Vet Clin Equine 20 (2004) 587–600

Multidrug-resistant Salmonella and

nosocomial infections
David A. Dargatz, DVM, PhDa,*,
Josie L. Traub-Dargatz, DVM, MSb
a
Animal and Plant Health Inspection Service, Veterinary Services, Centers for Epidemiology
and Animal Health, United States Department of Agriculture, 2150 Centre Avenue,
Building MS 2E7, Fort Collins, CO 80521, USA
b
Animal Population Health Institute, College of Veterinary Medicine and Biomedical
Sciences, Colorado State University, Fort Collins, CO 80523–1678, USA

The overall burden of nosocomial infection, approaches to control, and

concepts in monitoring for occurrence have been dealt with elsewhere.
Although the costs of multidrug-resistant (MDR) nosocomial infection are
not readily available for equine hospitals, the costs in human hospitals are
high. The National Foundation for Infectious Disease estimated that the
costs of nosocomial infections with antimicrobial-resistant organisms were
as high as $4 billion annually [1]. Even if equine hospitals experience less
of a problem than is seen in human hospitals, the costs could be
substantial. In addition, early intervention while nosocomial infections
with antimicrobial-resistant bacteria are less common may prevent the
development of problems on the scale seen in human hospitals. One of the
disease agents most frequently associated with nosocomial infection in
equine patients in veterinary teaching hospitals has been Salmonella spp
(see the article by Traub-Dargatz et al elsewhere in this issue for further
exploration of this topic). Salmonella infections in equine patients result in
many challenges, including treatment of affected patients as well as
dilemmas of how to control an outbreak and how to communicate with
owners and referring veterinarians of infected horses. When Salmonella
and other pathogenic organisms acquire genes coding for resistance
mechanisms to antimicrobial drugs, treatment decisions can become even
more difficult. This article focuses on the mechanisms of antimicrobial

* Corresponding author.
E-mail address: david.a.dargatz@aphis.usda.gov (D.A. Dargatz).

0749-0739/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.cveq.2004.07.008
588 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600

resistance, acquisition of multiple resistance determinants, mechanisms of

persistence in populations of bacteria, and common patterns among MDR
salmonellae.

Overview of antimicrobial resistance

A review of antimicrobial resistance and the occurrence of antimicrobial
resistance among equine pathogens has been published in an article in
a previous issue of Veterinary Clinics of North America Equine Practice [2].
Antimicrobial resistance can be intrinsic (constitutive) for certain bacteria or
can be acquired [3]. Bacteria lacking the cellular structures or functional
mechanisms that are the target of an antimicrobial drug are intrinsically
(inherently) resistant to that antimicrobial drug. For example, members of
the Enterobacteriaceae would generally not be expected to be susceptible to
vancomycin because of the characteristics of their cell wall structure
consistent with them being gram-negative bacteria. Bacteria can acquire the
means to resist the effects of antimicrobials through mutation or by
receiving genes from other bacteria. The spontaneous mutation rate for
most bacteria is approximately one mutation per 106 bases with each cell
division [4]. (As a point of reference, the genome of Escherichia coli K-12 is
approximately 4.6  106 base pairs.) Although this rate is relatively low, the
number of bacteria is high and the generation interval is short (eg, 30
minutes), especially under favorable growth conditions. The net effect is that
many spontaneous mutations arise in a replicating population of bacteria.
Most of these mutations adversely affect the survivability of the bacteria and
are not propagated, however. Further, many of these mutations occur at
points in the genome that do not affect the impact of antimicrobials on the
bacteria.
In contrast to the spontaneous mutations occurring in bacteria, the
ability to share resistance genes among bacteria of different genera and
species is a powerful way for bacteria to acquire resistance determinants
quickly. Bacteria can acquire genes that confer resistance by the uptake of
naked DNA from the environment (transformation), acquisition of new
DNA by phage transfer (transduction), or transfer among live cells
(conjugation) [3]. The most common of these mechanisms is gene transfer
via conjugation. Extrachromosomal DNA (plasmids or R-factors) can be
moved from one bacterial cell to another across a physical connection
between the two cells called a sex pilus. Unlike transformation, which relies
on some homology between the new DNA sequence and the recipient cell
DNA for incorporation, and transduction, which is limited by the specificity
of phages for homologous bacterial cells, conjugation requires little
similarity in the donor and recipient cells. For this reason, DNA that
includes resistance genes can be moved among cells of different species and,
indeed, among different genera by conjugation.
 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600 589

