https://doi.org/10.52973/rcfcv-e34418
Received: 13/03/2024 Accepted: 24/04/2024 Published: 25/07/2024
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Revista Científica, FCV-LUZ / Vol. XXXIV, rcfcv-e34418
ABSTRACT
In veterinary medicine, it is extremely important to use drugs that will
not put human health at risk. In the treatment of animal diseases, the
preference of drugs that accumulate in muscle tissue (meat) and are
excreted from the body with milk because they create low treatment
costs poses a public health and food safety risk. Veterinarians and
animal breeders should pay attention to the use of drugs that do not
leave residues in animal foods in the treatment of diseases of animals
whose meat is eaten. With this study, it was aimed to reveal the healing
time of Tilmicosin, which passed to milk and Cefquinome, which is
not passed to milk are used in the treatment of footrot, especially in
sheep raised for meat and milk, and what are the costs (medicine,
labor, etc.) of both drugs to animal owners. The study was conducted
on 80 sheep with footrot from sheep raised in Muş, Türkiye in 2020-21.
As a result of eld observations, anamnesis and clinical examinations,
sheep with footrot were divided into two groups in equal numbers.
One group was administered Cefquinome (1 mL·50 kg
-1
im. every 24
hours –h–, 3 applications), while the other group was administered
Tilmicosin (1 mL·30 kg
-1
sc. 48 h later, 2 applications) and the animals
were observed for 10 day (d). In the Cefquinome group, footrot could
be treated at a rate of 90% on the 4
th
d and did not bring additional
costs to the animal owners. It has been concluded that Cefquinome
should be preferred in treatment in terms of animal health, food safety
and public health due to its high treatment success, easy application
in pasture conditions, and the availability of milk during treatment.
Key words: Antibiotic; food safety; footrot; residue; sheep
RESUMEN
En medicina veterinaria, es extremadamente importante utilizar
medicamentos que no pongan en riesgo la salud humana. En el
tratamiento de enfermedades animales, la preferencia por los
medicamentos que se acumulan en el tejido muscular (carne) y
se excretan del cuerpo con la leche porque crean bajos costos de
tratamiento plantea un riesgo para la salud pública y la seguridad
alimentaria. Los veterinarios y criadores de animales deben prestar
atención al uso de medicamentos que no dejen residuos en los
alimentos de origen animal en el tratamiento de enfermedades de
los animales cuya carne se consume. Con este estudio, se pretendió
revelar el tiempo de curación de la Tilmicosina, que pasa a la leche
y el Cefquinome, que no se pasa a la leche que se utilizan en el
tratamiento de la podredumbre de los pies, especialmente en ovejas
criadas para carne y leche, y cuáles son los costos (medicamentos,
mano de obra, etc.) de ambos medicamentos para los dueños de los
animales. El estudio se llevó a cabo en 80 ovejas con podredumbre
de ovejas criadas en Muş, Türkiye, en 2020-21. Como resultado de
las observaciones de campo, la anamnesis y los exámenes clínicos,
las ovejas con podredumbre se dividieron en dos grupos en igual
número. A un grupo se le administró Cefquinoma (1 mL·50 kg
-1
i.m.
cada 24 horas –h–, 3 aplicaciones), mientras que al otro grupo se le
administró Tilmicosina (1 mL·30 kg
-1
s.c. 48 h después, 2 aplicaciones)
y los animales fueron observados durante 10 días (d). En el grupo
Cefquinome, la podredumbre del pie se pudo tratar a una tasa del
90 % en el 4º d y no supuso costes adicionales para los propietarios
de los animales. Se ha llegado a la conclusión de que el cefquinomo
debe ser preferido en el tratamiento en términos de sanidad animal,
inocuidad de los alimentos y salud pública debido a su alto éxito
en el tratamiento, su fácil aplicación en condiciones de pasto y la
disponibilidad de leche durante el tratamiento.
