Evaluation of oral administration of bacteriophages to neonatal calves: Phage survival and impact on fecal Escherichia coli

Diarrhea is an important cause of morbidity and mortality in neonatal calves. Several enteropathogens are associated with diarrhea in young calves, with Enterotoxigenic Escherichia coli (ETEC) infection being the most common type of colibacillosis. The rise of antibiotic resistance in a number of medically important bacterial pathogens has revived interest in the use of bacteriophages as anti-bacterial therapeutic agents. Here we describe the results of a randomized, placebo-controlled, double-blinded study designed to evaluate the effect of an oral bacteriophage cocktail on fecal E. coli colony-forming units (CFU). Ten calves were enrolled in the study to either the bacteriophage group or the placebo group for 22 feedings. Calves in the bacteriophage treatment group (n = 6) received a total of 10(6) plaque-forming units (PFU) (volume = 5 ml) of each of four bacteriophages while the placebo group (n = 4) received only phosphate-buffered saline (5 ml). Fresh fecal samples and blood samples were collected daily from each calf and analyzed for bacterial count and presence of bacteriophage. E. coli-infecting phages were recovered from all phage-treated calves at concentrations of 10² to 10³ PFU per gram of rectal contents, but none was detected in serum. Phage treatment caused a reduction in fecal E. coli when compared to the control group: the mean log CFU for the placebo-treated group was 9.25 (SE = 0.42) versus 9.11 (SE = 0.34) for the phage-treated group, but the difference was not statistically significant.