Veterinary Internal Medicne - 2008 - Morley - Antimicrobial Drug Use in Veterinary Medicine

ACVIM Consensus Statement
J Vet Intern Med 2005;19:617–629
Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians
with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of
the Consensus Statement is evidence-based medicine, but if such evidence is conflicting or lacking, the panel
provides interpretive recommendations on the basis of their collective expertise. The Consensus Statement is
intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical
judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents
with input from the general membership. A draft prepared and input from Diplomates is solicited at the Forum
and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by
the Board of Regents of the ACVIM before publication.
Antimicrobial Drug Use in Veterinary Medicine

Paul S. Morley, Michael D. Apley, Thomas E. Besser, Derek P. Burney, Paula J. Fedorka-Cray,
Mark G. Papich, Josie L. Traub-Dargatz, and J. Scott Weese
Recognizing the importance of antimicrobial resistance and the need for veterinarians to aid in efforts for maintaining the usefulness
of antimicrobial drugs in animals and humans, the Board of Regents of the American College of Veterinary Internal Medicine
charged a special committee with responsibility for drafting this position statement regarding antimicrobial drug use in veterinary
medicine. The Committee believes that veterinarians are obligated to balance the well-being of animals under their care with the
protection of other animals and public health. Therefore, if an animal’s medical condition can be reasonably expected to improve
as a result of treatment with antimicrobial drugs, and the animal is under a veterinarian’s care with an appropriate veterinarian-
client-patient relationship, veterinarians have an obligation to offer antimicrobial treatment as a therapeutic option. Veterinarians
also have an obligation to actively promote disease prevention efforts, to treat as conservatively as possible, and to explain the
potential consequences associated with antimicrobial treatment to animal owners and managers, including the possibility of pro-
moting selection of resistant bacteria. However, the consequences of losing usefulness of an antimicrobial drug that is used as a
last resort in humans or animals with resistant bacterial infections might be unacceptable from a public or population health
perspective. Veterinarians could therefore face the difficult choice of treating animals with a drug that is less likely to be successful,
possibly resulting in prolonged or exacerbated morbidity, to protect the good of society. The Committee recommends that voluntary
actions be taken by the veterinary profession to promote conservative use of antimicrobial drugs to minimize the potential adverse
effects on animal or human health. The veterinary profession must work to educate all veterinarians about issues related to
conservative antimicrobial drug use and antimicrobial resistance so that each individual is better able to balance ethical obligations
regarding the perceived benefit to their patients versus the perceived risk to public health. Specific means by which the veterinary
profession can promote stewardship of this valuable resource are presented and discussed in this document.
Key words: Antibacterial; Antibiotic; Prudent use; Resistance.
A ntimicrobial drugs are used in animals, humans, and

plants to treat and prevent bacterial infections and to
improve production efficiency in food-producing animals.
These drugs are among the most important tools available
to modern medicine. Few developments have had as dra-
From Colorado State University, Fort Collins, CO (Morley, Traub-Dar- matic an effect on human and veterinary medicine during
gatz); the Department of Veterinary Diagnostic and Production Animal the previous century as the development of antimicrobial
Medicine, Iowa State University, Ames, IA (Apley); Washington Animal drugs and their use for prevention and treatment of bacterial
Disease Diagnostic Laboratory, Washington State University, Pullman, diseases. However, soon after antimicrobial drugs became
WA (Besser); Gulf Coast Veterinary Specialists, Houston, TX (Burney);
readily available for use in human and veterinary medicine,
the Antimicrobial Resistance Research Unit, US Department of Agricul-
ture–Agriculture Research Service, Athens, GA (Fedorka-Cray); the Col-
it was recognized that decreased bacterial susceptibility
lege of Veterinary Medicine, North Carolina State University, Raleigh, NC could adversely affect clinical outcome. It is now widely
(Papich); University of Guelph, Guelph, Ontario, Canada (Weese). recognized that susceptibility to these drugs is not universal
Statements on potential conflicts of interest: Dr Apley has provided among all bacterial species, nor is it equal between different
remunerated consultation and training services or has had research fund- strains of the same bacterial species. Resistance mecha-
ed by Fort Dodge, Bayer Animal Health, Elanco, Pfizer Inc Animal Health
nisms can either be intrinsic or acquired through a variety
Group, Pharmacia, Intervet, Merial, Boerhinger-Ingelheim, Schering, No-
vartis, Vet Life, and the National Pork Board. Dr Papich has provided
of genetic means. Variability in susceptibility to different
remunerated consultation or has had research funded by Pfizer Inc Animal antimicrobial drugs has become a major factor affecting the
Health Group, Bayer Animal Health Division, Schering-Plough Animal successful treatment of bacterial diseases. It is also com-
Health Corporation, Idexx Laboratories Inc, and Merial. monly but incorrectly assumed that only the target bacteria
Reprint requests: Paul S. Morley, DVM, PhD, DACVIM, Depart- are being exposed to antimicrobial drugs when the host is
ment of Clinical Sciences, College of Veterinary Medicine and Bio- treated. Most if not all commensal and transient microbial
medical Science, Colorado State University, Fort Collins, CO 80523-
flora are exposed to varying amounts of antimicrobial drug
1678; e-mail: [email protected].
Copyright q 2005 by the American College of Veterinary Internal during treatment. Although resistance in these so-called by-
Medicine stander bacteria might not be of consequence in one host
0891-6640/05/1904-0023/$3.00/0 species, these organisms can cause disease in other hosts,
19391676, 2005, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2005.tb02739.x by El Salvador HINARI REGIONAL, Wiley Online Library on [05/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
618 Morley et al
and all resistant bacteria could serve as reservoirs of resis- disease specialists with considerable research experience re-
tance genes. lated to the action of antimicrobial drugs; their use in treat-
The extent to which antimicrobial resistance is affecting ment of animals; and the ecology, surveillance, and epi-
the health of humans and animals is not known. There are demiology of antimicrobial resistance. These professionals
concerns that emerging resistance among bacteria, if left work in private veterinary practice, academia, and the fed-
unchecked, could escalate to the point at which efficacy of eral government and are members and officers in more than
many of the most important drugs will no longer be pre- 20 professional organizations related to veterinary medicine
dictable and some bacterial infections could once again be- and animal health (see Appendix). Through extensive dis-
come untreatable. Although substantial debate surrounds cussions, this Committee prepared a draft of this document
this issue, research is needed to further document the risks that was presented at the 2003 ACVIM Forum and posted
to humans and animals posed by antimicrobial resistance for comment on a Web site. Comments were considered,
because scientifically sound information is largely unavail- and a final draft was sent for review and approval to the
able.1–3 However, there is increasing global pressure to de- ACVIM Board of Regents before publication.
velop strategies to protect the effectiveness of existing and Several veterinary organizations have previously pub-
new antimicrobials by reducing selection pressure driving lished and endorsed documents regarding principles of ju-
emerging resistance in bacteria. Not only is there substantial dicious antimicrobial drug use in veterinary medicine.5 The
pressure to do something, there is emphasis from many sec- Committee’s intent in drafting this statement was not to
tors to do it immediately, which has the unfortunate con- emulate or replace these previous efforts. Rather, the goal
sequence of causing authorities to sometimes act in the ab- of this Committee was to expand upon previous efforts by
sence of definitive scientific data. providing more in-depth discussion of issues faced by vet-
The World Health Organization (WHO), the US Centers erinarians when attempting to apply guidelines for judicious
for Disease Control and Prevention (CDC), the US Food use in everyday practice situations. Although all of the ac-
and Drug Administration (FDA), the US Department of Ag- tions recommended in this document relate to antimicrobial
riculture (USDA) and many other agencies involved in pro- use by individual practicing veterinarians, their scope could
motion and regulation of health activities around the world involve remedies on a larger scale, such as by the ACVIM,
are vigorously engaged in developing programs intended to the veterinary profession, the US government, or other reg-
monitor the emergence of antimicrobial resistance and to ulatory bodies.
