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 ORIGINAL RESEARCH
A global multilocation study to evaluate the effect of ceftiofur
sodium on preweaning mortality and growth performance
Chun Zhou, DVM, PhD; D. Dal Kratzer, PhD; Jing-Xin Zhuang,
DVM, MS; Tomio Ibayashi, MS; Jorge Izeta Mayorga, DVM; Alberto
Morillo, DVM, MS; Maria Sitjar, DVM, MS; Paloma Suarez, DVM, MS,
PhD; H. Neil Becker, DVM, MS
Zhou C, Kratzer DD, Zhuang J, et al. A global multilocation
study to evaluate the effect of ceftiofur sodium on preweaning
mortality and growth performance. Swine Health Prod. 2000;8(3):113-117.
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CZ, DDK, JXZ, TI, JIM, MS, PS, NB: Pharmacia & Upjohn,
7000 Portage Road, Kalamazoo, Michigan 49001-0199, email: czhou2@am.pnu.com;
AM: Monzon, Huesca, Spain
Summary
Objective: To evaluate the effectiveness of ceftiofur
sodium administered to preweaned piglets in reducing mortality
and improving growth performance.
Methods: This study was conducted at six sites in five
countries. Eligible farms had a history of neonatal diseases with
poor growth and/or abnormally high mortality in preweaned pigs.
Pigs received either 3 mg ceftiofur free acid equivalent (CFAE)
per kg bodyweight (n = 2693, "Ceftiofur"), or a placebo
(n = 2734, "Controls"), administered by intramuscular
(IM) injection on days 1 and 7 of age and at weaning (mean 20
days of age). Mortality and average daily gain (ADG) from birth
to weaning and from birth to 7 days postweaning were statistically
evaluated.
Results: Mortality tended (P =.06) to be reduced
in the Ceftiofur group (7.5%) compared to Controls (11.0%). Average
daily gain from birth to weaning was significantly (P=.04)
improved in the Ceftiofur group (0.215 kg, 0.473 lb) compared
to Controls (0.204 kg, 0.449 lb). Average daily gain in Ceftiofur-treated
pigs through the end of the trial (7 days postweaning) was significantly
(P =.02) improved over ADG in control pigs. The percentage
of lightweight piglets (i.e., pigs that were <3.63 kg [<8
lb] at weaning) was reduced by 16.2% in the Ceftiofur group, significantly
lower than Controls (P=.04). The effects of Ceftiofur treatment
were consistent for all six locations with numerical superiority
in at least one of the measured variables.
Implications: Ceftiofur sodium improved growth performance
and tended to decrease mortality in pigs from birth to weaning
and from birth to 7 days postweaning under a global variety of
commercial production conditions.
Keywords:  pig, swine respiratory
disease, ceftiofur sodium, average daily gain, mortality, preweaned
piglets
Received: June 6, 1999
Accepted: March 6, 2000
Microorganisms, transmitted
to piglets from their environment and their dams, pose a constant
challenge to preweaned pigs. Early in life, maternal antibodies
in milk may protect piglets from being colonized by these pathogens;1
however, this protection diminishes over time as maternal antibodies
decline. Pigs can then be overwhelmed by exposure to microbiological
challenges, which is clinically manifest as high mortality and
poor weight gain.
The objective of the present study was to determine, by comparing
production data from six production systems in five countries,
whether preweaning administration of ceftiofur sodium could improve
weight gain and mortality rate from birth through weaning and
into the nursery.
Materials and methods
This study included six sites in five countries (China, Japan,
Mexico, Spain, and the United States) with a total of 5427 neonatal
pigs. To be included in the study, herds had to have a history
of neonatal diseases (respiratory disease, streptococcal infection,
and/or diarrhea) accompanied by poor preweaning growth performance
and/or mortality rates higher than the industry averages in that
country. Before the trial began, a veterinarian and site coordinator
conducted a diagnostic evaluation of 10- and 21-day-old piglets
at each study location. This evaluation included any of several
procedures, such as necropsy of selected pigs, serological profiling,
clinical observations, and/or evaluation of growth performance
and herd mortality based on the historical data from the farms.
