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Veterinary Therapeutics • Vol. 6, No. 2, Summer 2005 

Comparative Efficacy of Tulathromycin versus 

Florfenicol and Tilmicosin against Undifferentiated 

Bovine Respiratory Disease in Feedlot Cattle* 

Terry L. Skogerboe, DVM, MBA Daniel J. Weigel, PhD 

Kathleen A. Rooney, MS, DVM Kimberly Gajewski, MS 

Robert G. Nutsch, DVM, MS, MBA W. Randal Kilgore, DVM 

Pfizer Animal Health 

Veterinary Medicine Research and Development 

7000 Portage Road 

Kalamazoo, MI 49001 

■ INTRODUCTION 

Bovine respiratory disease (BRD) is reported 

to be the most prevalent disease responsible for 

morbidity and mortality in feedlots. Beef in- 

*This work was sponsored by Pfizer. 

180 

CLINICAL RELEVANCE 

Four studies conducted at feedlots in Greeley and Wellington, Colorado; Nebraska; 

and Texas compared the efficacy of tulathromycin to florfenicol or tilmicosin 

for the treatment of cattle with undifferentiated bovine respiratory disease (BRD) 

and subsequent feedlot performance and carcass characteristics. In each study, 

100 calves with BRD were treated with tulathromycin given SC at 2.5 mg/kg body 

weight. At the Greeley, CO, and Nebraska study locations, 100 calves were treated 

with florfenicol given SC at 40 mg/kg body weight, and at the Wellington, CO, 

and Texas study locations, tilmicosin was given SC at 10 mg/kg body weight. 

Cure rate, a derived variable that included assessments of mortality, rectal temperature, 

and attitude and respiratory scores from day 3 to day 28 and day 3 

through harvest, was the primary assessment of BRD efficacy. Cure rates of 

calves treated with tulathromycin were significantly (P ≤ .009) higher than those 

calves treated with florfenicol. At Wellington, CO, the cure rate of calves treated 

with tulathromycin was significantly higher (P ≤ .018) compared with tilmicosintreated 

calves. The differences in cure rates between tulathromycin and tilmicosin 

treatment groups in the Texas study were not significantly different (P > .05). Tulathromycin 

was more efficacious in the treatment of undifferentiated BRD compared 

with florfenicol and, in one study, compared with tilmicosin. 

dustry feedlot practices, such as transport, 

commingling, processing, diet change, and 

stocking density, create a high-stress environment 

for recently weaned cattle arriving at 

feedlots. These new arrivals are at an increased

T. L. Skogerboe, K. A. Rooney, R. G. Nutsch, D. J. Weigel, K. Gajewski, and W. R. Kilgore 

risk of developing BRD, with morbidity peaks 

occurring within the first 3 weeks after arrival. 1 

Common pathogens associated with morbidity 

and mortality of BRD include Mannheimia 

haemolytica, Pasteurella multocida, Haemophilus 

somnus (Histophilus somni), and Mycoplasma 

spp, with M. haemolytica considered to 

be the primary bacterial pathogen. 2,3 Preconditioning 

programs, including vaccination and 

weaning management, may minimize the morbidity 

risk of BRD. 4 However, many factors, 

including ranchers’ efforts to decrease production 

costs, have not supported preconditioning 

programs as a standard operation within the 

industry. 5,6 

Tulathromycin is the first of a new class of 

macrolide antimicrobials that has been termed 

triamilides. Tulathromycin was synthesized and 

developed specifically for the treatment of 

bovine and swine respiratory disease. The 

pharmacokinetics of tulathromycin in cattle is 

well-characterized. 7 After subcutaneous admin- 

istration, tulathromycin is extensively distributed 

to lung tissue with a slow decline in drug 

concentration in the lung. The pharmacokinetic 

data of tulathromycin are consistent with 

a desired characteristic of extended retention of 

an antimicrobial, resulting in a prolonged period 

of antimicrobial exposure to bacterial 

pathogens associated with respiratory disease 

in cattle. 

In an earlier multistudy field efficacy program, 

tulathromycin provided superior clinical 

efficacy compared with tilmicosin over a 14day 

study period. 8 The objectives of these studies 

were to compare the efficacy of tulathromycin 

(Draxxin Injectable Solution, 

Pfizer Animal Health) with either florfenicol 

(Nuflor, Schering-Plough Animal Health) or 

tilmicosin (Micotil 300 Injection, Elanco Animal 

Health) injectable solutions for the treatment 

of undifferentiated BRD and the subsequent 

feedlot performance and carcass 

characteristics of the treated cattle. The primary 

assessment of BRD efficacy was cure rate, 

a derived variable of treatment success from 

day 3 through day 28 and day 3 through the final 

day of the study (harvest) that included assessments 

of mortality, rectal temperature, and 

attitude and respiratory scores. Husbandry and 

care of cattle in these studies were in accordance 

with the Guide for the Care and Use of 

Agricultural Animals in Agricultural Research 

and Teaching. 9 

■ MATERIALS AND METHODS 

Cattle 

Calves for these studies were purchased from 

auction markets and transported to four re- 

Tulathromycin is extensively distributed to lung 

tissue with a slow decline in drug concentration. 

search feedlots. Castrated male calves (n = 498, 

weighing 315–559 lb at enrollment) purchased 

from auction markets in Kansas, Minnesota, 

and North Dakota were transported to Adams 

Land & Cattle Co., Broken Bow, NE. Castrated 

male calves (n = 500, weighing 348–692 lb 

at enrollment) purchased from auction markets 

in Tennessee were transported to Farr 

Feeders, Greeley, CO. Castrated male calves (n 

= 774, weighing 414–745 lb at enrollment) 

purchased from auction markets in Colorado 

and Wyoming were transported to Horton 

Feedlot and Research Center, Wellington, CO. 

