Control of bovine respiratory disease, with and without co-morbidity by otitis media, in dairy heifers comparing gamithromycin, tulathromycin, or no medication at a commercial development facility.

The objective of this study was to evaluate one strategy for control (metaphylaxis) of bovine respiratory disease, with and without co-morbidity with otitis media, in dairy heifers at a commercial development facility. Individual heifers were the experimental unit. At weaning, 1 of 3 experimental treatments (gamithromycin, tulathromycin, or no medication) was randomly assigned to 1,567 heifers from 11 different dairies. Gamithromycin was administered to 631 heifers, tulathromycin was administered to 621 heifers, and no medication was administered to 315 heifers (negative control). Heifers were then commingled and penned according to body weight. Each pen contained heifers from each group, and periodically, larger numbers of heifers were penned together. All heifers were observed for the subsequent 42 d and treated according to protocols prescribed for the facility. Morbidity due to respiratory disease was less for heifers medicated with gamithromycin than for heifers medicated with tulathromycin. Morbidity due to respiratory disease was less for heifers medicated with gamithromycin than for heifers in the negative control group. Fewer heifers medicated with either antimicrobial were subsequently treated because of co-morbidity with otitis media. Mortality was not different among the treatment groups. Heifers medicated with either antimicrobial had greater average daily gain than did heifers in the negative control group.

Will antimicrobial resistance of BRD pathogens impact BRD management in the future?

Resistance is a qualitative interpretation of antimicrobial activity in vitro. Critical to management of bovine respiratory disease (BRD) is the clinical response in vivo. Attempts to connect activity in vitro to response in vivo have been complicated by the complexity of BRD, interpretation of antimicrobial activity in vitro, and inconsistent measures of clinical success or failure. During recent history, the discovery, development, and commercialization of antimicrobials have decreased. In response to resistance, voluntary and imposed restrictions on use of antimicrobials have been implemented. Resistance can be reversed using technology and knowledge of mechanisms of resistance. Perhaps approaches that reverse resistance will be used in clinical management of BRD in the future. The short answer to the question posed in the title is, 'yes.' Since antimicrobial drugs were discovered, resistance has been a consideration for selection of treatment of any infectious disease and BRD is not unique. In the opinion of the author, the more important question is, 'How will antimicrobial resistance of BRD pathogens impact BRD management in the future?'

Serologic response to Mannheimia haemolytica in calves concurrently inoculated with inactivated or modified-live preparations of M. haemolytica and viral combination vaccines containing modified-live bovine herpesvirus type 1.

OBJECTIVE: To assess the serologic response of calves to inactivated and modified-live (ML) Mannheimia haemolytica (MH) preparations given alone and concurrently with combination viral vaccines containing ML bovine herpesvirus type 1 (BHV-1). ANIMALS: 642 calves seronegative for BHV-1. PROCEDURES: In experiment 1, 192 calves received 1 of 3 MH preparations alone or concurrently received 1 of 3 MH preparations and 1 of 4 combination viral vaccines. In experiment 2, 450 calves received 1 of 4 MH preparations alone or concurrently received 1 of 4 MH preparations and 1 of 5 combination viral vaccines. Pretreatment and posttreatment blood samples were processed to obtain serum, which was analyzed to detect concentrations of antibodies against MH leukotoxin and BHV-1. RESULTS: In experiment 1, antibody titers against MH leukotoxin in calves receiving MH and ML virus vaccine appeared decreased, albeit nonsignificantly, compared with titers for calves receiving MH preparations alone. In experiment 2, all groups (except for 1) concurrently receiving an MH preparation and viral vaccine had a significant decrease in antibodies against MH leukotoxin. In both experiments, there was a significant decrease in the number of calves responding to MH leukotoxin when ML viral vaccine was coadministered. CONCLUSIONS AND CLINICAL RELEVANCE: Coadministration of ML BHV-1 and MH preparations interfered with the serologic response to MH leukotoxin in calves seronegative for BHV-1. Serologic response to MH leukotoxin may be substantially improved in seronegative calves when MH vaccination is delayed until after calves have received a dose of ML BHV-1 vaccine.

In vitro activities of tulathromycin and ceftiofur combined with other antimicrobial agents using bovine Pasteurella multocida and Mannheimia haemolytica isolates.

