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Antibiograms are important tools for antimicrobial stewardship that are often underutilized in veterinary medicine. Antibiograms summarize cumulative antimicrobial susceptibility testing (AST) data for specific pathogens over a defined time period; in veterinary medicine, they are often stratified by host species and site of infection. They can aid practitioners with empiric therapy choices and assessment of antimicrobial resistance trends within a population in support of one-health goals for antimicrobial stewardship. For optimal application, consideration must be given to the number of isolates used, the timeframe of sample collection, laboratory analytical methodology, and the patient population contributing to the data (eg, treatment history, geographic region, and production type). There are several limitations to veterinary antibiograms, including a lack of breakpoint availability for bacterial species, a lack of standardization of laboratory methodology and technology for culture and AST, and a lack of funding to staff veterinary diagnostic laboratories at a level that supports antibiogram development and education. It is vital that veterinarians who use antibiograms understand how to apply them in practice and receive relevant information pertaining to the data to utilize the most appropriate antibiogram for their patients. This paper explores the benefits and challenges of developing and using veterinary antibiograms and proposes strategies to enhance their applicability and accuracy. Further detail regarding the application of veterinary antibiograms by privately practicing clinicians is addressed in the companion Currents in One Health article by Lorenz et al (JAVMA, September 2023).
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Anti-Infecciosos , Gestão de Antimicrobianos , Saúde Única , Animais , Antibacterianos/uso terapêutico , Objetivos , Testes de Sensibilidade Microbiana/veterináriaRESUMO
Antimicrobial susceptibility testing (AST) is an important component of antimicrobial stewardship. This article discusses how AST methods and breakpoints are developed, describes when AST may or may not be useful in clinical practice, and discusses how to interpret AST results from bacterial isolates from cattle, sheep, and goats. Discussion of when AST is not appropriate or when veterinarians should have low confidence in AST results is also included. Applicability of genomic testing for antimicrobial susceptibility is briefly addressed.
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Antibacterianos , Animais , Bovinos , Ovinos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana/veterináriaRESUMO
The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528 kg were administered a single dose of 0.5 mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15 min, 30 min, 45 min, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean Cmax was 486 ng/ml (range 423-549 ng/ml), and Tmax was estimated to be 1.7 h (range 0.3-3.1 h). The estimated T1/2 was 7.5-8 h.
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Pirimidinas , Sulfonamidas , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida/veterinária , Cavalos , Maleatos , Pirimidinas/farmacocinética , Sulfonamidas/farmacocinéticaRESUMO
Veterinarians contribute substantially to the health of their patients and enhance the communities in which they live. Delivery of veterinary curricula continues to evolve to ensure that veterinary graduates are prepared to meet their professional obligations on Day One of their careers. In this study, veterinary practitioners were recruited to deliver telehealth case rounds to veterinary students at Kansas State University and Texas A&M University. Case discussions were hosted virtually once per month in the 2020-2021 and 2021-2022 academic years for a total of 16 sessions. Each presenting practitioner was instructed to develop a brief presentation for a case routinely seen in their practice, and to discuss important clinical decision points in diagnosis, treatment and management. Cases could also highlight important ethical or communication issues encountered in veterinary medicine. The overall goals of this project were to increase the quantity and diversity of clinical cases to which veterinary students were exposed during their professional training and to evaluate the feasibility and acceptability of telehealth technology as a teaching strategy. Student participants were surveyed to determine the effectiveness of telehealth sessions in increasing overall confidence and competence in case management, and veterinary presenters were surveyed to determine motivations for participating in the project and perceived value of the telehealth sessions. More than 95% of students indicated that participation in telehealth sessions increased their clinical confidence and competence. Presenting practitioners unanimously indicated that they would participate in similar instruction in the future. Recommendations are provided to improve the educational experience for future adopters of telehealth teaching sessions.
