Download Isoflupredone acetate as ancillary therapy for bovine respiratory

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
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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