Denagard Performance

M. hyopneumoniae/in vitro studies

Denagard® is highly active against

M. hyopneumoniae

KEY POINTS
lE
 nzootic pneumonia, caused by Mycoplasma hyopneumoniae, is a common and costly disease
of swine around the world.

l In vitro studies conducted in various countries have shown that Denagard (tiamulin) is highly active
against M. hyopneumoniae.

lW
 hen Denagard (tiamulin) is combined with doxycycline, there is a synergistic activity
against M. hyopneumonia.

Introduction
Enzootic pneumonia, caused by Mycoplasma hyopneumoniae,
affects pigs around the world and is considered one of the
most common and economically important diseases of swine.
Economic losses are due to reduced rate of gain and poor
feed efficiency 1.
developed solely for use in animals, not humans. In addition,
studies show that resistance to pleuromutilins develops slowly,
while resistance to some of the other antibiotics used against
mycoplasma pathogens can develop rapidly.

In vitro studies from several countries demonstrate that

pleuromutilin antibiotics such as Denagard® (tiamulin)
and Econor® (valnemulin) are highly active against Ulrich Klein Dr.med.vet
M. hyopneumoniae. Denagard is a versatile antibiotic Global Technical Services
that can be administered in feed, water or by injection, Manager pig and poultry

while Econor is conveniently administered in feed.

Pleuromutilins also minimize concern about the development of

antibiotic resistant bacteria developing in people, an important
concern among today’s consumers. Pleuromutilins were
United Kingdom
Since the development of resistance to antimicrobials
is an important concern for pig producers attempting
to control enzootic pneumonia, British investigators
determined MIC values to demonstrate whether
M. hyopneumoniae is likely to become resistant after
repeated exposure to tiamulin and two other antibiotics 2.
They used a “J” type strain obtained from a collection
of type cultures and a recent field isolate known
as MEVT G23.
lD
 espite 10 passages, resistance to tiamulin
was only slight in the type strain “J” and did
not occur in the field strain.
l T here was marked resistance of both isolates to
tylosin and moderate increases in resistance
to oxytetracycline, as shown in Table 1.
Their study, conclude the investigators, shows that
resistance does not develop readily in vitro to tiamulin.
“In contrast, high resistance developed quickly to tylosin,
an agent which has been in veterinary use for many
years,” they say.

Table 1. The results for two strains of M. hyopneumoniae passaged 10 times in vitro
“J” Strain Field Strain (MEVT G23))
Resistance Resistance
Before After Before After
Increase Increase
Tiamulin 0.1 0.25 2.5 0.05 0.05 0
Tylosin 0.25 >500 >2000 0.125 62.5 500
Oxytetracycline 0.25 1.0 4 0.25 1.0 4

Canada
A literature review by a Canadian veterinarian points out
that enzootic pneumonia does not always respond well
to treatment 3. Hence, products with low MICs for
M. hyopneumoniae should be favoured, the author says.
Table 2 is adapted from the review and reflects three
different studies summarizing the sensitivity results
of M. hyopneumoniae to various antimicrobials.
The investigator notes that fluoroquinolones have low
MICs for M. hyopneumoniae and have been effective in
treating enzootic pneumonia; however, because of their
importance in human medicine and current concerns
about antimicrobial resistance, particularly to drugs used
in both animals and people, the number of countries
that will allow or encourage the use of fluoroquinolones
in swine is being limited.

Table 2. The average MIC of four antimicrobials tested against M. hyopneumoniae

Reference No. of MIC (µg/ml)

Author/Year M. hyopneumoniae strains
Lincomycin Oxytetracycline Tylosin Tiamulin
Yamamoto ‘86 4
55 0.12 0.74 0.06 0.03
Inamoto ‘945 25 0.06 1.2 0.03 0.02
Hannan ‘97 20 ND 1 0.25 0.05
ND = Not determined
 Thailand Hungary
Investigators from Thailand determined MIC50 One of the most recent MIC studies of
and MIC90 values for nine antimicrobials using 27 M. hyopneumoniae strains was performed in Hungary 8.
M. hyopneumoniae field isolates 6. They found that: Ten strains of M. hyopneumoniae were isolated from
swine lungs and used to test the efficacy of several
lM
 . hyopneumoniae strains were very sensitive
antimicrobials. The investigators also tested combinations
to tiamulin and valnemulin. For instance, the range
of antimicrobials and determined both MIC50 and MIC90
for tiamulin, was <0.006-0.097.
values.
l T iamulin was two times more active
l Isolates were most susceptible to tiamulin.
than lincomycin.
See Table 3 for the MIC ranges.
lM
 . hyopneumoniae strains were only moderately
lW
 hen tiamulin was combined with doxycycline,
susceptible to tilmicosin, which had a range
there was synergistic activity (Table 4) against
of <0.024-3.125, and to chlortetracycline
M. hyopneumoniae pathogens.
and oxytetracycline.
lM
 . hyopneumoniae strains were less
Table 3. MIC ranges and MIC 90 of antibiotics tested
susceptible to spectinomycin, which for M. hyopneumoniae
had a range of <0.024-100.
Antimicrobial MIC range MIC 90