Heifer calves (n = 319, weighing 387–576 lb at 

enrollment) purchased from auction markets 

181


TABLE 1. Treatment Decision Chart Used after Administration of Tulathromycin, 

Tilmicosin (NE, TX, and Wellington, CO), or Florfenicol (Greeley, CO) 

Treatment (NE, TX, 

Study Period Response and Wellington, CO) Treatment (Greeley, CO) 

Days 3 to 28 First time animal met Oxytetracycline, Danofloxacin, 6 mg/kg SC 

nonresponse criteria 20 mg/kg SC given twice at a 2-d interval 

Second time animal met Enrofloxacin, Oxytetracycline, 

nonresponse criteria 11 mg/kg SC 20 mg/kg SC 

Third time animal met 

nonresponse criteria 

Removed as chronic Removed as chronic 

Day 29 to First time animal met Oxytetracycline, Danofloxacin, 6 mg/kg SC 

harvesta nonresponse criteria 20 mg/kg SC given twice at a 2-d interval 

Second time animal met Enrofloxacin, Oxytetracycline, 

nonresponse criteria 11 mg/kg SC 20 mg/kg SC 

Third time animal met 

nonresponse criteria 

Removed as chronic Removed as chronic 

a See Table 2 for harvest days. 

in Arkansas and Oklahoma were transported 

to Agri Research Center, Canyon, TX. After 

arrival, the calves were processed, held in feedlot 

pens, and observed daily until enrollment. 

Pre-enrollment processing was typical for 

commercial feedlot practices and included vaccination 

with viral and bacterin antigens and 

treatment for internal and external parasites 

(Greeley, CO: Bovi-Shield IBR-BVD and Dectomax 

Injectable, Pfizer Animal Health; 

Nebraska: Dectomax Pour-On, Ultrabac7, and 

Bovi-Shield 4, Pfizer Animal Health; Wellington, 

CO: Dectomax Injectable, Bovi-Shield 4, 

and Durasect II, Pfizer Animal Health; and 

Texas: Dectomax Injectable, Ultrabac7, and 

Bovi-Shield 4). At each site hormonal implants 

were also injected (Greeley, CO: ComponentE-S, 

Ivy Animal Health, Overland Park, 

KS; Nebraska: Ralgro, Schering, Canada; 

Wellington, CO: Synovex S, Fort Dodge Animal 

Health; and Texas: ComponentE-H, Ivy 

Animal Health). No antimicrobials were ad- 

182 

ministered during processing. Ear tags were 

used for individual animal identification. After 

processing, calves were observed daily until 

enrollment. 

Animal Selection, Clinical Assessments, 

and Treatments 

Selection, enrollment, and initiation of 

treatments occurred on day 0 at each site. At 

each of the four sites, 200 calves were randomly 

assigned to pen(s), blocks, and treatments 

(100 calves/treatment group). 

Calves that met the enrollment criteria of a 

clinical attitude score (CAS) of 1, 2, or 3 and 

pyrexia (rectal temperature ≥104.0˚F) were selected 

by the investigators and randomly assigned 

to receive one of two treatments at each 

location according to a randomized complete 

block design, with calves blocked by order of 

enrollment and enrollment completed over 2 

to 7 consecutive days across all four locations. 

Each block contained one calf from each treat-


TABLE 2. Comparative Efficacy of Tulathromycin versus Florfenicol and Tilmicosin for 

the Treatment of Cattle with BRD 

Location Study Period No. (%) of Cattle a P value b 

Greeley, COc Tulathromycin Florfenicol 

Cures Days 3–28 82 (82.0%) 64 (64.0%) .002 

Day 3–harvest 77 (79.4%) 63 (63.6%) .009 

Chronics and mortalitiesd Days 3–28 3 (3.0%) 9 (9.0%) .058 

Day 3–harvest 4 (4.1%) 10 (10.1%) .058 

Nebraskae Tulathromycin Florfenicol 

Cures Day 3–28 73 (73.7%) 30 (30.3%) .001 

Day 3–harvest 50 (53.2%) 23 (23.2%) .001 


Day 3–harvest 19 (20.2%) 47 (47.5%) .001 

Wellington, COf Tulathromycin Tilmicosin 

Cures Days 3–28 84 (85.7%) 63 (64.3%) .002 

Day 3–harvest 76 (77.6%) 57 (60.6%) .018 


Day 3–harvest 0 (0.0%) 7 (7.5%) .014 

Texasg Tulathromycin Tilmicosin 

Cures Days 3–28 78 (78%) 69 (69%) .160 

Day 3–harvest 73 (73%) 67 (67%) .355 


Day 3–harvest 2 (2.0%) 5 (5.0%) .257 

a % = n / No. of cattle (n = 100) in the treatment group at the start of the time period – No. of cattle removed for non- 

BRD reasons × 100. 

bWithin a row, P values are provided for contrasts between treatments by study location. 

cInitiation, March 2003; harvest, day 173, 174, or 175. 

dBRD-associated mortalities. 

eInitiation, October 2001; harvest, day 316 or 317. 

f Initiation, October 2001; harvest, day 224, 225, 226, 227, 228, 229, or 230. 

g Initiation, September 2001; harvest, day 257, 258, or 259. 

ment group and was filled in 1 day. The criteria 

for assigning CASs were: 

0 = Normal; bright, alert, and responsive 

1 = Mild depression 

2 = Moderate to marked depression; may be 

reluctant to stand 

3 = Severe depression; unable to stand without 

assistance 

4 = Moribund; unable to rise 

At each of the four study locations, tulathromycin 

was given SC at 2.5 mg/kg body 

weight (1.1 ml/100 lb). At Greeley, CO, and 

Nebraska, florfenicol was given SC at 40.0 

mg/kg body weight (6 ml/100 lb). At Wellington, 

CO, and Texas, tilmicosin was given SC at 

10.0 mg/kg body weight (1.5 ml/100 lb). 