decrease use of antimicrobial drugs. Use of antimicrobial This statement will specifically address antimicrobial
drugs in human medicine is thought to be responsible for drug use for treatment and prevention of disease in animals,
a large part, if not the majority, of the resistance problems and recommendations in this document are not intended to
observed today,1,4 but a considerable portion, if not the ma- be extrapolated to other uses. The use of antimicrobial
jority, of scrutiny has focused on antimicrobial use in ani- drugs for enhancement of production efficiency is not ad-
mals. This is because of the potential for and perceived dressed. The ACVIM acknowledges that antimicrobial re-
importance of zoonotic transmission of pathogenic and non- sistance is a complex issue with ramifications extending
pathogenic bacteria to humans through direct contact with beyond the scope of this paper.
animals, indirectly through contact with animals’ environ-
ments or through the food chain. Background
Veterinarians in the United States and many other coun-
tries are responsible for overseeing the use of most anti- Antibiotics are compounds produced by living organisms
microbial drugs in animals for therapeutic or disease pre- that impede the growth of other organisms. Antimicrobial
vention. Veterinarians should therefore critically evaluate drugs include antibiotics as well as synthetic and semisyn-
current antimicrobial use to identify ways to modify use thetic compounds that have the same effects. Antimicrobial
without adversely affecting the health and well-being of drugs have a variety of actions to affect bacterial survival
animals or humans. The American College of Veterinary and growth, including inhibition of cell wall synthesis (pen-
Internal Medicine (ACVIM) recognizes the importance of icillins and cephalosporins), inhibition of protein synthesis
this issue and the need for veterinarians to contribute to (tetracyclines, macrolides, phenicols, aminoglycosides), and
efforts intended to maintain the usefulness of antimicrobial inhibition of DNA function (sulfonamides and fluoroquin-
drugs in animals and humans and specifically to monitor olones). Antimicrobial drugs can be classified as having
and help assure that the use of antimicrobial drugs in vet- bactericidal or bacteriostatic action. Bactericidal antimicro-
erinary medicine has a minimal negative effect on human bial drugs have minimum inhibitory concentrations (MICs)
health. As such, the ACVIM Board of Regents approved and minimum bactericidal concentrations (MBCs) that are
convening a special committee and charged it with respon- only a few dilutions apart when evaluated in the laboratory.
sibility for drafting this position statement regarding anti- Bacteriostatic antimicrobial drugs inhibit or arrest growth
microbial drug use in veterinary medicine. Experts with without actually killing the bacteria and generally require a
diverse backgrounds related to this issue were identified to greater increase in concentration to inhibit visible growth
assist with this effort. Members of the Committee included in culture (MIC).
ACVIM Diplomates and other veterinarians clinically ex- The primary goal of antimicrobial drug use for treatment
perienced in working with small animals, equine, and food and prevention of bacterial infections should be to control
animal patients, in addition to specialists experienced in bacterial growth to enable host responses to contain or
food animal production. The group also included microbi- eliminate bacteria responsible for disease. Although anti-
ologists, pharmacologists, epidemiologists, and infectious microbial drugs can help the host contain and eliminate
Antimicrobial Use Consensus Statement 619
infections, these drugs should not be considered solely re- mosomal plasmids that replicate apart from the chromo-
sponsible for eliminating infections in the host because both somal DNA. Plasmids can contain smaller mobile genetic
innate and developed immune responses are critical in this elements called transposons that have the ability to move
process. Nor should antimicrobial drugs be applied for dis- from the plasmid to chromosome and vice versa. Transpo-
ease prevention with the mindset that they are the sole or sons can also be introduced into bacterial cells by bacterio-
most important means of preventing disease caused by bac- phages that act as a transport vectors, by uptake of naked
terial agents. For example, preventing or minimizing ex- DNA, or by transfer from other plasmids. Recently, smaller
posure to infectious agents are far more effective means of elements within transposons called integrons have also been
preventing infectious diseases, and optimizing immune sta- described. These can insert within the transposon and fa-
tus can minimize the effect of infections without use of cilitate the further acquisition of multiple resistance genes.
antimicrobial drugs. Plasmids can be lost when selective antimicrobial pressure
is no longer present, and resistance harbored on a plasmid
Mechanisms for Resistance to is typically lost when the plasmid is lost from the cell.
Antimicrobial Compounds Some scientists have suggested that once resistance genes
Bacteria can be resistant to the action of antimicrobial are inserted into the chromosomal DNA, resistance is rarely
drugs because of the inherent structure or physiology of the if ever lost from bacteria that compete successfully in an
bacteria (constitutive resistance), or they can develop mech- ecosystem. However, this theory has not been examined
anisms to circumvent action of the drugs through genetic extensively, and there are notable exceptions such as with
mutation or through acquisition of genetic elements (ac- Salmonella Typhimurium DT104. If genetic determinants
quired resistance). of resistance are retained even in the absence of antimicro-
It is important to note that contact with antimicrobial bial drug exposure, this would highlight the importance of
drugs is not believed to cause bacteria to actively mutate preventing development of antimicrobial resistance and
or develop new types of resistance. Genetic mutation is a would have important implications on policies regarding
normal process that occurs during bacterial replication and restrictions on antimicrobial drug use.
occurs spontaneously in DNA replication at a rate of 1 mu- Resistance genes are believed to transfer most commonly
tation per million bases per cell division.6 Because of the among bacteria of the same species. However, evidence is
large number of bacteria produced during replication and increasing that genetic elements can transfer among bacteria
the short generation interval, mutation is a common event. of different species, or even from different genera. Because
Although most mutations are likely detrimental to the or- of this ability for genetic elements to transfer among bac-
ganism, by random chance, a mutation can develop that teria and for bacteria to be exchanged between animals of
provides selective advantage to bacteria exposed to anti- the same or different species, it is theoretically possible for
microbial drugs, which therefore favors survival of strains resistance to emerge in bacterial populations in animals that
less susceptible to the antimicrobial drug. have never been exposed to antimicrobial drugs. Recent
Some examples of mechanisms for intrinsic or constitu- research findings characterizing the function of integrons
tive resistance include a lack of cellular mechanisms re-
and transposons indicate that resistance might also be prop-
quired for antimicrobial action (ie, penicillin resistance be-
agated for other reasons. Genetic determinants for resis-
cause of a lack of correct binding proteins), growth rates
tance to more than 1 antimicrobial can be linked together.
too slow for effective action (beta-lactam antimicrobials),
When bacteria are resistant to more than 1 antimicrobial,
and resistance in anaerobic bacteria to aminoglycosides
regardless of whether genetic elements are constitutively
from a lack of oxygen-dependent uptake of the antimicro-
linked, exposure of these resistant bacteria to 1 antimicro-
bial into the bacterial cell. Several mechanisms are also
associated with acquired antimicrobial resistance. These in- bial will inadvertently promote persistence of resistance to
clude drug inactivation, drug modification, production of the other antimicrobials, even if they have different mech-
competitive metabolites, target mutation, target substitution, anisms of action.
target modification, decreased cell wall permeability to After bacteria acquire genetic material conferring resis-
drugs, active efflux of drugs, and failure to metabolize a tance, continued exposure of bacterial populations to anti-
drug to its active form. Some antimicrobial drugs such as microbial drugs provides the selection pressure that might
tetracyclines and macrolides are associated with multiple allow the resistant population to increase in prevalence and
mechanisms of resistance that confounds development of subsequently become the dominant clone in the population.
effective means to overcome this resistance. Continued ex- Whether resistance will persist at a high prevalence in bac-
posure of bacterial populations to antimicrobial drugs or terial populations after removal of antimicrobial pressure
other factors affecting survival (such as disinfectants, met- depends on the characteristics of competing flora in the
als, pH, and presence of specific nutrients) after the bacteria ecosystem, the stability of the genetic determinants in the
acquire genetic material conferring resistance to antimicro- resistant organisms, and the fitness of the resistant organ-
bial drugs can provide a selection pressure resulting in an isms. Mutation or genetic transfer can, in addition to con-
increase in prevalence of resistance among populations of ferring mechanisms for antimicrobial resistance, bring
those bacteria. about changes that might adversely affect the survival of
progeny bacteria, especially when the selection pressure as-
Transmission of Genetic Elements sociated with antimicrobial exposure is removed. However,
Bacteria can acquire genes conferring resistance by a va- if there are no adverse consequences of maintaining resis-
riety of mechanisms, including acquisition of extrachro- tance genes, it is wrong to assume that antimicrobial resis-
620 Morley et al
tance will decline after withdrawal of antimicrobial pres- Consequences of Antimicrobial Resistance
sure.