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BACKGROUND: Although Beef Quality Assurance guidelines do not recommend use of darting methods to deliver drugs, cattle in the US may be raised on farms and ranches without restraint facilities, and reports from the field suggest that dart guns are being used to deliver antimicrobial drugs. Few studies report whether this route of administration results in altered drug disposition or carcass quality. METHODS: Forty steers were blocked by sire and then randomly assigned to treatment with saline, ceftiofur crystalline free acid, tildipirosin, or tulathromycin delivered via dart gun. To assess drug disposition, eight ceftiofur, six tulathromycin, and six tildipirosin-treated calves were selected to measure plasma concentrations of drugs up to 10 days after drug administration. Steers were then fed a balanced ration for approximately 6.5 months and slaughtered. To evaluate carcass quality, tenderness of steaks from darted-side and non-darted sides was evaluated via Warner-Bratzler shear force testing. Due to the prohibition of extralabel routes of administration for ceftiofur in the U.S., animals treated with this drug did not enter the food supply. RESULTS: Ceftiofur disposition differed from published reports with lower mean Cmax but similar mean apparent elimination half-life. Tildipirosin disposition differed from published reports with lower Cmax and shorter apparent elimination half-life. Tulathromycin was similar to previous published reports but Cmax and apparent elimination half-life was highly variable. All steaks (from darted and non-darted sides) from cattle treated with ceftiofur and saline were more tender than from cattle treated with tulathromycin or tildipirosin (P = 0.003). There was a trend toward more tenderness in steaks from the non-darted compared to the darted side. Steaks from the darted side for one treatment, tildipirosin, were less tender than the non-darted side. CONCLUSIONS: Pharmacokinetic parameters of ceftiofur crystalline free acid, tildipirosin, and tulathromycin to cattle using pressure-adjustable pneumatic gas-powered dart gun were estimated in this study. Delivery of tildipirosin and tulathromycin to cattle with dart gun may also result in detectable decreases in tenderness of harvested steaks.
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BACKGROUND: Combatting antimicrobial resistance requires a One Health approach to antimicrobial stewardship including antimicrobial drug (AMD) use evaluation. Current veterinary AMD prescribing data are limited. OBJECTIVES: To quantify companion animal AMD prescribing in primary care and specialty practice across 3 academic veterinary hospitals with particular focus on third-generation cephalosporins, fluoroquinolones, and carbapenems. ANIMALS: Dogs and cats presented to 3 academic veterinary hospitals from 2012 to 2017. METHODS: In this retrospective study, AMD prescribing data from 2012 to 2017 were extracted from electronic medical records at each hospital and prescriptions classified by service type: primary care, specialty practice or Emergency/Critical Care (ECC). Hospital-level AMD prescribing data were summarized by species, service type, AMD class, and drug. Multivariable logistic full-factorial regression models were used to estimate hospital, year, species, and service-type effects on AMD prescribing. Estimated marginal means and confidence intervals were plotted over time. RESULTS: The probability of systemic AMD prescribing for any indication ranged between 0.15 and 0.28 and was higher for dogs than cats (P < .05) apart from 2017 at hospital 1. Animals presented to primary care were least likely to receive AMDs (dogs 0.03-0.15, cats 0.03-0.18). The most commonly prescribed AMD classes were aminopenicillins/ß-lactamase inhibitors (0.02-0.15), first-generation cephalosporins (0.00-0.09), fluoroquinolones (0.00-0.04), nitroimidazoles (0.01-0.06), and tetracyclines (0.00-0.03). Among the highest priority classes, fluoroquinolones (dogs 0.00-0.09, cats 0.00-0.08) and third-generation cephalosporins (dogs 0.00-0.04, cats 0.00-0.05) were most frequently prescribed. CONCLUSIONS AND CLINICAL IMPORTANCE: Antimicrobial drug prescribing frequencies were comparable to previous studies. Additional stewardship efforts might focus on fluoroquinolones and third-generation cephalosporins.