Treatments were given once on the lateral side 

of the neck with a maximum volume of 10 ml/ 

183


TABLE 3. Frequency Distribution of Treatment Cures, Treatment Failures, and Non-BRD 

Removals from Day 3 through Harvest a 

Treatment 

Treatment Failures b 

Group First Second Third Fourth BRD Non-BRD 

(n = 100/group) Cure Nonresponse Nonresponse Nonresponse Nonresponse Chronicsc Mortalities Removals 

Greeley, CO 

Tulathromycin 77 12 3 1 0 3 1 3 

Florfenicol 63 19 6 1 0 10 0 1 

P value .009 

Nebraska 


Florfenicol 23 11 11 4 3 42 5 1 

P value .001 

Wellington, CO 


Tilmicosin 57 20 9 1 0 4 3 6 

P value .018 

Texas 


Tilmicosin 67 11 13 4 0 4 1 0 

P value .355 

aSee Table 2 for harvest days. 

bNonresponse frequency categories represent the number of times calves were BRD nonresponders. Nonresponse 

criteria for days 3–28 was: (1) a CAS of 1 or 2 and a rectal temperature ≥104.0˚F or (2) a CAS of 3 or 4. Nonresponse 

criterion after day 28 was a CAS of 1, 2, 3, or 4. 

cDepending on the study period (days 3–28 or after day 28), a calf was a chronic nonresponder the third, fourth, or fifth 

time it met the nonresponse criteria. 

injection site. Personnel not responsible for 

any other clinical assessments administered 

treatments during the course of the study. 

Clinical observations for adverse events were 

made before treatment and approximately 0.5 

to 5 hours after treatment. 

Except for the calves in the Greeley, CO, 

study, a randomly preselected set of cattle in 

each study (20 calves from each treatment 

group) had nasopharyngeal swab samples collected 

for bacterial culture and identification 

before treatment. Bacterial identification was 

performed by Colorado Animal Research Enterprise, 

Fort Collins, CO. 

184 

Body Weights 

Body weights for individual cattle were obtained 

in each study on the day of treatment 

(day 0), when a calf required additional treatment, 

when a calf was removed from the study, 

on day 28, at reimplanting and revaccination 

(on day 97, 98, or 99 in Greeley, CO [Component 

TE-S, Ivy Animal Health, and Bovi- 

Shield IBR]; day 139 or 140 in Nebraska [Synovex 

Plus and Pyramid IBR, Fort Dodge 

Animal Health]; day 75 in Wellington, CO 

[Bovi-Shield IBR and Revalor-IS, Intervet]; 

and day 82, 83, or 84 in Texas [Component T- 

H, Ivy Animal Health, and Frontier III, Inter-


vet]), and before shipment to packing plants 

(on day 173, 174, or 175 in Greeley, CO; day 

316 or 317 in Nebraska; approximately day 

227 in Wellington, CO; and day 257, 258, or 

259 in Texas). 

Clinical Assessments and 

Nonresponse BRD Treatments 

Clinical assessments of response to initial 

BRD treatments began 3 days after dose administration. 

From day 3 through day 28, CAS 

was assessed daily for each calf. Any calf assigned 

a score of 1 or 2 was removed from 

study pens to allow measurement of its rectal 

temperature. The nonresponse criteria for days 

3 through 28 were (1) a CAS of 1 or 2 plus a 

rectal temperature of ≥104.0˚F or (2) a CAS of 

3 or 4. From day 29 to the day of harvest 

(slaughter), cattle were observed according to 

standard feedlot practice; those with clinical 

signs of BRD (a CAS of 1, 2, 3, or 4 regardless 

of rectal temperature) met the nonresponse 

criteria. 

After the initial treatment for BRD, a treatment 

decision chart was used at each study location 

(Table 1). At three locations (Wellington, 

CO, Nebraska, and Texas), cattle fulfilling 

nonresponse criteria for the first time were retreated 

with oxytetracycline (Liquamycin LA- 

200, Pfizer Animal Health) given SC at 20 

mg/kg body weight (4.5 ml/100 lb). Calves fulfilling 

nonresponse criteria a second time were 

treated with enrofloxacin (Baytril 100, Bayer 

Animal Health) given SC at 11 mg/kg body 

weight (5 ml/100 lb). At the Greeley, CO, location, 

cattle fulfilling nonresponse criteria for 

the first time were retreated with danofloxacin 

(A180, Pfizer Animal Health) given SC at 6 

mg/kg body weight (1.5 ml/100 lb) and repeated 

approximately 48 hours later. Cattle fulfilling 

the nonresponse criteria the second time 

were treated with oxytetracycline given SC at 

20 mg/kg body weight (4.5 ml/100 lb). 

Except for allowing a minimum of 2 days after 

completing the danofloxacin dose regimen, 

cattle were allowed approximately 3 days following 

each retreatment before their clinical 

status was reassessed. At each study location, 

treatment regimens were reinitiated on day 29, 

allowing cattle that met the nonresponse criteria 

after study day 28 to receive additional 

treatments before they were classified as chronics. 