The purpose of this study was to determine the activities of two antibacterial agents used in the treatment of bovine respiratory infections-tulathromycin, a macrolide, and ceftiofur, a third-generation cephalosporin-alone, in combination with each other, and in combination with each of seven additional antibiotics (tilmicosin, florfenicol, enrofloxacin, danofloxacin, ampicillin, tetracycline, and penicillin G) against bovine Pasteurella multocida (n = 60) and Mannheimia haemolytica (n = 10) isolates for determination of synergy, antagonism, or indifference. Of 458 organism-drug combinations, 160 combinations of tulathromycin and 209 combinations of ceftiofur with eight antimicrobial drugs were indifferent. One combination was antagonistic (ceftiofur + florfenicol against one isolate of P. multocida). Time-kill studies showed loss of cidality for ceftiofur when combined with florfenicol at 1x the minimal inhibitory concentration. Overall, the in vitro data demonstrated that tulathromycin and ceftiofur, in combination with each other or seven other antimicrobial agents, primarily produce an indifferent response with no occurrences of synergism and rare occurrences of antagonism.

Melengestrol acetate as a tool for inducing early ovulation in transitional mares.

The efficacy of melengestrol acetate (MGA) to shorten the vernal transition of mares by synchronising and accelerating the first ovulation of the year after 60 days of phototherapy was determined by ultrasonographic monitoring. Sixteen mares in late transition were fed two doses of MGA (150 mg/mare/day and 100 mg/mare/day, respectively) for 10 days. A luteolytic dose of prostaglandin was administered to each mare one day after the end of MGA treatment. The presence and duration of oestrus, follicular growth, uterine oedema and presence of ovulation were monitored by ultrasonography and the cervical tone was evaluated by rectal palpation. Ovulation was detected in 87.5% of the mares treated with 150 mg MGA/mare/day for 10 days, and in 62.5% of the mares receiving 100 mg MGA/mare/day for 10 days. This was statistically different (P = 0.03) from the untreated control mares having an ovulation rate of 20%. Mares that received 150 mg MGA/day for 10 days had a mean treatment to ovulation interval of 13.1 +/- 5.97 days after the end of treatment, while mares that received 100 mg MGA/day for 10 days had a mean of 25.6 +/- 10.50 days (P = 0.01) to ovulation. These results suggest that MGA can be used for synchronising and hastening the first ovulation of the year in mares.

Pharmacokinetics and clinical effects of a subanesthetic continuous rate infusion of ketamine in awake horses.

OBJECTIVE: To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses. ANIMALS: 8 adult horses. PROCEDURES: Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Concentration of ketamine in plasma, heart rate, respiratory rate, blood pressure, physical activity, and analgesia were measured prior to, during, and following infusion. Analgesic testing was performed with a modified hoof tester applied at a measured force to the withers and radius. RESULTS: No signs of excitement and no significant changes in the measured physiologic variables during infusion rates of 0.4 and 0.8 mg of ketamine/kg/h were found. At 6 hours following infusions, heart rate and mean arterial pressure were decreased, compared with preinfusion measurements. An analgesic effect could not be demonstrated during or after infusion. Pharmacokinetic variables for 0.4 and 0.8 mg/kg/h infusions were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine can be administered to awake horses at 0.4 or 0.8 mg/kg/h without adverse behavioral effects. The observed pharmacokinetic values are different than those reported for single-dose IV bolus administration of this drug.

Use of antimicrobials in wound management.

Antimicrobial medication should be considered an adjunct to the general care of wounds rather than a substitute for lavage, drainage, or other physical care intended to promote healing. Judicious use is based on results of diagnostic procedures and the professional judgment of the attending veterinarian. Organisms that contaminate or infect wounds of horses are similar to those that can affect human patients, such that personal hygiene and protection are important when caring for these equine patients, because attendants can easily be exposed to them. Although those organisms are considered to be ubiquitous, the inoculum that may be present on or in an infected wound may be substantially greater than that encountered during other daily activities of the veterinarian. Proper disposal of the bandage materials and personal protective clothing is important. Bacterial resistance is one of many "survival tactics" of bacteria and has been an important clinical consideration for physicians and veterinarians since antimicrobial drugs were discovered. Controversies and insufficient understanding of bacterial resistance abound, however. The entirety of the subject is beyond the scope of this article, but it is important to the veterinary profession and for the formulation of wound management in horses. We and our animal patients live in a world populated by microbial organisms of various types. Resistance among bacteria is likely to continue to be a clinical consideration in the future as it has been during the past 60 to 70 years. As veterinarians, we must recognize the zoonotic nature of resistance and implement biosecurity procedures to protect ourselves, other people in contact with those pathogens, and our patients. We must also recognize the merits of judicious targeted use of antimicrobial drugs and apply appropriate principles during the course of professional care for the well-being of our animal patients.

