ARTICLE IN PRESS

International Journal of Medical Microbiology 296 (2006) S2, 33–38

www.elsevier.de/ijmm

Guidelines for prudent use of antimicrobials and their implications

on antibiotic usage in veterinary medicine
Fritz R. Ungemach, Dagmar Müller-Bahrdt, Getu Abraham
Institute of Pharmacology, Pharmacy and Toxicology, Veterinary Faculty, University of Leipzig, Leipzig, Germany

Abstract

Antibiotics are still deemed necessary for the treatment and prevention of infectious diseases in farm animals
intended for food production and to protect public health from food-borne diseases. All antibiotics used in veterinary
medicine are the same or closely related to antibacterials used in human medicine or may induce cross-resistance.
Consumption figures of antibiotics in the European Union (EU) indicate an about 10-fold higher number of treatment
days in human medicine when compared to veterinary usage with tetracyclines being the most frequently used group.
However, the conditions of antibiotic use in farm animals, mainly in swine and poultry by oral treatment of a large
number of animals for prolonged periods of time and risk of underdosing might favour the selection of bacterial
resistance. In order to reduce the use of antibiotics and thus to minimize the development of resistance in veterinary
medicine, compulsory guidelines for prudent use of antibacterials in animals were published in Germany in December
2000. These guidelines describe the minimum requirements to be followed by veterinarians when administering
antibiotics to animals. Key elements of the guidelines are the use of antibiotics on the basis of an exact (preferentially
microbiological) diagnosis, choice of the most suitable antibacterial substance (antibacterial spectrum as narrow as
possible, margin of safety as high as possible, good tissue penetration if necessary), restricted use of antibiotics with last
resort character, adherence to the label instructions (no underdosing or prolongation of dosing interval). Any
deviations from the guideline recommendations must be justified and recorded. Results of monitoring of antibiotic
usage as medicated feeding stuffs in pig production in the German state Sachsen-Anhalt from October 2000 until
March 2002 indicate a change of the prescribing attitude of veterinarians after implementation of the guidelines. The
consumption of antibiotics continuously declined from 4255 kg before the guidelines to 1145 kg in the first quarter of
2002 resulting in a reduction of the treatment days per animal from 31.6 (third quarter 2000) to 13.6 days (first quarter
2002). Simultaneously the use of chlortetracycline decreased from initially 76% of the total amount of antibiotics
prescribed to 14.7% at the end of the study, respectively. These results suggest an acceptance of the guidelines for
prudent antibiotic use by veterinarians as an important tool to reduce the usage of antibiotics and the consecutive
development of resistance.
r 2006 Published by Elsevier GmbH.

Keywords: Antibiotics; Veterinary medicine; Farm animals; Consumption figures; Prudent use

Introduction

Corresponding author. Tel.: +49 341 973 8130; Antibiotics are widely used in veterinary medicine for
fax: +49 341 973 8149. therapeutic, metaphylactic, or prophylactic treatment of
E-mail address: ungemach@rz.uni-leipzig.de (F.R. Ungemach). bacterial infections in farm animals intended for

1438-4221/$ - see front matter r 2006 Published by Elsevier GmbH.

doi:10.1016/j.ijmm.2006.01.059
 ARTICLE IN PRESS
34 F.R. Ungemach et al. / International Journal of Medical Microbiology 296 (2006) S2, 33–38

production of human food (meat, milk or eggs). The
rationale for veterinary use of antibiotics is to protect
animal welfare, to prevent epidemic spread of infectious
animal diseases, to provide high efficiency of animal
production, to prevent the transfer of zoonoses from
animals to the human population, to warrant safety of
food of animal origin and to prevent food-borne
diseases (Ungemach, 2000). Antibiotics are vital drugs
in veterinary medicine and cannot be replaced in the
near future due to the lack of suitable alternatives, e.g.
vaccines. The inherent risk of any use of antibiotics to
select for bacterial resistance poses a relevant risk for
public health by spreading of the resistance from farm
animals to the human population via different patterns
(Witte, 1998). Although, this risk is supposedly of minor
importance when compared to resistance selection by
antibiotic use in human medicine, some resistant
zoonotic pathogens like Salmonella, Campylobacter,
Listeria or Escherichia coli could be isolated in farm
animals and food of animal origin, or when sporadically
found in humans, they could be traced back to animal
origin (Mǿlbak, 2004).
Usage of antibiotics in human and veterinary
medicine
Data on the amounts of the antibiotics used in
veterinary medicine are scarce in Germany and in EU
member states with the only exception of Scandi-
navian countries. Estimates of sales volume of anti-
biotics in the EU and Switzerland were provided by the
Fédération Européenne de la Santé Animale (Fedesa)
for 1997 and 1999 (Table 1) (Fedesa, 1998, 2001). In
1997, in animals a total of 3494 tonne of active
ingredients were used as therapeutics. A portion of
66% was tetracyclines while macrolides amounted to
12% and penicillins to 9%; the other antimicro-
bial groups together comprised 12%. In contrast to
human medicine, newer potent antimicrobials such as
third-generation cephalosporins and fluoroquino-
lones are still used to a very minor extent (o1%).
Simultaneously, the estimated consumption of antibio-
tics in human medicine was 7659 tonne. In 1999, the
usage in veterinary medicine increased by 408 tonne
while in the meantime the non-therapeutic usage of
antibiotics as growth promoters in farm animals
declined by 51% to 786 tonne due to the ban of various
antibacterial feed additives which finally will be phased
out in 2006.
According to the EU usage figures of 1997, the
European human population, and the number of
food-producing animal species in the EU (cattle,
sheep, goat, pig, poultry) doses of 342 and 54 mg anti-
biotic/kg body mass/year, respectively, were esti-
mated revealing an approximately 6.3-fold higher use
of antibiotics in humans when compared to animals
(Table 1). The number of antimicrobial treatment
days was several folds higher for humans than for