Palabras clave: Antibiótico; seguridad alimentaria; pododermatitis;
residuo; oveja
A eld study on rational choice of medication: The use of Tilmicosin and
Cefquinome in ovine footrot treatment
Un estudio de campo sobre la elección racional de la medicación: el uso de
tilmicosina y cefquinoma en el tratamiento de la pododermatitis ovina
Ferit Yıldız
1
* , Musa Gençcelep
2
1
Provincial Directorate of Agriculture and Forestry. Muş, Türkiye.
2
Van Yüzüncü Yıl University, Faculty of Veterinary, Department of Surgery.Van, Türkiye.
*Corresponding author: ferit49@gmail.com, ferit.yildiz@tarimorman.gov.tr
FIGURE 1. Erosive-ulcerative lesion (*) in the interdigital region and deformations
(arrows) are observed in the surrounding areas
The use of tilmicosin and cefquinome in ovine footrot treatment / Yıldız and Gençcelep____________________________________________
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INTRODUCTION
Footrot, is the most common and contagious foot disease in
small ruminants with main factor Dichelobacter nodosus and causes
signicant yield losses in sheep (Ovis aries) breeding [1, 2, 3]. The
severity of the disease varies depending on factors such as sensitivity
of the animal, environmental conditions and farm practices. Footrot,
causes severe pain and lameness in the affected animals [3]. It is
usually characterized by hoof deformation, foul interdigital skin
smelling; necrotic-ulcerative dermatitis and inammatory reactions
spread towards the deep layers of the nail (FIG. 1) [4].
information about its treatment [4]. In this investigation in the Muş
plain it was found that some of the breeders applied substances like
tar to cover only the wound on the feet for the treatment of footrot
in eld and herd scans. It has also been observed that most of the
breeders used long-acting (LA) parenteral antibiotics without knowing
that they should not have consumed milk and meat for a certain
period of time after using antibiotics; they were unaware of the Drug
Residue Clearance Time (DRCT); and those who knew the subject did
not care much has been observed.
The unconscious and abusive use of antibacterial drugs creates
serious economic and public health problems. For this reason, it
has been reported that necessary measures should be taken to
prevent these negative effects [14, 15]. The uncontrolled use of
antibacterial drugs in this way does not only cause damage to human
and animal health and the environment, especially to foods obtained
from animals but also brings an additional burden to the country’s
economy [16]. Depending on the consumption of foods containing
antibiotic residues, the danger of superinfection in humans, changes
in the bacterial ora of the small and large intestine, teratogenic,
carcinogenic and mutagenic effects may be observed [17, 18, 19, 20].
It has been understood that we are facing a serious problem for
food safety, public health and animal health due to the fact that the
meat and milk produced by the breeders enter the food chain without
waiting for DRCT.
In this study; In the treatment of footrot disease, which occurs in
sheep raised especially for meat and milk in Muş province, Türkiye,
it is aimed to ensure rational drug use and to protect animal health,
as well as food safety and public health, by comparing the success
rates of two antibiotics whose residues and excretion from the body
are done through different systems.
MATERIALS AND METHODS
This study was carried out on 80 mature Morkaraman-Akkaraman
sheep in small ruminant farms engaged in pasture-based rearing in
Muş. The sheep with footrot problems included in the study were
determined based on anamnesis and clinical examinations during
the pasture period.
Two different antibiotics with different mechanisms of action were
used for the treatment of footrot. These are:
A.
Cefquinome (Cefalosporin group antibiotic): According to the
drug prospectus; it does not pass into milk and leaves a short-
term (5 days –d–) residue in meat. 50 mg·mL
-1
cefquinome.
B.
Tilmicosin (Macrolide group antibiotic): According to the drug
prospectus; it leaves residue in milk for 15 d (30 milking) and
42 d in meat. 300 mg·mL
-1
Tilmicosin.
A certicate was obtained from the Ministry of Agriculture and
Foresty that there was no need for an ethics committee approval
certicate for the animals used in this study.