Susceptibility of Mycobacterium avium sbsp paratuberculosis to monensin sodium or tilmicosin phosphate in vitro and resulting infectivity in a murine model.

This study was designed to determine the susceptibility in vitro and infectivity of 1 field isolate of Mycobacterium avium sbsp paratuberculosis after exposure to monensin sodium and tilmicosin phosphate. Minimum inhibitory concentrations (0.39 microg monensin sodium/mL; 1.60 microg tilmicosin phosphate/mL) were determined in quintuplicate. Organisms were then incubated with 3 different concentrations of each medication for 3 different lengths of time, then washed and resuspended in sterile physiologic saline and injected intraperitoneally into mice that were genetically susceptible to infection. Mice were euthanatized 50 d later and the number of hepatic granulomas was used as the indicator of infectivity. Neither time of incubation nor concentration of medication had any effect on the infectivity of the organisms. Monensin sodium significantly reduced the number of hepatic granulomas in genetically susceptible mice while tilmicosin phosphate did not. Antimycobacterial activity of monensin sodium suggests that the role of monensin in the control of bovine paratuberculosis should be evaluated further.

Neonatal adjustments.

Pharmacodynamic responses by neonates are the same as those for adults, but physiologic differences and pathophysiologic changes can affect pharmacokinetic values sufficiently to require adjustments in dosage regimens used for calves. Adjunctive care may be necessary for some patients to correct or maintain perfusion and temperature of tissues so that absorption and distribution may be adequate. Intravenous administration may be the only route appropriate for some critically ill patients. Anatomic sites and formulation of products administered by extravascular parenteral routes markedly can affect absorption of those products and subsequent clinical response to treatment.

How to respond to adverse drug reactions.

Adverse drug reactions (ADRs) are part of the risks, professional responsibilities, and liabilities inherent to veterinary medicine. The incidence of proven ADRs is not known, but veterinarians should anticipate, plan, and practice a response for patients that experience adverse reactions. The attending veterinarian should work closely with professional services personnel at pharmaceutical manufacturers to provide care for those patients, to investigate causes of ADRs, and to factually improve reports of ADRs that can be of considerable medicolegal benefit to the client and the profession.

Effectiveness of a unique dihydropyridine (BAYTG 1000) for prevention of laminitis in horses.

OBJECTIVE: To determine whether a unique dihydropyridine (BAYTG 1000) would be beneficial in preventing laminitis in horses. ANIMALS: 16 clinically normal adult horses. PROCEDURE: 8 pairs of horses were used in a controlled double-blind study, using sex- and age-matched horses randomly assigned to treatment or control groups. Horses were subjected to carbohydrate overload to induce laminitis. Treated horses were administered BAY TG 1000 (30 mg/kg, PO, q 24 h) for 3 days. Hoof wall surface temperature (HWST) and lameness were recorded at 4-hour intervals. The HWST was adjusted on the basis of time of onset of lameness and evaluated, using a repeated-measures ANOVA. Lameness 8 hours after onset and clinical status 72 hours after onset of lameness were evaluated, using Mann-Whitney procedures. RESULTS: Analysis revealed that BAYTG 1000 did not decrease the incidence of lameness but significantly ameliorated prodromal hypothermia, lessened the severity of lameness 8 hours after onset of lameness, and improved the clinical status of horses 72 hours after onset of lameness. CONCLUSION AND CLINICAL RELEVANCE: Results support the conclusion that BAYTG 1000 was protective when used in prevention of laminitis. The drug decreased severity and improved clinical status (recovery) of induced lameness, which was interpreted to mean that the drug's actions were on mechanisms important but secondary to primary causal mechanisms of laminitis. Therefore, drugs that enhance digital perfusion via alteration of rheologic activity may have potential use in the prevention and management of laminitis in horses.

Effect of tilmicosin on chemotactic, phagocytic, and bactericidal activities of bovine and porcine alveolar macrophages.

