitis remain without a clear etiological diagnosis¹  Disruption of the normal GI microbiome must, however, be considered a likely key factor.  In characterising the fecal microbiome of healthy horses and comparing it with that of horses with undifferentiated colitis, Costa and colleagues² observed marked differences between the two microbiomes (Figure 1).  Acknowledging that cause versus effect cannot be discerned, the authors raise some interesting questions about the occurrence of various microbial groups, including Fusobacteria in colitic horses and the predominance of clostridia and related organisms in healthy horses.  In light of the marked differences in the microbiome of healthy and colitic horses, Costa and colleagues observed that colitis may be a disease of dysbiosis in the GI microbiome, rather than one that occurs simply through overgrowth of an individual pathogen.  Such a notion undoutedly warrants further investigation.

Figure 1

Intra-phylum variation present in faeces of healthy horses and horses affected by colitis.

References

¹Chapman, A.M., 2009.  Acute diarrhea in hospitalized horses.  Veterinary Clinics of North America:  Equine Practice 25(2):  363-380.

²Costa, M.C., Arroyo, L.G., Allen-Vercoe, E., Stampfli, H.R., Kim, P.T., Sturgeon, A. and Weese, J.S., 2012.  Comparison of the Fecal Microbiota of Healthy Horses and Horses with Colitis by High Throughput Sequencing of the V3-V5 Region of the 16S rRNA Gene.  PLosONE 7(7):  e41484.

Description

Also known as Pituitary Pars Intermedia Dysfunction or PPID, equine Cushing’s disease is a condition that results from a dysfunction of the pituitary gland.  The latter is caused by the growth of a pituitary tumour, usually an adenoma, and is reflected in abnormal levels of the adrenocorticotropic hormone (ACTH) and alpha-MSH (melanocyte-stimulating hormone).  ACTH production stimulates cortisol production by the adrenal glands, and in equids with Cushing’s disease, insensitivity of the pituitary adenoma to negative feedback inhibition results in hypercortisolism.  In horses and ponies increased cortisol levels causes the development of long, shaggy hair with coats failing to shed or shedding only partially.  Horses and ponies with Cushing’s disease may also drink and urinate excessively, sweat excessively or inappropriately, and exhibit muscle wasting and development of a “potbelly”, lethargy, infertility and lowered immunity.  They are also prone to Laminitis, and may develop insulin resistance secondarily.

Treatment

Although there is no definitive treatment for equine Cushing’s disease, there are a handful of ways to manage and effectively control it.  Pergolide, a dopamine receptor agonist that helps control ACTH production, is commonly employed and can lead to a significant improvement in quality of life.  If a poor response to Pergolide is observed, other drugs including Bromocriptine, Cyproheptadine, and Trilostane may be employed.  Other management practices that can, and should, be adopted for horses and ponies with Cushing’s disease include regular farrier visits, dental check-ups, monitoring of faecal egg counts and de-worming when appropriate, coat clipping and maintenance on good quality forage and a complete feed supplying nutrients, vitamins and minerals.  Those practices help combat laminitis, large parasite burdens and infections that results from immune suppression, and weight loss.

Association with the GI microbiome

While no research has been carried out to date concerning a link between the GI microbiome and Cushing’s disease, Al Jassim and Andrews assert that “the ingestion of a diet high in starch or rich in non-structural carbohydrate is [also] associated with diseases such as fermentative acidosis, equine metabolic syndrome, equine Cushing’s disease, laminitis, and colic”¹.  Such diets undoubtedly create disturbance in the equine GI tract, both in terms of its microbial composition and activity, and its physiologic conditions^2,3,4.  Furthermore, those disturbances have been clearly linked with various disease states including laminitis and colitis^5,6.  That such a link has not been established for Cushing’s disease may simply reflect the fact that our knowledge of the role of the GI microbiota in equine disease is far from complete.  What is clear, though, is that the development of a balanced GI microbiome will undoubtedly improve the quality of life/health of horses and ponies affected by Cushing’s disease, reducing their susceptibility to parasites and other pathogens, and laminitis, and enabling them to utilise feedstuffs effectively.

References

¹ Al Jassim, R.A.M. and Andrews, F.M., 2009.  The Bacterial Community of the Horse Gastrointestinal Tract and Its Relation to Fermentative Acidosis, Laminitis, Colic, and Stomach Ulcers.  Veterinary Clinics of North America - Equine Practice  25(2):  199-215.