SAFETY OF ROFENAID new broad spectrum coccidiostat-antibacterial, in chickens. Poultry Sci. 48: 217-222. Marusich, W. L., E. F. Ogrinz, B. Hecht and M. Mitrovic, 1971. Safety of sulfadimethoxine potentiated mixture (Rofenaid), a new broad spectrum coccidiostat-antibacterial, in turkeys. Poultry Sci. 50: 512-517. Mitrovic, M., G. Fusiek and E. G. Schildknecht,
525
1969a. Antibacterial activity of sulfadimethoxine potentiated mixture (Ro 5-0013) in chickens. Poultry Sci. 48: 1151-1155. Mitrovic, M., E. G. Schildknecht and G. Fusiek, 1969b. Anticoccidial activity of sulfadimethoxine potentiated mixture (Ro 5-0013) in chickens. Poultry Sci. 48: 210-216.
M. MITROVIC, G. FUSIEK AND E. G. SCHILDKNECHT Chemical Research Department, Hoffmann-La Roche Inc., Nutley, New Jersey 07110 (Received for publication August 31, 1970)
T
HE anticoccidial and antibacterial activity (Mitrovic et al., 1969a, b) as well as the safety and compatibility (Marusich et al., 1969) of Rofenaid, sulfadimethoxine ormetoprim-potentiated mixture, in chicks have already been reported; its anticoccidial activity (Mitrovic et al., 1971) and its safety (Marusich et al., 1971) in turkeys have also been discussed. The present report deals with its antibacterial activity in turkeys. MATERIALS AND METHODS
The chemoprophylactic antibacterial studies were carried out in battery and floor pen trials. Battery trials. Day-old Broad Breasted White (B.B.W.) poults were used throughout these studies. Ten birds, evenly distributed by sex and body weight, were used per group. Each test was repeated four times. The poults, fed and watered ad libitum, were kept in electrically-heated wirefloored battery brooders throughout the experiments. Purina turkey starter mash, free of * Rofenaid is the Hoffmann-La Roche trademark for a coccidiostat and antibacterial containing sulfadimethoxine and ormetoprim.
drugs, was used as the basal ration. The medicated feed was prepared by adding to the basal ration enough Rofenaid to obtain the desired 0.02 and 0.01% concentrations of active drug in feed. The drug was thoroughly mixed into the mash just prior to use to provide a uniform blend. In all instances, the medicated feed was fed one week before infection and for three consecutive weeks thereafter. For experimental infections, cultures of Salmonella typhimurium, Escherichia coli (82:K:H5), Pasteurella multocida (X-73) and Paracolon arizona (7:1,7,8), tryptose broth propagated and properly titrated, were used. The inocula consisted of: 0.2 ml. per bird of 10° for S. typhimurium; 0.1 ml. of 10-2 for E. coli; 0.1 ml. of 10' 4 for P. multocida; 0.1 ml. of 10° for P. arizona. Intratracheal routes of administration were employed for E. coli and P. multocida, oral and intraperitoneal for S. typhimurium and P. arizona, respectively. The birds were infected at one week of age. Parallel sets of uninfected, unmedicated controls (U.U.C.) and infected, unmedicated controls (I.U.C.) were included in each trial. At the completion of each trial (4 weeks of age), the surviving birds were sacrificed,
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Antibacterial Activity of Sulfadimethoxine Potentiated Mixture (Rofenaid®)* in Turkeys
526
M. MITEOVIC, G. FUSIEK AND E. G. SCHILDKNECHT
als. Parallel sets of I.U.C. and U.U.C. were also included in each study. alsi 1Parameters of activity for both battery and floor pen trials were submitted to staanc tistical analysis. tist RESULTS AND DISCUSSION
