Progress 07/01/21 to 06/30/24
Outputs
Target Audience:The information below describes all presentations completed and respective target audiencessince initiation of the project: A poster describing the planned research was presented vitrually at the USDA Project Directors meeting held at the 2021 Conference for Research Workersin Animal Disease (CRWAD) in Chicago, IL. The target audience for this poster presentation was research workers andgraduate students studying diseases of animals. An oral abstract of the microbiological results obtained from both clinical efficacy studieswas presented in person at the2024Conference for Research Workersin Animal Disease (CRWAD) in Chicago, IL. The target audience for this oral presentation was research workers and graduate students studying diseases of animals. A poster describing themicrobiological results obtained from both clinical efficacy studieswas presented at the 2024 American Association of Bovine Practitioners (AABP) andAmerican Association of Small Ruminant Practitioners (AASRP)joint annual meeting held in Columbus, OH. The target audience wasresearch workers andgraduate students studying diseases of animals, as well as practicing veterinarians. Research data has also been incorporated into continuing education (CE) presentations given to veterinarians at the 2024 Iowa Veterinary Medical Association Annual Meeting held in Ames, IA,and the 2024 American Association of Small Ruminant Practitioners (AASRP) CE presentations held at the American Dairy Goat Association (ADGA) annual convention in Lake Geneva, WI. The target audience was practicing veterinarians. Research data from this project has also been incorporated into a webinar presentation for the 2024 Dairy Goat Webinar Series for the Iowa State University Extension Program. The target audience for this was goat producers. Finally, several informal data presentations have been given to the FDA Office of Minor Use Minor Species (MUMS) Animal Drug Development Team and the drug sponsor (Zoetis). The target audience of these presentations was government and industry regarding use of the data for pursuit of FDA label claim for use of tulathromycin in goats. Written reports of the research have also been completed or are in the process of completion for the following audiences: A yearly update has been submitted to theMinor Use Animal Drug Program (MUADP) for each year of the grant. The target audience for this are the regional directors of the MUADP program as well as government officials in USDA and FDA. A technical protocol was submitted to FDA MUMS and received concurrence for completion of the clinical efficacy study work performed. The target audience for this protocol was government officials in FDA. A final study report which is required for completion of the clinical efficacy technical section for label approval for tulathromycin for goats is currently in preparation.The target audience for this report will begovernment officials in FDA. Several research publications detailing the results of the completed work arein preparation at this time. The target audience for those publications when complete will beresearch workers andgraduate students studying diseases of animals, as well as practicing veterinarians and producers. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?For the first clinical efficacy study in summer 2022, six veterinary students were hired to assist in the project over the courseof the summer. A post-doctoral researchassociate was also recruited to assist with the study.These students and post-doc received training in physical examinations, necropsies, and diagnostic sample collection whichwill greatly benefit them in their future veterinary studies. In addition, two of the veterinary students were selectedas Foundation for Food and Animal Research (FFAR) summer scholars and utilized samples obtained from the goatson arrival at the research facility for additional antimicrobial susceptibility testing research projects.This opportunity is furthering their interest in potential careers in animalhealth research. For the second clinical efficacy study completed in summer 2023, six veterinary students were again hired to assist in the projectover the course of the summer (3 previous students from summer 2022 / 3 new students). A post-doctoral research associate was also recruited to assist with thestudy.These students and post-doc received trainingand experience in physical examinations, necropsies, and diagnostic sample collection which will greatly benefit them in theirfuture veterinary studies. In addition, one of the veterinary students participated in the ISU College of Veterinary Medicinesummer scholars program and utilized samples obtained from the goats on arrival at the research facility foradditionalantimicrobial susceptibility testing research projects. This student is also in the process ofcompletinga Masters degree utilizing the data generated during this project. How have the results been disseminated to communities of interest?The information below describes all presentations completedsince initiation of the project: A poster describing the planned researchwas presented vitrually at the USDA Project Directors meeting held at the 2021 Conference for Research Workersin Animal Disease (CRWAD) in Chicago, IL. An oral abstract of the microbiological results obtained from both clinical efficacy studieswas presented in person at the2024Conference for Research Workersin Animal Disease (CRWAD) in Chicago, IL. A poster describing themicrobiological results obtained from both clinical efficacy studieswas presented at the 2024 American Association of Bovine Practitioners (AABP) andAmerican Association of Small Ruminant Practitioners (AASRP)joint annual meeting held in Columbus, OH. Research data hasbeen incorporated into continuing education (CE) presentations given to veterinarians at the 2024 Iowa Veterinary Medical Association Annual Meeting held in Ames, IA,and the 2024 American Association