Efficacy of DRAXXIN or Baytril for treatment of naturally ... · than for those treated with...

H

H C3

H C3

H C3

H C3

H C3

H C3

H C3

H C3

H C3

HO

OCH

N

HN

NOH HO

OH

OH

NH

OH

OH

O

OO

O

O

O

O

O

O

OO

O

OH

OH

OH

CH3

2

3

3

3

3 3

3

3

3

3

3

3 2

3

3

3

3

3

CH

CH CH

CH

(CH )

CH

CH

CH

CH

CH

CH

OCH

CH

HN

N(CH )

CH

IntroductionDRAXXIN is a highly effective, single-dose antimicrobial medication indicated for control of BRD in cattle at high risk of developing BRD caused by Mannheimia haemolytica, Pasteurella multocida and Histophilus somni, and for treatment of BRD caused by these three organisms and Mycoplasma bovis. When administered according to the label dose of 2.5 mg tulathromycin/kg body weight (BW), tulathromycin is rapidly absorbed, distributes widely and provides concentrations in bovine lung for an extended period.1 Clinical efficacy of

DRAXXIN for treatment of BRD, as well as for control of respiratory disease in cattle at high risk of developing BRD, has been well documented in multiple studies.2,3,4 This technical bulletin presents the results of a multilocation study designed to compare the efficacy of DRAXXIN or Baytril for treatment of naturally occurring BRD in feedlot calves. The same study protocol was used at all three sites. Results were analyzed separately by site, and results from two sites have been published in the peer-reviewed literature.5

DRX07033

8

August 2007

Efficacy of DRAXXIN or Baytril for treatment of naturally occurring bovine respiratory disease in calves at 3 feedlots

Key Points• Clinical success was significantly higher (P=0.009, P=0.031, P=0.031) for calves

treated with DRAXXIN® (tulathromycin) Injectable Solution (87.9%, 80.0%, 87.8%) than for those treated with Baytril® (enrofloxacin) Injectable Solution (70.2%, 62.5%, 74.7%).

• Fewer animals treated with DRAXXIN required second (n=44) and third (n=13) treatments than animals treated with Baytril (n=97 and n=27, respectively). Consequently, fewer total treatments were administered to cattle in the DRAXXIN groups than to cattle in the Baytril groups.

• DRAXXIN administered as a single subcutaneous (SC) injection was safe and effective for the initial treatment of bovine respiratory disease (BRD) in calves at 3 feedlots.

Materials and MethodsIn October and November 2005, calves were purchased at livestock markets in Mississippi and Texas and transported to the commercial feedlots in Colorado (n=806 mixed-breed steers), Texas site I (n=742 mixed-breed heifers) and Texas site II (n=802 mixed-breed heifers). Animals were processed on arrival using standard methods for commercial stocker/feeder operations, but were not vaccinated against Mannheimia or Pasteurella species. Calves with clinical signs of BRD were evaluated and enrolled if they had a clinical attitude score (CAS) of 1, 2 or 3 and pyrexia (rectal temperature ≥ 104ºF). According to the CAS system, 0=normal, bright, alert, responsive; 1=mild depression, signs of weakness usually not present; 2=moderate depression, some signs of weakness, may be reluctant to stand; 3=severe depression, difficulty standing, head lowered or extended; or 4=moribund. Calves that met the inclusion criteria were randomly assigned to treatment with either Baytril (5.7 mg enrofloxacin/lb; 12.5 mg/kg BW) or DRAXXIN (1.1 mg tulathromycin/lb; 2.5 mg tulathromycin/kg BW; Figure 1). Animals were blocked (2 animals per block, 1 from each group) by order of enrollment to avoid bias. One-hundred-twenty-five animals per treatment group were enrolled at each site and commingled in treatment pens to maintain masking of the treatment groups. Enrollment occurred during a 3-day period in Colorado, an 18-day period in Texas I and a 13-day period in Texas II.