Multidrug resistance
The development of MDR forms of bacteria was not initially predicted
after the discovery of antimicrobials. The likelihood of a bacterial cell
developing multiple mutations that do not adversely affect survivability and
confer some resistance to antimicrobial agents is extremely small. MDR
forms do occur, however, and are not rare. The number of bacteria resistant
to two or more antimicrobials is growing. With the discovery of additional
mechanisms of resistance acquisition, the basis of multidrug resistance is
becoming better understood.
The discovery of transposons has improved our understanding of how
resistance genes can be grouped together in the bacterial genome. Trans-
posons, also known as ‘‘jumping genes,’’ are structures that can reside on
plasmids or the chromosome [3,5]. These structures allow genes within the
structure to move from the chromosome to a plasmid and back again.
Movement of genes into a plasmid has implications for their availability for
transfer to other bacterial cells via conjugation.
Another recently discovered structure is the integron. Integrons have been
described as ‘‘sticky flypaper’’ for resistance genes [6]. Because of the structure
of the integron, groups of genes tend to accumulate within the structure.
Frequently, the genes that accumulate in integrons are those that enable the
bacterium to escape the effects of antimicrobial drugs or disinfectants [7].
Antimicrobial resistance genes can persist within a population of bacteria
because the genes have conferred an advantage to the cells in the face of
exposure to antimicrobials. Resistance genes can also persist in a population
of bacteria in the absence of exposure to the antimicrobial, however.
Bacteria have evolved mechanisms to downregulate the expression of the
resistance genes, lessening the metabolic cost of maintaining them in the
genome. These genes can be retained and activated in the presence of
antimicrobial agents, leading to expression and protection of the bacteria
from the effects of the antimicrobial [3,8].
It is important to clarify that antimicrobials are not mutagens. Bacteria
that have the ability to avoid killing by these drugs have a survival
advantage because of environmental selection pressure, however. Some
antimicrobials have been shown to stimulate conjugation among bacteria,
which may lead to the transfer of resistance genes, ultimately resulting in
bacteria becoming more resistant [9]. More commonly, however, the
presence of the antimicrobial simply selects for previously existing resistant
forms. This selection pressure then results in a growing proportion of the
bacterial population with the resistance genes, because these are the
organisms that survive and continue to replicate. Selection is not necessarily
specific for a single antimicrobial. Because resistance genes can become
closely associated in integrons, they tend to persist together. In this way,
selection based on use of one of the antimicrobials represented by resistance
genes in the integron can select for resistance to all the antimicrobials
590 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600

represented in the integron. Antimicrobials can also apply pressure on

bacterial populations to develop ways to avoid being killed by these drugs.
In addition, there are certain nonspecific resistance mechanisms that can
be selected for by a variety of antimicrobial agents. One such nonspecific
mechanism is related to a multiple antimicrobial resistance (MAR) locus in
the genome of the bacteria. The MAR locus controls the expression of an
efflux pump, which precludes the accumulation of sufficient antimicrobial in
the bacteria’s cytoplasm by actively pumping the antimicrobials back out
across the cell wall after they have diffused in, thus minimizing the adverse
effect on the bacterial cell [10]. In some situations, these efflux pumps
function to eliminate a variety of antimicrobial drug classes from the cell.
The expression of the MAR locus, when present, is normally repressed until
there is exposure to various drugs or agents that turn the repressor off and
make it functional. In this way, the metabolic cost of this resistance
mechanism is minimized until it is needed. Exposure of the bacterial cell to
antimicrobial classes on the MAR locus can activate the pump, conferring
a selective advantage to that segment of the population of bacterial cells and
allowing them to proliferate. In addition, other non-antimicrobial drugs,
such as acetaminophen and sodium salicylate, activate the MAR locus of
some bacteria [10,11]. This raises the concern that treatment with
nonsteroidal anti-inflammatory drugs (NSAIDs) may potentially induce
the MAR locus to become functional or active.
To complicate the issue of antimicrobial resistance in the hospital setting
further, one must also consider the possibility that commensal organisms
can serve as a reservoir for resistance genes. In this scenario, resistance genes
could be maintained in bacteria present in the environment or in commensal
flora of the animals present in the hospital population, such as non-
pathogenic enteric bacteria like non–type-specific E coli. The maintenance of
these resistance genes within an ecosystem, such as among hospitalized
equine patients or the hospital environment, could follow the same
conditions as described previously, except that they could be harder to
identify and track because they are present in what are typically considered
nonpathogenic bacteria. These resistance genes could then be available for
transfer to pathogens by any of the three mechanisms discussed previously
(transformation, transduction, or conjugation).