of Small Ruminant Practitioners (AASRP) CE presentations held at the American Dairy Goat Association (ADGA) annual convention in Lake Geneva, WI. Research data from this project has also been incorporated into a webinar presentation for the 2024 Dairy Goat Webinar Series for the Iowa State University Extension Program. Finally, several informal data presentations have been given to the FDA Office of Minor Use Minor Species (MUMS) Animal Drug Development Team and the drug sponsor (Zoetis). Written reports of the research have also been completed or are in the process of completion: A yearly update has been submitted to theMinor Use Animal Drug Program (MUADP) for each year of the grant. A technical protocol was submitted to FDA MUMS and received concurrence for completion of the clinical efficacy study work performed. A final study report which is required for completion of the clinical efficacy technical section for label approval for tulathromycin for goats with the FDA is currently in preparation. Several research publications detailing the results of the completed work arein preparation at this time and will serve as the Masters thesis for a graduate student. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
1. Determine the efficacy of tulathromycin for treatment of naturally occuring respiratory disease in non-lactating goats Two randomized controlled clinical efficacy studies havebeen completed during summer2022 and summer 2023 to collect data to determine the efficacy of tulathromycin for treatment of naturally occuring respiratory disease in non-lactating goats. While full data analysis is ongoing, initial data analysis indicates that there was a statistically significant difference (P <0.001) in treatment success for animals treated withtulathromycin compared to the placebo during year 1, and close to statistical significance (P =0.06) during year 2. The difference in outcome between these two studies is hypothesized to be a result of the presence of genetically confered antimicrobial resistance to tulathromycin in the Mannheimia haemolytica isolates obtained from the animals deemed treatment failures during year 2 but not year 1 of the study. This data represents critical information for veterinarians and producers when faced with clinical decision-making regarding treatment of bacterial pneumonia in non-lactating goats, and indicates that in the absence of antimicrobial resistance to the macrolide class of antibiotics, tulathromycin is an efficacious choice for treatment. A final study report detailing these results is currently being drafted for submissionto FDA for completion of the clinical efficacy technical section required for FDA label approval.When completed and if accepted by FDA, this will leave only the human food safety (HFS) technical section yet to be completed for FDA label approval; the work necessary for the HFS section is currently underway at ISU through funding provided by the FDA MUMS program. 2. Document the current species distribution of bacterial causes of pneumnia in non-lactating goats in the United States Data was collected from the two randomized controlled clinical efficacy studies completed during summer2022 and summer 2023 to achieve this objective.Sample collection for isolation of bacteria from the nasopharynx at the time of diagnosis of respiratory disease and from lung swabs from animalsdeemed to be a treatment failures was completed for both studies, and a final report of the data has been received from the contract researchorganization (Microbial Research, Inc)that completed the work. BothMannheimia haemolyticaandPasteurella multocidawere equally distrubuted in both the nasopharyngeal and lung data and remain the primary bacterialpathogens identified from goats;whileBibersteinia trehalosiwas present in the samples, very few animals tested positive for this organism and thus it remains a rarely encountered pathogen. This information represents critical knowledge for veterinarians and producers when faced with making emperical treatment decisions in the face of respiratory disease outbreaks in goats. Isolates obtained during this study are currently under further investigation including whole genome sequencing, serotyping, and antmicrobial resistance (AMR) gene determination. When this work is completed, it will provide the research community with criticalinformation on currently circulating serotypes and AMR genes which can then be used for vaccine development and AMR surveillance. 3. Collect antimicrobial resistance data necessary for establishment of species-specific breakpoints for respiratory pathogensin goats. Data was collected from the two randomized controlled clinical efficacy studies completed during summer2022 and summer 2023 to achieve this objective.Antimicrobial susceptibility testing of bacteria from the nasopharynx at the time of diagnosis of respiratory disease and from lung swabsfrom animals deemed to be a treatment failures was completed for both studies,and data has been received from thecontract research organization that completed the work. This information representscritical knowledge for veterinarians and producers when faced with making emperical treatment decisions in the face of respiratory disease outbreaks in goats. Specifically, our work has documented that while minimal AMR was seen in the P. multicidaisolates, a uniqueresistance pattern includingresistance tomacrolides (gamithromycin and tulathromycin, but not tildipirosin), tetracyclines, spectinomycin, and beta-lactams (ampicillin, penicillin) was observed (interpretations based on extrapolated bovine breakpoints). If treatment failure is observed in the field, producers and practitioners should be aware that AMR genes are nowcirculating in goat respiratory pathogens, and diagnostic testing should be pursued to determine if AMR is the cause of the treatment failure. A database of the minimum inhibitory concentration (MIC) data from all bacterial isolates tested has been generated, and this data will be made available to the Clinical and Laboratory Standards Institute (CLSI) for establishment of clinical breakpoints following FDA label approval of tulathromycin in goats.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2024
