Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France.

Slides:



Advertisements
Similar presentations
The prudent use of antibiotics in veterinary medicine: the right drug, the right time, the right dose & the right duration of treatment P.L. Toutain National.
Advertisements

BEEF PRODUCTION Beef. Introduction  The beef industry in Ireland is the largest sector of the Irish Agricultural Economy  There are 4.5 million beef.
“Suis-cide” Disease and Nursery Production Kevin J. Vilaca, B.Sc., M.Sc., DVM Maitland Swine Services Ontario, Canada.
PRACTICAL APPLICATION OF VACCINATIONS PREVENTING DISEASES IS ESSENTIAL TO CONTROLLING PRODUCTION HEALTH RISKS. PREVENTING ANIMAL HEALTH PROBLEMS INVOLVES.
 Health and Disease in Calves and Heifers. Overview  Common Disease Problems  Neonatal Calf Diarrhea (Scours)  Bovine Respiratory Disease (Pneumonia)
Great Plains Veterinary Educational Center Beef Feedlot Industry Structure / Economics / Marketing / Husbandry / Management / etc.
ALL IN – ALL OUT for BEEF PRODUCTION Tuovinen, V., Saarikivi, M., Hartikainen, K., Kauppinen, R., Herva, T., Manninen, U. and Kivinen, T. Tuesday 14:20.
Bovine Respiratory Disease Risk Reduction from Bloodlines to Fencelines Susan Kerr and Don Llewellyn WSU Extension, Animal Science, and Veterinary Medicine.
Prophylaxis & Metaphylaxis in Veterinary Antimicrobial Therapy
What do we know about genetics role in cattle diseases? Larry Kuehn Research Geneticist US Meat Animal Research Center.
Severe Sepsis Initial recognition and resuscitation
U.S. Food and Drug Administration Notice: Archived Document The content in this document is provided on the FDA’s website for reference purposes only.
1 PK/PD modeling within regulatory submissions Is it used? Can it be used and if yes, where? Views from industry 24 September 2008.
Zampelas A, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C. Associations between coffee consumption and inflammatory markers in healthy persons:
The Healthy Livestock Pneumonia Initiative Thomas Rees Steve Grills.
PNEUMONIA OF CALVES. Definition it is multifactorial respiratory disease of calves caused by different types of virus and characterized by variable degree.
ABSTRACT Two thousand three hundred and sixty-four high-risk calves were procured through sale barns by three order buyers in Arkansas, Mississippi, and.
Preventive Herd Health and Vaccination Cow/Calf Production Unit.
What Do Toxicologists Do?
Unit 8: Respiratory Diseases
Respiratory Diseases in Cattle Hannah, Anne, Emily, and Arielle.
The Genetics of Feedlot Health—an Update R. Mark Enns Department of Animal Sciences Colorado State University.
CRITICAL POINTS IN THE FEEDING OF HIGH YIELDING DAIRY COWS Gergácz, Z., †Báder, E., Szűcs, E. University of West Hungary, Faculty of Agricultural and Food.
Copyright myhealthyherd.com 2015 BRD CONTROL PROGRAMMES: A GUIDE FOR VETS.
Injections: How to give them and where to give them Chris Ellason.
Preparation and Evaluation of an Inactivated Multi-Strain PRRS Vaccine Made with Viruses Isolated from Vietnam Central Vietnam Veterinary Institute This.
Pink Eye James Reecy Annette O’Connor Abebe Hassen Gary Snowder.
B.V.D. Bovine Viral Diarrhoea Virus. BVD Highly contagious viral infection Most infections have no clinical signs Sero-conversion, virus elimination and.
Improvement in the Cattle Industry Stephanie Stimpson.
Pinkeye or Infectious Bovine
Economic Benefits of using Genetic Selection to Reduce the Prevalence of Bovine Respiratory Disease Complex in Beef Feedlot Cattle H.L. Neibergs 1, J.S.
Central Vietnam Veterinary Institute
 2011 Calf-ETERIA Study Benchmarking Ontario dairy calf and heifer raising practices Dairy Farmers of Ontario Dairy Research Communication Extension Event.