Foot rot is typically classified by most countries based on the
prevalence and severity of clinical foot lesions using a different scoring
system or a modication of the Swiss scoring system. In this study,
since it would be very dicult to score and control the lesions on all
feet of 80 sick animals in different ocks every day, sheep with foot
rot and lesions on their feet based on clinical examination, which is a
more practical way in eld conditions, were classied according to the
In addition to the decrease in meat, milk and wool yield, it causes
signicant economic losses as it reduces fertility, lamb growth rates and
the opportunities of animal sales in infected farms. Therefore, footrot
is a serious animal welfare problem in sheep-raising countries [5, 6, 7].
Various antibiotics such as Penicillin, Streptomycin, Lincomycin,
Spectinomycin, Oxytetracycline, Tylosin and Erythromycin were used
alone or in combinations by parenteral route for footrot treatment.
In addition, antiseptics such as Zinc Sulphate, Copper Sulphate
and Formalin were applied in the bath style [8, 9, 10, 11]. It has been
reported that Penicillin-Streptomycin, Amoxicillin, Tilmicosin and
long-acting Oxytetracyclines should be used in the treatment of
animals with severe lesions [3, 11, 12]. Many researchers suggested
that practices such as regular nail cutting, foot baths, antimicrobials,
vaccination, quarantine and decommissioning should be applied
together for the treatment, control and eradication of footrot [3, 12,
13]. As stated in a study conducted in Muş and its region, due to the
humid environments in the province of Muş, which is located in the
east of Türkiye and receives a signicant amount of rainfall in three
seasons of the year except for the summer months, piyeten, which is
the most important foot disease of small ruminants, was detected at
a rate of 9.14%, but it was seen that the breeders did not have enough
TABLE II
Comparison of lameness degree by days and groups.
S–Group (n: 40) T–Group (n: 40)
P**
Mean±SEM Mean±SEM
Before application 3.85 ± 0.06
aA
3.80 ± 0.06
aA
0.562
Day 1 3.03 ± 0.09
bA
3.00 ± 0.09
bA
0.850
Day 2 1.65 ± 0.12
cB
2.28 ± 0.12
cA
0.001
Day 3 1.30 ± 0.10
cA
1.50 ± 0.11
dA
0.182
Day 4 1.18 ± 0.09
cA
1.23 ± 0.09
dA
0.704
Day 5 1.18 ± 0.09
cA
1.20 ± 0.09
dA
0.847
Day 6 1.13 ± 0.09
cA
1.18 ± 0.09
dA
0.689
Day 7 1.15 ± 0.10
cA
1.18 ± 0.09
dA
0.855
Day 8 1.10 ± 0.07
cA
1.18 ± 0.09
dA
0.503
Day 9 1.03 ± 0.03
cA
1.15 ± 0.08
dA
0.159
Day 10 1.00 ± 0.00
cA
1.15 ± 0.08
dA
0.079
P*
0.001 0.001
*: Signicance levels according to ANOVA Test results in repeated measurements.
a,b,c,d
: Dierent lowercase letters in the same columns indicate a statistical dierence
between days according to Bonferroni Post Hoc multiple comparison test.
**: Signicance levels of the dierence between groups according to Independent
T-test results.
A,B
: Dierent uppercase letters in the same rows indicate a statistical
dierence between groups. SEM: Standard Error of Mean
TABLE I
Table of percentages (%) of recovery of sheep in
groups T and S during 10 days of follow-up period
Days T–Group (n=40) S–Group (n=40)
Before application 0 0
1 0 0
2 12.5 50.0
3 60.0 77.5
4 85.0 90.0
5 87.5 90.0
6 90.0 95.0
7 90.0 95.0
8 90.0 95.0
9 92.5 97.5
10 92.5 100
_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34418
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lameness classication of Samsar et al. [21]. Accordingly; 1 -No Lameness,
2 –Mild Lameness: Lameness is imperceptible, 3 –Moderate Lameness:
There is no noticeable abnormality when standing, but a more or less
obvious dysfunction is seen in walking and trotting, 4 –Severe Lameness:
The animal cannot step on the sick foot at all or this foot crawls on the
ground. The movement is mostly done on three legs and by hopping.