Animals were assessed daily and CAS scores recorded for 28 days following enrollment; animals were observed for treatment response/nonresponse for 63 days in Colorado, 59 days in Texas I and 58 days in Texas II. Clinical assessors were masked to treatments. Animals were eligible for secondary treatments on day 3 after enrollment (day 0). On days 3 to the end of the study, animals with CAS scores of 1 or 2 and pyrexia (rectal temperature ≥ 104ºF) were considered nonresponders and received a second treatment with LIQUAMYCIN® LA-200® (9.0 mg oxytetracycline/lb; 20.0 mg oxytetracycline/kg). Animals that were a minimum of 2 days following treatment with LA-200 and met nonresponder criteria received a third treatment with Nuflor® (florfenicol) Injectable Solution (18.0 mg florfenicol/lb; 40.0 mg florfenicol/kg). Animals that met nonresponder criteria and were a

minimum of 2 days post-treatment with Nuflor were classified as chronics and received the standard feedlot treatment (SFLT).

According to the study protocol, animals were to be removed from the study before analysis for non-BRD reasons (concurrent disease or other physical conditions that might interfere with the progression of BRD or evaluation of response to therapy) or protocol deviations (allotment entry errors, errors in administration of medication, animals not evaluated/treated in a timely manner). Clinical success was defined as requiring no subsequent treatment. Mortality, CAS scores, body weights and weight gains were summarized for each treatment. Treatment differences were assessed at the 5% level of significance (P<0.05).

ResultsColorado

The clinical success for study days 0 to 59 was significantly higher (P=0.009) for animals treated with DRAXXIN (87.9%) than for those treated with Baytril (70.2%; Table 1). Figure 2a displays the cumulative treatment success by day. Animals with an in-pen CAS equal to 0 (normal) after the initial treatment are displayed in Figure 3a. Second treatments were administered to 37 animals in the Baytril group and 15 in the DRAXXIN group. Third treatments were administered to 9 animals in the Baytril group and 4 in the DRAXXIN group. Weight gains were numerically greater (P=0.0510) for animals treated with DRAXXIN (180.9 lb) than for those treated with Baytril (173.0 lb). One animal in the Baytril group was declared a chronic; no deaths due to BRD occurred in either group. DRAXXIN was significantly more efficacious than Baytril for treatment of naturally occurring BRD at this site.

Texas I

The clinical success for study days 0 to 63 was significantly higher (P=0.031) for animals treated with DRAXXIN (80.0%) than for those treated with Baytril (62.5%; Table 1). This is also displayed in Figure 2b as cumulative treatment success by day. Animals displaying an in-pen CAS equal to 0 after the initial treatment are displayed in Figure 3b. Second treatments were administered to 44 animals in the Baytril group and 23 in the DRAXXIN group. Third treatments were administered to 17 animals in the Baytril group and 9 in the DRAXXIN group. Seventeen animals were classified as chronics, 7 in the DRAXXIN group and 8 in the Baytril group. One animal in each group died before SFLT. Weight gains were numerically greater (P=0.3589) for animals treated with DRAXXIN (78.1 lb) than for those treated with Baytril (71.6 lb). Mortality was similar for both groups: 6 animals in the DRAXXIN group and 5 in the Baytril group. DRAXXIN was significantly more efficacious than Baytril for treatment of naturally occurring BRD at this site.

Texas II

Two-hundred-fifty animals were enrolled in the study. Seventy-seven animals were excluded from the study analyses for non-

BRD reasons or protocol deviations defined before the study began. Additionally, for the 37 animals excluded for protocol deviations, 29 block mates were also excluded to avoid potential bias. (The numbers differ because in some instances both animals in a block were excluded for protocol deviations.) Data collected from 83 animals in the Baytril group and 90 animals in the DRAXXIN group were analyzed and are reported here. Because of the number of animals affected by protocol deviations, preliminary analysis of all cattle at this site was conducted and demonstrated no effect on statistical results.

Table 1 summarizes the response to treatment at this site. As depicted in Figure 2c, clinical success was significantly greater (P=0.031) for animals treated with DRAXXIN (87.8%) than for those treated with Baytril (74.7%). Second treatments were administered to 16 animals in the Baytril group and 6 in the DRAXXIN group. Third treatments were administered to 1 animal in the Baytril group and 0 in the DRAXXIN group. Animals displaying an in-pen CAS equal to 0 after the initial treatment are displayed in Figure 3c. A significant advantage (P=0.0035) in mean weight gains was observed for animals treated with DRAXXIN (202.7 lb) compared to those treated with Baytril (172.9 lb). Nine animals in the Baytril group and 5 in the DRAXXIN group died.

