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Isoflupredone acetate as ancillary therapy for bovine respiratory disease in high-risk stocker calves C.E. Crews1, J.G. Powell1, E.B. Kegley1, J.L. Reynolds1, and J.A. Hornsby1 Story in Brief The objective of this study was to evaluate the use of isoflupredone acetate as ancillary therapy in the treatment of bovine respiratory disease. Crossbred beef steers (n = 103) were acquired from regional auction markets and were transported to the University of Arkansas Stocker and Receiving Unit located near Savoy. Calves were administered a 5-way modified-live virus vaccine, an 8-way clostridial vaccine, and a dewormer at receiving. Calves were observed daily for signs of respiratory illness, and antibiotic treatment was administered if calves displayed signs of illness and rectal temperature was ≥104 °F. Calves (n = 31) requiring antibiotic treatment for respiratory illness were assigned to either treatment 1 (injection of antibiotic therapy) or treatment 2 (injection of antibiotic therapy with isoflupredone acetate). Both treatment groups were rechecked 48 hours post treatment to determine treatment efficacy. Blood was collected twice (treatment and recheck) via jugular venipuncture to evaluate complete blood count. Weights were recorded over the 46-day trial to assess weight gain. No difference in average daily gain (P = 0.52) or rectal temperature (P ≥ 0.73) was evident among treatments. Calves that did not receive isoflupredone acetate had a numerically greater (P = 0.63) medical cost ($2.04) because their repull rate tended to be greater (P = 0.10). No difference existed in overall white blood cell count or lymphocytes at treatment (P = 0.91 and 0.72, respectively) or recheck (P = 0.73 and 0.23, respectively). Upon recheck, neutrophils decreased to normal for calves that received only antibiotic therapy but remained above normal for calves that also received isoflupredone acetate. At recheck, the neutrophil to lymphocyte ratio was greater (P = 0.03) in calves that received isoflupredone acetate. Monocytes at recheck were greater (P = 0.02) in calves that did not receive isoflupredone acetate. Results indicate that fewer calves required subsequent antibiotic treatment when receiving an injection of isoflupredone acetate in addition to antibiotic therapy. Introduction Bovine respiratory disease (BRD) is the leading cause of illness and death in U.S. cattle. The disease results from a complex interaction between infectious viral and bacterial pathogens, the environment, and the host. It is often initiated when an animal is exposed to one or multiple stress contributors which cause the animal’s immune system to be suppressed, allowing viral or bacterial agents to initiate infection in the body. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be a useful method for treating BRD when used in adjunct to antibiotics (Lockwood et al., 2003; Friton et al., 2005). These drugs do not impair the immune system, and they have pain and fever reducing effects. Corticosteroid pharmaceuticals have also been used as ancillary therapy, but studies have yielded conflicting results (Bednarek et al., 2003; Sustronck et al., 1997). These drugs have anti-inflammatory properties, and isoflupredone acetate is a corticosteroid that has shown notable results when used as ancillary therapy in treatment of BRD in a challenge model study conducted by Hewson et al., 2011. Isoflupredone acetate is approved in the U.S. for food animal use and has label indications for critical infections in cattle. Therefore, the study objective was to evaluate the use of isoflupredone acetate as ancillary therapy in the treatment of naturally occurring bovine respiratory disease in newly received stocker calves. Materials and Methods Crossbred beef steers (n = 103) were acquired from regional auction markets and were transported to the University of Arkansas Stocker and Receiving Unit located near Savoy. Upon arrival (day 1 -1), calves were weighed, received an ear tag, and were tested for persistent infection with bovine viral diarrhea virus (PI-BVDV) using the ACE ear notch test (CattleStats -LLC, Oklahoma City, Okla.). Calves were then stratified by body weight and allocated randomly to 1 of 8 pens such that average pen weights were similar. On day 0, calves were weighed again and they received a 5-way modified-live virus vaccine (Pyramid 5®, Boehringer Ingelheim Vetmedica, St. Joseph, Mo.), an 8-way clostridial vaccine (Covexin 8®, Merck Animal Health, Summit, N.J.), and a dewormer (Cydectin®, Boehringer Ingelheim Vetmedica, St. Joseph, Mo.). During the 46-day trial, calves were monitored daily (~8:00 a.m.) for signs of BRD. If 2 or more signs of clinical illness existed (i.e. depression, decreased appetite, coughing, nasal discharge), calves were pulled from the group and rectal temperature was recorded via digital thermometer (GLA Agricultural Products, San Luis Obispo, Calif.). If rectal temperature was ≥104 °F, calves were treated according to a predetermined antimicrobial protocol consisting of either treatment 1: [florfenicol (n = 17; Nuflor®, Merck Animal Health, Summit, N.J.)] or treatment 2: [florfenicol plus isoflupredone acetate (n = 14; Predef 2X®, Pfizer Animal Health)]. Both treatment groups were rechecked 48 hours post treatment to determine treatment efficacy. If clinical signs persisted and rectal temperature was ≥104 °F, then follow-up antibiotic therapy was administered. Calves received enrofloxacin (Baytril®, Bayer Animal Health, Shawnee Mission, Kan.) as a secondary treatment and ceftiofur hydrochloride (Excenel®, Pfizer Animal Health, Kalamazoo, Mich.) as a tertiary treatment. Vaccine and antimicrobial handling and administration followed Beef Quality Assurance guidelines and manufacturer dosage recommendations. In addition to weight being recorded upon treatment and recheck, it was also recorded on days 14, 28, 45, and 46. Blood University of Arkansas System Division of Agriculture, Department of Animal Science, Fayetteville, Ark. 22 Arkansas Animal Science Department Report 2013 was collected (7 mL) twice (treatment and recheck) via jugular venipuncture into evacuated tubes (Vacutainer®, BD Inc, Franklin Lakes, N.J.) containing EDTA to evaluate complete blood count. Over the 46-day trial, calves were fed an identical feed ration of up to 4 lb per day per calf and were given ad libitum access to bermudagrass hay and water. The predetermined quantity of feed was hand fed each morning (~8:30 am). Data were analyzed using the Mixed Models procedure (PROC MIXED) of SAS (SAS Inst. Inc., Cary, N.C.). Statistical significance was considered for a P-value of less than or equal to 0.05. Results and Discussion During processing, no calves tested positive for PI-BVDV. No difference in average daily gain (P = 0.52) or rectal temperature (P ≥ 0.73) was evident among treatment groups during the 46-day trial. Though not significant, the difference in medical cost between treatment groups was $2.04 per head (P = 0.63). Calves that did not receive isoflupredone acetate had a numerically greater medical cost than calves that received isoflupredone acetate in addition to the antibiotic because of a greater tendency (P = 0.10) for those calves to be treated with a second or third antibiotic. The repull rate for calves that did not receive isoflupredone acetate was 14% (7 out of the 17 animals), whereas the repull rate for calves that received isoflupredone acetate was 7% (1 out of the 14 animals). No difference existed in overall white blood cell count or lymphocytes at treatment (P = 0.91 and 0.72, respectively) or recheck (P = 0.73 and 0.23, respectively). Upon recheck, neutrophils decreased to normal for calves not receiving isoflupredone acetate but remained above normal for those that received isoflupredone acetate (normal = 0.6 to 4.0 × 103/µL). During infection, an increase in neutrophils is to be expected due to their migration into tissues