Monitoring of antimicrobial use patterns in equine veterinary practices

Despite implications that antimicrobial use in veterinary hospital
facilities might select for and aid in the maintenance of MDR Salmonella,
there has been little work to monitor antimicrobial use in hospital facilities
or to evaluate the effects of antimicrobial use prospectively on the resistance
profiles of enteric bacteria. In the absence of such information, it is difficult
to make specific recommendations on how and when antimicrobials ought
to be used. Based on a review of prescribing records from the James L. Voss
 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600 591

Veterinary Teaching Hospital at Colorado State University from 1994 to

2001, 54% of hospitalized equine patients received antimicrobial drugs, the
highest portion of any patient species group [12]. The most commonly
prescribed class of antimicrobials among equine patients was penicillin/
ampicillin (39% of equine prescriptions). Clearly, antimicrobials are
commonly used in hospital facilities, and there is opportunity for selection
pressure on the enteric and environmental flora. The extent to which such
use actually results in more resistant populations is unknown, however. If
prospective monitoring programs could be initiated in hospital facilities,
perhaps such data would be useful for retrospective analysis of an outbreak
or for prospective surveillance of newly emerging forms.

Multidrug-resistant Salmonella of concern

Many of the documented nosocomial outbreaks in veterinary hospital-
ized equine patients have been associated with Salmonella. Some of
these Salmonella outbreaks have been associated with MDR strains.
These documented outbreaks include S Infantis [13], S Anatum [14–16],
S Heidelberg [17], S Agona, [16,18], S Krefeld [19], S Saintpaul [19,20],
S Give [16], and S Newport [16]. These MDR forms do not seem to occur
commonly in the general equine population. In a broad geographic study of
Salmonella isolated from the feces of horses on farms in the United States, it
was estimated that only 0.8% of horses on 1.8% of premises shed Salmonella
at any particular point in time [21]. Less than 5% of these Salmonella isolates
from the feces of horses in the general population were resistant to any one of
the antimicrobials tested. By comparison, isolates from clinically ill horses
whose samples were submitted for serotyping to the National Veterinary
Service Laboratories tended to be more resistant (Table 1).
During the S Infantis outbreak in 1996, it was reported that after the first
week of the outbreak, isolates were only sensitive to amikacin and
enrofloxacin [13]. The change in the antibiogram from the initial isolates
in the outbreak to one with more resistance may indicate the acquisition of
additional resistance genes within the hospital environment or the induced
expression of existing resistance genes based on selective factors in the
hospital environment.
MDR S Anatum isolates were associated with an outbreak of
salmonellosis in a private veterinary hospital as well as with an outbreak
at a veterinary teaching hospital that spanned 1.5 years (1991 and 1992)
[14,15]. The S Anatum isolates exhibited resistance that could be
characterized by four groupings. The grouping with the least number of
resistance phenotypes was resistant to ampicillin, tetracycline, chloramphen-
icol, carbenicillin, and ticarcillin. The most resistant grouping was resistant
to tetracycline, chloramphenicol, ampicillin, carbenicillin, ticarcillin, ceph-
alothin, gentamicin, tobramycin, and sulfamethoxazole/trimethoprim in its
resistance phenotype. Concurrent environmental sampling at the private
592 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600