Citation:
Kreuder AJ, Griffith RW, Hayman K, Buckley M, Michael A, Friedrich R, Gorden P, Plummer PJ, Hooyer H, Sterzinger N, Musco R, Peterson H, Payne J, Harris C, Mannery E, Kraemer A, Yantis L, Steffensmeier A. Efficacy of tulathromycin for treatment of respiratory disease in goats: microbiological data. Conference for Research Workers in Animal Disease (CRWAD) Proceedings, 2024.
- Type:
Conference Papers and Presentations
Status:
Awaiting Publication
Year Published:
2024
Citation:
Steffensmeier A, Sahin O, Elankumaran P, Shen H, Li G, Mou K, Kreuder AJ. Antimicrobial resistance of Pasteurellaceae in the upper respiratory tract of feedlot goats. AASRP/AABP Annual Conference, 2024. (abstract to be published in Bovine Practitioner)
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Progress 07/01/22 to 06/30/23
Outputs
Target Audience:
Nothing Reported
Changes/Problems:The following changes in our approach have been made at this time: 1. We have increased the number of animals to be diagnosed with clinical respiratory disease and enrolled in the study from a minimum total of 60 per arm (120 total) to a minimum total of 72 per arm (144 total). FDA has required that data from a minimum of 60 "evaluable" animals be available at the end of both studies to meet the required threshold to demonstrate efficacy. To dealwith the potential for case dropout due to unexpected comorbidities or data anomolies, we have added a 20% buffer to ourcase numbers to ensure that a minimum of 120 animals meet the study criteria in the end. To acheive this number ofenrolled animals, we anticipate needing to have 250-300 (instead of 200) animals available during each study to identify enough sick animals for enrollment. 2. Due to the timing of the award and available labor, the first clinical efficacy study was performed during summer2022. The second clinical effiacy study willbe performed summer 2023 based on availability of study animals and labor and requireda no-cost extensionto complete theplanned work. 3. Due to several unanticipated requirements by the FDA for completing the study, the labor required for the study haschanged substantially. This issue was communicated with the program officer in spring 2022, and permission was grantedto perform a rebudget of the grant spending categories to meet the requirements for FDA. In addition, since the grant was submitted and funded, Dr. Joseph Smith has left Iowa State University and is no longer available to provide support on theproject, and Dr. Paul Plummer is now associate dean for research with minimal available time to assist with the project. To address this, additional faculty (Dr. Patrick Gorden, Dr. Alyona Michael) have been recruited to serve in their place. A graduate student was not hired, and instead additional summer students and temporary post-doctoral scholarswere hired to complete the work as proposed. 4. Over the past year, we were able to secure the ability to complete study #2 at a local goat producer. However, completing the second study at this site required shifting of funds to pay for transportation, storage, and facilities at the site. However, the ability to perform the study at this site will allow us to complete the second study without applying for additional funding. What opportunities for training and professional development has the project provided?For the first clinical efficacy study in summer 2022, six veterinary students werehired to assist in the project over the course of thesummer. These studentsreceived training in physical examinations, necropsies, and diagnostic sample collection which will greatly benefit them in their future veterinary studies. In addition, two of the veterinary students were selected asFoundation for Food and Animal Research (FFAR) summer scholars and utilizedsamples obtained from the goats onarrival at the research facility for additional antimicrobial susceptibility testing research projects. A post-doctoral research associate was also recruited to assist with the study.This opportunity is furtheringtheir interest in potential careers in animal health research. For the secondclinical efficacy study planned forin summer 2023, six veterinary students werehired to assist in the project over the course of thesummer (3 previous students from summer 2022 / 3 new students). These studentswill receive training and experience in physical examinations, necropsies, and diagnostic sample collection whichwill greatly benefit them in their future veterinary studies. In addition, oneof the veterinary students will participate in the ISU College of Veterinary Medicine summer scholars program andutilizesamples obtained from the goats onarrival at the research facility for additional antimicrobial susceptibility testing research projects.A post-doctoral research associate was also recruited to assist with the study. How have the results been disseminated to communities of interest?Results cannot be disseminated until completion of second study and full data analysis. What do you plan to do during the next reporting period to accomplish the goals?During the third year of funding under the no-cost extensionwe plan to complete the secondclinical efficacy study and then will be able to complete all data analyses associated with bothstudies. Following completion and data analysis, final study reports will be completed for submission to the FDA ONADE to obtain acceptance of the data as proof of clinical efficacy of tulathromycin for label claim for treatment of respiratory disease in goats. Data will also be shared with CLSI to establish clinical breakpoints for goat respiratory pathogens. Finally, we anticipate multiple research publications from these projects which we will initiate during the NCE.