DiscussionAt all three sites, clinical success was significantly higher for calves treated with DRAXXIN (87.9%, 80% and 87.8%) than for those treated with Baytril (70.2%, 62.5%, 74.7%). The results of the primary study variable — first-treatment success — were similar at all sites. The treatment success for cattle treated with DRAXXIN was better at each individual site and collectively for all three sites. The numbers of cattle treated with DRAXXIN that required further treatment ranged from 6 to 15 per site compared to 16 to 44 per site for the cattle treated with Baytril. The first-treatment success and total number of treatments administered were more favorable at every site for the cattle treated with DRAXXIN. At all three sites, a total of 57 calves in the DRAXXIN groups and 124 calves in the Baytril groups required second and third treatments. Consequently, fewer antimicrobial treatments were administered to animals in the DRAXXIN groups than in the Baytril groups.

Taken together, evidence from the three sites demonstrates that DRAXXIN provides effective and consistent results in treating BRD in feedlot calves compared with Baytril. Enrollment times (3, 18 and 13 days) reflect realistic variances in groups of cattle and typical commercial-receiving conditions. The initial variable for enrollment was the CAS, which relies on clinical signs as evidence of BRD. Numerous factors could result in different CAS values among sites, including cattle source, disease exposure, transport conditions and local weather. The individuals responsible for evaluation and treatment of the cattle were blinded to the treatments administered and to the allocation and blocking of cattle in the treatment groups, so the

cattle were treated similarly within each site regardless of the time required for treatment allocation. In addition, the results were similar across sites in that there was a similar magnitude of difference in first-treatment successes between the treatment groups and no difference in mortality or chronics.

It is important to note that in this three-site study, comparing DRAXXIN to Baytril, cattle were eligible for retreatment three days following initial treatment. This interval was chosen in part to preserve masking of the treatments. However, the trend of successful treatment of BRD with DRAXXIN is supported by other studies with longer post-treatment intervals (PTIs).2,3,4 The PTI is a period of time after treatment with an antimicrobial when no further treatment is administered. DRAXXIN significantly reduced mortality and lung lesions in cattle if given as long as 9 days before experimental intratracheal inoculation of M. haemolytica.6 In a companion study, cattle with naturally occurring BRD were treated with DRAXXIN and no additional treatments were allowed for intervals of 7 days, 10 days or 14 days.6 There was no difference in first-treatment success, mortality or weight gain in the three groups. These two additional studies provide experimental and clinical evidence that DRAXXIN exerts a clinical effect against BRD in cattle for longer than the three-day PTI reported here for the three feedlot sites.

Clinical effect in response to bacterial pneumonias is, in part, a function of spectrum of activity, as most cases of bacterial pneumonias are the result of a mixed bacterial infection. Multiple factors, many of which are not clearly defined, make up the biological equation termed “response to treatment” or in this study CAS. From an anti-infective standpoint, spectrum of activity against the important target pathogens and length of effective treatment are important components. DRAXXIN is labeled for treatment of all four major bacterial pathogens causing BRD in cattle, including Mycoplasma bovis. Recent studies indicate that the two most common microbial agents associated with nonresponsive BRD are M. bovis and BVDV.7,8 The improved first-treatment success seen with DRAXXIN vs. Baytril in this three-site study parallels the results of studies comparing DRAXXIN with Micotil® 300 (tilmicosin injection) and Nuflor.3,4 The antimicrobial spectrum and pharmacokinetics of DRAXXIN in cattle provide measurable clinical advantages over these other antimicrobials used to treat BRD.

ConclusionsUsing DRAXXIN for initial treatment of BRD in calves resulted in significantly greater first-treatment success and fewer second and third treatments than achieved with Baytril at three feedlots.

Do not use DRAXXIN in female dairy cattle 20 months of age or older. Do not use in calves to be processed for veal. DRAXXIN has a pre-slaughter time of 18 days.

Prepared from study reports 1133R-60-05-491, 1133R-60-05-492 and 1133R-60-05-493.