Table 1
Antimicrobial resistance among Salmonella isolates from ill horses (percentage of resistant
isolates)
Antimicrobial 1999 (n = 123) 2000 (n = 202) 2001 (n = 95)
Amikacin 0.0 0 0
Amoxicillin/clavulanic acid 11.4 16.3 30.5
Ampicillin 30.9 27.7 52.6
Apramycin 0.8 0 1.1
Cefoxitin 16.8 29.5
Ceftiofur 10.6 15.3 33.7
Ceftriaxone 0.8 0.5 0
Cephalothin 15.4 18.3 45.3
Chloramphenicol 18.7 15.8 45.3
Ciprofloxacin 0.0 0 0
Gentamicin 17.1 11.9 24.2
Imipenem — — 0
Kanamycin 18.7 11.9 35.8
Nalidixic acid 0.8 2.0 4.2
Streptomycin 30.9 25.2 51.6
Sulfamethoxazole 34.1 25.7 52.6
Tetracycline 39.8 26.2 46.3
Trimethoprim/sulfamethoxazole 18.7 12.9 27.4
Data from National Antimicrobial Resistance Monitoring System for Enteric Bacteria.

veterinary hospital resulted in the isolation of Citrobacter freundii, Enter-

obacter cloacae, and E coli, which were also resistant to numerous
antimicrobial agents, including tetracycline, chloramphenicol, ampicillin,
carbenicillin, and ticarcillin, prompting the investigators to speculate that
S Anatum may have acquired some of its antimicrobial resistance deter-
minants from these environmental bacteria.
Over the course of a 6-year period, S Heidelberg that was resistant to
multiple antimicrobial drugs was isolated repeatedly from horses and
environmental samples at an equine hospital [17]. Using characterization
techniques, including pulsed field gel electrophoresis, IS200 element profiles,
antimicrobial resistance patterns, plasmid profiles, and phage typing, it was
determined that all the isolates from the hospital and a single isolate from
the community (from a sample of meat meal) represented a single MDR
strain. These isolates were resistant to ampicillin, streptomycin, tetracycline,
chloramphenicol, sulfathiazole, trimethoprim, kanamycin, spectinomycin,
and gentamicin. Although there was some genetic variability early in the
outbreak, there was increasing uniformity of the isolates over time,
suggesting the selection of a stable genotype in the hospital environment.
With the exception of the resistance genes to sulfathiazole and tri-
methoprim, it appeared that all the other resistance genes resided on
plasmids. Over the 6-year period, the antimicrobials commonly used to treat
patients in the hospital included penicillin, gentamicin, and sulfonamide/
trimethoprim. Tetracycline, streptomycin, and amoxicillin were used
 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600 593

occasionally. Chloramphenicol and kanamycin had not been used in the

hospital in the previous 10 years, however, with the exception of the use of
chloramphenicol as an antimicrobial eye ointment. This demonstrates that
resistance genes can be maintained in bacteria for prolonged periods, even in
the absence of recent or current use of those specific antimicrobials in
hospitalized patients. These isolates were not evaluated for the presence of
transposons or integrons; thus, the genetic components leading to resistance
are unknown, but genetic linkage within such structures is one potential
explanation for the observed persistence.
S Saintpaul was responsible for an outbreak in a veterinary teaching
hospital beginning in June 1981 and lasting for 10 months [19]. Initially,
S Saintpaul isolates were susceptible to all antimicrobials tested. Later
isolates were resistant to penicillin, streptomycin, neomycin, kanamycin,
gentamicin, chloramphenicol, sulfas, and ampicillin. Notably, these isolates
were all susceptible to tetracycline [22]. In evaluating patient and patient
management factors that were associated with the detection of S Saintpaul
from these patients, the receipt of parenteral antimicrobials (odds ratio
[OR] = 10.9), nasogastric intubation (OR = 3.9), and being hospitalized
with a complaint of colic (OR = 2.2) were all associated with a greater risk
of having S Saintpaul detected in the feces [22]. It is unclear how these
factors are related to the outcome of Salmonella detection, that is, whether
these factors predisposed the animal to infection or whether they were
simply a part of the treatment of the animal’s preexisting condition or
disease caused by Salmonella infection. It is plausible that the use of
antimicrobials could result in a disruption of the gut microflora to allow
infection with Salmonella or potentially could aid in the selection of MDR
forms of Salmonella, however. A study of the data on isolation of
Salmonella spp other than S Saintpaul from horses (with or without signs
consistent with salmonellosis) at the same institution over a longer period
also showed an association between receipt of antimicrobials, especially with
the addition of oral antimicrobials to the treatments given, with the
detection of Salmonella in the feces. In that study, horses that received
antimicrobials parenterally were 6.4 times more likely to be shedding
Salmonella in their feces and those receiving antimicrobials parenterally and
orally were 40.4 times more likely to be shedding Salmonella in their feces.
Although cause and effect are hard to determine from these case-control
studies, they do serve as a reminder that the selection and use of
antimicrobials in the hospital environment should be considered carefully.
Before, during, and after the outbreak of S Saintpaul discussed
previously, there were repeated isolations of S Krefeld in the same facility
[19]. Isolations from horses occurred in each year from 1977 through
1983, with the exception of 1978, ranging from 1 to 16 cases per year. The
R-plasmid for the S Krefeld isolates was identical to that of the S Saintpaul
isolates, prompting speculation that the plasmid may have originated in
S Krefeld. This report raises the concern that resistance determinants can be
594 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600