All danofloxacin, enrofloxacin, and oxy- 

Cure rates were significantly higher for 

tulathromycin-treated cattle in three of the four studies. 

tetracycline injections were given SC on the 

lateral side of the neck with a maximum volume 

of 10 ml/injection site. 

Cattle that met the nonresponse criteria 

three times in the period from day 3 through 

day 28 or three times between day 29 and harvest 

were classified as chronics and removed 

from the study. To determine cause of mortality, 

necropsies were performed on all cattle that 

died during the study. 

Precautions were taken to avoid any undue 

animal suffering during these studies. All applicable 

animal husbandry and animal welfare 

guidelines were followed. The investigator or 

a designee could recommend euthanasia for 

humane reasons if the animal was moribund or 

if the clinical condition of the calf warranted 

euthanasia. Calves with severe clinical signs 

associated with BRD were classified as BRDrelated 

mortalities. 

All remaining cattle were shipped to harvest 

185


TABLE 4. Cumulative Frequency of Antimicrobial Treatments a from Day 3 through Harvest 

No. of BRD 

Greeley, CO Nebraska Wellington, CO 

Treatment Regimensb Tulathromycin Florfenicol Tulathromycin Florfenicol Tulathromycin Tilmicosin 

1 12 19 8 13 17 22 

2 8 12 42 74 6 20 

3 12 30 18 36 6 15 

4 0 4 8 12 0 0 

5 0 0 20 50 0 0 

Total 32 65 96 185 29 57 

a BRD nonresponse treatments were oxytetracycline, enrofloxacin, or danofloxacin (see Table 1 for treatment decision 

chart by study location). Once a calf was declared a chronic, it was removed from the study and given standard feedlot 

therapy; such therapy is not included in this summary. 

b There were 100 cattle with BRD in each treatment group at each study location. 

on a single day. Carcass data were obtained on 

the day following shipment to the packing 

plant and included the following: hot carcass 

weight; yield grade; quality grade; kidney, 

pelvic, and heart (KPH) fat; fat (inches); and 

rib eye area. 

Housing 

Greeley, CO 

Cattle were housed in commercial feedlot 

pens. For the first 28 days, the cattle were 

housed in 10 pens with 10 blocks of two calves/ 

pen. From day 29 until harvest, all the cattle 

were housed in a single pen. Pen space throughout 

the study was approximately 200 sq ft/calf. 

The feed bunk was a concrete fence line bunk 

feeder, and the pens had dirt flooring. 

Nebraska 

Cattle were housed in a commercial feedlot 

pen that was divided approximately in half by 

a fence and a gate into two pens; one measured 

199 × 215 ft and the other was 147 × 186 ft. 

Each pen had 50 blocks of two calves each. 

The feed bunk was a concrete fence line bunk 

feeder, and the pen had dirt flooring. 

186 


Cattle were housed in 20 typical cattle finishing 

pens with each pen housing five blocks 

of two calves. Each pen was similar in design 

(20 × 80 ft) and condition with approximately 

16 inches/calf bunk space. Feed bunks were 

concrete fence line bunks with dividers between 

pens. 

Texas 

Cattle were initially housed in 20 outdoor, 

dirt-floor pens constructed of pipe and cable. 

Each pen housed five blocks of two calves each. 

Each pen was similar in design (18 × 52 ft) and 

condition and provided adequate space (approximately 

93.6 sq ft/calf). The pens contained 8foot 

long in-line concrete feed bunks extending 

the width of the pens, thus allowing the cattle 

21.6 inches of bunk space. Later, all cattle were 

commingled into one large pen for approximately 

3 months; then, until harvest, the cattle 

were housed in four pens of equal size. 

Across all study locations, pen space ranged 

from 100 to 200 sq ft for each calf, and cattle 

were fed to appetite according to standard 

practice; fresh water was available ad libitum.


Masking 

At each study 

Texas 

location, individuals 

Tulathromycin Tilmicosin who performed clin- 

20 

10 

11 

30 

ical observations and 

assigned CASs were 

unaware of treat- 

6 21 ment group assign- 

0 0 ment. The personnel 

0 

36 

0 

62 

who administered 

treatments were unmasked 

to assignment 

of individual 

cattle to treatment 

group. Individuals 

who determined carcass 

evaluations were 

masked to treatment assignments. 

Data Analysis 

Each calf was an experimental unit with the 

determination of efficacy being cure rate, a derived 

variable determined by CAS and BRD 

mortality or CAS, rectal temperature, and 

BRD mortality. Clinical cure percentage (cure 

rate) was defined as follows: 

(No. of animals completing 

the study not classified as 

nonresponders, not BRD-related 

mortalities, and not removed 

for reasons unrelated to BRD) 

100 × 

(No. of animals enrolled – 

No. of animals removed for 

reasons unrelated to BRD) 

In each study, responses to treatment were 

categorized as a cure (responding to treatment), 

as a treatment failure (nonresponse indicated 

by requiring additional treatment, including 

BRD-related mortalities and removals/ 

chronics), or as a non-BRD removal. Frequencies 

of cure/failure responses were analyzed using 

a Cochran-Mantel-Haenszel row mean 

score test with a separate analysis for days 3 to 

28 and for the overall study. 