DRAXXIN and LIQUAMYCIN LA-200 are registered trademarks of Pfizer Inc. Baytril is a registered trademark of Bayer Aktiengesellschaft. Micotil is a registered trademark of Eli Lilly and Company. Nuflor is a registered trademark of Schering-Plough Veterinary Corp. ©2007 Pfizer Inc. All rights reserved.

Success

Removed

DRAXXIN

Chronics SFLT

Eligible for 2nd treatment

LA-200

Eligible for 3rd treatmentNuflor

3 days

2 days

2 days

Response/No response

CAS on days 1 to 28Observed on days 1 to 60 (+_ 3)SFLT=standard feedlot treatment

n=125

Abnormal CAS & T >_ 104ºF

1st treatment, day 0

Response/No response

3 feedlots: CO, TX I, TX II

Figure 1. Experimental Design

Baytriln=125

2 3

*P=0.009 *P=0.031

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55

aB yt lirDRAXXIN

days daysdays

days daysdays

*

Figure 2a. Cumulative Treatment Success (Colorado)

0010203040506070809001

0 5 10 51 02 52 03 53 04 54 05

aB yt lirDRAXXIN*P=0.031

aB yt lirDRAXXIN

*

Figure 2b. Cumulative Treatment Success (Texas I)

0

02

04

06

08

001

021

aD y 0 Day 3 D ya 6 D ya 9 D ya 21 Day 51 yaD 81 yaD 12 aD y 42 yaD 72

% o

ftre

atm

ent g

roup

s

Figure 3a. Clinical Appearance After Treatment (Colorado): Animals with CAS of 0 through Day 28

0

02

04

06

08

001

021


%of

trea

tmen

tgro

ups

Figure 3b. Clinical Appearance After Treatment (Texas I): Animals with CAS of 0 through Day 28

% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55

Figure 2c. Cumulative Treatment Success (Texas II)

88

90

92

94

96

98

100

102


%of

trea

tmen

tgro

ups

Baytril DRAXXINBaytril DRAXXINBaytril DRAXXIN

Figure 3c. Clinical Appearance After Treatment (Texas II): Animals with CAS of 0 through Day 28

*

Clinical success was significantly higher (P=0.009) for animals treated with DRAXXIN (87.9%) than for those treated with Baytril (70.2%).


Clinical success was significantly higher (P=0.031) for calves treated with DRAXXIN (87.8%) than for those treated with Baytril (74.7%).

References1 Nowakowski MA, Inskeep P, Risk J, Skogerboe TL,

Benchaoui HA, Meinert TR. Sherington J, Sunderland SJ. Pharmacokinetics and lung tissue concentrations of tulathromycin, a new triamilide antibiotic, in cattle. Vet Ther 2004;5:60-74.

2 Nutsch RG, Skogerboe TL, Rooney KA, Weigel DJ, Gajewski K, Lechtenberg KF. Comparative efficacy of tulathromycin, tilmicosin and florfenicol in the treatment of bovine respiratory disease in stocker cattle. Vet Ther 2005;6(2):167-179.

3 Skogerboe TL, Rooney KA, Nutsch RG, Weigel DJ, Gajewski K, Kilgore WR. Comparative efficacy of tulathromycin versus florfenicol and tilmicosin against undifferentiated bovine respiratory disease in feedlot cattle. Vet Ther 2005;6(2):180-196.

4 Rooney KA, Nutsch RG, Skogerboe TL, Weigel DJ, Kimberly K, Kilgore WR. Efficacy of tulathromycin compared with tilmicosin and florfenicol for the control of respiratory disease in cattle at high risk of developing bovine respiratory disease. Vet Ther 2005:6(2):154-166.

5 Robb EJ, Tucker CM, Corley L, et al. Efficacy of tulathromycin versus enrofloxacin for initial treatment of naturally occurring bovine respiratory disease in feeder calves. Vet Ther 2007;8(2):127-135.

6 Rooney KA, Meeuwse DM, Nutsch RG, et al. The efficacy and timing of tulathromycin (DRAXXIN Injectable solution) administration in calves challenged with Mannheimia haemolytica or managed in a feedlot. 2007; in press.

7 Shahriar FM, Clark EG, Janzen E, West K, Wobeser G. Coinfection with bovine viral diarrhea virus and Mycoplasma bovis in feedlot cattle with chronic pneumonia. Can Vet J 2002;43(11):863-868.