OBJECTIVE: To evaluate chemotactic, phagocytic, and bactericidal activities of bovine and porcine alveolar macrophages (AM) exposed to tilmicosin. ANIMALS: 12 healthy calves and 12 healthy pigs. PROCEDURES: Lungs were obtained immediately after euthanasia; AM were collected by means of bronchoalveolar lavage and density gradient centrifugation. Chemotactic activity was evaluated by exposing AM to lipopolysaccharide or macrophage inhibitory peptide during incubation with tilmicosin. Phagocytic activity was evaluated by incubating AM with tilmicosin for 24 hours and then with tilmicosin-resistant Salmonella serotype Typhimurium. Bactericidal activity was evaluated by incubating AM with tilmicosin (0, 10, or 20 microg/ml for bovine AM; 0 or 10 microg/ml or 10 microg/ml but washed free of tilmicosin for porcine AM) and then with Mannheimia haemolytica (bovine AM) or with Actinobacillus pleuropneumoniae or Pasteurella multocida (porcine AM). RESULTS: Tilmicosin had no significant effects on chemotactic or phagocytic activities of bovine or porcine AM. The time-course of bactericidal activity was best described by polynomial equations. Time to cessation of bacterial growth and area under the time versus bacterial number curve were significantly affected by incubation of AM with tilmicosin. CONCLUSIONS AND CLINICAL RELEVANCE: Results show that bactericidal activity of bovine and porcine AM was enhanced by tilmicosin, but not in proportion to the reported ability of AM to concentrate tilmicosin intracellularly. With or without exposure to tilmicosin, the time-course of bactericidal activity of bovine AM against M haemolytica and of porcine AM against A pleuropneumoniae or P multocida was too complex to be reduced to a simple linear equation.

Inducción experimental de anestesia general en potros con la administración intravenosa de isoflurano / Experimental induction of general anesthesia in foals with an intravenous administration of isoflurane

Se realizaron dos fases para evaluar la factibilidad de la inducción a la anestesia general con la administración intravenosa de isofluorano. Para la fase I, in vitro, se utilizó sangre de equinos heparinizada, y para la fase II, in vivo, se utilizaron cinco potros. Los resultados de la fase in vitro mostraron cambios en los valores de hematócrito (HCT), glóbulos rojos (GR), glóbulos blancos (HB) y concentración de hemoglobina corpuscular media (CHCM). Sin embargo, no hubo daño importante en la integridad de las células sanguíneas, por lo que se continuó con el desarrollo de la fase in vivo, cuyos valores hemáticos antes y después de la administración de isoflurano fueron diferentes únicamente para la dosis de 0.01 mL de isoflurano/kg de peso corporal. No se vieron afectadas las respuestas de las variables fisiológicas por las diferentes dosis de isoflurano. Las variables clínicas (tiempo antes de que el animal se levante y tiempo total acostado) fueron diferentes con las dosis de 0.04 o 0.06 mL de isoflurano/kg en comparación con las dosis más bajas. Estas dosis (0.04 o 0.06 mL) mostraron un efecto de inducción de anestesia aceptable. Con base en los resultados de esta investigación piloto, la vía intravenosa para la administración de isoflurano puede convertirse en una opción para inducir anestesia, aunque se reconoce que es indispensable realizar estudios adicionales para determinar todas las recomendaciones clínicas necesarias para su uso.

Farmacología clínica de los aminoglicósidos y los aminociclitoles en medicina veterinaria / Clinical pharmacology of aminoglycoside and aminocyclitol antibacterials in veterinary medicine

Dada la importancia de los aminoglicósidos y aminocilitoles en la clínica veterinaria, y en virtud de la enorme cantidad de información que se genera en torno a estos antimicrobianos, se consideró de importancia llevar a cabo un análisisi farmacológico y clínico de la literatura especializada. La intención primordial de realizar estudios documentales de esta naturaleza es estrechar las actividades del clínico con las del investigador para procurar un mejor manejo de estos medicamentos en el campo, aunque también se hace énfacis en las áreas que aún requieren atención de los investigadores. Este ensayo no pretende ser enciclopédico y solamente se incluye un porcentaje del enorme caudal de información que se genera con estos dos grupos de antimicrobianos. Se hace énfasis en los aspectos farmacológicos que pueden ser de importancia para el clínico, incluyendo rasgos generales de los grupos, datos farmacocinéticos, de espectro, residuos, toxicidad y usos. Cuando resulta neceario, se presenta la opinión de los autores