The repeatedly measured response variable, 

body weight, was analyzed using a general linear 

mixed model. Appropriate contrasts between 

treatments were made at each day of 

study after requiring a significant treatment or 

treatment-by-day of study effect. Least squares 

means of average daily gains (ADGs) were estimated 

within PROC MIXED of SAS (SAS 

Version 6.12, SAS Institute, Cary, NC) using 

the appropriate estimate statements. 

Body weights obtained only on day 0, day 

28, day of reimplant, and before harvest were 

included in the repeated measures mixed model. 

Cattle that died or were removed from the 

study before day 28 had only day 0 body 

weights and could not be included in the 

analyses. Thus, any negative effects they may 

have contributed to the estimate of gain and 

ADG for that treatment group were not captured. 

Body weights were not available for cattle 

that died (mortalities) or were removed 

from the study (chronics) before the day of 

reimplanting or the day of harvest. The more 

times an animal was available to be weighed, 

the more that animal’s body weight contributed 

to the model’s estimate of weight gain. 

All quantitative carcass measures were analyzed 

using a general linear mixed model. Categoric 

responses for carcass variables were analyzed 

using the Cochran-Mantel-Haenszel row 

mean score statistic for tests of association. Continuous 

carcass response variables were analyzed 

using a general linear mixed model analysis. 

The 5% level of significance was used to assess 

statistical differences for all tests. 

■ RESULTS 

Greeley, CO 

The cure rate from day 3 through day 28 was 

significantly higher (P = .002) for calves that received 

tulathromycin (82 of 100; 82.0%) than 

187


BRD Nonresponse (cumulative %) 

for calves that received florfenicol (64 of 100; 

64.0%) (Table 2). The cure rate from day 3 

through harvest was also significantly higher (P 

= .009) for calves that received tulathromycin 

(77 of 97; 79.4%) than for calves that received 

florfenicol (63 of 99; 63.6%). Chronic/mortality 

rates from day 3 through day 28 and from 

day 3 through harvest were not significantly 

lower (P = .058 for both) for calves that received 

tulathromycin (three of 100 [3.0%] and four of 

97 [4.1%], respectively) than for calves that received 

florfenicol (9 of 100 [9.0%] and 10 of 99 

[10.1%], respectively). Three tulathromycinand 

10 florfenicol-treated cattle were classified 

as chronics. After removal from the study, one of 

the tulathromycin-treated cattle died and two 

went on to harvest. Six of the florfenicol-treated 

cattle died and four went on to harvest. 

The frequency distribution of the treatment 

cures, treatment failures (BRD morbidities and 

mortalities), and non-BRD removals for the 

duration of the study (i.e., through harvest) is 

summarized in Table 3. The cumulative frequency 

of danofloxacin and oxytetracycline 

nonresponder treatments from day 3 through 

188 

40 

35 

30 

25 

20 

15 

10 

5 

0 

Cumulative Percentage of Nonresponse was Lower in Tulathromycin-Treated Cows 

Tulathromycin Florfenicol 

3 5 7 9 11 13 15 17 19 21 23 25 27 End a 

Day of Study 

Figure 1. Cumulative percentage of first-time BRD nonresponse from day 3 through end of study (Greeley, CO). 

a See Table 2 for harvest days (end of study). 

// 

harvest is presented in Table 4. The cumulative 

frequencies of first-time BRD nonresponders 

from day 3 through the end of the study are 

summarized in Figure 1. 

The ADG from day 0 through day 28 and 

from day 0 to day of harvest was not significantly 

different (P = .7152 and P = .1113, respectively) 

for calves that received tulathromycin 

(2.78 and 3.71 lb, respectively) than 

for calves that received florfenicol (2.72 and 

3.85 lb, respectively) (Table 5). The least 

squares means final live body weights (Table 5) 

and the hot carcass weights (Table 6) were not 

significantly different (P = .9240 and P = 

.7473, respectively). Except for a significantly 

greater (P = .0396) rib eye area in tulathromycin-treated 

cattle, differences in the other 

carcass variables (Table 6) were not significant. 

The descriptive statistics of ADG with chronics 

and deads included are summarized in Table 7. 

Nebraska 

The treatment cure rate from day 3 through 

day 28 was significantly higher (P = .001) for 

calves that received tulathromycin (73 of 99;


TABLE 5. Repeated Measures Mixed Model Least Squares Means Estimates of Body 

Weight a and Average Daily Gain (ADG) 

Study Group Initial Body Weight (lb) Final Body Weight (lb) ADG (lb) 

Greeley, CO 

Tulathromycin 534 1,176 3.71 

Florfenicol 513 1,178 3.85 

P value b .0858 .9240 .1113 

Nebraska 


Florfenicol 441 1,404 3.04 

P value b .5306 .5449 .3877 



Tilmicosin 526 1,340 3.58 

P value b .5912 .3311 .3760 

Texas 


Tilmicosin 493 1,235 2.88 

P value b .5038 .8788 .9421 

a Cattle removed before day 28 did not contribute to the estimate of weight gain and ADG for their treatment group. 

Day 0 weights included all cattle enrolled. Body weights were not available for cattle that died (mortalities) or were removed 

from the study (chronics) before time of reimplant or day of harvest. 

b Within a column, P values are provided for contrasts between treatments by study location. 

73.7%) than for calves that received florfenicol 

(30 of 99; 30.3%) (Table 2). The cure rate 

from day 3 through harvest was also significantly 

higher (P = .001) for calves that received 

tulathromycin (50 of 94; 53.2%) than for 

calves that received florfenicol (23 of 99; 

23.2%). Chronic/mortality rates from day 3 

through day 28 and day 3 through harvest 

were significantly lower (P = .001 for both) for 

calves that received tulathromycin (5 of 99 

[5.1%] and 19 of 94 [20.2%], respectively) 

than for calves that received florfenicol (26 of 

99 [26.3%], and 47 of 99 [47.5%]). Eighteen 

cattle treated with tulathromycin and 42 treated 

with florfenicol were classified as chronics. 