The sheep with footrot in the farms/herd were divided into two groups
with equal numbers; both drugs were applied under eld conditions or
in the sheep’s own farm; and the care and feeding differences between
the groups were eliminated. Sheep with 3-Moderate and 4-Severe
lameness degrees were included in the created treatment groups. The
head and tail parts of the sheep in the treatment groups were painted
in different colors so that they can be easily found in the herd and the
following antibiotics were applied at the specied dose and duration,
and the treatment process of the disease was followed for 10 d. The
recovery data obtained were recorded and evaluated statistically.
1. S-Group (Cefquinome Group – 40 animals): The drug was used
intramuscularly at a dose of 1 mg·kg
-1
(1 mL·50 kg
-1
as a practical
dose, repeated every 24 h). Due to its toxicity, a maximum of 5
applications were made and the animals were observed for 10 d.
2.
T-Group (Tilmicosin Group – 40 animals): 10 mg·kg
-1
of the drug
was administered subcutaneously (1 mL·30 kg
-1
as practical dose,
to be repeated 48h later). To avoid toxicity, a maximum of two
applications were made and the animals were observed for 10 d.
Statistical analysis
In this study, the Power (Test Power) was determined by taking at
least 0.80 and Type-1 Error 0.05 in calculating the sample width (size).
Descriptive statistics for the variables in the study were expressed as
Mean, Standard Error, Number (n) and Percent (%). Shapiro-Wilk (n<50)
and Skewness-Kurtosis tests were used to determine whether the
continuous measurement averages were normally distributed, and
because the variables were normally distributed, Parametric tests
were applied. Independent T-test was calculated to compare the
mean of measurements according to the groups. ANOVA was used in
repeated measurements to compare the measurements according to
the measurement times (days) separately in the groups. “Bonferroni
Post-Hoc (Multiple) Comparison Test” was used to determine the
days that made up the difference following the Repeated ANOVA. The
statistical signicance level (α) was taken as 5% in the calculations, and
the SPSS (IBM SPSS for Windows, ver. 24) statistical package program
was used for the calculations. The follow-up status of the patients in
the T and S groups with regard to lameness is also shown graphically.
RESULTS AND DISCUSSIONS
Clinical results
The conditions of the diseased animals before the treatment and
during 10 d of follow-up period were shown in the TABLE I.
At the end of the rst 24h (d 1), there was no sign of improvement in both
groups, while at the end of the second day there was an improvement of
12.50% in the T–Group and 50% in the S–Group. After the 3
rd
d, it can be
seen that the recovery values of both groups are close to each other. At
the end of the 4
th
d, an improvement of 85-90% was observed in both
groups, and at the end of the 6
th
d, this rate increased to 90-95%. At the
end of the 10
th
d, full recovery was observed in the S–Group, while there
were still unhealed animals in the T–Group (TABLE I).
Statistical data
As indicated in TABLE II, there was a statistically significant
difference (P<0.001) only on the 2
nd
d between the two groups, and no
statistical difference was found on the other d (P>0.05). This situation
is shown graphically in FIG. 2, and it was observed that the degree of
lameness between the two groups was close to each other almost
every day except the 2
nd
d, and the degree of the disease decreased
signicantly from severe to mild gradually.
FIGURE 2. Control chart of lameness degree of sheep in T and S Groups (10 d)
The use of tilmicosin and cefquinome in ovine footrot treatment / Yıldız and Gençcelep____________________________________________
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Footrot disease is contagious disease and can infect healthy
animals when left untreated or detected late. In regions where
pasture husbandry is common the disease can be transmitted to
the herd at any time as the pastures are contaminated, and it means
an undeniable loss of income in sheep breeding.