Objective, systematic risk analysis has been endorsed by
Origins of Antimicrobial Resistance authorities throughout the world as the most reasonable ba-
sis for evaluating and weighing risks, benefits, and conse-
It is not possible to pinpoint how or when resistance to quences to society for various issues, as well as to promote
antimicrobial agents 1st developed, but we can make some better policy development and regulatory decision making
reasonable deductions about why bacteria develop resis- by basing them on science.7 Optimally, the risk analysis
tance. Because the single driving goal of bacterial popula- process should include a quantitative consequence assess-
tions appears to be survival and propagation, resistance ment that attempts to determine the magnitude of conse-
mechanisms are most likely inherent in the molecular ar- quences associated with the adverse outcome, such as an-
chitecture of the cells. Although some might argue that all timicrobial resistance that affects human or animal health.
resistance is at some level acquired, the acquisition of re- The basic measure used in this quantification of risk is de-
sistance genes requires that insertion occur either in the rived by multiplying the magnitude of the adverse conse-
chromosome or plasmid, and a logical conclusion is that quence by the probability that the adverse event will occur.
these insertion sites have been programmed, or evolved, If the magnitude of the consequences is very large, from a
over time to accommodate molecular additions. Resistance societal perspective, the risk to the population will be great
to antimicrobial agents was 1st recognized by scientists even if the probability of that event is moderate or low. In
soon after penicillin was widely used in World War II. Re- other words, if the consequences of the adverse event are
sistance has subsequently been recognized after introduc- disastrous, corrective or mitigative action could be war-
tion of each new antimicrobial drug, prompting the contin- ranted even if the likelihood of occurrence is small. This is
ued need for development of new types of antimicrobial the rationale that many agencies use when applying the so-
drugs. However, since the early 1990s, a crisis has loomed called ‘‘precautionary principle,’’ a position of extreme risk
in that few new antimicrobial drugs have been developed aversion, when making policy decisions related to antimi-
for human use, and pharmaceutical companies have ceased crobial resistance and other public health concerns.
or dramatically reduced efforts to develop new antimicro- The exact probability that antimicrobial drug use in an-
bials. At the same time, new mechanisms that bacteria use imals adversely affects the health of humans is unknown,
to acquire resistance have been identified. The combined but the potential selective effects of antimicrobial drugs
effect has been a decreased ability to effectively treat some cannot be denied and is most likely not zero. Regardless,
bacterial diseases, an outcome that was considered unthink- if resistance to important antimicrobial drugs became com-
able just a few decades ago. Treatment failure associated mon it would truly be devastating for the well-being of
with antimicrobial resistance has probably been most com- animals and humans. Widespread antimicrobial resistance
monly seen in human rather than in animal patients. in important pathogens would result in increased morbidity
and mortality among infected individuals and increased
Transmission of Resistant Bacteria costs for treating infections. In addition to the associated
suffering related to these infections, a cascade of other ad-
There are other causes of evolving resistance in animal verse consequences would follow. The detrimental effect
populations related to interactions at other levels of the eco- on production costs would affect the livelihood of produc-
system. These include movement of carrier animals be- ers, consumers would be affected by the availability and
tween herds (regionally, nationally, or even internationally), cost of animal products, and there would be potential for
managing animals in ways that increase the likelihood of international trade implications. Even if resistance were
transmission, exposure through feed and water, exposure only common among bacteria in animals, the potential for
through the environment (eg, contaminated soils and facil- transmission to humans could stimulate regulatory action
ities), transmission through direct or indirect contact with intended to restrict the use of certain antimicrobial drugs
infected humans, and transmission and movement through and reduce exposure of humans to resistant bacteria.
vectors and vehicles such as wildlife, insects, and birds. Ideally, quantitative risk assessment allows for objective
Studies addressing the effect of vectors and management comparison of hazards and benefits to allow logical and
on movement of bacteria have been described.1 For exam- reasonable decision making. However, the answers obtained
ple, animal feces in holding ponds or used as fertilizer for from the risk assessment process are only as valid as the
crops can be a potential source for bacterial contamination assumptions used for the models. Currently, the gaps in data
of soil, water, and crops, and these sources have in turn related to antimicrobial drug use and antimicrobial resis-
been implicated as potential sources for human exposure to tance are a major issue affecting wider acceptance of risk
resistant bacteria. However, animals are not the sole source analysis models. In the absence of data, it seems prudent
of this type of environmental contamination because human that all health professionals, including veterinarians, should
waste (treated and untreated) is often distributed in the en- actively promote reasonable efforts intended to maintain the
vironment in a similar manner. It is important to remember efficacy of these drugs. There are undoubtedly antimicro-
that bacteria are ubiquitous in our ecosystems, and it is bial use practices that have greater potential for promoting
difficult if not impossible to point at 1 potential source (eg, development of resistance, just as there are undoubtedly use
food animals) as the sole or primary source of resistant practices that have lesser effects. Although caution is war-
bacteria of public health or veterinary significance. ranted in the absence of data, information obtained from
objective, scientifically valid studies should be allowed to lococcus aureus, Streptococcus pneumoniae, Enteroccocus
trump the precautionary principle when it is appropriate. spp., Escherichia coli, or Salmonella collected from human
patients or isolated from animals. At the same time, it is
Basic Questions for the Veterinary Profession not clear that antimicrobial susceptibility has changed
meaningfully over time among other important bacteria
In reviewing issues related to antimicrobial drug use in such as Mannheimia haemolytica, Streptococcus zooepi-
animals, the Committee identified a single overarching demicus, or Bordetella bronchiseptica. Unfortunately there
question that needed to be addressed to determine which are insufficient data to make objective assessments regard-
comments or actions were most relevant to the charge: Is ing many and possibly most important bacteria in other
antimicrobial drug use causing resistance to develop? If specific host species (eg, Klebsiella, Pseudomonas, Entero-
there is no evidence to support concerns expressed by var- coccus spp.).
ious parties, then this would seem to be more of a public 2. Is There Evidence That Previous and Current An-
relations issue than a scientific or medical problem. This timicrobial Use Practices Have Helped to Select for In-
general question is best addressed by breaking the issue into creased Prevalence of Resistance in Bacterial Popula-
3 more basic questions. tions? In theory, any use of antimicrobial drugs results in
1. Is Decreased Susceptibility to Antimicrobial Drugs the development of resistant populations of bacteria. A big-
More Common Today than It Was in the Past? The gen- ger question is whether these resistant populations survive
eral belief by many scientists, physicians, and veterinarians and persist. Antimicrobial use applies a selection pressure
is that resistance is more commonly observed in bacterial to exposed bacterial populations favoring resistant strains,
populations today than it was in the past.8–11 However, in- and continued exposure theoretically allows resistant bac-
terest in antimicrobial resistance has fluctuated over time. teria to become more prevalent. In vitro studies conducted
Susceptibility was closely monitored when antimicrobial under very specific conditions support this theory of selec-
drugs were 1st introduced, and resistance was observed to tion and persistence. However, in vitro studies are not avail-
develop shortly after introductions, particularly among the able regarding every bacterial species of interest in com-
penicillins, streptomycin, and tetracyclines. Interestingly, bination with every drug that is commonly used in veteri-
there seems to have been no foresight among the medical nary medicine, and in vivo studies evaluating these effects
or veterinary communities to establish long-range surveil- in most drug-bacteria combinations are largely unavailable.
