ANTIMICROBIAL RESISTANCE AMONG E COLI ISOLATES FROM CATTLE RECEIVING IN- FEED CHLORTETRACYCLINE AND INJECTABLE OXYTETRACYCLINE
A. O’Connor1, C. Poppe2, S.W. Martin1 and S.A. McEwen1
1Department of Population Medicine, University of Guelph and
2Laboratory for Foodborne Zoonoses, Health Canada
us to estimate effects on resistance of in-feedmedication alone, and in combination with injectable
In this feedlot bull study, the proportions of E. coli
isolates resistant to ampicillin, kanamycin, neomycin,oxytetracycline, spectinomycin, streptomycin, and
Materials and Methods
sulfamethoxazole increased after in-feed treatment
A nested case-control study was conducted in fall
with chlortetracycline. In spite of the fact that all
1998 with the co-operation of Beef Improvement
study animals received the in-feed treatment,
Ontario, at the University of Guelph Arkell bull test
treatment of individual cattle with oxytetracycline
station. Case animals required treatment for either
was also associated with increased prevalence of
undifferentiated bovine respiratory disease or
resistance to oxytetracycline, spectinomycin and
infectious interdigital dermititis with injectable long-
sulfamethoxazole. These findings demonstrate that
acting oxytetracycline (200mg/ml) used according to
treatment of feedlot animals for clinical disease does
the manufacturer’s instructions. At the time of
select for antimicrobial resistance among enteric
treatment a freshly voided faecal sample, referred to
bacteria. Producers and veterinarians should be aware
as the selection sample, was collected. Animals were
of this and use antimicrobials prudently.
selected as cases between the 30th October and the23rd December 1998. For each case animal, a freshly-
Introduction
voided faecal sample was also collected from twountreated animals to act as controls. For convenience,
Until recently, the principal food safety and quality
control animals were usually selected from animals in
problem arising from antimicrobial use in food
animals was the presence of residues in edible tissues. World-wide, concerns about antimicrobial resistancein humans are rapidly changing this situation. Much
On the 26th of December 1998, due to the diagnosis of
greater scrutiny is now placed on antimicrobial use
several animals with chronic respiratory disease, in-
and development of resistance in commensal and
feed antibiotics were prescribed for all animals in the
pathogenic organisms that may be transmitted from
facility for a period of three weeks. Aureomycin
food animals to humans. This is a controversial and
(chlortetracycline) was added in the feed at the rate of
complex issue and the public health effects are not
8 mg/lb body weight per day for approximately 8 days
well understood. Even if these effects are minor
and then at 3 mg/lb body weight per day for
however, veterinary and producer groups should
approximately 8 days. On the 9th of February 1999,
encourage prudent antimicrobial use practices that
faecal samples (referred to as the final sample) were
achieve intended animal health goals while
collected from all animals in the facility. After
minimizing resistance problems. In order to
collection of the samples, they were transported to the
accomplish this, we need to better understand how
laboratory for culture and sensitivity testing.
different routes and timing of antimicrobialadministration affect resistance.
Five faecal E. coli were isolated from each sampleusing standard methods and representative isolates
We had the opportunity to investigate resistance
tested for resistance using the “SensitreR” system.
prevalence among fecal E coli before and after
Each E coli isolate was tested for resistance as
treatment of cattle with injectable oxytetracycline.
follows: ampicillin 32 mg/ml, amikacin 16 mcg/ml,
During the course of the study, the entire group of
apramycin 16 mcg /ml, ceftifur 8 mcg/ml, ceftriaxone
cattle was treated for respiratory disease with
32 mcg/ml, ciprofloxacin 0.125 mcg/ml, gentamycin
chlortetracycline in the feed. Thus, this study enabled
16 mcg/ml, kanamycin 64 mcg/ml, florfenicol
100mcg/ml, nalidixic acid 32 mcg/ml, nitrofurantoin
impact on resistance than is observed in some studies.