8 Haines DM, Martin KM, Clark EG, Jim GK, Janzen ED. The immunohistochemical detection of Mycoplasma bovis and bovine viral diarrhea virus in tissues of feedlot cattle with chronic, unresponsive respiratory disease and/or arthritis. Can Vet J 2001;42(11):857-860.

*P=0.009 *P=0.031

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55

aB yt lirDRAXXIN

days daysdays

days daysdays

*


0010203040506070809001

0 5 10 51 02 52 03 53 04 54 05


aB yt lirDRAXXIN

*


0

02

04

06

08

001

021


% o

ftre

atm

ent g

roup

s


0

02

04

06

08

001

021


%of

trea

tmen

tgro

ups


% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55


88

90

92

94

96

98

100

102


%of

trea

tmen

tgro

ups



*




*P=0.009 *P=0.031

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55

aB yt lirDRAXXIN

days daysdays

days daysdays

*


0010203040506070809001

0 5 10 51 02 52 03 53 04 54 05


aB yt lirDRAXXIN

*


0

02

04

06

08

001

021


% o

ftre

atm

ent g

roup

s


0

02

04

06

08

001

021


%of

trea

tmen

tgro

ups


% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55


88

90

92

94

96

98

100

102


%of

trea

tmen

tgro

ups



*




4 5

Tabl

e 1.

Sum

mar

y of

Res

pons

e to

Tre

atm

ent

Co

lora

do

Texa

s I

Texa

s II

An

imal

sTr

eatm

ents

, No

.A

nim

als

Trea

tmen

ts, N

o.

An

imal

sTr

eatm

ents

, No

.

Bay

tril

DR

AX

XIN

Bay

tril

DR

AX

XIN

Bay

tril

DR

AX

XIN

Bay

tril

DR

AX

XIN

Bay

tril

DR

AX

XIN

Bay

tril

DR

AX

XIN

Enr

olle

d, n

o.12

512

512

512

512

412

5

Rem

oved

fro

m A

ll A

naly

ses*

11

55

4135

Num

ber

that

Rec

ieve

d 1s

t Tre

atm

ent

124

124

124

124

120

120

120

120

8390

8390

1st T

reat

men

t S

ucce

ss, n

o.87

109

7596

6279

1st T

reat

men

t Fa

ilure

, no.

3715

4524

2111

1st T

reat

men

t S

ucce

ss, %

**70

.2a

87.9

b62

.5c

80.0

d74

.7e

87.8

f

Die

d be

fore

2nd

Trea

tmen

t, n

o.0

00

15

5

Rem

oved

Non

-BR

D-R

elat

ed o

r Pr

otoc

ol

Dev

iatio

ns a

fter

2nd

Trea

tmen

t, n

o.0

01

01

00

Num

ber

that

Rec

ieve

d 2n

d Tr

eatm

ent

3715

3715

4423

4423

166

166

2nd

Trea

tmen

t S

ucce

ss, n

o.27

1124

1211

6

2nd

Trea

tmen

t Fa

ilure

, no.

104

2011

50

2nd

Trea

tmen

t S

ucce

ss, %

73.0

73.3

54.5

52.2

68.8

100.

0

Die

d be

fore

3rd

Trea

tmen

t, n

o.0

02

14

0

Rem

oved

Non

-BR

D R

elat

ed o

r Pr

otoc

ol

Dev

iatio

ns, n

o.1

01

11

00

Num

ber

that

Rec

ieve

d 3r

d Tr

eatm

ent

94

94

179

179

10

10

3rd

Trea

tmen

t S

ucce

ss, n

o.8

48

11

N/A

3rd

Trea

tmen

t Fa

ilure

, no.

10

10

98

00

3rd

Trea

tmen

t S

ucce

ss, %

88.9

100

47.1

11.1

100.

00.

0

Die

d be

fore

SFL

T1

1

Rem

oved

Non

-BR

D R

elat

ed o

r Pr

otoc

ol

Dev

iatio

ns, n

o.1

00

SFL

T/C

hron

ics,

no.