lance systems, and reports on resistance have been limited Furthermore, most investigations have largely ignored the
to anecdotal observations and sporadic studies. As addi- nontarget species, which are unavoidably exposed when-
tional drugs were introduced, antimicrobial susceptibility ever the host is treated. Although this general association
testing methods were refined, but monitoring and surveil- is consistent with the proposed theory that exposure is as-
lance remained sporadic at best. Interest in the issue of sociated with increased prevalence of resistance in bacterial
resistance has increased as resistant strains of bacteria have populations, in vitro studies cannot mimic all of the eco-
emerged. Therefore, making appropriate comparisons of logic factors present in natural settings and therefore cannot
historical data is difficult. It is somewhat difficult to deter- be used to fully predict how actual use practices will affect
mine whether apparent increases in resistance resulted from the prevalence of resistance among bacteria of interest.
increased use of antimicrobials or whether this is a biased Probably a great deal of variability exists among current
perception created by use of more sensitive bacterial re- antimicrobial use practices with regard to their likelihood
covery methods or increased investigation of interesting to promote antimicrobial resistance, but much more re-
bacterial strains that have developed specific resistant pat- search is needed to characterize the risks associated with
terns (eg, Salmonella Typhimurium DT104 and Salmonella specific use practices. Although specific information is
Newport). lacking for most bacteria-drug-host combinations, it does
Nonetheless, if antimicrobial susceptibility patterns of not negate the general impression that the longer an anti-
isolates obtained 30 or more years ago are compared with microbial drug is used, the more common resistance be-
susceptibility profiles of isolates obtained recently, there are comes in bacteria.
good examples where resistance appears to be most com- 3. Are There Actions That Can Slow or Reverse an
mon to the older drugs such as tetracyclines, streptomycin, Apparent Increase in the Prevalence of Resistance? Un-
penicillins, and sulfonamides.8–10,12–15 Resistance appears to fortunately, no actions have been proven to completely re-
be less prevalent, but emerging at varying rates, among the verse the emergence of resistance once it becomes common
newer cephalosporins, quinolones, and macrolides.16–19 in a bacterial population. However, in theory, removing ex-
However, it is critical to note that there are drug-bacteria posure of bacterial populations to antimicrobial drugs might
interaction factors that must be considered. Although resis- eliminate the survival advantage for bacteria that is provid-
tance among some genera of bacteria to some drugs is prev- ed by resistance mechanisms. Prevalence of resistance
alent, the prevalence of resistance is not uniform across all might then remain static or even decrease in response to
types of drugs, all drugs in a specific class, or among bac- this action as other advantageous traits dilute out resistance
terial species. Therefore, care should be taken to avoid ov- traits (that would no longer provide a survival advantage).
erinterpreting results, and it is critical to consider epide- Restrictions on antimicrobial drug use in specific institu-
miologic differences when analyzing these data. Still, when tions or premises have been correlated with subsequent de-
comparable banks of bacteria isolated over time are eval- creasing prevalence of resistance in bacterial pathogens,20–22
uated by the same methods, generally, resistance has been but there are also examples in which the prevalence has not
found to be more common in recent times among Staphy- changed after limiting the use of antimicrobial drugs.23,24
622 Morley et al
However, the potential or theoretical benefits of curtailing ever, to protect public health, the veterinarian also has an
antimicrobial drug use with the goal of reducing antimicro- obligation to actively promote disease prevention efforts,
bial resistance, or even reducing the rate of increasing re- treat as conservatively as possible, and explain the potential
sistance prevalence, rely critically on infection control. Dis- consequences associated with antimicrobial treatment to an-
semination of resistant clones is central to the increase in imal owners and managers, including the possibility of pro-
prevalence of antimicrobial resistance in nearly every major moting selection of resistant bacteria. The consequences of
bacterial group in which resistance is a problem, and failure losing beneficial effects of a particular antimicrobial drug,
to control dissemination renders ‘‘rational use’’ guidelines such as one that is used as a last resort in human and animal
essentially ineffective. patients with multiply resistant bacterial infections, could
The Committee believes that there is reason for the vet- be unacceptable from a public or population health per-
erinary profession to be concerned about its role in the spective. In these situations, veterinarians might face the
promotion of antimicrobial resistance and justification for difficult choice of treating animals with a drug that is less
development of a reasonable action plan in response to this likely to be successful, possibly resulting in prolonged or
problem. The consequences of losing antimicrobial drugs exacerbated morbidity, to protect the good of society. It is
as tools for combating bacterial diseases are grave. Just as not possible to dictate actions for these circumstances or
is true for identifying ‘‘proof’’ of any scientific concept, for expect regulations to fit all situations in which this might
some, there probably never will be enough evidence to be encountered. Rather, the veterinary profession must ed-
show that the use of antimicrobial drugs is associated with ucate all veterinarians about issues related to antimicrobial
increased prevalence of resistance. However, given the se- drug use and antimicrobial resistance so that they are better
rious nature of possible consequences, it is unwise to deny able to balance ethical obligations regarding the benefit to
the selective effects of antimicrobial drugs, and it is only their patients versus the risk to public health. The veterinary
prudent to carefully consider and possibly minimize use of profession lacks reliable scientific data about which use
these drugs where possible. It is logical that these efforts practices are most risky and which are less likely to pro-
should 1st be concentrated on those drugs that are consid- mote resistance. The profession also lacks information
ered treatments of last resort for pathogens that are resistant about the efficacy of actions for reducing the prevalence of
to other antimicrobial drugs. resistance in bacterial populations. Although the severity of
the consequences suggests that the veterinary profession
Ethical Questions for Veterinarians Regarding should act conservatively in the use of antimicrobial drugs,
Antimicrobial Drug Use and the ACVIM, other veterinary organizations, and regulatory
Antimicrobial Resistance agencies should vigorously promote research activity that
will provide information and tools to practicing veterinari-
What are the Ethical Obligations to Our Patients, Our ans about these issues.
