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![Page 1: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/1.jpg)
Gamithromycin
A new azalide antibiotic for the treatment and control of Bovine
Respiratory Disease
Andy Forbes, BVM&S PhD MRCVS
Merial, Lyon, France
![Page 2: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/2.jpg)
OutlineProduct Profile
ChemistryPharmacokineticsAntibacterial activityChallenge studies
European Field trialsRegistration
TreatmentPrevention (metaphylaxis)
Post-launch experiencesItalyFrance
Closing remarks
![Page 3: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/3.jpg)
Gamithromycin is an Azalide
Azalides have a core 15-membered nitrogen-containing lactone ring
Azalide chemistry – Marked tissue affinity– Extensive uptake by cells– Broad antibacterial spectrum
![Page 4: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/4.jpg)
Pharmacokinetics
Gamithromycin is present in the bronchioalar macrophages at concentrations >60x those in plasma within 6 hours of administration
Gamithromycin is present in the lungs at concentrations >100x those in plasma for >20 days after administration
Gamithromycin is rapidly absorbed from the injection site and is re-distributed to tissues and cells, where it
persists for many days at effective concentrations
![Page 5: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/5.jpg)
Antibacterial potency
Species (European strains)
n
MIC50 MBC50 MIC90s MBC90s
µg/ml
Mannheimia haemolytica 96 0.25 0.5 0.5 1
Pasteurella multocida 120 0.5 1 1 2
Histophilus somni 39 0.5 1 1 2
![Page 6: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/6.jpg)
Lung Pharmacokinetics and in vitro Antibacterial activity
MIC mcg/ml 0.5 1.0
T> MIC 15 days 12 days
![Page 7: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/7.jpg)
Therapeutic efficacy M.haemolytica challenge
Cattle ~8 months old, mixed breed & sex
Challenge Day 0– Mannheimia haemolytica– MIC 0.5 mcg/ml– 3.03 x 1010 cfu
Treatment on Day 1– Saline– Gamithromycin @ 6 mg/kg
+
+
![Page 8: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/8.jpg)
Therapeutic efficacy
Depression
![Page 9: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/9.jpg)
Preventive efficacy M.haemolytica challenge
Dairy calves <3 months old, mixed breed & sex
Treatment Days -10, -5 & -1– Gamithromycin @ 6 mg/kg
Challenge Day 0– Mannheimia haemolytica– MIC 1.0 mcg/ml– 1.0 x 108 cfu
Treatment on Day +1– Saline
+
+
![Page 10: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/10.jpg)
Day-10Zactran
Day-5Zactran
Day-1Zactran
Day+1Saline
0
10
20
30
40
50
60
70
80
Treatment
Lung
Les
ion
Sco
re
1,00E+00
1,00E+01
1,00E+02
1,00E+03
1,00E+04
Zactran - 10 Zactran - 5 Zactran - 1 Saline +1
Lung lesion scores
Lung bacterial counts
Post-mortem lung bacteriology and pathology
Day -10 -5 -1 controlDay -10 -5 -1 control
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Score: 74 Score: 14
Control Zactran Day -10
Lung lesions
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European registration trials
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European treatment studies
Sites Locations Breeds Total numbers
19 BelgiumFranceGermanyItaly
Belgian BlueBrown SwissCharolaisHolsteinLimousinMontbelliardSalersSimmentalX-breds
528
Non-ruminating Ruminating
230 298
2-24 weeks old 10-88 weeks old
43-169 kg 55-495 kg
Single injection of gamithromycin @ 6 mg/kgPositive control
![Page 14: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/14.jpg)
Therapeutic studiesBRD inclusion criteria
Depression Score ≥1 andRespiratory Score ≥1 andRectal Temperature ≥40.0°C
![Page 15: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/15.jpg)
European prevention studies
Sites Locations Breeds Total numbers
5 FranceGermanyItaly
AubracBlonde d’AquitaineCharolaisFleckviehLimousinSalerX-breds
802
Non-ruminating Ruminating
246 556
2-13 weeks old 28-92 weeks old
54-139 kg 152-582 kg
Single injection of gamithromycin @ 6 mg/kgSaline control
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Prevention studiesBRD inclusion criteria
Cattle sharing an air-space where ≤10 animals had BRD>5% of cattle sharing an air-space had BRD within 3 days of the first caseAt least one of the main pathogens was present, confirmed through culture of nasal swabs– Mannheimia haemolytica– Pasteurella multocida– Mycoplasma bovis
![Page 17: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/17.jpg)
European Field Trials on Undifferentiated BRD
Bacteria present– Mannheimia haemolytica– Pasteurella multocida– Histophilus somni– Mycoplasma bovis
Viral status– Not identified– Some farms had used viral vaccines
Response to single s/c injection of gamithromycin at 6 mg/kg)
Therapeutic
• 82% Success Rate
Control (metaphylactic)
• 86% Success Rate
Treatment Success– Depression Score <1– Respiratory Score <1– Rectal Temperature <40.0°C
Prevention Success– Depression Score 0– Respiratory Score 0– Rectal Temperature >40.0°C
![Page 18: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/18.jpg)