Experimental design
The experimental units were litters made up of natural and
cross-fostered pigs, resulting in an average of 10 pigs per litter
from sows or gilts. Eligible gilts and sows were assigned to a
farrowing room, each of which contained at least 24 farrowing
crates. Separate randomization lists were provided for gilts and
sows. Cross-fostering was allowed only before the first injection
was given at 1 day of age.
Although weaning age varied from one location to another based
on the local practice, it was recommended that weaning occur at
14-20 days in an all-in-all-out (AIAO) fashion. All pigs were
identified by treatment group and litter of origin with colored
ear tags at 1 day of age. In the nursery, littermates were kept
together and penned only with those in the same treatment group.
Piglet birthweight, sex, genetic origin, and other potential confounding
variables were assumed to be randomly distributed within farrowing
rooms.
All piglets in a room were allocated to the same treatment,
either:
- a "Control" group that received a placebo (sterile
water injection); or
- a "Ceftiofur" group that received ceftiofur (ceftiofur
free acid equivalent) at the dose of 3 mg per kg bodyweight.
To prepare ceftiofur for injection, a 1-g vial of the medication
was reconstituted with 20 mL of sterile water for injection to
achieve a concentration of 50 mg CFAE per mL (Table
1).
Herd staff administered the respective intramuscular (IM) injection
to piglets on each of days 1 and 7 of age and at weaning (approximately
20 days of age).
In each location, the trial was either run once in four rooms
(two Control, two Ceftiofur), or in two rooms and replicated once.
Piglets were individually weighed at birth, at weaning (days
14-20 of age), and 7 days postweaning. Weight and mortality data
were recorded by herd staff at each location.
Statistical analysis
Trial site block, treatment, and random error were included
in the model, using litter as unit of analysis. Overall mortality
rate and ADG at weaning and 7 days postweaning were
decision variables. Mortality rate (%), ADG from birth to weaning,
and ADG from birth to 7 days postweaning were transformed by Freeman-Tukey
arcsine. Each ADG variable analysis was based on location, treatment
averages, and the number of pigs contributing to the weight gain.
Secondary variables for descriptive purposes were litter weight
at weaning, number of pigs per sow, age at weaning, and weights
at birth, weaning, and 7 days postweaning. An analysis of lightweight
piglets (i.e., piglets weighing <3.63 kg [<8 lb]) at weaning
was also conducted. Piglets with weaning weights < standard
were coded as 1, those >= were coded as 0.
An ANOVA was conducted using the PROC GLM and PROC MIXED procedures
in the SAS system.2 The models included location, treatment,
and error, with location as a random effect and treatment as a
fixed effect. The analyses were weighted by the number of pigs
at each location and treatment average. The least-squares means
for the decision variables reflect these weights. A coefficient
of variation (CV) was calculated for each variable as the standard
deviation divided by the overall mean to measure the relative
amount of biological variation present for each variable.
A two-tailed test was used to analyze treatment effect for
all decision variables. The percentage of lightweight pigs was
calculated for each litter and a Freeman-Tukey transformation
performed by litter to obtain P values. Calculations, using
location and treatment in the model, were performed for mean squares,
treatment means, least significant differences, and P value.
Results
An overall total of 551 newborn litters with 5427 piglets were
included in the study, with a mean of 9.9 pigs per sow (Table
2). The overall mean weaning age was 20 days, ranging from
approximately 16-28 days of age. Within a given location, the
weaning age was relatively consistent. The mean weight of a pig
at birth was 1.55 kg (SD = 0.36) with some variations in different
locations.
Overall mortality tended (P =.06) to be improved in
Ceftiofur-treated pigs (7.5%) compared to controls (11.0%).
[See also Table 3]
Average daily gain (ADG) from birth to weaning was significantly
improved in the Ceftiofur-treated litters compared to Controls
(P =.04) (Figure 1). This
difference persisted through 7 days postweaning (P=.02).
The ADG advantage resulting from Ceftiofur treatment was observed
in all locations. Among all locations, the ADG advantage of Ceftiofur
treatment over Controls was the highest when the weaning age was
21 days, followed by pigs weaned at 18 and 24 days, respectively.