Clients, and the Public Regarding Antimicrobial Drug If Disease Prevention Methods Are Available to Signif-
Use in Animals? The American Veterinary Medical As- icantly Reduce the Effect of an Infectious Disease in An-
sociation’s Veterinarian’s Oath25 places equal emphasis on imals Without the Use of Antimicrobial Drugs, but an An-
professional obligations for protecting animal health, relief imal Owner or Manager Chooses Not to Adopt This Ap-
of animal suffering, conservation of animal resources, and proach, Can a Veterinarian Ethically Support Therapeutic
promoting public health, as do similar oaths from other or Prophylactic Use of Antimicrobial Drugs? This is a
countries. Conceptually, it might seem possible to achieve difficult question that again is not aided by equal weighting
this balance in our daily activities. However, when faced of obligations to patients and to public welfare. Given the
with the practical realities of antimicrobial drug use in daily potentially serious consequences of antimicrobial resis-
practice activities, it is likely that veterinarians will be tance, veterinarians should use antimicrobial drugs conser-
forced to prioritize among these obligations even though vatively whenever possible to minimize the adverse effect
they have no desire to act in a manner that is harmful to on animal or human health. However, when asked to treat
the public, their patients, or their clients. If any antimicro- ill animals by a client who has ignored veterinary recom-
bial drug use has the potential to promote antimicrobial mendations that might have prevented the illness, it is dif-
resistance, then these drugs cannot be used in animal or ficult to say that a higher moral imperative would be ful-
human patients without potentially posing some risk to hu- filled by declining to provide services to the client by re-
man and animal health. However, the Committee strongly fusing to treat the animals. This obviously puts veterinari-
believes that veterinarians are ethically obligated to use an- ans in conflict with professional obligations to alleviate
timicrobial drugs, when indicated, to aid in the promotion suffering and promote animal well-being. On the other
of the health and well-being of animals. Veterinarians are hand, a management system that results in continued prob-
also obligated, to the best of their ability, to balance the lems with infectious diseases also conflicts with the same
well-being of animals under their care with the protection obligation to alleviate suffering and to promote animal
of other animals and public health. Therefore, if an animal well-being. Furthermore, it is difficult to say that our ob-
with a medical condition can be reasonably expected to ligations regarding the well-being of clients or their animals
improve as a result of treatment with antimicrobial drugs, are completely outweighed by conflicting considerations for
and the animal is under a veterinarian’s care with a veter- the general public welfare. Last, situations might exist in
inarian-client-patient relationship, then the veterinarian has which clients are essentially required to use management
an obligation to offer antimicrobial treatment to the owner practices that result in adverse animal health consequences
or manager as a therapeutic option for their animal. How- (including drug use practices that could encourage resis-
tance development) to successfully compete economically. use of antimicrobial drugs to minimize the potential adverse
These situations beg for an appropriate industry compliance effects on animal or human health. We do not believe that
policy or, failing that, a regulatory approach that is sup- regulatory action is needed to reduce availability of anti-
ported and encouraged, if not led, by the veterinary pro- microbial drugs to veterinarians. However, we do believe
fession. The veterinary profession is concerned about pub- that it is appropriate to require that antimicrobial drugs ap-
lic health and animal welfare because of antimicrobial re- plied in animals are restricted to use by a veterinarian or
sistance. Achieving appropriate balance for all of these con- on their explicit order. More specific recommendations that
cerns is the essence of the dilemma. The Committee are endorsed by the Committee to promote conservative
believes that the best outcome for all involved in these de- application of antimicrobial drugs in animals are listed be-
cisions is for the veterinary profession to make a long-term low.
commitment to aggressively promote disease prevention
whenever possible, to promote conservative use of anti-
Recommendation A
microbial drugs whenever they are needed and to draw an-
imal industry and public attention to situations in which The Committee recommends that the sale of antimicro-
economic pressures encourage less conservative antimicrobial drugs for use in all animals be restricted such that these
bial drug use so that they can help provide solutions for drugs are only used by a veterinarian or in accordance with
these issues. This balance cannot be achieved through reg- their explicit order. (Note: ‘‘Antimicrobial drug use in ac-
ulation alone and will be best achieved by training veteri- cordance with a veterinarian’s explicit order’’ refers to use
narians that are well grounded in their understanding of by nonveterinarians according to the explicit verbal or writ-
these issues and are sophisticated in their ability to provide ten instructions of their veterinarian or through issuance of
effective disease prevention protocols combined with con- a valid prescription, in the same manner that antimicrobial
servative antimicrobial drug treatment.
drug use is restricted for use in humans in the United States
What Are the Ethical Obligations When a Veterinarian
and other countries. Specifically, this does not preclude vet-
or a Diagnostician Becomes Aware of Illegal Antimicro-
erinarians from dispensing antimicrobial drugs directly to
bial Use Practices by an Animal Owner or a Veterinarian?
clients for use in their animals.) This is not a new issue,
It is clearly unethical for veterinarians to use antimicrobial
drugs illegally, just as it is unethical to promote illegal use and it has been addressed previously in panels and discus-
by others. Ignoring illegal use could be viewed as supplying sion forums.29 It is hard to reconcile restricting the sale of
tacit approval and therefore promotes this activity, even if antimicrobial drugs licensed for humans to prescription
this is not the intent of inaction. Identifying and acting in only, while allowing the sale of some of the same drugs in
these situations, although ethically necessary, should be animals without approval of a veterinarian. The Committee
viewed as a failure of the profession to adequately educate believes that wise, conservative use of antimicrobial drugs
veterinarians and the public about the importance of these requires a sophisticated, integrated understanding of pre-
issues. The Committee believes that the veterinary profes- ventive medicine, internal medicine, microbiology, and
sion can voluntarily regulate use of antimicrobial drugs to pharmacology, as well as a thorough understanding of an-
balance the benefit of our animal patients and the public imal management. Veterinarians are uniquely trained to
well-being. provide expertise in these disciplines. Therefore, to promote
Should Veterinarians Profit from the Sale of Antimi- judicious use, antimicrobial drugs should only be used in
crobial Drugs? The issue underlying this question is animals under the direction of a veterinarian. Scientific data
whether profit or other incentives provide motivation for are not available showing that use of antimicrobial drugs
unethical overprescription of antimicrobial drugs, as has without veterinary prescription or veterinary supervision
been implied by the World Health Organization.26–28 With- has had an effect on the prevalence of resistance any more
out question, veterinarians should expect to receive reason- than it might have if the drugs were only available by vet-
able compensation for their professional services and ma- erinary direction. It is true that the antimicrobial drugs that
terials used to care for the health of their patients. Unlike health professionals are most concerned about are the more
the human health care system, there is not a well-estab- advanced, newer drugs that are only available by prescrip-
lished network of pharmacists or other 3rd-party individuals tion in most countries. However, inappropriate use of other
that are trained, licensed, and experienced in dispensing drugs has the potential to increase the prevalence of resis-
antimicrobial drugs for use in animals. As such, veterinar- tance that would necessitate increased use of a higher cat-
ians play a vital role as educated dispensers of veterinary egory of drugs. Given the serious potential consequences
drugs in North America, Europe, and other parts of the of diminished clinical efficacy of antimicrobial drugs, the
world that cannot be readily replaced. There are no other Committee believes that conservative use should prevail.
currently available mechanisms for controlled distribution As such, the Committee recommends that veterinary or-
of antimicrobial drugs, and the Committee strongly believes ganizations and regulatory bodies promote prescription-
that veterinarians can and do act in an ethical manner re- only dispensing for antimicrobial drugs used in animals,
garding prescribing and dispensing of antimicrobial drugs. including birds and fish. This includes restricting legal sales
of preparations currently available without prescription, as
Recommendations
well as increasing restrictions and consequences associated
General Recommendation with illegal sale and importation of prescription antimicro-
The Committee recommends that voluntary actions be bial drugs from foreign countries or other black market
taken by the veterinary profession to promote conservative sources.
624 Morley et al
Recommendation B should be discussed with all clients. These infection control

plans must go beyond vaccination and deworming pro-
The Committee believes that veterinarians, because of grams. Veterinarians should educate owners and managers
their unique and specialized training, are the individuals about increases in disease risk whenever their animals con-
best able to make recommendations regarding the use of tact other animals through travel, showing, or introduction
antimicrobial drugs in animals, both from a policy perspec- of new animals to the premises (regardless how long they
tive as well as with regard to specific animal populations stay).
or individuals (assuming that veterinarians have established Although this might seem to be an obvious and simple
veterinarian-client-patient relationships). recommendation, the practicalities of formalizing and insti-
Any treatment of animals by owners or their agents tuting such policies will have a marked effect on day-to-
should be carried out in full accordance with orders pro- day activities. Daily routines must be characterized and
vided by veterinarians responsible for the health of these standardized. These include, but are not limited to, cleaning
animals. Veterinarians should encourage owners to follow procedures, disinfection practices, animal and personnel
all recommendations completely, especially in regard to movement, personal hygiene, routine housing practices, iso-
dose, frequency, and duration of treatment with antimicro- lation and quarantine practices, and waste disposal. In ad-
bial drugs, but also in regard to prevention and supportive dition, protocols must be developed to manage uncommon
care. Furthermore, we recommend that owners and man- situations or emergencies when they arise, such as disease
agers always seek veterinary advice before initiating treat- outbreaks. Exact recommendations will need to be tailored
ment with antimicrobial drugs in animals, which would be to individual premises and different animal populations.
an implicit requirement if antimicrobial use in animals was Veterinarians are uniquely qualified to assist with tailoring
restricted to a prescription-only basis. Expert advice from plans for specific populations and needs of owners and
veterinarians (including those experienced in clinical prac- should use this opportunity to market their talents.
tice) should always be sought when developing policy or
legislation regarding antimicrobial use or availability.
