The conduct of clinical trials and good clinical practices: the sponsor's perspective. Food and Drug Administration.

The Guideline, "Conduct of Clinical Investigations: Responsibilities of Clinical Investigators and Monitors for Investigational New Animal Drug Studies," which was issued by the Center for Veterinary Medicine (CVM) in October 1992 is intended to improve standards of clinical research. The purpose of clinical trials is to obtain data to support dose selection and to confirm the dose for regulatory approval of New Animal Drug Applications (NADA). The processes and procedures described in the Guideline should improve the "fitness for use" of data from clinical trials. Clinical investigators who desire to work with drug sponsors must understand the tenor of the Guideline and implement its recommendations when conducting pivotal clinical research. Protocols in which procedures are clearly described and responsibilities for monitors and investigators defined, in concert with a preplanned definitions of source data supported by appropriate quality control and quality assurance procedures, will ensure that the basis of approval for new animal drugs is defensible.

Eficácia de soluçäo oral de ivermectin contra larvas de Dermatobia hominis (Linnaeus Jr. 1871) em bovinos / Efficacy of ivermectin oral solution in cattle against larval stages of Dermatobia hominis (Linnaeus Jr. 1781)

Os resultados do presente experimento, realizado em duas fazendas do município de Campinas, SP, demonstram que o ivermectin, quando aplicado por via oral, numa única dose de 200 mcg/kg de peso vivo, é altamente eficaz no tratamento e controle dos estágios parasitários das larvas de D. hominis (bernes) em bovinos

Efficacy of sulbactam-ampicillin in an induced Pasteurella haemolytica pneumonia model in calves.

Therapeutic efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin was evaluated in an ampicillin-resistant Pasteurella haemolytica pneumonia model in cattle, using an IV agar emboli method of infection. Groups of cattle given vehicle (group 1, n = 19) or ampicillin (group 2, n = 8) had 74% and 50% mortality, respectively, whereas group 3 (n = 11) given sulbactam-ampicillin had no mortality. Morbidities were 100% in groups 1 and 2 and 27% in group 3. Retrospectively, mortalities and morbidities were significantly (P less than 0.001) lower for group 3 given sulbactam-ampicillin when compared with those in groups 1 and 2 given vehicle or ampicillin, respectively. Evidence of embolic pneumonic pasteurellosis was observed histologically.

Long-acting oxytetracycline for control of induced Pasteurella multocida rhinitis in swine.

A long-acting oxytetracycline formulation was evaluated for control of rhinitis induced experimentally in pigs with a capsular type A, toxin-negative, low-passage strain of Pasteurella multocida. The pigs were 6 to 7 weeks old and were naturally infected with Haemophilus parasuis. The H parasuis infection was thought to predispose to establishment of P multocida in the nasal cavity. A long-acting oxytetracycline formulation was given IM at the rate of 20 mg/kg, 4 times at 5-day intervals. Medication reduced (P less than 0.05) the severity of turbinate atrophy and the proportion of pigs with P multocida and H parasuis in their nasal cavities. Numbers of colonies of P multocida and H parasuis isolated were also less in medicated pigs.

Evaluation of an induced Pasteurella multocida swine pneumonia model.

A reproducible swine pneumonia model was developed, utilizing Pasteurella multocida (strain MSU 7) and a rapid endotracheal inoculating technique. The model provided a means of testing various factors, such as therapeutic agents that may influence the course of pulmonary pasteurellosis. In a series of experiments, 81 infected nonmedicated pigs had a morbidity of 96% and a mortality of 22%. Pasteurella multocida was isolated from 62% of the lungs at necropsy; 86% of the lungs had gross lesions characteristic for strain MSU 7 pneumonic pasteurellosis when the pigs were necropsied 7 days after inoculation.

Parenteral vaccination of young swine against Bordetella bronchiseptica.

The efficacy of Bordetella bronchiseptica bacterins for the prevention of nasal turbinate atrophy caused by induced B bronchiseptica infection in young swine was evaluated. Vaccination of pigs at an early age (eg, at 1 and 4 weeks of age) with potent B bronchiseptica strain D-1 bacterins resulted in high concentrations of circulating antibody up to 12 weeks of age or longer and in a significant (P less than 0.01) reduction in the frequency of turbinate atrophy.

Effect of carbadox on growth, feed utilization, and development of nasal turbinate lesions in swine infected with Bordetella bronchiseptica.

Carbadox in combination with sulfamethazine did not interfere with the activity of sulfamethazine in clearing experimentally induced Bordetella bronchiseptica nasal infection. Evaluations in three field cases of infectious atrophic rhinitis indicated that carbadox in the feed was as effective as chlortetracycline + sulfamethazine + penicillin for improving growth rate and feed efficiency, as compared with nonmedicated controls, and in reducing the prevalence of lesions of infectious atrophic rhinitis.

Evaluation of diagnostic procedures for detection of mycoplasmal pneumonia of swine.

The complement-fixation test (CFT), a latex-agglutination test (LAT), and Mycoplasma hyopneumoniae isolation procedures were compared with gross and microscopic lung evaluations for the routine diagnosis of mycoplasmal pneumonia (MP) of swine. The difficulty and variability of M hyopneumoniae isolation rendered this technique unacceptable. In market-weight swine, the finding of typical gross lesions was correlated with CFT results (P less than 0.005). The MP status of a herd could not be determined by use of these techniques in 4- to 9-week-old pigs. No technique could be used alone to establish a diagnosis. Gross and microscopic examination of all slaughter specimens, CFT, and clinical evaluation of the herd, used in combination, were the most useful means of determining the MP status of the herd.

Evaluation of nasal culturing procedures for the control of atrophic rhinitis caused by Bordetella bronchiseptica in swine.

Control of infectious atrophic rhinitis in swine breeding herds by culturing of 3 series of nasal swab specimens from each animal, with subsequent elimination of Bordetella bronchiseptica culture-positive animals, was evaluated. Thirteen of 17 (77%) B bronchiseptica-infected herds experiencing clinical atrophic rhinitis were feedic rhinitis were freed of clinical signs of the disease by the use of this nasal culturing procedure. In 15 of 23 (65%) B bronchiseptica-infected herds, pigs were cultured negative for this organism at 4 to 10 weeks of age.

Prevalence of Bordetella bronchiseptica in certain central Iowa.

Bordetella bronchiseptica was isolated from 6 of 13 short-tailed shrews (Blarina brevicauda) and 1 of 47 house sparrows (Passer domesticus) trapped in the vicinity of a swine Bordetella rhinitis experimental area. The organism was found in four of 50 foxes (Vulpes fulva), 2 of 36 opossums (Didelphis marsupialis) and 1 of 37 raccoons (Procyon lotor) trapped in the Ames, Iowa area. This bacterium was not culturally isolated from 14 deer mice (Peromyscus maniculatus), 64 house mice (Mus Musculus), 10 masked shrews (Sorex cinereus) and 54 starlings (Sturnus vulgaris).