After removal from the study, four of the 18 

cattle treated with tulathromycin died or were 

euthanized, six were processed/salvaged, and 

eight were transferred to a different group. Fifteen 

of the florfenicol-treated cattle were euthanized, 

six were processed/salvaged, and 21 

were transferred to a different group and then 

shipped for salvage harvest. 



mortalities), and non-BRD removals for the duration 

of the study is summarized in Table 3. 

The cumulative frequency of oxytetracycline 

and enrofloxacin nonresponder treatments from 

day 3 through harvest is presented in Table 4. 

The cumulative frequencies of first-time BRD 

nonresponders from day 3 through the end of 

the study are summarized in Figure 2. 

Nasopharyngeal samples from 21 of 40 

189


TABLE 6. Least Squares Means, Hot Carcass Weight, Carcass Adjusted ADG, and Carcass 

Characteristics 

Kidney, 

Hot Carcass Pelvic, and 

Carcass Adjusted Yield Choice Heart Fat Rib Eye 

Study Group Weight (lb) ADG (lb) Grade (%) (%) Fat (in.) Area (in 2 ) 

Greeley, CO 

Tulathromycin 723 3.33 2.62 22 3.2 0.47 14.0 

(n = 93) 

Florfenicol 719 3.42 2.82 24 3.2 0.50 13.5 

(n = 88) 

P value a .7473 .3290 .0612 .8570 .6104 .9798 .0396 

Nebraska 


(n = 75) 

Florfenicol 892 2.93 3.12 73 2.0 0.56 14.3 

(n = 52) 

P value a .8194 .7161 .1640 .835 .5474 .0997 .5278 



(n = 98) 

Tilmicosin 821 3.31 3.66 58 2.0 0.66 12.6 

(n = 86) 

P value a .0649 .0484 .1194 .537 .7938 .2903 .7228 

Texas 


(n = 98) 

Tilmicosin 759 3.02 3.19 49 3.0 0.60 13.5 

(n = 95) 

P value a .5881 .8396 .7833 .3270 .5049 .8469 .8499 

a Within a column, P values are provided for contrasts between treatments by study location. 

ADG = average daily gain. 

calves and lung samples from two cattle yielded 

P. multocida, M. haemolytica, and H. somnus 

(H. somni) species with nine, 13, and two isolates, 

respectively, confirming the presence of 

BRD pathogens. 

The ADG from day 0 through day 28 was significantly 


tulathromycin (3.46 lb) than for calves 

that received florfenicol (2.40 lb), but there was 

190 

no significant difference (P = .3877) in ADG 

from day 0 through day of harvest (3.09 lb for 

tulathromycin-treated calves and 3.04 lb for florfenicol-treated 

calves) (Table 5). The least 

squares means final live body weights (Table 5) 

and the hot carcass weights (Table 6) were not 

significantly different (P = .5449 and P = .8194, 

respectively). Differences in individual carcass 

variables were not statistically different (Table 6).


TABLE 7. Cattle Weight Gain Including Deads and Chronics a 

Study Total Body Total Body Deads/ 

Location/ Weight Enrolled No. of Head Weight Chronics 

Group in Study (lb) Marketed b,c Marketed (lb) in ADG 

Greeley, CO 

Tulathromycin 51,846 93 111,790 3.57 

Florfenicol 50,459 88 110,770 3.52 

Nebraska 


Florfenicol 43,492 52 73,442 0.95 



Tilmicosin 49,301 86 116,555 3.15 

Texas 


Tilmicosin 49,267 95 122,189 2.83 

aDeads/chronics in ADG = [Weight sold to harvest – (Weight enrolled – Non-BRD removals)] / [(Total head in count – 

Non-BRD removals) / Days on feed] 

bSee Table 2 for harvest days. 

cTotal head marketed includes only cattle remaining in the study pens for the entire study duration. 

ADG = average daily gain. 

The descriptive statistics of ADG with chronics 

and deads included are summarized in Table 7. 



day 28 was significantly higher (P = .002) for 

calves that received tulathromycin (84 of 98; 

85.7%) than for calves that received tilmicosin 

(63 of 98; 64.3%) (Table 2). The cure rate from 

day 3 through the day of harvest was also significantly 


tulathromycin (76 of 98; 77.6%) than 

for calves that received tilmicosin (57 of 94; 

60.6%). Chronic/mortality rates from day 3 

through day 28 and day 3 through harvest were 

significantly lower (P = .025 and P = .014, respectively) 

for calves that received tulathromycin 

(0% and 0%) than for calves that 

received tilmicosin (six of 98 [6.1%] and seven 

of 94 [7.5%], respectively). Seven tilmicosin- 

treated cattle were removed from the study as 

BRD-related mortalities or chronics. Of these 

cattle, three died of BRD. Of the four chronics, 

three went on to harvest and one died. 



mortalities), and non-BRD removals for the duration 

of the study is summarized in Table 3. 


and enrofloxacin nonresponder treatments from 

day 3 through harvest is presented in Table 4. 

The cumulative frequencies of first-time BRD 

nonresponders from day 3 through the end of 

the study are summarized in Figure 3. 