The incidence of the disease varies according to the regions
depending on the predisposing conditions. Sağlıyan [22] reported that
the incidence of footrot was 18.95% in his study in the Elazığ region,
and in another study conducted in the Eastern Anatolian Region the
incidence of the disease was found to be 8.3% in Malatya, 15.4% in
Elazığ and 9.1% in Bingöl [17]. Yıldız and Gençcelep [4] reported that
the incidence of footrot was 9.14% in Muş region.
Animal welfare is a major concern in today’s society. In sheep
breeding one of the main animal welfare problems is footrot [23].
Forbes et al. [24] reported successful results in the treatment of the
entire herd with antimicrobials in the elimination of the disease, and
Strobel et al. [25]
reported recovery rates of more than 99% after one or
two systemic antimicrobial applications. Whittington [26] stated that
antibiotics should be used for a long time for the treatment of footrot
and must remain at the therapeutic level for at least 18 h to be effective.
In this study, the effectiveness of antibiotics in the treatment of
footrot was demonstrated, and a treatment success rate of over 90%
was observed after 2-3 applications. In this respect, it is consistent with
the ndings of Strobel et al. [25]. In the study, a signicant treatment
difference (12.5 – 50%) was detected between the T and S groups,
especially on the 2
nd
d, and this is thought to be due to the application
of the second dose of Tilmicosin after 48 h and the repetition of
cefquinome after 24 h. As a matter of fact, Whittington [26] supports
this situation with the determination that antibiotics must remain at
therapeutic doses for at least 18 h in order to be effective.
Casey and Martin [27] reported that with the intramuscular
aplication of the combination of Penicillin + Streptomycin and the
application of 10% CuSO
4
solution as bath, recovery can be achieved
within three months. Gönül et al. [28] reported that the combination
of Penicillin + Streptomycin was 92% successful with parenteral
application of 5% Copper Sulfate (CuSO
4
) solution as bath. Bruere
and West [29], also reported that they were 90% successful in their
application by keeping it in a 10% ZnSO
4
bath for 5 minutes with the
combination of Penicillin + Streptomycin. In their study conducted
in Muş and its surrounding, Yıldız and Gençcelep [4]
reported that
they achieved 90% recovery rate by applying Ceftiofur + Flunixin
Meglumine to the sheep with footrot, and they saw this medication
choice as an advantageous treatment option in terms of eliminating
the need for milk disposal. Karslı and Elma [30] also stated that the
application of Zinc Sulfate (ZnSO
4
) footbath, which they use alone as
an antiseptic, is insucient in the treatment, but the application of
Zinc Sulfate (ZnSO
4
) footbath together with parenteral Spiramycin and
vitamin E application is more effective in the treatment. Greber et al.
[13]
and Kraft et al. [31]
stated in their studies that a single macrolide
combined with footbath in an infected herd can treat the entire herd
and eliminate the footrot disease and its causative agent (D. nodosus).
As mentioned above, many researchers have tried to treat footrot with
different treatment options, but treatment options have always been
supported by an antibiotic agent and it has been observed that foot
baths or vitamin supplements are not sucient. As a matter of fact,
Yarsan [32]
mentioned that residues in animal foods are an increasing
global problem. Groenevelt and Grogono-Thomas [33]
stated that
a single antimicrobial agent signicantly improves animal welfare
in treatment, and it has been reported by many researchers that
systemic antibiotics do not show any difference in the recovery of
the disease [10, 11]. In this study, by applying two different antibiotics
with different mechanisms of action to two different groups, the
ecacy of antibiotic application alone was proven, and by making
rational drug selection, the risk of residue, which is a very important
problem, was eliminated without reducing the chance of treatment.