Table 1. Sales volume and dosage of antibacterial drugs in the European Union and Switzerland in human and veterinary medicine
in the years 1997 and 1999

Human Animals
(Farm animal)

Antibiotics
1999 8528a 3902a  0.8b
1997 7659a 3494a  0.8b
Population (1997)
Numberc Body weight Numberc Body weightc
(  106) (kg  106) (  106) (kg  106)
Men (60 kg)d 373 22 380
Cattle/calves 56.7 17 130
Sheep/goats 71.1 2539
Pigs 190.5 20 398
Poultry (2 kg)e 5804 51 496
Dosage (mg/kg b.w.) 342 54
Treatment days 34–68 2.7–5.4
MDDf (mg/kg) 5–10 10–20
a
Data according to Fedesa (1998, 2001).
b
80% farm animals/20% companion animals.
c
Data (animal number and slaughter weight) according to Eurostat (1997).
d
Mean body weight of 60 kg.
e
Mean body weight at slaughter (1997).
f
Mean daily doses of antibacterial groups used in human/veterinary medicine.
 ARTICLE IN PRESS
F.R. Ungemach et al. / International Journal of Medical Microbiology 296 (2006) S2, 33–38
Table 2. Veterinary use of medicated feeding stuffs with
antibacterial drugs in Schleswig-Holstein (Germany) 1998
Total (kg) 22 053
Antibacterial groups (% of total)
Tetracyclines 65.7
Trimethoprim/sulphonamides 22.2
Macrolides/lincosamides 2.4
Tiamulin 2.1
Aminoglycosides 3.8
b-Lactams 3.1
Colistin 2.9
Fluoroquinolones 0.06
Combinations (% of total prescriptions)
1 Ingredient 51.4
2 Ingredients 30.7
3–5 Ingredients 17.9
Treatment days 12 (range 1–40)
Prescriptions for the treatment of 2.3  106 pigs (body weighto40 kg
for 85% of the animals). According to Broll et al. (2002).
animals indicating a significantly higher use of ther-
apeutic antibiotics in human medicine as compared to
treatment of farm animals (Table 1).
Although animals are treated to a lesser extent
with antibiotics when compared to men, the conditions
of antibacterial use in farm animals may favour the
development of resistance. For practical reasons oral
treatment is the usual administration route in calves,
pigs and poultry, and about 88% of the antibiotics
are administered via medicated feeding stuffs and drink-
ing water. This mode of application allows the treat-
ment of whole animal herds over extended periods of
time. Oral flock treatment exceeds 80% whereas indi-
vidual therapy with injectables is less than 20% (Goodyear,
2004). Thus, a large number of animals may be under
long-term exposure of preferentially broad spectrum
antibiotics exerting a high pressure for selection of
bacterial resistance. A further problem linked to mass
medication via feed or water is the likelihood of inad-
vertent under dosing due to reduced bioavailability,
e.g. by inhomogeneous mixtures, chemical degrada-
tion of the drug, adverse interactions with feed compo-
nents, or other drugs, and reduced feed intake by the
diseased animals. Table 2 shows the results of a sur-
vey of usage of medicated feeding stuffs in about
3 million pigs in the German state Schleswig-Holstein
in 1998. The disproportionally high use of tetracy-
clines (as in other EU member states) and treatment
periods of up to 40 days suggest some indiscriminate
antibiotic use. In more than 50% of the treatments
the antibiotics were used for prophylaxis or metaphy-
laxis, indications which often lack a precise diagnosis (Broll
et al., 2002).
35
Guidelines for prudent use of antibiotics in
veterinary medicine
In November 2000, the German Federal Veterinarians
Association (BTK) and the Working Group of Chief
Veterinary Officers (ArgeVet) published the guidelines
for prudent use of antibacterials in animals with the aim
to minimize the development of resistance in veterinary
medicine (BTK and ArgeVet, 2000). The guidelines are
the minimum requirements which must always be
followed by veterinarians when administering antibi-
otics to animals in order to reduce the use of antibiotics
to the lowest indispensable level. The guidelines
constitute the rules of veterinary science which are to
be complied with during any use of antibiotics in
animals and which must be observed each and every
time an animal is treated properly in accordance with
the drug legislation. The antibiotics can only be pre-
scribed by a veterinarian and used by the animal owner
according to written instructions under veterinary
supervision. The veterinarian must check this at suitable
intervals by monitoring the success of the treatment.
The use of antibiotics is only justified for therapy or
metaphylaxis (no symptoms have yet appeared in
infected animals) if it has been proven by appropriate
and objective diagnostic measures that the animals are
infected by a pathogen sensitive to the antibiotic that is
to be administered. Prophylaxis is only admissible in
substantiated exceptional cases (e.g. immunosuppres-
sion, perioperative). The diagnosis may generally be
based on the identification of the pathogen and an