Recommendation E
Recommendation C Veterinarians should identify common case scenarios in
The Committee commends the work performed by many which antimicrobial drugs are often employed (eg, respi-
veterinary organizations to promote conservative use of an- ratory disease) and develop standardized antimicrobial drug
timicrobial drugs and recommends that all veterinarians use recommendations tailored for use in their practices. In
study and apply the science-based principles of judicious addition, the Committee recommends that the ACVIM and
use endorsed and promoted by many veterinary organiza- other veterinary organizations should commission experts
tions.5 to develop clinical practice guidelines addressing important
animal diseases commonly seen in veterinary practice.
Recommendation D The factors that should guide decisions regarding how
antimicrobial drugs are used should first and foremost in-
The Committee strongly recommends that veterinarians clude objective data regarding efficacy, toxicity, and pre-
assist in developing formal infection control plans for all disposition for use, to affect the prevalence of resistant bac-
facilities in which animals are reared or managed, including teria in target and bystander bacterial populations, and in-
all veterinary hospitals or clinics. The Committee strongly formation regarding importance of specific drugs for human
recommends that veterinary organizations assist veterinar- health care.30 In the absence of these specific data, caution
ians by developing resources to aid in the development of is warranted to ensure appropriate consideration for the
tailored disease control plans. safety of specific patients and the well-being of the larger
The 1st step in decreasing use of antimicrobial drugs is animal and human populations. For many case scenarios
to decrease the risk of bacterial infections when possible. that are commonly encountered, it would be most efficient
The most effective means of reducing this risk is to use and help to ensure consistency if practicing veterinarians
effective prevention practices for infectious diseases. It is formally considered and standardized antimicrobial uses
easy to become overwhelmed with the details of treating that they will employ for typical case presentations. These
disease to the point at which disease prevention efforts are antimicrobial drug use plans can be incorporated into in-
not given a priority in disease management. One way to fection control plans for veterinary practices and other an-
bring prominence to disease prevention efforts is to develop imal facilities. Veterinarians should evaluate these antimi-
formalized recommendations for disease control at animal crobial regimens to ensure that they are minimizing use
premises and veterinary facilities. where possible and using antimicrobial drugs wisely when-
It is important to realize that infection control plans are ever they are used. Antimicrobial drug use plans for a spe-
relevant for all types of animal facilities: for small and large cific practice or for groups of practices can be developed
animals, pleasure and business operations, rural agriculture that encourage the formation and use of infection control
facilities, and urban situations, among others. Infection con- committees whose job is to decrease the risk of hospital-
trol plans are especially important for complex operations associated infections and to decrease the consequences of
with large or transient populations of animals, but it is also these infections when they occur. Developing use policies
important to have infection control plans for households for antimicrobial drugs and monitoring programs for
with only a few pet animals. Infection control and hygiene emerging antimicrobial resistant pathogens in the hospital
should be considered in the management of all animals and environment is a logical aspect of this task.
Practice guidelines have become an important tool for include older drugs and those with a narrower spectrum of
physicians that use evidence-based medicine in practice31 coverage (eg, simple penicillins, tetracyclines, sulfon-
and would be a welcome source of information to veteri- amides). It is anticipated that these drugs will be used for
narians as well. Practice guidelines are typically prepared the majority of infections. It is important to remember that
by 1 or more clinical and diagnostic experts to assist prac- Primary Use drugs are not necessarily less potent or less
titioners in making decisions about appropriate health care useful than other drugs and can be very appropriate for use
for specific clinical circumstances. The intent is to improve in critically ill animals. Drugs assigned to the Secondary
appropriateness of care, improve cost effectiveness, and Use category include newer drugs with an extended spec-
serve as educational tools. These are not intended to dictate trum of coverage compared with Primary Use drugs and
standards of practice or detract from the ‘‘art’’ of veterinary those of added importance in the treatment of serious or
medicine. Rather, they are intended to ensure that the art frequently resistant infections in humans. Drugs for which
of medicine is applied on a solid, scientific basis. They will antimicrobial resistance appears to develop relatively easily
typically address various aspects of disease management, should also be included in this class. Secondary Use drugs
such as diagnosis, treatment, nursing care, and nutrition, should generally be reserved for use when culture and sen-
that are pertinent for a specific clinical conditions.32 To be sitivity results indicate that Primary Use drugs are not ap-
most useful, these guidelines should be evidence based and propriate. Drugs that are very important for human and an-
scientifically valid. However, practice guidelines are intend- imal health care, especially those most recently developed
ed to enhance clinical decision-making and should therefore and those that have extended spectra of coverage and are
never be a substitute for clinical discretion and judgment. useful against the most resistant bacteria, should be clas-
These guidelines will inherently be broad based because no sified for Tertiary use. Tertiary Use drugs should only be
guideline can ever be specific enough to be applied in all prescribed for animals with clinically important infections
situations. Examples of specific conditions for which clin- caused by bacteria that have been demonstrated to be re-
ical practice guidelines would be useful include, but are not sistant to all reasonable Primary and Secondary Use drugs.
limited to, the following: septicemia, infectious respiratory Veterinarians should also consider whether an antimicrobial
disease, gastrointestinal disease (including colitis, intestinal drug’s value to human welfare is so important that its use
obstruction, diarrhea, and inflammatory bowel disease), should be voluntarily prohibited in animals. Specifically,
major organ failure, and perioperative prophaylaxis for this voluntary prohibition should be considered for drugs
postsurgical infection in small and large animals; cancer, that are not licensed for use in veterinary medicine and are
cystitis, otitis, and dermatitis in small animals; and failure very important for treating resistant infections in humans.
of passive transfer of immunity or other health problems in To determine whether the occasional use of antimicrobial
large animal neonates. Ideally, practice guidelines are for- drugs that are very important for human health care is war-
mulated by summarizing and only considering the most ob- ranted, veterinarians are encouraged to develop procedural
jective and valid published research. However, the body of guidelines that outline advantages and disadvantages of use
published literature regarding some health conditions of an- according to the species of the patients, duration of use,
imals is meager. The committee recommends that the vet- and management that would reduce risk of transmitting re-
erinary profession promote the call for appropriate clinical sistant bacteria (if present) among in-contact people and
trials and other objective scientific studies that are needed animals. When developing treatment plans involving anti-
to strengthen recommendations that would be forwarded microbial use, veterinarians should seek to employ drugs
from clinical guidelines. conservatively when possible before using drugs in a more
aggressive manner. This includes considering use of local
Recommendation F rather than systemic application when possible. Higher cat-
egory drugs should not be employed in place of primary or
To facilitate appropriate empirical selection of antimicro- secondary drugs unless it is reasonable to believe that these
bial drugs on a routine basis, the Committee recommends drugs will provide meaningful aid to the recovery of pa-
that veterinarians categorize all antimicrobials used in their tients. More specifically, these drugs should not be em-
practice into Primary, Secondary, and Tertiary Use cate- ployed in patients that are likely to recover without treat-
gories. The Committee recommends that veterinary asso- ment, in patients that are as likely to be helped through
ciations foster communication with infection control and treatment with lower category drugs, or in patients that are
infectious disease specialists in human medicine to assist unlikely to survive regardless of the therapeutic regimen.