]1. The chemoprophylactic antibacterial activity of Rofenaid against S. typhimuact rium is shown in Table 1. The battery data riw show that Rofenaid, at dosages of 0.02 and she 0.01% active drug in feed, was effective in 0.0 preventing mortality among the medicated pre poults. From the morbidity, gross patholpoi ogy and culture isolation points of view, og} Rofenaid (0.02 and 0.01%)-medicated Ro birds bir performed well at both dosages tested and were superior to those of the I.U.C. anc The Th medicated birds appeared clinically normal, while the I.U.C. showed evident noi signs of disease following challenge. The sigi dat data pertinent to weight gain and feed conversion show that Rofenaid (0.02 and ver 0.01%)-medicated birds gained well and 0.0 cor converted feed efficiently at both dosages. The medication was tolerated well, and no Th side effects were noted. sid The floor pen data show that Rofenaid
TABLE 1.—Antibacterial activity of Rofenaid against S. typhimunum in turkeys Cone, in feed, %
Weight gain, %
Feed conversion
07 /o Mortality
% Positive cultures—surviving birds H
L
S
I
0 0 0 0
0 8 5 5
0 40 15 20
0 0 0 0
0 8 2 3
0 15 8 3
Battery trials (av. 4X10) 0-U.U.C. 0-I.U.C. 0.02 0.01
100 100 104 104
1.82 1.81 1.84 1.76
0 5 0 0
0 0 0 3
Floor pen trials (av. 2X30) 0-U.U.C. 0-I.U.C. 0.02 0.01
100 103 103 109
1.65 1.59 1.58 1.56
0 2 0 0
U.U.C. = Uninfected, unmedicated controls, I.U.C, =Infected, unmedicated controls.
0 0 0 0
H=sHeart; L=Liver; S=Spleen; I=Intestine.
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igical autopsied, examined for gross pathological lesions specific to each disease, and culleart, tured. The organs cultured were the heart, yhich liver, spleen and intestine. All birds which died during the experiment were also) auledia topsied and cultured. The culture media terial employed were selective for each bacterial infection, and the positive isolates were boraidentified in accordance with usual laboratory procedures. jased The parameters of activity were based upon the weight gain, feed conversion, prevention and reduction of mortality and ected bacterial findings of the medicated-infected itrols versus the infected-unmedicated controls ected (I.U.C.) and the unmedicated-uninfected controls (U.U.C.). Floor pen trials. Poults of the same breed were used in these tests. They were ay to floor-reared and medicated from one day four weeks of age. Thirty poults were used per group and each trial repeated twice, wice. The Rofenaid concentrations used, thee experimental infections, the inocula, the routes of administration, the bacteriological igical and procedures, the parameters of activity' and the duration of each experiment were identical to those applicable for the batteryy tri-
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ANTIBACTERIAL ACTIVITY OF ROFENAID
TABLE 2.—Antibacterial activity of Rofenaid against E. coli in turkeys Cone, in feed, %
Weigl-t gain, %
Feed conversion
°7 Mortality
% P ° s ' t i v e cultures surviving birds H T S
Battery trials (av. 4X10)
o-u.u.c. 0-I.U.C. 0.02 0.01
100 86 99 99
1.55 1.61 1.57 1.60
0 15 3 5
0 0 0 0
Floor pen trials (av. 2X30) 100 53 89 87
1.75 1.96 1.74 1.80
0 50 8 12
was effective at both dosages tested (0.02 and 0.01%) in preventing mortality, reducing morbidity and suppressing the carriers, compared with those of the I.U.C The data pertinent to weight gain and feed conversion show that Rofenaid-medicated birds did as well as those in the other groups (U.U.C. and I.U.C). The efficacy parameters, combined for both groups (battery and floor pen) and submitted to statistical analysis, show that both dosages (0.02 and 0.01%) of Rofenaid were equally effective (N.S.) and superior to I.U.C, pertinent to mortality (P < .05) and positive cultures—dead and surviving birds combined (P < .01 to .005). Other parameters were not statistically significant. 2. The chemoprophylactic antibacterial activity of Rofenaid against E. coli is shown in Table 2. The battery data show that Rofenaid, fed to turkeys at dosages of 0.02 and 0.01% active drug in feed, was highly effective at both dosages tested in reducing mortality and morbidity among the medicated birds. Rofenaid-medicated birds showed less pathology and overall fewer positive cultures from the heart, liver and spleen, in comparison to the I.U.C. The data pertinent to weight gain and feed conversion show that Rofenaid-medicated