64 mcg/ml, polymixin B 16 mcg/ml, streptomycin 64
In this investigation, treatment of the entire group
with in-feed chlortetracycline appeared to increasethe proportion of resistant strains to to ampicillin,
Proportions of resistant isolates for cases and controls
n e o m y c i n , o x y t e t r a c y c l i n e,
at time of selection and final sampling were compared
spectinomycin, streptomycin, and sulfamethoxazole.
using non-parametric tests and regression analyses,
While it was not possible to completely separate
and the effects of different types of treatment were
individual from group-level treatment effects,
injection of some animals with oxytetracyclineappeared to further increase resistance to some of
Results and Discussion
these drugs. Clearly, industry-sponsored programsthat are intended to encourage the prudent use ofantimicrobials should provide for both types of
Nine hundred and five (905) E coli isolates were
treatment at the individual and group level.
used in the final analysis. Prior to treatment, nodifference existed in the number of animals identified
Conclusions
with no resistant strains for all antimicrobials tested. However at the final sampling, cattle that had
In this feedlot bull study, the proportions of E. coli
received injectable oxytetracycline (cases) were more
isolates resistant to ampicillin, kanamycin, neomycin,
likely to have at least one oxytetracycline resistant
oxytetracycline, spectinomycin, streptomycin, and
strain than those animals not treated (controls)
sulfamethoxazole increased after in-feed treatment
(Fig.1). More cases had sulfamethoxazole resistant
with chlortetracycline. In spite of the fact that all
strains and there was some indication of increased
study animals received the in-feed treatment,
resistance to spectinomycin. For the other
treatment of individual cattle with oxytetracycline
antimicrobials tested, the odds ratio included unity
was also associated with increased prevalence of
(i.e. no difference). In-feed medication increased the
resistance to oxytetracycline, spectinomycin and
proportion of strains resistant to ampicillin,
sulfamethoxazole. These findings demonstrate that
k a n a m y c i n , n e o m y c i n, o x y t e t r a c y c li n e ,
treatment of feedlot animals for clinical disease does
spectinomycin, streptomycin, and sulfamethoxazole,
select for antimicrobial resistance among enteric
but not ceftiofur, gentamycin, florfenicol, nalidixic
acid, nitrofurantoin, and polymixin B (all strains weresensitive to amikaycin, apramycin, ceftriaxone and
Significance to the Industry
Producers and veterinarians should use antimicrobials
Antimicrobials exert a potent selective pressure on
prudently and in ways that maximize therapeutic
bacteria and it is no surprise that resistance emerges
benefit and minimize resistance. This will help to
in populations of exposed animals – that this
maintain the efficacy of these drugs for treatment of
sometimes happens has been known for decades. The
cattle diseases and reduce any risks to public health.
speed and extent with which resistance occurs in
In the past, the principal food quality and safety
individuals and groups of cattle is less well
concern with antimicrobial use has been residues.
understood, however. Conventional wisdom has it
Resistance has the potential to be a much more
that in-feed medications tend to have a greater impact
important food safety issue for the industry.
on resistance than individual-animal treatments. Thisis, of course, a generalization as there are many other
Acknowledgements
factors to consider, including the drug administered,dose, age of animal, etc. In-feed medications tend to
Financial support for this study was provided by the
be administered to larger numbers of animals for
Ontario Cattlemen’s Association, the Ontario
longer periods of time, and at lower doses than
Ministry of Agriculture, Food and Rural Affairs and
individual animal treatments. These factors along
with the pharmacological properties of the drugsinvolved are probably responsible for the greater
Figure 1 : Frequency distribution of the proportion (r/n) of faecal E coli isolates resistant to oxytetracycline at 64 mcg/ml in case and control animals after treatment with injectable oxytetracycline at the Arkell bull testing station, Fall 1998.
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Figure 1 : Frequency distribution of the proportion (r/n) of faecal E coli isolates resistant to oxytetracycline