antibiogram. This microbiological diagnosis is always
necessary when switching the therapy to another
antibiotic, in the case of use of not fixed antibiotic
combinations, when the antibiotic is not used in
compliance with the label instructions (other dosage or
animal species than designated) and regularly in the case
of repeated or long-term use in larger animal herds.
The German guideline for prudent antibiotic use does
not demand the selection of antibiotics from defined lists
of antibiotics of first, second or third choice. Instead of
such rather inflexible lists, the selection is based on
Good Veterinary Practice. It is left to the veterinarian to
deliberately select the most suitable antibiotic which best
matches with following criteria of choice:
 spectrum of antibacterial activity as narrow as
possible;
 margin of safety (dose ratio of desired and adverse
effects) as high as possible;
 good tissue penetration if necessary and
 antibacterials used as last resort in human medicine
(e.g. fluoroquinolones, 3rd generation cephalospo-
rins) may only be used in single animals for a limited
number of strict indications where other antibiotics
fail.
 ARTICLE IN PRESS
36 F.R. Ungemach et al. / International Journal of Medical Microbiology 296 (2006) S2, 33–38
Fig. 1. Flow-chart of antibiotic selection according to the
guidelines of prudent use. According to BTK and ArgeVet
(2000).
Fig. 1 depicts the flow chart for selecting antibiotics
and conducting antibiotic treatment of animals in
compliance with the guidelines. Any deviations from
the recommendations must be justified and recorded.
Acceptance of the guidelines for prudent use of
antibiotics by veterinarians
The adherence to the rules of the guideline on prudent
use of antibiotics forces the veterinarian to a more
precise clinical and microbiological diagnosis, to de-
tailed knowledge of the features of antibacterials, to
keep a sufficient assortment of various antibiotics, and
the readiness for documentation. The impact of the
guidelines on the attitude of veterinarians to prescribe
antibacterials may best be checked by a broad-scale
monitoring of the resistance development as well as of
the consumption of antibiotics specified for the different
animal species. In Germany, to date no system has been
established to monitor antibiotic consumption.
After implementation of the guidelines only one
survey has been performed on the use of antibiotic-
medicated feeding stuffs in the German state Sachsen-
4500
4000 total antibiotics
3500 tetracyclines
3000
2500
2000
1500
1000
500
0
3rd 2000 1st 2001 3rd 2001 1st 2002
Quarter of the year
⇑ ⇑ ⇑ ⇑
Implementation "scandal" discussion and proposal
of guidelines of drug misuse in of more strict veterinary
for prudent use pig production drug legislation in Germany
of antibiotics in Bavaria
Fig. 2. Use of antibiotics in medicated feed stuffs in pigs of
Sachsen-Anhalt (Germany) 2000–2002.
Anhalt (Müller-Bahrdt, 2004). A total of 1088 prescrip-
tions of antibiotic-medicated feeding stuffs for fattening
pigs were evaluated, which have been issued by 63
veterinarians in the 3rd quarter of the year 2000 (just
before publication of the guidelines) and in the following
quarters January 2001, March 2001 and January 2002.
The number of treated animals remained almost
constant with a mean of 241 000 pigs per quarter
throughout the study with usual seasonal changes
and comprised about 30% of the total pig popula-
tion of that state. The number of prescriptions per
quarter continuously declined from about 350 to 250 in
the last quarter. Simultaneously, the amount of anti-
biotics prescribed decreased by 73% from 4255 to
1145 kg per quarter. This strong decrease was mainly
due to a dramatic reduction of the use or chlortetracy-
cline which constituted 76% at the beginning and only
14.7% of all antibiotics at the end of the monitoring
period (Fig. 2). Since the number of treated animals
remained almost constant throughout the observation
period, the total number of defined daily doses
continuously declined from 8.2  106 in the 3rd quarter
of the year 2000 to 2.9  106 in the 1st quarter 2002
which resulted in a reduction of treatment days per
animal from 31.6 to 13.6 days, respectively (Table 3).
The lesser use of chlortetracycline was only partly
substituted by prescription of other antibiotics, e.g. by
the newer macrolide tilmicosin with a narrower anti-
bacterial spectrum (Table 3).
The results of this study provide first evidences of an
adherence to the guidelines for prudent antibiotic use by
veterinarians indicating the following changes of their
attitude to prescribe antibiotics:
 less prescriptions and a marked reduction of treat-
ment days,
 ARTICLE IN PRESS
F.R. Ungemach et al. / International Journal of Medical Microbiology 296 (2006) S2, 33–38 37