0 2 0 0
0 5 0 0
0 7 0 0
birds gained well and converted feed more efficiently than the I.U.C. The floor pen data show that Rofenaid, fed to turkeys at dosages of 0.02 and 0.01% active drug in feed, was highly effective at both dosages tested in reducing mortality, morbidity and bacterial isolations among the medicated birds. The data pertinent to weight gain and feed conversion show that Rofenaid-medicated birds gained and converted feed very well, in comparison to the I.U.C. and U.U.C. The combined efficacy parameters (battery and floor pen) submitted to statistical analysis show that both dosages (0.02 and 0.01%) of Rofenaid were equally effective (N.S.) and superior to I.U.C, pertinent to mortality (P < .01 to .005) and positive cultures—dead and surviving birds combined—(P < .005). Other parameters were not statistically significant. 3. The chemoprophylactic antibacterial activity of Rofenaid against P. multocida is shown in Table 3. The battery data show that Rofenaid, fed to turkeys at dosages of 0.02 and 0.01% active drug in feed, was highly effective at both dosages tested in preventing mortality and morbidity among the medicated birds. Rofenaid-medicated birds showed no mortality, negligible pathology and yielded few positive cultures.
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o-u.u.c. 0-I.U.C. 0.02 0.01
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M . MlTROVIC, G. FUSIEK AND E . G. SCH1LDKNECHT TABLE 3.-—Antibacterial
Cone, in feed, %
Weight gain, %
•p
activity ofRofenaid against P. multocida in turkeys
.
m
conversion
% Positive cultures surviving birds
Alortality
H
T
S
Battery trials (av. 4X10)
o-u.u.c. 0-I.U.C 0.02 0.01
100 73 95 89
0 28 0 0
1.45 1.58 1.53 1.60
Floor pen trials (av. 2X30) 0-I.U.C 0.02 0.01
100 36 97 85
1.68 1.72 1.73 1.72
0 0 0 0
72 2 7
The data pertinent to weight gain and feed conversion show that Rofenaid-medicated birds gained well in comparison to the I.TJ.C. The floor pen data show that Rofenaid, fed to. turkeys at dosages of 0.02 and 0.01% active drug in feed, was highly effective at both dosages tested in reducing mortality and morbidity among the medicated birds. Rofenaid-medicated birds showed low mortality, negligible pathology and yielded, overall, considerably fewer positive cultures from the organs cultured, in contrast to the.I.U.C. The data pertinent to weight gain and feed conversion show that Rofenaid-medicated birds gained better than the I.U.C.
The combined efficacy parameters (battery and floor pen), submitted to statistical analysis, show that both dosages (0.02 and 0.01%) of Rofenaid were equally effective (N.S.) and superior to I.U.C. pertinent to mortality (P < .005), positive cultures— dead and surviving birds combined—(P < .005) and weight gain (P < .05). Other parameters were not statistically significant. 4. The chempprophylactic antibacterial activity of Rofenaid against P. arizona is shown in Table 4. The battery data show that Rofenaid, fed to the turkeys at dosages of 0.02 and 0.01% active drug in feed, was highly effective at both dosages tested in reducing mortality and morbidity among the medicated birds. Rofenaid-medicated
TABLE 4.—Antibacterial activity of Rofenaid against P. arizona in turkeys Cone, in feed, %
Weight gain, %
Feed conversion
% Positive cultures--surviving birds
% Mortality
H
L
S
I
0 5 2 . 8
0 8 20 8
0 0 •1 0
0 7 - 18 26
Battery trials (av. 1X10) •
o-u.u.c. 0-I.U.C. 0.02 0.01
100 70 87 89
1.57 1.70 1.61 1.60
0 3 0 0
0 25 8 5
0 10 2 3
'
Floor pen trials ( av. 2X30) O-U.U.C. 0-I.U.C. 0.02 0.01
100 54 •73 • 57
1.59 1.70 1.51 1.73
0 20 '
7
12
'
•
0 0 0 0
0 0 0 0
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o-u.u.c.