The percentage of lightweight pigs overall was significantly
reduced in the Ceftiofur-treated litters compared to Controls
(P=.04) (Figure 2). Litter
weight at weaning was (P =.12) improved for Ceftiofur-treated
pigs compared to Control pigs (Figure
3).
Discussion
Our observation that mortality was numerically decreased and
ADG significantly increased in the Ceftiofur-treated pigs is consistent
with a number of field studies which indicate that using ceftiofur
in weaned pigs with swine respiratory disease improved disease
control and resulted in higher daily weight gains and lower mortality
and cull rates.4-7 A model study of colibacillosis
also shows ceftiofur is effective in reducing mortality, bacterial
shedding, and diarrhea, and in increasing weight gain.8
In the present global multilocation study, greater reduction
of mortality was achieved in those operations with the highest
relative rates of mortality.
The cost-effectiveness of treatment with ceftiofur depends
on several factors in addition to its biological impact. These
factors include, minimally, the cost of the drug, the cost of
feed, and the market price for hogs. Such variables will vary
widely from country to country. A rigorous multinational economic
analysis of ceftiofur treatment, however, is beyond the scope
of this study. However, in a cursory cost:benefit analysis for
the United States industry--using mean values for drug and feed
costs and market hog prices--we found that ceftiofur treatment
resulted in a positive return on investment in this study herd
(D. Holtcamp, personal communication, 1999).
Decreasing the number of lightweight pigs at weaning is a constant
challenge for the swine industry. A few production techniques
(split weaning, split nursing) have been shown in a research
setting to decrease the number of lightweights at weaning, but
are too expensive or difficult to implement in commercial herds.
In this study, treatment with ceftiofur not only increased
mean weaning weight, but also reduced the number of lightweight
pigs.
Weaning age plays an important role in controlling disease
pathogens for improving herd health.1 For practical
reasons, the actual weaning ages used in herds included in this
study varied from one location to another. Although we did not
statistically evaluate the effect of weaning age on any of the
performance parameters monitored in this study, we did observe
that growth performance and mortality in Ceftiofur-treated pigs
was numerically improved in those pigs that were weaned at older
ages. Theoretically, the earlier pigs are weaned, the more pathogens
can be eliminated.1 However, early weaning may not
reduce mortality in operations where early weaning requirements
for nutrition, housing, and management technology cannot be adequately
met.
Because this study ended at 7 days postweaning, long-term outcomes
could not be directly observed in later production stages. Additional
trials could be conducted to follow the treatment effects all
the way to market. However, based on previous reports, the advantages
provided by this program are likely to continue on into the later
phases of production.7,10
Antibiotic programs are health management tools recognized
to enhance good husbandry practice to prevent, treat, and enhance
production. Adding ceftiofur to a health program can easily be
incorporated into the existing management practices. Such programs,
however, cannot replace sound farm management and veterinary practices.
Producers should be aware that key management strategies--including
AIAO animal flow, strict biosecurity, herd vaccinations, herd
health management, and segregated early weaning, if feasible--should
not be neglected in a herd whether or not an antibiotic program
is in place.
Implications
- A preweaning program using ceftiofur sodium increased ADG
at weaning by 5.4% (P=.04). The effect continued through
7 days postweaning, for a significant total weight gain improvement
of 8.5% in treated pigs (P=.02).
- Using ceftiofur also significantly reduced the percentage
of lightweight piglets at weaning (P=.04).
- The treatment effects were consistent across scattered global
locations.
Acknowledgements
The authors would like to acknowledge the following individuals
for their dedicated roles in the study: Prof. Liren Xu, Dr. Ichrou
Haginori, Drs. Joaquin Becerril and Gerardo Iglesias,Dr. Jose
Herrera, Dr. Jeff Harker, Dr. Rob Jackman, Ken Dame, Andrea Flower,
Dr. John H. Luchsinger, Dr. Jim W. Van Buren, Doug J. Ricke, Dr.
Fabian M. Kausche, and Rose A. Dame.
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induced colibacillosis in neonatal swine. Am J Vet Res.
1990;51(3).
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