Impacts
What was accomplished under these goals?
Because the proposed work is specifically targeted towards generating data necessary for FDA label approval of tulathromycin for treatment of respiratory disease in goats, the first step of our funded project was to ensure that the work performed would meet the requirements for data acceptable for submission to FDA for label approval documentaion. Therefore, during the first year of this grant, extensive background work was done to prepare to meet FDA's requirements.Specifically, several meetings were held with FDA ONADE to discuss the goals of the project, and a protocol concurrence forthe first clinical efficacy study was obtained in February 2022. This concurrence specifically states that FDA "fundamentallyagree[s] with your proposed design, execution, and analyses and represents a commitment that we will not later alter our perspectives on these issues...". For our specific objectives, the following work was accomplished towards our objectives during years 1 and 2of the grant: 1. Determine the efficacy of tulathromycin for treatment of naturally occuring respiratory disease in non-lactating goats As of June 2023, the first of two randomized controlled clinical efficacy studies has been completed during summer 2022. While full data analysis of this study cannot be undertaken until completion of the second study, initial data analysis indicates that there was a statistically significant difference (P <0.05) in treatment success for animals treated with tulathromycin compared to the placebo. For study #2, the updated protocol has been completed, staff hired, and plans have been made for completion during summer 2023. Full analysis of data will not be completed until study #2 has been completed. 2. Document the current species distribution of bacterial causes of pneumnia in non-lactating goats in the United States As of June 2023, the first of two randomized controlled clinical efficacy studies hasbeen completed. Sample collection for isolation of bacteria from the nasopharynx at the time of diagnosis of respiratory disease and from lung swabs fromanimals deemed to be a treatment failures has been completed forstudy #1 and data has been received from the contract research organization that completed the work. For study #2, the updated protocol has been completed, staff hired, and plans have been made for completion during summer 2023. Full analysis of data will not be completed until study #2 has been completed. 3. Collect antimicrobial resistance data necessary for establishment of species-specific breakpoints for respiratorypathogens in goats. As of June 2023, the first of two randomized controlled clinical efficacy studies hasbeen completed. Antimicrobial susceptibility testing of bacteria from the nasopharynx at the time of diagnosis of respiratory diseaseand from lung swabs fromanimals deemed to be a treatment failureshas been completed forstudy #1 and data has been received from the contract research organization that completed the work. For study #2, the updated protocol has been completed, staff hired, and plans have been made for completion during summer 2023. Full analysis of data will not be completed until study #2 has been completed.
