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Propionic acidaemia is a life threatening inborn error of propionate metabolism, which usually presents in the neonatal period with vomiting, lethargy, hypoglycaemia, hyperammoniaemia, and ketoacidosis. Its treatment consists of minimising propionate load from all sources, promotion of detoxification and excretion of propionyl CoA through the use of l carnitine, and careful management during acute intercurrent illnesses. 1 In addition to its formation during the catabolism of amino acids (isoleucine, valine, methionine, and threonine) and β oxidation of fatty acids containing odd numbers of carbon atoms, propionyl CoA is also derived from anaerobic bacterial fermentation of carbohydrates in the colon. 2 The maximum contribution of catabolism of propiogenic amino acids to total propionate production has been assessed to be between 5% and 66%, 2 3 with gut bacterial fermentation accounting for a large proportion of the rest. 2 Therefore, effective reduction of the latter source is important for adequate metabolic control.
Using an in vitro fermentation technique, it has been shown that the addition of metronidazole greatly reduces the production of short chain fatty acids, including propionic acid. 4 In a study of four children with propionic acidaemia, the administration of metronidazole resulted in substantial reductions in gut bacterial activity, as measured by changes in the lactulose breath hydrogen test and reduced faecal bacterial colony counts, as well as large reductions in stool propionate excretion. 5 This observation has led to the suggestion that metronidazole should be used as an adjunct to other therapeutic manoeuvres in the management of propionic acidaemia.
On the other hand, Hoverstad et al , studying the effects of a number of orally administered antibiotics on short chain fatty acid excretion in healthy adult volunteers, found that metronidazole did not produce any alteration in faecal short chain fatty acid excretion and neither was it detectable in the faeces. 6 However, non-absorbable antibiotics such as clindamycin and vancomycin greatly reduced excretion of short chain fatty acids, including propionic acid. 7 Accordingly, it was postulated that orally administered metronidazole was almost completely absorbed in the small intestine and was not secreted into the large bowel in sufficient concentrations to affect fermentation by anaerobic bacteria.
Our study was prompted by these discrepant findings and the implication that orally administered metronidazole might not have as great...