Mycoplasmal pneumonia in Swine
Swine Influenza (SI), Flu Dr. Zuhair Bani Ismail Jordan University of Science and Technology.
George R. Wiggans Animal Improvement Programs Laboratory Agricultural Research Service, USDA, Beltsville, MD National Association.
"Clinical Trials and Clinical Endpoints" James R. Bradford, DVM, Dipl. ABVP Pharmacia Animal Health.
LAB 3 RESPIRATORY / QUIZ QUESTION 1 Define the following terms: Atelectasis Bronchiectasis.
13 years in 20 minutes: Badger vaccine development and efficacy Dr Mark A. Chambers TB Science Lead Animal Health and Veterinary Laboratories Agency, U.K.
Status of Podolic cattle in Greece
Development and assessment of multivalent recombinant vaccines for bovine respiration disease Dr Tim Mahony Queensland Alliance Agriculture & Food Innovation.
An Outbreak of Viral Respiratory Disease in an Ontario Dairy Herd Jenna Donaldson OVC 2013
Great Plains Veterinary Educational Center Beef Feedlot Industry Structure / Economics / Marketing / Husbandry / Management / etc.
Selecting for Favorable Genetic Response to Disease
ORTHOMYXOVIRIDAE- INFLUENZA VIRUSES PETER H. RUSSELL, BVSc, PhD, FRCPath, MRCVS Department of Pathology and Infectious Diseases, The Royal Veterinary College,
Dr. drh. Maxs U.E. Sanam, M.Sc. PASTEURELLACEAE.
Respiratory System.
Charolais By: Maria and Aaron. Breed Characteristics They are usually white in color with a pink muzzle and pale hooves. There are now Charolais cattle.
CONTAGIOUS BOVINE PLEUROPNEUMONIA (CBPP). Mycoplasma mycoides subspecies mycoides SC (bovine biotype). subacute or symptomless infections persistence.
An Introduction to Biotechnology LECTURE 1: Biotechnology; 3 Credit hours Atta ur Rahman School of Applied Biosciences (ASAB) National University of Sciences.
Richard A. Vierling, Ph.D. May 12, 2016 Fargo, ND.
Great Plains Veterinary Educational Center What You Need to Know &Think About When Selecting Antibiotics The objective will be to help folks better understand:
Principles and methods of vaccine production and fish immunization
T. Allen 1, D. O’Toole 1, R. Hunter 2, L. Corbeil 3 1. University of Wyoming, Department of Veterinary Science Sybille Creek Road, Wheatland, WY.
Weaning Stress. Calves can be weaned any time after their rumens become functional Bottle fed calves can be weaned after one month of age Nursing cows.
Isolation of Mycoplasma ovipneumoniae and M. arginini from a goat flock affected with atypical respiratory symptoms Francione E. 1, Dellamaria D. 1, Minghetti.
Impact of Rotavirus Vaccination in Latin America
CASE 2 This is an interactive module working through a case from history to diagnosis. In “Slideshow” view, follow the hyperlinks into each lab/test and.
Vaccines and Livestock Medicine
Validation of three multiplex real-time PCR for Diagnosis of six Major Respiratory Pathogens in Cattle.
Figure 1 Protective effects of acellular pertussis vaccines (A–F) in the respiratory infection model. Mice were challenged by exposure to an aerosol of.
An Introduction to Medicinal Chemistry 3/e
Demonstration of early protection against foot-and-mouth disease virus
Vaccinations and Prevention of Infectious Disesase
Animal Husbandry By: DHRUBA MANDAL.
… genetics will someday make BRD as we know it a distant memory
THE SEROLOGICAL RESPONSE INDUCED BY INACTIVATED FMD VACCINE IN ISRAEL – CLINICAL TRIALS IN A DAIRY FARM Ehud Elnekave, Aldo Dekker, Phaedra Eble, Froukje.
Prepared by :Goran Rebwar Classification and Identification of Cattle Breeds.
Prepared by :Goran Rebwar Classification and Identification of beef Cattle Breeds.
Presentation transcript:

Gamithromycin A new azalide antibiotic for the treatment and control of Bovine Respiratory Disease Andy Forbes, BVM&S PhD MRCVS Merial, Lyon, France

Outline Product Profile Chemistry Pharmacokinetics Antibacterial activity Challenge studies European Field trials Registration Treatment Prevention (metaphylaxis) Post-launch experiences Italy France Closing remarks

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

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

Antibacterial potency Species (European strains) n MIC 50 MBC 50 MIC 90s MBC 90s µg/ml Mannheimia haemolytica Pasteurella multocida Histophilus somni

Lung Pharmacokinetics and in vitro Antibacterial activity MIC mcg/ml T> MIC15 days12 days

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 cfu Treatment on Day 1 –Saline 6 mg/kg + +

Therapeutic efficacy Depression

Preventive efficacy M.haemolytica challenge Dairy calves <3 months old, mixed breed & sex Treatment Days -10, -5 & -1 6 mg/kg Challenge Day 0 –Mannheimia haemolytica –MIC 1.0 mcg/ml –1.0 x 10 8 cfu Treatment on Day +1 –Saline + +

Lung lesion scores Lung bacterial counts Post-mortem lung bacteriology and pathology Day control

Score: 74 Score: 14 Control Zactran Day -10 Lung lesions

European registration trials

European treatment studies SitesLocationsBreedsTotal numbers 19Belgium France Germany Italy Belgian Blue Brown Swiss Charolais Holstein Limousin Montbelliard Salers Simmental X-breds 528 Non-ruminatingRuminating weeks old10-88 weeks old kg kg Single injection of 6 mg/kg Positive control

Therapeutic studies BRD inclusion criteria Depression Score ≥1 and Respiratory Score ≥1 and Rectal Temperature ≥40.0°C

European prevention studies SitesLocationsBreedsTotal numbers 5France Germany Italy Aubrac Blonde d’Aquitaine Charolais Fleckvieh Limousin Saler X-breds 802 Non-ruminatingRuminating weeks old28-92 weeks old kg kg Single injection of 6 mg/kg Saline control

Prevention studies BRD 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 case At least one of the main pathogens was present, confirmed through culture of nasal swabs –Mannheimia haemolytica –Pasteurella multocida –Mycoplasma bovis

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

European post-launch trials

Italian prevention trial Animals: 250 Charolais males –Zactran group 125 animals 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)

Microbiology of controls Day 14 Not present on Day 0

Responses in animals treated with gamithromycin for BRD Morbidity rate Control34% Gamithromycin5% Growth rate to Day 30 Control1.1 kg/day Gamithromycin1.9 kg/day

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

Number of animals requiring re- treatment Re-treatment rate Tulathromycin82% Gamithromycin31% Animals moved to hospital pen Tulathromycin28% Gamithromycin 0%

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

Methodology 167 young cattle 8 different sources Males et females 4,5 to 11 months old 188 to 420 kg Limousin and Charolais Start March 09 On arrival –Weighed –Vaccinated Rispoval RSV/BVD Iffavax IBR –Parasiticide Ivomec D

Start of the study 4 days after arrival 13 animals had clinical BRD All 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

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 2 Group 3

By Day 8 – 26 animals treated in Group 3

Pattern of clinical cases in Group 3 Arrival Day -4 73% of cases within 1 week of arrival

Microbiology (PCR deep nasal swabs)

Results By 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

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 norm BRD control is not easy and results may be inconsistent In addition to Management & Vaccination, Antibiotics can provide powerful tools to control BRD and treat clinical cases The 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