Total per animal

switching from older tetracyclines with high rate of
inaccurate dosing (mainly underdosing) to more
modern and exactly dosed antibiotics (Table 4);
 a trend towards more therapeutic indications (79% in
March 2000 versus 90% in January 2002) instead of

31.6
19.7
13.4
13.6
prophylaxis.

No data is available on the use of antibiotics during

Chlortetracycline

the monitoring period by other routes of administration.

Therefore, it cannot be ruled out that the reduction of
(30 mg/kg)

antibiotic use via medicated feeding stuffs might have

been at least partly compensated by injectables or by
4310
1460
250
231

other modes of oral application.

During the observation period and shortly after
publication of the antibiotic guideline, a large-scale
misuse of antibiotics in pigs was uncovered in Bavaria
Oxytetracycline

and Austria at the end of January 2001 which caused a

Treatment days with antibiotics as medicated feeding stuffs in pigs in Sachsen-Anhalt (Germany) 2000–2002

strong debate within the veterinary profession as well as

(40 mg/kg)

in the public on a more restrictive use of antibiotics in

food-producing animals (Fig. 2). To this end, an
6.0
39.7
8.2
10.7

amendment of the German drug legislation came into

force in November 2002 which restricted the veterinary
prescription of antibiotics for food-producing animals
to a maximum of seven treatment days. After that
Tetracycline
(20 mg/kg)

period the veterinarian has to check again the need of a

continuation of the antibiotic treatment by re-examining
358.2
634.4

810
1058

the animals. It is reasonable to assume that the

discussions around this ‘‘antibiotic scandal’’ might have
promoted the acceptance of the guidelines of prudent
antibiotic use by the veterinarians.
(5 mg/kg)
Selected antibiotics (  103)

Colistin

619.6
741.5
778.4
674.2

Conclusions
First results of monitoring of antibiotic consumption
Number of treated animals (see Fig. 2) (mean body weight 25 kg).
(10 mg/kg)
Tilmicosin

in farm animals after implementation of the antibiotic

guidelines in Germany provide evidence of a more
9.6
78.4
91.2
67.2

prudent use of antibiotics by veterinarians in farm

animals.
These results suggest compulsory guidelines for
prudent use of antibiotics in animals as an important
Treatment days

tool of risk management to reduce the consumption of

Total (  106)a

antibiotics and the consecutive development of resis-

Recommended daily doses in brackets.

tance. To promote the adherence to the guideline in

veterinary medicine and to increase its efficacy suppor-
All antibiotics in all animals.
8.2
4.7
3.5
2.9

tive measures are deemed necessary such as repre-

sentative monitoring of antibiotic resistance and con-
sumption, implementation of mandatory guidelines in
the drug legislation, a straightforward control, training
Quarter of year

of the veterinarians, adaptation of the drug registration

January 2001

January 2002
March 2000

March 2001

and label instructions for antibiotics to the rules of the

Table 3.

guidelines, and legally based limitations of the amounts

of antibiotics to be prescribed and dispensed for use in
a

farm animals intended for production of human food.

 ARTICLE IN PRESS
38 F.R. Ungemach et al. / International Journal of Medical Microbiology 296 (2006) S2, 33–38

Table 4. Antibiotics used as medicated feeding stuffs in pigs in Sachsen-Anhalt (Germany) 2000–2002: dosage accuracy of all
prescriptions

Quarter of year Antibiotics

CTC Colistin Amoxicillin Tilmicosin

k DDD m k DDD m k DDD m k DDD m

March 2000 47 13 40 29 26 45 0 33 67 0 100 0

January 2002 87 11 2 40 34 26 0 0 100 0 100 0
All 61 15 24 40 34 26 0 20 80 0 100 0

DDD: Defined daily dose (70–130% of recommended dose).

m: Over dosage (4130% of recommended dose).
k: Under dosage (o70% of recommended dose).
CTC: Chlortetracycline.

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