Korea Tiamulin 0.06-1.0 1.0

Minimum inhibitory concentrations (MICs) were
Doxycycline 0.5-32.0 16.0
determined for different antimicrobials used to treat M.
hyopneumoniae 7. MICs (µg/ml) were defined as the Tylosin 0.25-16.0 16.0
lowest concentration of antibiotics at which complete Lincomycin 0.25-8.0 8.0
inhibition of growth occurs. The seven isolates used
for testing antimicrobials in the study were taken from Chlortetracycline 4.0-32.0 32.0
Korean pigs ages 20 to 24 weeks old. Key findings Tilmicosin 0.125-2.0 2.0
follow:
l All M. hyopneumoniae isolates were highly Table 4. Average MIC values alone and in combination with doxycycline
susceptible to tiamulin.
Combined Synergy
Organism Tiamulin Doxycycline
lA
 ll isolates were moderately susceptible to tylosin, Tia/Doxy Factor
lincospectin and norfloxacin. Tia Doxy Tia Doxy
M. hyopneumoniae 0.219 5.169 0.094 0.659 2.3 7.8

The investigators conclude that the mycoplasma strains

they tested showed a high susceptibility to tiamulin,
and that the trial results prove the synergistic activity of
tiamulin against mycoplasma pathogens when used in
combination with doxycycline.
The synergistic activity of Denagard with other
tetracyclines like chlortetracycline and oxytetracycline
against mycoplasmal pathogens was demonstrated
in previous studies by Miller and Stipkovits in 19919
and Koh et al in 1994.

For further information or clinical data queries

please email: ulrich.klein@novartis.com
Visit our website: www.denagard.com
Summary
In vitro studies highlight the high susceptibility
of M. hyopneumoniae strains to tiamulin. Denagard
offers pig producers an effective agent for controlling
enzootic pneumonia due to M. hyopneumoniae.
The trial results also demonstrate the synergistic activity
of Denagard when used in combination with doxycycline.

References
1 Ross RF. Mycoplasma disease. In: Diseases of Swine, ed 7.
1992;537-551. Edited by Leman AD, et al. State University
Press, Ames, Iowa USA.

2 Hannan PC, et al. In vitro susceptibilities of recent field

isolates of Mycoplasma hyopneumoniae and Mycoplasma
hyosynoviae to valnemulin (Econor), tiamulin and enrofloxacin
and in the in vitro development of resistance to certain
antimicrobial agents in Mycoplasma hyopneumoniae. Res.
Vet. Sci. 1997;63:157-160.

3 Desrosiers R. A review of some aspects of the epidemiology,

diagnosis, and control of Mycoplasma hyopneumoniae
infections. J. Swine Health Prod. 2001;9(5):233-237.

4 Yamamoto K, et al. In vitro susceptibility of Mycoplasma

hyopneumoniae to antibiotics. Jpn. J. Vet. Sci. 1986;48:1-5.

5 Inamoto T, et al. Antibiotic susceptibility of Mycoplasma

hyopneumoniae isolated from swine. J. Vet. Med. Sci.
1994;56:393-394.

6 Thongkamkoon P, et al. In vitro susceptibility test of

Mycoplasma hyopneumoniae to antimicrobial agents. 17th
International Pig Veterinary Society Congress, Des Moines,
Iowa, USA 2002. Proceedings, p44.

7 Koh HB, et al. Minimum inhibitory concentrations of

tiamulin and oxytetracycline in combination in field isolates
of Mycoplasma hyopneumoniae. 13th International Pig
Veterinary Society Congress, Bangkok, Thailand 1994.
Proceedings, p353.

8 Stipkovits L, et al. Sensitivity testing of mycoplasma

pathogens to antimicrobials. Proceedings of the 18th
International Pig Veterinary Society Congress, Hamburg,
Germany 2004. Volume 2, p518.

9 Miller DJS and Stipkovits L. Recent advances in the control of

enzootic pneumonia. In: Proc. World Veterinary Congress, Rio
de Janeiro, Brasil 1991.

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