European post-launch trials
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Italian prevention trial
Animals: 250 Charolais males
– Zactran group• 125 animals - 349 Kg
– Control group(no treatment)• 125 animals – 353 Kg
Arrival date: October 29
Respiratory vaccination on arrival– IBR/PI3+RSV+M. haemolytica
Start of the trial: October 30– Microbiology– Single treatment with gamithromycin 6mg/kg
(1ml/25kg)
![Page 20: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/20.jpg)
Microbiology of controls Day 14
Not present on Day 0
![Page 21: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/21.jpg)
Responses in animals treated with gamithromycin for BRD
1,6
4 4
0,8
3,2
0,8
3,2
4,8
1,6
4
1,6
6,4
1,6 1,6
0
1
2
3
4
5
6
7
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Control GamithromycinDay
Mo
rbid
ity r
ate
Morbidity rateControl 34%Gamithromycin 5%
Growth rate to Day 30Control 1.1 kg/dayGamithromycin 1.9 kg/day
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Italian therapeutic trial
Animals: 24 Limousin females with severe respiratory disease
– Gamithromycin group•13 animals – 258±32 Kg
– Tulathromycin group•11 animals – 259±33 Kg
Arrival date: December 1
Respiratory vaccination on arrival– IBR+PI3+BVD+RSV
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Number of animals requiring re-treatment
1 1 1 1 1
2
1
2
1 1 1
0
0,5
1
1,5
2
2,5
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Tulathromycin Gamithromycin
Days after arrival
n° o
f a
nim
als
wit
h r
es
pir
ato
ry
dis
ea
se
re
lap
se
s
Re-treatment rateTulathromycin 82%Gamithromycin 31%
Animals moved to hospital penTulathromycin 28%Gamithromycin 0%
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Practical ‘System’ approach, France
Objective– Evaluate the therapeutic efficacy
and the practicality & profitability of group metaphylaxis and individual treatments with gamithromycin.
– Economic factors included•Costs of treatment•Costs of handling •Growth rate
![Page 25: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/25.jpg)
Methodology
167 young cattle 8 different sourcesMales et females4,5 to 11 months old188 to 420 kgLimousin and Charolais
Start March 09On arrival– Weighed– Vaccinated
• Rispoval RSV/BVD• Iffavax IBR
– Parasiticide• Ivomec D
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Start of the study
4 days after arrival 13 animals had clinical BRDAll animals were then divided into 3 groups
– Group 1 : 13 sick• Day 0: Gamithromycin + ketoprofen
– Group 2 : 62 animals* metaphylaxis • Day 0: Gamithromycin
– Group 3 : 92 animals treated on a case-by-case basis• Day n: Gamithromycin + ketoprofen
*high risk, lower live weight, mainly Limousin heifers
![Page 27: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/27.jpg)
Allocation
16 pens, 8 each side of the central passage– One side
• Group 1: 2 pens for sick animals (13) • Group 2: 6 pens for metaphylactic group (62)
– Other side• Group 3: 8 pens for case-by-case treatment (92)
Group 1
Group 2Group 3
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By Day 8 – 26 animals treated in Group 3
![Page 29: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/29.jpg)
Pattern of clinical cases in Group 3
Arrival Day -4
73% of cases within 1 week of arrival
![Page 30: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/30.jpg)
Microbiology (PCR deep nasal swabs)
Résultats PCR du lot 1 à J 0 et J 14
60%
0%
100%100%
25% 25%
50%
100%
50%
20%
60%
20%
0%
20%
40%
60%
80%
100%
120%
Pou
rcen
tag
e d
e p
ools
posit
ifs
J 0 0% 20% 60% 20% 60% 0% 100%
J14 100% 25% 25% 50% 100% 50%
BVDMannheimia haemolytica
Pasteurella multocida
RSV PI3Mycoplasma
bovis
Coronavirus respiratoire
bovin
![Page 31: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/31.jpg)
ResultsBy Day 14 all animals in all groups were clinically normal
No animals in any group required re-treatment
BRD challenge appeared high– 28% new cases within 8 days in untreated animals
Mixture of common BRD pathogens– Mannheimia haemolytica and Mycoplasma bovis
predominated by Day 14
Growth performance and full economic analysis to follow
![Page 32: Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.](https://reader035.fdocuments.us/reader035/viewer/2022062516/56649e185503460f94b04608/html5/thumbnails/32.jpg)
Concluding Remarks
BRD remains a common disease– Bovine Lung anatomy & physiology, breed & genetics– Pathogens are numerous, diverse and ubiquitous– Predisposing factors are part of normal cattle husbandry
• Moving, mixing, crowding
BRD is a complex disease because it is multifactorial, in every sense of the word & variability is the normBRD control is not easy and results may be inconsistentIn addition to Management & Vaccination, Antibiotics can provide powerful tools to control BRD and treat clinical casesThe introduction of a dual-purpose antibiotic that provides good therapeutic activity and prolonged protective efficacy after a single treatment can deliver obvious benefits to the animal, the farmer and the veterinarian