Nasopharyngeal samples from 27 calves and a 

lung sample from one calf yielded P. multocida, 

M. haemolytica, and H. somnus (H. somni) species 

with one, 25, and two isolates, respectively, 

confirming the presence of BRD pathogens. 

The ADG from day 0 through day 28 was 

191



Figure 2. Cumulative percentage of first-time BRD nonresponse from day 3 through end of study (Nebraska). 


significantly higher (P = .0005) for calves that 

received tulathromycin (3.81 lb) than for 

calves that received tilmicosin (3.34 lb), but 

there was no significant difference (P = .3760) 

in ADG from day 0 through day of harvest 

(3.63 lb for tulathromycin-treated calves and 

3.58 lb for tilmicosin-treated calves) (Table 5). 

The least squares means final live body weight 

was 1,354 lb for tulathromycin-treated cattle 

and 1,340 lb for tilmicosin-treated cattle (P = 

.3311) (Table 5). Tulathromycin-treated cattle 

yielded a least squares means hot carcass weight 

of 840.8 lb compared with 821.3 lb (P = 

.0649) in tilmicosin-treated cattle (Table 6). 

Except for carcass adjusted ADG, differences 

in individual carcass variables were not statistically 

different (Table 6). The descriptive statistics 

of ADG with chronics and deads included 

are summarized in Table 7. 

Texas 


day 28 was not significantly higher (P = .160) 

192 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 


Tulathromycin Florfenicol 

3 5 7 9 11 13 15 17 19 21 23 25 27 End a 

Day of Study 

// 

for calves that received tulathromycin (78 of 

100; 78%) than for calves that received tilmicosin 

(69 of 100; 69%) (Table 2). The cure rate 

from day 3 through harvest was not significantly 

higher (P = .355) for calves that received tulathromycin 

(73 of 100; 73%) than for calves 

that received tilmicosin (67 of 100; 67%). 

Chronic/mortality rates from day 3 through 

day 28 and day 3 through harvest were not significantly 

different (P = .414 and P = .257) for 

calves that received tulathromycin (two of 100 

[2%] for both) than for calves that received 

tilmicosin (four of 100 [4%] and five of 100 

[5%], respectively). Two tulathromycin- and 

four tilmicosin-treated cattle were classified as 

chronics. After removal from the study, all 

chronics were euthanized. 



mortalities), and non-BRD removals for the 

duration of the study is summarized in Table 3. 


and enrofloxacin nonresponder treatments


45 

40 

35 

30 

25 

20 

15 

10 

5 

0 



Tulathromycin Tilmicosin 

3 5 7 9 11 13 15 17 19 21 23 25 27 End a 

Figure 3. Cumulative percentage of first-time BRD nonresponse from day 3 through end of study (Wellington, CO). 


from day 3 through harvest is presented in 

Table 4. The cumulative frequencies of firsttime 

BRD nonresponders from day 3 through 

the end of the study are summarized in 

Figure 4. 

Nasopharyngeal samples from 40 calves 

yielded P. multocida and M. haemolytica species 

with six and 11 isolates, respectively, confirming 

the presence of BRD pathogens. 

The ADG from day 0 through day 28 was 

significantly higher (P = .0018) for calves that 

received tulathromycin (4.00 lb) than for 

calves that received tilmicosin (3.62 lb), but 

there was no significant difference (P = .9421) 

in ADG from day 0 through harvest (2.88 lb 

for both groups) (Table 5). The least squares 

means final live body weight of tulathromycintreated 

cattle was 1,233 lb and of tilmicosintreated 

cattle was 1,235 lb (P = .8788) (Table 

5). Tulathromycin-treated cattle yielded a least 

squares means hot carcass weight of 755 lb 

compared with a tilmicosin-treated cattle carcass 

weight of 759 lb (P = .5881) (Table 6). 

Differences in individual carcass variables were 

Day of Study 

not statistically different (Table 6). The descriptive 

statistics of weight gains with chronics 

and deads included are summarized in 

Table 7. 

Overall 

No suspected adverse experiences were observed 

from antimicrobial product administration 

in any of the studies. 

■ DISCUSSION 

In three of these four studies, cattle with undifferentiated 

BRD that were treated with tulathromycin 

had superior BRD cure rates over 

the duration of the feeding period from the 

time of feedlot entry to harvest compared with 

cattle treated with florfenicol or tilmicosin. At 

the Greeley, CO, and Nebraska study locations, 

where tulathromycin was compared with 

florfenicol, the percentage differences in cure 

rates were 14% and 27%, respectively. For the 

tilmicosin comparisons, the Wellington, CO, 

study had a 19% difference in cure rates. In the 

Texas study, which had the smallest percentage 

// 

193



Figure 4. Cumulative percentage of first-time BRD nonresponse from day 3 through end of study (Texas). 


difference in cure rates, 6% more tilmicosintreated 

cattle required further BRD treatment 

than did tulathromycin-treated cattle, but the 

cure rates of 73% for tulathromycin-treated 

cattle and 67% for tilmicosin-treated cattle 

were not significantly different. Many factors, 

such as pathogen exposure, immunosuppression, 

physiologic status, environment, and 

management practices, contribute to the severity 

of BRD; thus, although cattle in these studies 

were purchased at several auction markets, 

commingled, and shipped to the study site, 

one or more of these factors may have mitigated 

the disease challenge. 