Box 1. American Veterinary Medical Association suggested

principles for judicious therapeutic use of antimicrobials
 Preventive strategies, such as appropriate husbandry and
hygiene, routine health monitoring, and immunization, should
be emphasized.
 Other therapeutic options should be considered before
antimicrobial therapy.
 Judicious use of antimicrobials, when under the direction of
a veterinarian, should meet all requirements of a valid
veterinarian-client-patient relationship.
 Prescriptions, veterinary feed directives, and extralabel use of
antimicrobials must meet all the requirements of a valid
veterinarian-client-patient relationship.
 Extralabel antimicrobial therapy must be prescribed only in
accordance with the Animal Medicinal Drug Use Clarification
Act amendments to the Food, Drug, and Cosmetic Act and
its regulations.
 Veterinarians should work with those responsible for the care
of animals to use antimicrobials judiciously regardless of
the distribution system through which the antimicrobial
was obtained.
 Regimens for therapeutic antimicrobial use should be
optimized using current pharmacologic information and
principles.
 Antimicrobials considered important in treating refractory
infections in human or veterinary medicine should be used
in animals only after careful review and reasonable
justification. Consider using other antimicrobials for initial
therapy.
 Use narrow-spectrum antimicrobials whenever appropriate.
 Use culture and susceptibility results to aid in the selection of
antimicrobials when clinically relevant.
 Therapeutic antimicrobial use should be confined to
appropriate clinical indications. Inappropriate uses, such as
for uncomplicated viral infections, should be avoided.
 Therapeutic exposure to antimicrobials should be minimized
by treating only for as long as needed for the desired
clinical response.
 Limit therapeutic antimicrobial treatment to ill or at-risk
animals, treating the fewest animals indicated.
 Minimize environmental contamination with antimicrobials
whenever possible.
 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600 595

 Accurate records of treatment and outcome should be used to

evaluate therapeutic regimens.

From American Veterinary Medical Association. Judicious therapeutic use of

antimicrobials (approved by the American Veterinary Medical Association
[AVMA] Executive Board, November 1998; amended and reapproved April
2004). Available at: http://www.avma.org/policies/jtua_avma.asp. Accessed Sep-
tember 2004; with permission.

acquired within the hospital setting over the course of an outbreak from
other organisms, including nosocomial pathogens.
In one outbreak in 1988, four serotypes of Salmonella, three of which
were MDR, were recovered from patients or the environment [16]. S Give
and S Newport were isolated from equine patients and the environment. In
addition, S Anatum was isolated from equine patients only, and S Agona
was isolated from the environment only. The S Anatum isolates were only
resistant to sulfisoxazole or were pansensitive. The other isolates were
resistant to at least ampicillin, chloramphenicol, gentamicin, kanamycin,
and sulfisoxazole. A plasmid was isolated from all the environmental
isolates and most (69.2%) of the equine patient isolates. The most frequently
observed plasmid was associated with transfer of resistance to ampicillin,
chloramphenicol, gentamicin, kanamycin, and sulfisoxazole. This report
illustrates that a consistent antibiogram pattern does not necessarily indicate
that a single organism is involved in an outbreak. Given the transferability
of plasmids, it is conceivable that the consistent base pattern of resistance
could be the result of acquired resistance from a common origin. It is also
noteworthy that at the time of the report, it was not unexpected to recover
the MDR S Agona from the hospital environment; it had been isolated so
often from the environment that it was ‘‘considered to be part of the
background microflora of the Veterinary Medical Teaching Hospital.’’
S Agona isolates from Kentucky were evaluated for antimicrobial
resistance [18]. These isolates were not specifically from a hospital-based
study; they were from equids from 56 farms in the central Kentucky region.
Overall, 95.2% (79 of 83) of the isolates were resistant to multiple
antimicrobial drugs, including chloramphenicol and gentamicin. Many of
the isolates were resistant to ampicillin (96.3%), carbenicillin (96.3%),
cephalothin (77.1%), chloramphenicol (95.2%), erythromycin (100%),
gentamicin (95.2%), kanamycin (96.3%), neomycin (81.9%), penicillin
(100%), streptomycin (79.5%), tetracyclines (78.3%), or sulfas (96.3).
Horses on these farms could easily have been referred to a hospital for care
because they were clinically ill when the samples yielding the Salmonella
were collected. This demonstrates once again that Salmonella from ill
animals tends to be more resistant; these ill animals may enter a hospital,
thus challenging the infection control mechanisms in these facilities.
596 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600

