Although various approaches have been developed and tried to control the spread of antimicrobial resistance（AMR）, a definitive strategy is yet to be established. Phage therapy that has been used for many years in the Eastern European countries is attracting a renewed attention as a promising approach against AMR. In the United States, the recent cure of Tom Patterson, who was in a critical condition from an infection with multidrug-resistant Acinetobacter baumannii, has accelerated the clinical application of phage therapy. In the present paper, we will provide an overview of phage therapy, review its potential clinical problems learned from Patterson’s case and discuss its possibilities in veterinary medicine.

　In November 2017, 23 of 60 calves and cows（38.3%, 17 cows）developed severe respiratory symptoms at a dairy farm in Hokkaido. The outbreak resulted in the deaths of four animals, including those that were euthanized due to poor prognosis. At the farm, 45 cows were kept in a tie-stall housing system within a barn, which had a separate calving area and an outdoor paddock. The onset of the disease was first noted on November 14th in three cows as they developed fever, hyperpnea and marked respiratory sounds in both anterior lung lobes. The disease spread along the feeding line, and similar symptoms were noted in other animals in the same barn by November 21st. All symptomatic animals were treated with cefazolin as the first line of treatment; however, the treatment was ineffective. Subsequent bacteriological examinations of nasal swabs revealed the presence of Mannheimia haemolytica serotype 1. Drug susceptibility tests were performed, and kanamycin and marbofloxacin were administered resulting in overall improvement in the symptoms. Serological examinations performed after the onset of the disease revealed elevated antibody titers against bovine respiratory syncytial（RS）virus. On gross pathological examinations of the dead animals, adhesions between the pleura and the lobes of both left and right lungs were noted in addition to fibrinous pleuropneumonia. Diffuse pulmonary interstitial emphysema was observed primarily in the posterior lobe. Collectively, these findings indicate a mixed infection with bovine RS virus and M. haemolytica. Unlike previous reports, the isolated M. haemolytica serotype 1 was resistant to ampicillin and had a low susceptibility to cefazolin.

　Cryptosporidiosis causes watery diarrhea in calves younger than one month of age. There is no treatment for cryptosporidiosis, but an egg yolk immunoglobulin（IgY）product, which contains the anti-cryptosporidium IgY, has been developed to prevent the calf diarrhea. In this study, the effect of this product on cryptosporidiosis was examined. Twelve calves were divided into three groups: an untreated control group; a colostrum group（received 60 g of IgY mixed in the colostrum）and a 2-week treatment group（received 60 g of IgY in the colostrum and then 10 g/day of IgY mixed in milk for two weeks）. During the 21-day study period, all calves were naturally infected with Cryptosporidium parvum and developed watery diarrhea. The mean number of oocysts per gram of feces was significantly lower in the 2-week treatment group than in the colostrum and control groups（p<0.05）. The total IgY and anti-cryptosporidium IgY concentrations in the serum and feces increased in both the colostrum and 2-week treatment groups, and the total fecal IgY concentration was significantly higher in the 2-week treatment group than in the colostrum group from day 5 to day 14（p<0.05）. The fecal anti-cryptosporidium IgY concentration was significantly higher in the 2-week treatment group on day 5 and 7 than in the colostrum group（p<0.05）. Thus, oral administration of IgY for two weeks reduced oocyst shedding in cryptosporidium-infected calves, indicating that anticryptosporidium IgY may be useful for the prevention of cryptosporidiosis.

　A 76-day-old Holstein female calf presented with astasia, reduced consciousness and convulsion. The local veterinarians suspected cerebrocortical necrosis, and symptoms subsided after the administration of vitamin B1, Ringer’s solution, saline and 25% glucose. At 130 days of age, however, similar clinical signs recurred and were not controlled by the same therapy. Serum ammonium and bile acid levels were markedly elevated（490μg/dℓ and 153.2μM, respectively）. Two hours after suckling, serum bile acid was further increased. Ultrasound examination of the liver revealed an abnormal vessel running in parallel with the caudal vena cava and a high turbulent blood flow where these vessels merged. These findings strongly suggest hepatic encephalopathy caused by hepatic portosystemic shunt（PSS）, which was confirmed during necropsy. Histopathological findings included vacuole formation in the cerebral white matter. Although PSS is a rarely recognized disease in cattle, it should be added to the differential diagnosis list for calves exhibiting neurologic symptoms consistent with cerebrocortical necrosis.