to destroy pathogenic bacteria (Morris, 2009). After receiving treatment, neutrophils should decrease as the bacteria become less prevalent. No difference was evident in lymphocytes between groups at treatment (P = 0.72) or recheck (P = 0.23). For both treatment groups, the neutrophil to lymphocyte ratio at recheck was above the normal range (0.3-0.6), and it was greater (P = 0.03) in calves that received isoflupredone acetate. This was to be expected since the post treatment neutrophil count in calves receiving isoflupredone acetate tended to be greater (P = 0.07) than in calves not receiving isoflupredone acetate. A greater neutrophil to lymphocyte ratio is associated with more stressed cattle. Monocytes at recheck were greater (P = 0.02) in calves that did not receive isoflupredone acetate. These cells circulate in the blood for 1 to 3 days then enter tissues and convert into macrophages. The primary functions of tissue macrophages include removing dead and damaged tissue, tissue repair and remodeling, and regulation of the immune response (Morris, 2009). Implications Results indicate that fewer calves required subsequent antibiotic treatment when receiving an injection of isoflupredone acetate. Further investigation of isoflupredone acetate is needed to evaluate effects on treatment cost and post treatment gains in newly received stocker calves. Literature Cited Bednarek, D., B. Zdzisinska, M. Kondracki, and M. KanderferSzerszen. 2003. Effect of steroidal and non-steroidal anti-inflammatory drugs in combination with long-acting oxytetracycline on non-specific immunity of calves suffering from enzootic bronchopneumonia. Vet. Microbiol. 96:53-57. Friton, G. M., C. Cajal, and R. Ramirez-Romero. 2005. Long-term effects of meloxicam in the treatment of respiratory disease in fattening cattle. Vet. Rec. 156:809-811. Hewson, J., L. Viel, J. L. Caswell, P. E. Shewen, and J. G. BuchananSmith. 2011. Impact of isoflupredone acetate treatment on clinical signs and weight gain in weanling heifers with experimentally induced Mannheimia haemolytica bronchopneumonia. Am. J. Vet. Res. 72:1613-1621. Lockwood, P. W., J. C. Johnson, and T. L. Katz. 2003. Clinical efficacy of flunixin, carprofen, and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease. Vet. Rec. 152:392-394. Morris, D. D. 2009. Alterations in the Leukogram. In: B. P. Smith, editor, Large animal internal medicine. 4th ed. Mosby, Inc., St. Louis, Mo., p. 405-407. Sustronck, B., P. Deprez, G. Van Loon, J. Coghe, and E. Muylle. 1997. Efficacy of the combination sodium ceftiofur-flumethasone in the treatment of experimental Pasteurella haemolytica bronchopneumonia in calves. J. Vet. Med. 44:179-187. Table 1. Effects of isoflupredone acetate as ancillary therapy for bovine respiratory disease on morbidity and growth performance. Repull rate, % Time to second pull, days Treated twice, calves Treated thrice, calves Medical cost, $ Temperature at treatment, °F Temperature at recheck, °F Change in Temperature, °F Average daily gain, lb Gain total over 46-‐day study, lb Antibiotic treatment 41.2 9 4 3 20.13 104.8 103.0 1.8 2.2 101.0 Antibiotic treatment with isoflupredone acetate 7.1 7 1 0 18.09 104.7 103.0 1.7 2.0 91.9 P-‐value 0.10 0.59 0.17 0.12 0.63 0.73 0.99 0.85 0.52 0.52 23 AAES Research Series 612 Table 2. Effects of isoflupredone acetate as ancillary therapy for bovine respiratory disease on blood count analysis. Antibiotic treatment with Antibiotic treatment isoflupredone acetate Initial 3 White blood cells, n x 10 /µL 11.0 11.2 3 Neutrophils, n x 10 /µL 4.2 4.1 3 Lymphocytes, n x 10 /µL 3.8 4.0 Neutrophil:Lymphocyte, % 121 118 3 Monocytes, n x 10 /µL 0.9 0.8 3 Platelets, n x 10 /µL 376.8 306.6 Recheck 3 White blood cells, n x 10 /µL 10.0 10.4 3 Neutrophils, n x 10 /µL 3.2 4.2 3 Lymphocytes, n x 10 /µL 4.1 3.5 Neutrophil:Lymphocyte, % 86 129 3 Monocytes, n x 10 /µL 1.0 0.8 3 Platelets, n x 10 /µL 381.1 367.8 24 P-‐value 0.91 0.92 0.72 0.94 0.30 0.03 0.73 0.07 0.23 0.03 0.02 0.73