Box 2. Prudent use guidelines for antimicrobial drugs from the

AAEP
American Association of Equine Practitioners Prudent Drug
Usage Guidelines
(Approved by the AVMA Executive Board, June 2001)
The health and welfare of horses and their owners is the primary
goal of members of the American Association of Equine
Practitioners (AAEP). We believe that these guidelines merely
reiterate the standard of practice and what is common in
equine veterinary medicine. The AAEP provides continuing
education for veterinarians that focuses on the appropriate use
of antimicrobial drugs. Our members are committed to the
practice of preventive immune system management through
the use of vaccines, parasiticides, stress reduction, and proper
nutritional management. The AAEP recognizes that proper and
timely management practices can reduce the incidence of
disease and therefore reduce the need for antimicrobials;
however, antimicrobials remain a necessary tool to manage
infectious disease in horses. To reduce animal pain and
suffering, prudent use of antimicrobials is encouraged. The
following are general guidelines for the prudent therapeutic
use of antimicrobials in horses:
1. The veterinarian’s primary responsibility is to aid in the
design of management, immunization, housing, and nutrition
programs that will reduce the incidence of disease and the
need for antimicrobials.
2. Antimicrobials should be used only within the confines of
a valid veterinarian-client-patient relationship; this includes
both dispensing and issuance of prescriptions.
3. Veterinarians should:
a. Participate in continuing education programs that
include therapeutics and emerging or development of
antimicrobial resistance.
b. Avoid antimicrobial use in transient virus associated
conditions.
c. Have clinical evidence of the identification of the
pathogen associated with the disease based upon
history, clinical signs, laboratory data, and experience.
d. Select antimicrobials that are appropriate for the target
organism and should be administered at a dosage and
route that are likely to achieve effective levels in the
target organ.
 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600 597

e. Make product choices and use regimens that are based

on available laboratory and package insert information,
additional data in the literature, and consideration of the
pharmacokinetic and pharmacodynamic aspects of the
drug.
f. Use products that have the narrowest spectrum of
activity and known efficacy in vivo or in vitro against the
pathogen causing the disease problem.
g. Use antimicrobials at a dosage appropriate for the
condition treated for as short a period of time as
reasonable (ie, therapy should be discontinued when it
is apparent that the immune system can manage the
disease, reduce pathogen shedding, and minimize
recurrence of clinical disease or development of the
carrier state).
h. Select antimicrobials of lesser importance in human
medicine in preference to newer generation drugs that
may be in the same class if this can be achieved while
protecting the health and safety of the animals.
i. Use antimicrobials labeled for treating the condition
diagnosed, and whenever possible, at the labeled dose,
route, frequency, and duration if the available scientific
information still supports their efficacy.
j. Use antimicrobials on an extra-label basis only within the
provisions contained within Animal Medicinal Drug Use
Clarification Act amendments to the Food, Drug, and
Cosmetic Act and its regulations.
k. When appropriate, use local therapy over systemic
therapy.
l. Be discouraged from using combination antimicrobial
therapy unless there is information to show an increase
in efficacy or suppression of resistance development for
the target organism.
m. Protect integrity through proper handling, storage, and
observation of the expiration date.
4. Veterinarians should endeavor to ensure proper on-farm
drug use.

