Evaluating the effect of metronidazole plus amoxicillin-clavulanate versus amoxicillin-clavulanate alone in canine haemorrhagic diarrhoea: a randomised controlled trial in primary care practice
Ortiz, V (2018) Evaluating the effect of metronidazole plus amoxicillin‐clavulanate versus amoxicillin‐clavulanate alone in canine haemorrhagic diarrhoea: a randomised controlled trial in primary care practice. Journal of Small Animal Practice, 59 (7), pp. 398-403
In primary care practice antibacterial agents are commonly prescribed for dogs presenting with haemorrhagic diarrhoea. Antibacterial treatment is recommended in cases that have systemic signs of disease, such as pyrexia and where sepsis is a possibility. Given the multiple possible causes of haemorrhagic diarrhoea, there are no clear recommendations as to which antibacterial agents are appropriate as a first line treatment, when no specific diagnosis has been made.
Amoxicillin, often combined with clavulanic acid, is one of the most commonly prescribed antibiotics for haemorrhagic diarrhoea. This is often supplemented by the use of metronidazole, an antibacterial frequently used to treat gastrointestinal disease in humans because of its activity against Clostridial species. However, the benefits of metronidazole for canine haemorrhagic diarrhoea remain unclear.
The aim of this prospective randomised controlled trial was to show whether the use of a combination of metronidazole and amoxicillin-clavulanic acid when compared to amoxicillin-clavulanic acid therapy alone is superior in treating acute haemorrhagic diarrhoea in dogs.
Dogs with acute diarrhoea of less than three days duration presenting at a primary care practice, from February 2016 to January 2018, were recruited to the study if the owner reported profuse bloody diarrhoea and if the dog required admission for intravenous fluid therapy (IVFT) to treat clinical signs of depression. Dogs were excluded if antibacterial treatment had been administered in the preceding three days or if there was evidence of kidney or liver disease.
The dogs were randomly assigned to receive either 10mg/kg metronidazole intravenously every 12 hours (treatment group) or a dose of 2mL/kg saline intravenously every 12 hours (control group). All cases received 8.75 mg/kg amoxicillin-clavulanic acid subcutaneously or intravenously every 8 hours. Cases also received: IVFT at a rate determined by the clinician for each individual case; an analgesic dose of buprenorphine on admission and then as required every 6 to 8 hours; and a dose of 1 mg/kg omeprazole intravenously once daily.
Treatment efficacy was assessed primarily by the duration of hospitalisation required as measured in hours, calculated from admission to the time the clinician deemed the patient fit for discharge, and secondarily by daily clinical progress using a modified version of the ‘canine haemorrhagic gastroenteritis activity index’. A retrospective analysis of 30 hospitalised dogs at the same practice had found the mean hospitalisation duration of haemorrhagic gastroenteritis cases to be 47.8 hours (s.d. 25.3 hours). Based on this, for one treatment to be superior to the other a difference in hospitalisation of more than 18 hours was set for this trial. Midway through the trial, this was adjusted to a difference of 14 hours because an interim analysis showed the mean hospitalisation time to be lower than anticipated. Detailed hospitalisation charts were completed every four hours.
A total of 36 dogs were recruited; 15 dogs were in the control group and 21 in the treatment group. Two dogs did not complete the trial, one from each group.
Results showed that the duration of hospitalisation between the treatment (29.6 hours) and control group (26.3 hours) was not statistically significant: There was also no significant difference in daily clinical scores between the groups.
Limitations of the study included: small sample size; possible bias at the time of recruitment as a result of some clinicians’ concerns about not giving both amoxicillin-clavulanic acid and metronidazole to dogs with severe signs of haemorrhagic diarrhoea; and the fact that it did not include a group just on supportive therapy or on metronidazole alone. Duration of hospitalisation would also be affected by owner ability to collect and discharges occurring only during daytime working hours.
This study provides evidence that the addition of metronidazole to amoxicillin-clavulanic acid when treating dogs with haemorrhagic diarrhoea may not be necessary because it did not affect treatment outcomes. Further studies with a larger cohort and a group receiving just supportive therapy are encouraged.
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