with classification of the relative importance of resistance It is very important that Secondary or Tertiary category
associated with different antimicrobial drugs in humans. antimicrobial drugs not be used when a Primary category
These assignments would be made by practicing veteri- drug could be just as effective. Decisions to advance from
narians relative to their individual practice circumstances a Primary category drug to a Secondary or Tertiary cate-
and would not be formally made by licensing agencies or gory drug should be based on culture and sensitivity infor-
pharmaceutical companies. Drugs will be assigned to dif- mation whenever possible or on inadequate response to
ferent use categories depending on the practice type and therapy with a lower category drug after allowing sufficient
patient profiles (ie, a drug could be assigned to a more time to evaluate response. Although it seems logical and
restrictive category in primary care and wellness practices practical that antimicrobial drugs should be used for some
but might be assigned to more permissive categories for minimum amount of time before reaching a conclusion
emergency, critical care, or referral specialty care practic- about failure to respond to treatment that would predicate
es). Drugs assigned to the Primary Use category would a change in treatment plans (ie, change drugs, route, dose,
626 Morley et al
etc), the Committee believes that science-based duration of resistance in small animals is still of concern because these
treatment information is lacking that would allow evidence- animals often share home environments with people.
based determination of this duration. This will obviously Antimicrobial drugs will always need to be used empir-
be affected by variation among patients in the adequacy of ically in some patients on the basis of previous experience
their defensive responses to infections, as well as by vari- and knowledge of the agents that are most likely to be
ation in pathogenicity among bacteria. The Committee rec- recovered from a particular species with disease in a par-
ommends that further research be conducted in this area of ticular organ system. Initial empirical treatment should rely
patient management. on drugs assigned to the Primary Use category, not in Sec-
Veterinarians should consider instituting more rigorous ondary or Tertiary Use categories, unless specific evidence
patient management protocols whenever Secondary or Ter- suggests that Secondary or Tertiary category drugs are
tiary category drugs are employed. These protocols might needed. Response to treatment should always be used in
include increased biosecurity and barrier nursing precau- evaluating the success of this drug treatment, but changes
tions to decrease the risk of direct and indirect transmission in treatment regimens should be based on culture and sus-
of resistant bacteria, careful management and disposal of ceptibility information as much as possible.
waste and bedding materials, more vigorous cleaning and
disinfection protocols, and specific client education regard- Recommendation I
ing home premises biosecurity.
The Committee believes that prophylactic and metaphy-
Recommendation G lactic use of antimicrobial drugs is appropriate for control
and prevention of infectious diseases in animals. However,
The Committee recommends the submission of appro- as is true for all uses of antimicrobial drugs, treatment in
priate specimens for bacterial culture, pathogen identifica- the absence of clinical disease should be conservative and
tion, and susceptibility testing by standardized methods should emphasize drugs assigned to the Primary Use cate-
whenever possible to allow an evidence-based approach for gory, except in situations in which specific information sug-
drug selection. gests that Secondary or Tertiary category drugs are needed.
Although this can increase the costs associated with pa- Veterinarians should reserve prophylactic or metaphylac-
tient care, other costs associated with improper drug selec- tic use for high-risk situations in which research or clinical
tion (prolonged treatment, unnecessary use of expensive an- experience has clearly shown that these applications pro-
timicrobial drugs, increased morbidity and mortality) can vide measurable clinical benefit. The Committee recom-
outweigh the cost of this testing. It is important to note that mends that further research be conducted to objectively
laboratory methods and standardized breakpoints still need evaluate the effectiveness of common prophylactic antimi-
to be established for numerous bacteria-drug combinations crobial drug uses in veterinary medicine. Veterinarians
that are important to veterinary medicine. The ACVIM ad- should consider whether animal husbandry situations in
vocates that additional research be conducted to improve which excessive problems with infectious diseases require
the veterinary profession’s ability to make evidence-based frequent or repeated prophylactic or metaphylactic use of
decisions about antimicrobial drug use. antimicrobial drugs constitute objectionable violations of
animal welfare standards.
Recommendation H It is not necessary to use antimicrobial drugs in all sur-
gical cases to prevent infections. It is possible to effectively
The Committee recommends that selection of resistant minimize the likelihood of postoperative infections by vig-
bacteria through use of antimicrobial drugs should be con- orously promoting aseptic technique, minimizing surgical
sidered an important potential risk associated with treat- time, and minimizing tissue manipulation. This is especially
ment. This potential outcome should not necessarily pre- true for clean surgeries, as opposed to clean-contaminated
clude use of antimicrobial drugs in animals that require or contaminated procedures, as classified by the National
treatment, but development of resistance should always be Academy of Sciences.33 Objective evaluations of human
considered as an important potential sequela of treatment surgical patients have allowed formulation of clinical prac-
and avoided whenever possible. tice guidelines regarding prophylactic antimicrobial use in
The consequences of developing resistance should be surgical patients.34,35 The Committee recommends that the
considered most important when it is associated with drugs American College of Veterinary Surgeons or other expert
that are most important for human health care or bacteria groups work to develop practice guidelines regarding an-
that are resistant to multiple drugs. There are many poten- timicrobial prophylaxis in veterinary surgical patients and
tial routes of zoonotic transmission of resistant bacteria. to pursue research on techniques that would reduce the use
Although foodborne transmission is frequently recognized of antimicrobial drugs as well as decrease the risk of sur-
for its potential importance, it is not necessarily more im- gical complications. Similarly, antimicrobial prophylaxis is
portant than transmission facilitated by direct and indirect not needed for all patients with indwelling catheters or
contact. Thus, resistance that emerged in companion ani- those undergoing invasive diagnostic procedures. Rigorous
mals could be as important a risk to human health as resis- use of aseptic technique and precautions known to mini-
tance that might emerge in food-producing animals. And mize risk of local infections can eliminate the need for an-
although large animals might have a greater potential to timicrobial drug treatment for these procedures in most pa-
contribute to environmental contamination with resistant fe- tients. Prophylaxis is appropriate in some patients that have
cal organisms compared with small animals, emergence of a diminished ability to appropriately respond to bacterial
infections, such as those with acquired immune dyscrasias, comycin resistance. These results should not be reported
those treated with immunosuppressive medications, or an- unless resistance is noted to alternative, lower priority
imals with other serious illnesses. However, the Committee drugs. Bacteriology laboratories should communicate with
strongly believes antimicrobial prophylaxis is not needed or infection control and infectious disease specialists in vet-
recommended for all patients with these conditions. Clinical erinary medicine to monitor the emergence of specific mul-
judgment will be needed to evaluate individual cases to tidrug-resistant organisms such as vancomycin-resistant en-
assess the likelihood of benefit from antimicrobial prophy- terococci and methicillin-resistant S aureus.
laxis. The Committee recommends that practice guidelines
be developed to assist practicing veterinarians with deci- Recommendation K
sions about conservative use of antimicrobial drugs in these
situations. Monitoring and surveillance are an important part of any
control program because they provide feedback on the sta-
Recommendation J tus of the program. As such, the Committee recommends
that the monitoring of antimicrobial drug use and surveil-
Diagnostic laboratories that test samples obtained from lance for trends in the prevalence of resistant bacteria be
animals through testing and reporting policies can have a promoted as important tools for the veterinary profession.