Scientists state that more than 131.000 tons of antibiotics were
used in animals worldwide in 2013, and the projected consumption will
exceed 200.000 tons by 2030, an increase of 53% [34]. Van Boeckel
et al. [35], on the other hand, reported that the use of antibiotics in
animal husbandry in the world far exceeds the amount of human use,
and although there are no regularly recorded data on antibiotic use in
some regions. Turkey is the country with the highest rate of antibiotic
use in the world (47.86 daily dose per 1000 people) in human medicine
[36]. Gülmez [37] reported that antibiotic resistance in Turkey has
increased to 35%, but this rate has been reduced to 5% in some
European countries. In veterinary medicine, there is no reliable data
on the amount of use of veterinary drugs. It is reported by Yarsan [38]
that this situation can be corrected by applying data matrix and creating
traceability plans, especially in drugs. With this study, we tried to create
an approach and awareness for veterinarians and animal breeders to
make rational drug choices while treating their sick animals, taking into
account the residue problem, and to protect human health.
Before implementing a footrot elimination program based on
antimicrobials, it should be investigated whether strict biosecurity
measures can be taken to avoid relapses, repetitive antimicrobial
treatments and economic losses [31]. If antibiotics that pass into
milk are used during the treatment process of footrot disease, it
should not be used as human food for 10-30 milkings depending on the
drug. Odabaşıoğlu [39] stated that the lactation period of Akkaraman
sheep is 146.9 d; the milk yield is 73.6 kg, while the lactation period of
the Morkaraman sheep is 167.2 d, and the total milk yield is 92.0 kg.
Therefore, 500-550 mL (per sheep) of milk is taken daily from them
during the lactation period, and when it is considered on a ock
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basis, milk is an extremely valuable source of income for breeders.
According to the information we received from the breeders during
our study, it was determined that they did not look forward to the
destruction of milk as it caused a serious loss of income in previous
treatment attempts.
In the light of this information, in this study carried out in Muş and
its region, where Morkaraman and Akkaraman sheep breeds are
common, a treatment comparison was made between the preparation
with Cefquinome active ingredient that does not pass into milk and
the preparation with Tilmicosin which leaves residue in milk and meat
for a long time so that the breeders use the milk with peace of mind
and do not have to waste the milk.
It has been determined that both antibiotics are strong in terms of
therapeutic ecacy and there is no signicant difference between
them. This is in line with the report by Venning et al. [10] and Winter
[11] that systemic antibiotics do not differ in the recovery of the
disease. In addition, in terms of treatment success it was observed
that both drugs cured the disease by 90-95% after the 6
th
d, and the
success rates increased further in the following days. This situation is
also consistent with the above-mentioned literature data on systemic
antibiotics [4, 24, 25, 26, 27, 28, 29, 30].
In the market conditions of 2021, it is seen that the same dose of
Cefquinome preparations are sold at the same price as Tilmicosin
preparations or 20-30% more. As stated in the materials and methods
section for drug use and dosage, Tilmicosin will be practically calculated
according to 1ml/30kg body weight and a maximum of two applications
can be made due to drug toxicity, and for Cefquinome, 3-5 applications
can be made corresponding to 1 mL·50 kg
-1
body weight. In our study,
three applications were sucient because over 90% treatment success
was achieved after the third application of Cefquinome. The average
live weight of the sheep included in the study groups was 50-55 kg, a
total of 124 mL of Cefquinome was applied to the S-Group, and a total
of 136 mL of Tilmicosin was applied to the T-Group. Therefore, since
both drugs are very close to each other in terms of consumption and
cost, there is no need to make an evaluation on this issue.
CONCLUSION
In conclusion, when planning treatment in animals raised for food
purposes, rational drug selection should be made, taking into account
the risk of drug residue. On this occasion, when the drug containing
the active ingredient Cefquinome is used in the treatment of footrot
disease with antibiotics, the success rate exceeds 90% after the
4
th
d, it is capable of treating the disease in a short time with three
applications, it does not require additional costs, it can be easily
obtained by growers and it can be used easily in eld conditions. It
has been evaluated that it can be preferred by breeders as it does
not pass into milk and does not pose a risk of residue and milk is not
wasted. Thus, it was concluded that it should be recommended for
both animal health and welfare, food safety and public health.
Financial support
This study was supported with the project code TSA-2020-8176 by
the Presidency of Van YYU Scientic Research Project.
Conict of interest
The authors declare that there are no conicts of interest.
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