19

48

78

70

01

Tota

l Tre

atm

ents

Adm

inis

tere

d, n

o.†

172

143

190

159

101

96

*P=0.009 *P=0.031

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55

aB yt lirDRAXXIN

days daysdays

days daysdays

*


0010203040506070809001

0 5 10 51 02 52 03 53 04 54 05


aB yt lirDRAXXIN

*


0

02

04

06

08

001

021


% o

ftre

atm

ent g

roup

s


0

02

04

06

08

001

021


%of

trea

tmen

tgro

ups


% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55


88

90

92

94

96

98

100

102


%of

trea

tmen

tgro

ups



*




*P=0.009 *P=0.031

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55

aB yt lirDRAXXIN

days daysdays

days daysdays

*


0010203040506070809001

0 5 10 51 02 52 03 53 04 54 05


aB yt lirDRAXXIN

*


0

02

04

06

08

001

021


% o

ftre

atm

ent g

roup

s


0

02

04

06

08

001

021


%of

trea

tmen

tgro

ups


% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55


88

90

92

94

96

98

100

102


%of

trea

tmen

tgro

ups



*




*P=0.009 *P=0.031

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55

aB yt lirDRAXXIN

days daysdays

days daysdays

*


0010203040506070809001

0 5 10 51 02 52 03 53 04 54 05


aB yt lirDRAXXIN

*


0

02

04

06

08

001

021


% o

ftre

atm

ent g

roup

s


0

02

04

06

08

001

021


%of

trea

tmen

tgro

ups


% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

% c

attle

rem

aini

ng fr

ee o

f BR

D

0010203040506070809001

0 5 01 51 20 52 03 53 04 54 05 55


88

90

92

94

96

98

100

102


%of

trea

tmen

tgro

ups



*




6 7

*

Thes

ean

imal

sw

ere

rem

oved

from

the

stud

yb

efor

ean

alys

esfo

rno

n-B

RD

reas

ons

orp

roto

cold

evia

tions

defi

ned

bef

ore

the

stud

yb

egan

.The

reas

ons

for

excl

usio

nat

Tex

asII

incl

uded

:1=

allo

tmen

tent

ry

e

rror

,3=

err

ors

ina

dmin

istr

atio

nof

med

icat

ions

,7=

CA

So

f2a

ndn

ote

valu

ated

furt

her

for

resp

ond

er/n

onre

spon

der

cla

ssifi

catio

n,3

7=

CA

So

f2a

ndw

ere

note

valu

ated

/tre

ated

ina

tim

ely

man

ner.

For

the

37

a

nim

als

excl

uded

for

prot

ocol

dev

iatio

ns,2

9b

lock

mat

esw

ere

also

exc

lud

edto

avo

idp

oten

tialb

ias.

The

num

ber

sd

iffer

bec

ause

ins

ome

inst

ance

sb

oth

anim

als

ina

blo

ckw

ere

excl

uded

for

prot

ocol

dev

iatio

ns.

**

Bac

k-tr

ansf

orm

ed le

ast

squa

res

mea

n(L

SM

).a,

bD

iffer

ent

sup

ersc

ripts

ind

icat

esi

gnifi

cant

lyd

iffer

ent

valu

es(P

=0.

009)

.c,

d D

iffer

ent

sup

ersc

ripts

ind

icat

esi

gnifi

cant

lyd

iffer

ent

valu

es(P

=0.

031)

.e

,fD

iffer

ent

sup

ersc

ripts

ind

icat

esi

gnifi

cant

lyd

iffer

ent

valu

es(P

=0.

031)

.

†D

ead

sex

clud

ed.

Table 1. Summary of Response to Treatment

Colorado Texas I Texas II

Animals Treatments, No. Animals Treatments, No. Animals Treatments, No.