ANTIBACTERIAL ACTIVITY OF ROFENAID
SUMMARY AND CONCLUSIONS
1. Rofenaid chemoprophylactic antibacterial efficacy data in battery and floor pen trials against Salmonella typhimurium, Escherichia coli, Pasteurella multocida and Paracolon arizona infections in turkeys have been presented and discussed. 2. The data show that Rofenaid, at dosages of 0.02 and 0.01% active drug in feed, was highly and equally effective at both dosages tested. The Rofenaid (0.02 and 0.01%)-medicated birds showed statistically significant prevention and/or reduction in mortality, pathology and bacterial
isolations, in comparison with the I.U.C. Rofenaid-medicated birds, in addition, showed no to negligible clinical signs as the result of experimental infections and tolerated the drug well. 3. Since no statistically significant differences in the chemoprophylactic antibacterial activity between the two dosages (0.02 and 0.01%) were noted, Rofenaid at 0.01% active drug in feed is suggested as an aid in the prevention and control of salmonellosis, colibacillosis, fowl cholera and paracolon infection in turkeys. 4. The antibacterial activity of Rofenaid at the recommended coccidiostatis use dosage (0.01%) is unique in that it introduces a new concept in the prevention of turkey diseases through its dual coccidiostatic-antibacterial effect. REFERENCES Marusich, W. L., E. Ogrinz, M. Brand and M. Mitrovic, 1969. Safety and compatibility of sulfadimethoxine potentiated mixture (Ro 5-0013), a new broad spectrum coccidiostat-antibacterial in chickens. Poultry Sci. 48: 217-222. Marusich, W. L., E. F. Ogrinz, B. Hecht and M. Mitroyic, 1971. Safety of sulfadimethoxine potentiated mixture (Rofenaid), a new broad spectrum coccidiostat-antibacterial, in turkeys. Poultry Sci. 50:512-517. Mitrovic, M., G. Fusiek and E. G. Schildknecht, 1969a. Antibacterial activity of sulfadimethoxine potentiated mixture (Ro 5-0O13) in chickens. Poultry Sci. 48: 1151-1155. Mitrovic, M., E. G. Schildknecht and G. Fusiek, 1969b. Anticoccidial activity of sulfadimethoxine potentiated mixture (Ro 5-0013) in chickens. Poultry Sci 48: 210-216. Mitrovic, M., E. G. Schildknecht and G. Fusiek, 1971. Anticoccidial activity of sulfadimethoxine potentiated mixture (Rofenaid) in turkeys. Poultry Sci. 50: 517-525.
MAY 16-18. ANNUAL MEETING, EASTERN BRANCH, CANADIAN SOCIETY OF ANIMAL PRODUCTION, TRURO, NOVA SCOTIA. MAY 30-JUNE 2. 54TH CANADIAN CHEMICAL CONFERENCE AND EXHIBITION, THE CHEMICAL INSTITUTE OF CANADA, HALIFAX.
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birds showed less mortality, negligible pathology and yielded, overall, fewer positive cultures in contrast to the I.U.C. The data pertinent to weight gain and feed conversion show that Rofenaid-medicated birds gained well and converted feed more efficiently than the I.U.C. The floor pen data show that Rofenaid, fed to the turkeys at dosages of 0.02 and 0.01% active drug in feed, reduced mortality and morbidity among the medicated birds at both dosages tested. Overall, the bacterial isolations were higher for the Rofenaid-medicated groups than for I.U.C. Feed conversion and weight gain were good only at the 0.02% level. The combined efficacy parameters (battery and floor pen) submitted to statistical analysis show that both dosages (0.02 and 0.01%) of Rofenaid were equally effective (N.S.) and superior to I.U.C. pertinent to mortality (P < .01 and < .005) and positive cultures—dead and surviving birds combined—(P < .05). Other parameters were not statistically significant.
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