Prescription or dispensed drug quantities should be appropriate so that

stockpiling of antimicrobials on the farm is avoided.
From American Association of Equine Practitioners. Prudent drug usage
guidelines (approved by the AVMA Executive Board, June 2001). Available at:
http://www.avma.org/policies/jtua_equine.asp. Accessed September 2004; with
permission.
598 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600

S Agona was recovered from horses on six of the farms in 2 or more years,
indicating some persistence in the farm environment, in the horses, or in
other residents of the farm or the possibility of repeated introductions.
One of the newest MDR strains of Salmonella of concern to those that
track MDR salmonellae is S Newport [23,24]. Although there have not been
any reports of outbreaks in hospitalized equine patients associated with
S Newport, there have been a growing number of isolations from human
beings and animals in the United States. The strain of S Newport of most
concern has a resistance profile that includes resistance to ampicillin,
chloramphenicol, streptomycin, sulfa, tetracycline, extended-spectrum
cephalosporins, and ampicillin/clavulanic acid. The first MDR isolate of
S Newport in the archives of the National Antimicrobial Resistance
Monitoring System for Enteric Bacteria (NARMS-EB) was from an ill horse
in 1997 (P.J. Fedorka-Cray, DVM, personal communication, September,
2003). The second isolate of MDR S Newport was from an ill dog (P.J.
Fedorka-Cray, DVM, personal communication, September, 2003). Sub-
sequently, numerous cases of illness caused by MDR S Newport were
identified in human beings and cattle [24]. Future monitoring will determine
whether this strain becomes more important as a pathogen for horses.
Although most of the concern surrounding nosocomial infections has
centered around impacts on the patient and decisions regarding patient care,
one must remember that some of these nosocomial agents can be zoonotic
or anthroponotic (ie, they can be transferred from animals to people or from
people to animals, respectively). Multidrug resistance is a growing concern
for public health as well as individual animal care. Animal caretakers,
owners, and patient caregivers often have sufficiently close contact with
patients to warrant concern about transmission of disease agents or MDR
plasmids or integrons [23]. Although horse meat is not often consumed in
the United States, an outbreak of MDR S Newport in France was attributed
to consumption of contaminated horse meat [25].

Actions to deal with multidrug-resistant Salmonella

The data to suggest direct and specific actions to limit the potential for
nosocomial infections with MDR Salmonella are extremely sparse. For
instance, there is a lack of information on which antimicrobial use practices
could be considered ‘‘risky uses’’ in terms of selection for MDR strains.
Regardless of the organism, in the end, one is left with the practice of
judicious antimicrobial drug use and intuitive approaches to infection
control and prevention of nosocomial bacterial transmission. Approaches to
infection control for the hospital setting have been covered elsewhere in this
issue. Many organizations have developed guidelines for judicious antimi-
crobial drug use, including the American Veterinary Medical Association
(AVMA; http://www.avma.org/scienact/jtua/default.asp) and the American
 D.A. Dargatz, J.L. Traub-Dargatz / Vet Clin Equine 20 (2004) 587–600 599

Association of Equine Practitioners (AAEP; http://www.avma.org/scienact/

jtua/equine/jtuaequine.asp) (Boxes 1 and 2).

Summary
Nosocomial infections are a serious threat to optimum patient care. In
addition, nosocomial infections can have far-reaching consequences for the
hospital personnel and the financial aspects of the hospital. Nosocomial
infections with Salmonella spp have been described among hospitalized
equine populations more frequently than any other agent. Salmonella spp
associated with hospitalized equids often possess more antimicrobial
resistance determinants than do Salmonella spp isolated from healthy
horses in the general population. There is little evidence to suggest that
resistant salmonellae are more virulent than nonresistant forms. MDR
forms of Salmonella complicate the selection of appropriate antimicrobials
when they are indicated, however. Furthermore, the use of some
antimicrobials may apply selection pressure toward enhanced ability of
MDR Salmonella to colonize equine patients. Further research should help
to elucidate the risky uses of antimicrobials in the hospital setting and define
the role of disinfectants and treatments such as NSAIDs in the ecology of
MDR forms of nosocomial infections, including Salmonella. In the
meantime, thoughtful selection of when and how to use antimicrobials in
equine patients, together with deliberate selection of which antimicrobials
to use based on monitoring data and other factors, such as safety and
spectrum, is advised.

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