Publications
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Progress 07/01/21 to 06/30/22
Outputs
Target Audience:A poster was presented vitrually at the USDA Project Directors meeting held at the 2021 Conference for Research Workers in Animal Disease (CRWAD) in Chicago, IL. The target audience for this poster presentation was research workers and graduate students studying diseases of animals. Changes/Problems:The following changes in our approach have been made at this time: We have increased the number of animals to be diagnosed with clinical respiratory disease and enrolled in the study from a total of 60 per arm (120 total) to a total of 72 per arm (144 total). FDA has required that data from a minimum of 60 "evaluable" animals be available at the end of both studies to meet the required threshold to demonstrate efficacy. To deal with the potential for case dropout due to unexpected comorbidities or data anomolies, we have added a 20% buffer to our case numbers to ensure that a minimum of 120 animals meet the study criteria in the end. To acheive this number of enrolled animals, we anticipate needing to have 250-300 (instead of 200) animals available during each study to identify enough sick animals for enrollment. Due to the timing of the award and available labor, the first clinical efficacy study is being performed during summer 2022. The second clinical effiacy study will either be performed during fall 2022 or summer 2023 pending availability of study animals. If the second study is performed during summer 2023, a no-cost extension will be necessary to complete the planned work. Due to several unanticipated requirements by the FDA for completing the study, the labor required for the study has changed substantially. This issue was communicated with the program officer in spring 2022, and permission was granted to perform a rebudget of the grant spending categories to meet the requirements for FDA. In addition, since the grant was submitted and funded, Dr. Joseph Smith has left Iowa State University and is no longer available to provide support on the project. Additional faculty (Dr. Patrick Gorden) have been recruited to serve in his place. Since the grant was originally submitted, the cost of animal procurement, number of animals needed (as described above), labor, and supplies has increased dramatically. At this time we are evaluating if addtional funds may be necessary to complete the second clinical efficacy study. If necessary, additional funding may be applied for through the FDA MUMS program which is specifically available for projects such as this which are for completion of work on an FDA concurred protocol towards label approval of a product for minor animal species. What opportunities for training and professional development has the project provided?For the first clinical efficacy study, six veterinary students have been hired to assist in the project over the course of the summer. These students have received training in physical examinations, necropsies, and diagnostic sample collection which will greatly benefit them in their future veterinary studies. In addition, two of the veterinary students were selected as Foundation for Food and Animal Research (FFAR) summer scholars and are utilizing samples obtained from the goats on arrival at the research facility for additional antimicrobial susceptibility testing research projects. This opportunity is furthering their interest in potential careers in animal health research. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?During the second year of funding, we plan to complete the first clinical efficacy study and data analysis associated with that study. Pending availability of study animals, the second clinical efficacy study will either be initiated in fall 2022 or summer 2023. Due to unanticipated increased costs associated with completion of the project (animal procurement, supplies, and labor cost increases), additional funding for completion of the second clinical efficacy study may also be pursued during the next year through the FDA MUMS grant program to ensure that both clinical efficacy studies can be fully completed.
Impacts
What was accomplished under these goals?
Because the proposed work is specifically targeted towards generating data necessary for FDA label approval of tulathromycin for treatment of respiratory disease in goats, the first step of our funded project was to ensure that the work performed would meet the requirements for data acceptable for submission to FDA for label approval documentaion. Therefore, during the first year of this grant, extensive background work was done to prepare to meet FDA's requirements. Specifically, several meetings were held with FDA ONADE to discuss the goals of the project, and a protocol concurrence for the first clinical efficacy study was obtained in February 2022. This concurrence specifically states that FDA "fundamentally agree[s] with your proposed design, execution, and analyses and represents a commitment that we will not later alter our perspectives on these issues...". For our specific objectives, the following work was accomplished towards our objectives during the first year of the grant: Determine the efficacy of tulathromycin for treatment of naturally occuring respiratory disease in non-lactating goats As of June 2022, the first of two randomized controlledclinical efficacy studies have been initiated. Animal enrollment and data collection for clinical signs associated with respiratory disease and recovery following treatment with tulathromycin versus a placebois ongoingat this time. Document the current species distribution of bacterial causes of pneumnia in non-lactating goats in the United States As of June 2022, the first of two randomized controlled clinical efficacy studies have been initiated. Animal enrollment and sample collection for isolation ofbacteriafrom the nasopharynxat the time of diagnosis and from lung swabs from animals deemed to be a treatment failures is ongoingat this time. Collect antimicrobial resistance data necessary for establishment of species-specific breakpoints for respiratory pathogens in goats. As of June 2022, the first of two randomized controlled clinical efficacy studies have been initiated. Animal enrollment and data collection for bacterial isolates from the nasopharynx at the time of diagnosis and from lung swabs from animals deemed to be a treatment failureis ongoingat this time. Following isolation, full dilution antimicrobial susceptibility testing is being performed as isolates are identified.
Publications
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