Baytril DRAXXIN Baytril DRAXXIN Baytril DRAXXIN Baytril DRAXXIN Baytril DRAXXIN Baytril DRAXXIN

Enrolled, no. 125 125 125 125 124 125

Removed from All Analyses* 1 1 5 5 41 35

Number that Recieved 1st Treatment 124 124 124 124 120 120 120 120 83 90 83 90

1st Treatment Success, no. 87 109 75 96 62 79

1st Treatment Failure, no. 37 15 45 24 21 11

1st Treatment Success, %** 70.2a 87.9b 62.5c 80.0d 74.7e 87.8f

Died before 2nd Treatment, no. 0 0 0 1 5 5

Removed Non-BRD-Related or Protocol Deviations after 2nd Treatment, no. 0 0 1 0 1 0 0

Number that Recieved 2nd Treatment 37 15 37 15 44 23 44 23 16 6 16 6

2nd Treatment Success, no. 27 11 24 12 11 6

2nd Treatment Failure, no. 10 4 20 11 5 0

2nd Treatment Success, % 73.0 73.3 54.5 52.2 68.8 100.0

Died before 3rd Treatment, no. 0 0 2 1 4 0

Removed Non-BRD Related or Protocol Deviations, no. 1 0 1 1 1 0 0

Number that Recieved 3rd Treatment 9 4 9 4 17 9 17 9 1 0 1 0

3rd Treatment Success, no. 8 4 8 1 1 N/A

3rd Treatment Failure, no. 1 0 1 0 9 8 0 0

3rd Treatment Success, % 88.9 100 47.1 11.1 100.0 0.0

Died before SFLT 1 1

Removed Non-BRD Related or Protocol Deviations, no. 1 0 0

SFLT/Chronics, no. 1 9 4 8 7 8 7 0 0 1

Total Treatments Administered, no.† 172 143 190 159 101 96

*P=

0.009*P

=0.031

0 01 02 03 04 05 06 07 08 09 001

05

0151

2052

0353

0454

0555

aB

ytlir

DR

AXXIN

daysdays

days

daysdays

days

*

Figure 2a. Cumulative Treatm

ent Success (Colorado)

0 01 02 03 04 05 06 07 08 09 001

05

1051

0252

0353

0454

05

aB

ytlir

DR

AXXIN

*P=

0.031a

Byt

lirD

RA

XXIN

*

Figure 2b. Cumulative Treatm

ent Success (Texas I)

0 02 04 06 08 001

021

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72

% of treatment groups

Figure 3a. Clinical Appearance After Treatment (Colorado):

Anim

als with CAS of 0 through Day 28

0 02 04 06 08 001

021

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72


Figure 3b. Clinical Appearance After Treatment (Texas I):

Anim


% cattle remaining free of BRD



0 01 02 03 04 05 06 07 08 09 001

05

0151

2052

0353

0454

0555

Figure 2c.Cumulative Treatm

ent Success (Texas II)

88 90 92 94 96 98

100

102

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72


BaytrilDRAXXIN

BaytrilDRAXXIN

BaytrilDRAXXIN

Figure 3c. Clinical Appearance After Treatment (Texas II):

Anim


*

Clinical success was significantly higher (P=0.009) for anim

als treated with

DRAXXIN (87.9%

) than for those treated with Baytril (70.2%

).Clinical success w

as significantly higher (P=0.031) for animals treated w

ith DRAXXIN

(80.0%) than for those treated w

ith Baytril (62.5%).