The differences in efficacy between tulathromycin 

and florfenicol or tilmicosin are 

more remarkable in the comparison of the cumulative 

frequency of first-time BRD nonresponders 

(morbidities). At all four locations, 

the majority of the first-time nonresponders after 

initial BRD therapy occurred during the 

28-day period after treatment. In the Greeley, 

CO, comparison with florfenicol, the number 

of florfenicol BRD morbidities showed a 

steady increase beginning at day 7 and contin- 

194 

35 

30 

25 

20 

15 

10 

5 

0 


Tulathromycin Tilmicosin 

3 5 7 9 11 13 15 17 19 21 23 25 27 End a 

Day of Study 

// 

uing through day 9; thereafter, the BRD morbidity 

rates were similar between the florfenicol- 

and tulathromycin-treated calves through 

the end of the study. After initial treatments at 

the Nebraska location, morbidity rates were 

nearly equal until day 13, when the number of 

florfenicol-treated calves classified as BRD 

morbidities steadily increased through day 21 

compared with calves treated with tulathromycin. 

After that, cumulative BRD morbidities 

of both treatments were similar 

through the end of the study. Calves treated 

with tilmicosin at Wellington, CO, had three 

times more BRD morbidities at 3 days after 

treatment compared with tulathromycin-treated 

calves. The number of tilmicosin BRD morbidities, 

relative to tulathromycin-treated 

calves, was much higher than those treated 

with tulathromycin until day 7, at which time 

the two groups of cattle had similar morbidity 

rates through the end of the study. Although 

the differences in cure rates were the least in 

the Texas study when compared with the other 

three studies, more tilmicosin-treated calves 

showed BRD morbidity on days 3, 4, 5, and 6


than calves treated with tulathromycin, with 

negligible differences in morbidity rates from 

day 7 through the end of the study. 

An outcome of the greater number of BRD 

treatment failures (first through fourth nonresponders, 

chronics, BRD mortalities) of calves 

treated with either florfenicol or tilmicosin was 

that a higher number of antimicrobial treatments 

were administered to those cattle compared 

with those treated with tulathromycin. 

Although in the Greeley, CO, study, the second- 

and third-line antimicrobials used for 

nonresponse therapy were different than in the 

other three studies, the same antimicrobials 

were used in each study following initial BRD 

treatments; thus, these are valid comparisons. 

Notably, the ratio of BRD nonresponse antimicrobial 

treatments of florfenicol- and 

tilmicosin-treated calves compared with tulathromycin-treated 

calves ranged from 1.7 to 

2.0 across all four studies. 

Except for the Texas study, in which ADGs 

were the same for both tulathromycin and 

tilmicosin, ADGs of tulathromycin-treated 

cattle were numerically higher than tilmicosin 

or florfenicol in the three other studies. This is 

attributable to the weight gain analyses that 

only body weights collected on all animals at a 

single time point in each study were included 

in the repeated measures mixed model analyses. 

Thus, the calves that would be expected to 

have the greatest negative effect on performance 

were not included in these analyses. Of 

more importance is the live body weight of cat- 

tle to market. Because there were more chronics 

and mortalities in the groups of cattle treated 

with florfenicol or tilmicosin, more cattle 

treated with tulathromycin were marketed, resulting 

in a higher total pounds of body weight 

than for those cattle treated with florfenicol or 

tilmicosin. In the two locations that had more 

florfenicol- or tilmicosin-treated chronics and 

mortalities, the differences in deads/chronics 

in ADG between tulathromycin- and tilmicosin- 

or florfenicol-treated calves was 0.48 

and 1.25 lb, respectively, while these differences 

were only 0.05 lb in the other two comparisons. 

It is worth mentioning that the management 

of the chronics in these studies 

followed acceptable industry practices. After 

The differences in efficacy between 

tulathromycin and florfenicol or tilmicosin 

are more remarkable in the comparison of the 

cumulative frequency of first-time BRD nonresponders. 

meeting criteria of a chronic designation, these 

cattle were removed from their home pens and 

the study. Although some of the calves classified 

as chronics did eventually reach harvest, 

after removal from the study they were not experimental 

units for data analyses, as they were 

managed differently than calves still remaining 

in the studies. 

Both tilmicosin and florfenicol are extensively 

used in feedlots as first-line BRD therapeutics 

because of their single-dose regimens 

and spectrum of activity against bacteria most 

commonly associated with BRD. Thus, the 

comparison of tulathromycin to each of these 

products was useful in evaluating the efficacy 

of tulathromycin under typical feedlot conditions 

from the time of treatment for BRD 

through harvest. 

195


■ CONCLUSION 

Tulathromycin given as a single SC injection 

at 2.5 mg/kg body weight was effective and 

safe for the treatment of undifferentiated 

BRD. In comparison with florfenicol and 

tilmicosin, treatment of undifferentiated BRD 

with tulathromycin showed significantly higher 

cure rates in the two comparisons to florfenicol 

and the one comparison to tilmicosin. 

■ ACKNOWLEDGMENTS 

The authors thank the following investigators and their staffs 

for conducting these studies: Mary Wray, PhD, Horton 

Feedlot and Research Center, Wellington, CO; E. G. Johnson, 

DVM, Johnson Research LLC, Parma, ID; David T. 

Bechtol, DVM, Agri Research Center, Inc., Canyon, TX; 

Karen Rogers, DVM, and Delbert Miles, DVM, Veterinary 

Research and Consulting Services, Greeley, CO; and Donald 

J. Bade, BS, Colorado Animal Research Enterprises, Fort 

Collins, CO. The authors are also grateful for the assistance 

of Korb W. Maxwell, DVM; Andrea C. Brake, PhD; Sam E. 

Ives, DVM, PhD; and Chad E. Guyer, BS. 

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