major effect on antimicrobial use practices of client veter- This should include active surveillance for dissemination of
inarians. As such, the Committee recommends that veteri- pathogens both within and between populations of different
nary diagnostic laboratories develop standardized protocols host species (including humans). In addition, the Commit-
regarding laboratory procedures and reporting of results for tee recommends that veterinary organizations urge the fed-
bacterial cultures and susceptibility testing. eral government fund the development of a national system
Bacteriology laboratories should consider refraining from for monitoring antimicrobial drug use in humans and ani-
reporting isolation of normal flora in normal numbers oc- mals.2
cupying a normal biological niche. If the bacterial growth Monitoring and surveillance will allow antimicrobial
cannot be distinguished from normal flora by its species drug use to be evaluated at various levels of the veterinary
identification, by identification of specific virulence factors profession: within practices, within practice specialties, re-
or correlated markers, or by clear demonstration of over- gionally, and even nationally. Individual veterinary practic-
growth, laboratory reports should clearly indicate that their es should devise methods for recording and periodically
presence in samples could be considered normal. For ex- (eg, quarterly, semiannually, or annually) summarizing an-
ample, a report stating ‘‘normal flora isolated’’ or ‘‘no Sal- timicrobial use data. These data should be reviewed and
monella isolated’’ is less likely to generate a request for compared with antimicrobial use protocols (described
unneeded susceptibility testing than a report noting ‘‘nu- above) to identify drug use that appears to be inconsistent
merous E coli isolated.’’ Antimicrobial susceptibility should or of concern. This is especially important for large, com-
generally not be reported for these normal flora, and testing plex veterinary practices. Surveillance for epidemics of re-
might not be necessary for specific pathogens with pre- sistant bacteria will allow assessment of the underlying
dictable susceptibilities or proven specific treatments with causes of changes in resistance prevalence and in some cas-
a high likelihood of efficacy.36 Decisions regarding which es will help to identify specific problems with biosecurity
bacteria should be selectively tested and reported should be and infection control.
made by the clinical microbiologist in conjunction with the The Committee also recommends that veterinary orga-
veterinarian and other relevant professionals, such as phar- nizations call for expansion of national systems for moni-
macists or the infection control committee for a hospital.37 toring antimicrobial susceptibility to include important an-
Although in many cases clinical microbiology laborato- imal pathogens and that diagnostic laboratories and veteri-
ries use broad, standardized panels of antimicrobial drugs nary practices strive to develop uniform methods for testing
when testing susceptibility in a variety of bacterial isolates, and reporting susceptibility information, including regular
it is the responsibility of the laboratory to limit the results summarization and reporting of susceptibility information
reported to those drugs appropriate to the bacterium, the to veterinarians. Currently, national surveillance efforts for
animal species of the patient, and the site of infection. The antimicrobial susceptibility target a few human and zoo-
spectrum of drug susceptibility results reported should be notic pathogens, especially foodborne pathogens. Suscep-
appropriate to the setting and could be different for animals tibility of other agents is only evaluated through smaller
seen by primary caregivers and referral centers. Guidelines investigations that often use different investigation meth-
published by the National Committee for Clinical Labora- ods, making it difficult to extrapolate among studies. Ex-
tory Standards provide suggestions for the most appropriate panding current surveillance efforts to include important
drugs to be tested for the major bacterial pathogens, in ad- animal pathogens (such as M haemolytica collected from
ditional to rational guidelines for selective or cascade re- cattle with respiratory disease or S aureus and E coli col-
porting of susceptibility information for higher order drugs lected from small animals with dermatitis or cystitis) would
if resistance is detected to the Primary Use drugs.37 provide important information about the ability to empha-
Bacteriology laboratories should routinely test certain size drugs in the Primary Use category, as well as the prev-
bacteria for resistance patterns that are of compelling con- alence of resistance to important antimicrobial drugs.
cern in human and veterinary medicine. For example, S On a smaller scale, active and passive surveillance
aureus isolates should be tested for methicillin resistance should be employed whenever possible to enhance early
when indicated, and enterococci should be tested for van- detection of transmission and amplification of resistant bac-
628 Morley et al
teria in animal populations. This is especially critical in promotion of resistance in bacteria). Furthermore, the Com-
larger animal populations and in veterinary hospitals and mittee recommends that veterinary organizations encourage
clinics. Veterinarians should record susceptibility informa- the pharmaceutical industry to follow the example of their
tion for their practices and compare these data with those industry leaders in promoting conservative antimicrobial
collected nationally, as well as locally or regionally. These drug use in veterinary medicine.
susceptibility data should be compared with antimicrobial Advertising can markedly influence use and prescription
use summaries, as well as antimicrobial use protocols. It is patterns for antimicrobial drugs. This is why pharmaceuti-
important that these data be categorized by treatment his- cal companies invest in this type of marketing. Although
tory so that data collected from animals after they have not universal, there are numerous examples of advertise-
been treated with an antimicrobial drug do not bias data ments for antimicrobial drugs that appeal more to emotion
intended to represent pretreatment susceptibility data for than to science in attempting to influence prescription pat-
animal pathogens. Routine monitoring of animals treated terns.
with higher category drugs (Secondary or Tertiary) should
be given a priority in order to detect emergence of bacterial Recommendation N
resistance to these important drugs. Veterinary practices
should consider including monitoring of bacterial suscep- The Committee recommends that governmental and non-
tibility data for all isolates obtained from animals with nos- governmental funding agencies prioritize research regard-
ocomial or postoperative infections. It might also be useful ing antimicrobial use, antimicrobial resistance, alternatives
to institute routine culture of environmental samples ob- to antimicrobial treatment, and infection control practices.
tained in areas in which patients treated with Tertiary cat- There is a dearth of information regarding factors that are
egory drugs are managed or housed. associated with development of antimicrobial resistance in
bacteria from animals and the risks of antimicrobial resis-
Recommendation L tance in veterinary isolates on animal and human health.1,2
Education is an essential cornerstone of the veterinary References

profession. The Committee believes that increasing educa-
tional efforts regarding antimicrobial resistance and con- 1. Phillips I, Casewell M, Cox T, et al. Does the use of antibiotics
servative antimicrobial drug use will be critical for the suc- in food animals pose a risk to human health? A critical review of
cess of efforts aimed at mitigating the hazards associated published data. J Antimicrob Chemother 2004;53:28–52.
with emerging antimicrobial resistance. 2. US General Accounting Office. Antibiotic resistance: Federal
agencies need to better focus efforts to address risk to humans from
These efforts should be targeted at all levels of the vet-
antibiotic use in animals. Washington, DC: GAO-04-490, April 2004.
erinary profession (veterinary students, practitioners, in- Available at: www.gao.gov/cgi-bin/getrpt?GAO-04-490. Accessed
terns, residents, and specialists), as well as owners and May 30, 2004.
managers of animals. The Committee believes that conser- 3. Isaacson RE, Torrence ME, eds. The role of antibiotics in ag-
vative use of antimicrobial drugs requires that veterinarians riculture. Washington, DC: American Academy of Microbiology,
become more sophisticated in their understanding of phar- 2002. Available at: http://www.asm.org/Academy/index.asp?bid5
macology and microbiology to most appropriately apply an- 2114. Accessed May 30, 2004.
timicrobial drugs. Efforts such as the Veterinary Antimi- 4. National Academy of Sciences–Committee on Drug Use in Food
crobial Decision Support System, which is designed to as- Animal, National Research Council, Institute of Medicine. The Use of
sist veterinary practitioners in making the best possible de- Drugs in Food Animals: Benefits and Risks. Washington, DC: National
Academy Press; 1999:79.
cisions about antimicrobial use, have the potential to greatly
5. American Veterinary Medical Association. AVMA Guidelines for
facilitate these efforts.38 Development of this and other tools judicious therapeutic use of antimicrobial drugs. Available at: http://
is highly encouraged to aid appropriate decision making by www.avma.org/scienact/jtua/default.asp. Accessed May 30, 2004.
busy veterinarians. In addition, the ACVIM and other vet- 6. Prescott JF, Baggot JD. Antimicrobial susceptibility testing and
erinary organizations should sponsor in-depth seminars on antimicrobial drug dosage. J Am Vet Med Assoc 1985;187:363–368.
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ACVIM Consensus Statement

J Vet Intern Med 2005;19:617–629

Antimicrobial Drug Use in Veterinary Medicine

A ntimicrobial drugs are used in animals, humans, and

Recommendation B should be discussed with all clients. These infection control

Education is an essential cornerstone of the veterinary References

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