Clinical success was significantly higher (P=0.031) for calves treated w

ith DRAXXIN



*P=

0.009*P

=0.031

0 01 02 03 04 05 06 07 08 09 001

05

0151

2052

0353

0454

0555

aB

ytlir

DR

AXXIN

daysdays

days

daysdays

days

*



0 01 02 03 04 05 06 07 08 09 001

05

1051

0252

0353

0454

05

aB

ytlir

DR

AXXIN

*P=

0.031a

Byt

lirD

RA

XXIN

*



0 02 04 06 08 001

021

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72



Anim


0 02 04 06 08 001

021

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72



Anim





0 01 02 03 04 05 06 07 08 09 001

05

0151

2052

0353

0454

0555



88 90 92 94 96 98

100

102

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72


BaytrilDRAXXIN

BaytrilDRAXXIN

BaytrilDRAXXIN


Anim


*


als treated with

DRAXXIN (87.9%




ith DRAXXIN




ith DRAXXIN



*P=

0.009*P

=0.031

0 01 02 03 04 05 06 07 08 09 001

05

0151

2052

0353

0454

0555

aB

ytlir

DR

AXXIN

daysdays

days

daysdays

days

*



0 01 02 03 04 05 06 07 08 09 001

05

1051

0252

0353

0454

05

aB

ytlir

DR

AXXIN

*P=

0.031a

Byt

lirD

RA

XXIN

*



0 02 04 06 08 001

021

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72



Anim


0 02 04 06 08 001

021

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72



Anim





0 01 02 03 04 05 06 07 08 09 001

05

0151

2052

0353

0454

0555



88 90 92 94 96 98

100

102

aD

y0

Day

3D

ya6

Dya

9D

ya21

Day

51ya

D81

yaD

12a

Dy

42ya

D72


BaytrilDRAXXIN

BaytrilDRAXXIN

BaytrilDRAXXIN


Anim


*


als treated with

DRAXXIN (87.9%




ith DRAXXIN




ith DRAXXIN



67

*Theseanimalswereremovedfromthestudybeforeanalysesfornon-BRDreasonsorprotocoldeviationsdefinedbeforethestudybegan.ThereasonsforexclusionatTexasIIincluded:1=allotmententry error,3=errorsinadministrationofmedications,7=CASof2andnotevaluatedfurtherforresponder/nonresponderclassification,37=CASof2andwerenotevaluated/treatedinatimelymanner.Forthe37 animalsexcludedforprotocoldeviations,29blockmateswerealsoexcludedtoavoidpotentialbias.Thenumbersdifferbecauseinsomeinstancesbothanimalsinablockwereexcludedforprotocoldeviations. **Back-transformedleastsquaresmean(LSM).a,bDifferentsuperscriptsindicatesignificantlydifferentvalues(P=0.009).c,dDifferentsuperscriptsindicatesignificantlydifferentvalues(P=0.031).e , fDifferentsuperscriptsindicatesignificantlydifferentvalues(P=0.031). †Deadsexcluded.

H

H C3

H C3

H C3

H C3

H C3

H C3

H C3

H C3

H C3

HO

OCH

N

HN

NOH HO

OH

OH

NH

OH

OH

O

OO

O

O

O

O

O

O

OO

O

OH

OH

OH

CH3

2

3

3

3

3 3

3

3

3

3

3

3 2

3

3

3

3

3

CH

CH CH

CH

(CH )

CH

CH

CH

CH

CH

CH

OCH

CH

HN

N(CH )

CH

IntroductionDRAXXIN is a highly effective, single-dose antimicrobial medication indicated for control of BRD in cattle at high risk of developing BRD caused by Mannheimia haemolytica, Pasteurella multocida and Histophilus somni, and for treatment of BRD caused by these three organisms and Mycoplasma bovis. When administered according to the label dose of 2.5 mg tulathromycin/kg body weight (BW), tulathromycin is rapidly absorbed, distributes widely and provides concentrations in bovine lung for an extended period.1 Clinical efficacy of

DRAXXIN for treatment of BRD, as well as for control of respiratory disease in cattle at high risk of developing BRD, has been well documented in multiple studies.2,3,4 This technical bulletin presents the results of a multilocation study designed to compare the efficacy of DRAXXIN or Baytril for treatment of naturally occurring BRD in feedlot calves. The same study protocol was used at all three sites. Results were analyzed separately by site, and results from two sites have been published in the peer-reviewed literature.5

DRX07033

8

August 2007

Efficacy of DRAXXIN or Baytril for treatment of naturally occurring bovine respiratory disease in calves at 3 feedlots

Key Points• Clinical success was significantly higher (P=0.009, P=0.031, P=0.031) for calves

treated with DRAXXIN® (tulathromycin) Injectable Solution (87.9%, 80.0%, 87.8%) than for those treated with Baytril® (enrofloxacin) Injectable Solution (70.2%, 62.5%, 74.7%).

• Fewer animals treated with DRAXXIN required second (n=44) and third (n=13) treatments than animals treated with Baytril (n=97 and n=27, respectively). Consequently, fewer total treatments were administered to cattle in the DRAXXIN groups than to cattle in the Baytril groups.

• DRAXXIN administered as a single subcutaneous (SC) injection was safe and effective for the initial treatment of bovine respiratory disease (BRD) in calves at 3 feedlots.

Efficacy of DRAXXIN or Baytril for treatment of naturally ... · than for those treated with...

Documents

Transcript of Efficacy of DRAXXIN or Baytril for treatment of naturally ... · than for those treated with...