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Anti-Infecciosos , Doenças do Gato , Doenças do Cão , Preparações Farmacêuticas , Animais , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Gatos , Doenças do Cão/tratamento farmacológico , Cães , Prescrições de Medicamentos/veterinária , Atenção Primária à Saúde , Estudos RetrospectivosRESUMO
The objective of this study was to determine the pharmacokinetics of firocoxib after oral administration in un-weaned calves. Eight Holstein calves with a mean age of 36 days and a mean weight of 55 kg were administered a single oral dose of 227 mg firocoxib. The resulting mean dosage was 4.2 mg/kg (range 3.5-5.0 mg/kg). Blood was collected prior to drug administration and at 2, 4, 6, 8, 24, 48, 72, and 96 h after treatment. Firocoxib concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Using computer software, pharmacokinetic parameters were found to fit best with a one-compartment model. Mean Cmax was 0.9 µg/ml (range 0.570-1.254), and Tmax was estimated to be 7 h (range 4-8 h). The estimated T1/2 was 15.3 h. The pharmacokinetics of firocoxib after oral dosing are similar to those in dogs, with the exception of a T1/2 that is approximately twice as long. Based on the similar pharmacokinetics, it is possible that a dose of 227 mg firocoxib orally could provide an analgesic effect in un-weaned calves.
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4-Butirolactona , Sulfonas , 4-Butirolactona/análogos & derivados , Administração Oral , Animais , Bovinos , Cromatografia Líquida/veterinária , CãesRESUMO
Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidime in neonatal foals was determined. Six healthy one to two-day-old foals were given 25 mg/kg of ceftazidime by IV and IM routes in a cross-over design, with a 48-h washout period between doses. Non-compartmental analysis was used to estimate plasma pharmacokinetic parameters. Median t1/2 was 2 h and median AUC0-last was 364 µg h/ml for both IV and IM administration. Median Cmax after IM administration was 101 µg/ml, with a median Tmax of 0.7 h. Relative bioavailability of IM injection was 90%. There were no statistically significant differences between estimated IV and IM pharmacokinetic parameters. Plasma concentrations remained above the human CLSI susceptible breakpoint for Enterobacteriaceae for over 8 h following IV and IM administration.
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Antibacterianos/administração & dosagem , Cavalos , Administração Intravenosa/veterinária , Animais , Ceftazidima , Cefalosporinas , Cavalos/sangue , Injeções Intramusculares/veterináriaRESUMO
The recent changes in curricula in veterinary medicine have changed the delivery and focus on veterinary pharmacology and therapeutics, resulting in a perceived lack of knowledge of pharmacology and therapeutic decision making in recent graduates. To aid veterinary pharmacologists and clinicians teaching clinical pharmacology, core competencies were drafted by a working group. Following this process, a Delphi study was performed to come to a consensus on day-1 competencies in veterinary pharmacology and therapeutics. The described competencies could be useful to a variety of stakeholders in veterinary pharmacology, including those teaching veterinary pharmacology worldwide. Secondly, they could form the basis of vertical alignment of the subject within schools and across the world, as well as serving to frame the integration of veterinary pharmacology and therapeutics into competency-based veterinary education.
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Farmacologia Clínica , Animais , Currículo , Técnica DelphiRESUMO
The objectives of this study were to report a recipe for making antibiotic impregnated Plaster of Paris (AI-PoP) beads using penicillin, ampicillin, tetracycline, tulathromycin, and florfenicol and to determine the in vitro elution rates of those antibiotics in the beads. The AI-PoP beads were made using Plaster of Paris powder, antibiotic, and water, cured for 24 h, sterilized by ethylene oxide, and stored up to 5 months before testing. For each antibiotic, 20 beads were combined with bovine serum in sterile tubes and incubated at 37°C on a rocker. Serum was replaced at intervals over the 14 days study period, and antibiotic concentrations were determined by high pressure liquid chromatography with mass spectrometry. Separately, in a proof-of-concept study, the growth of E. coli and T. pyogenes in eluent from 10 beads for each antibiotic was quantified by flow cytometry. Antibiotic was detected in AI-PoP bead eluent for 14 days for all but the ampicillin beads, for which antibiotic was detected for 8 days. The concentration of antibiotic in eluent was greater than the minimum inhibitory concentration (MIC) of tested bacteria for the entire study period for penicillin, tetracycline, tulathromycin, and florfenicol. The concentration of ampicillin remained greater than the MIC of E. coli for 4 days and T. pyogenes for 6 days. The colony forming units (CFU)/ml of live E. coli and T. pyogenes was reduced over a 72-h period by 1-3 log10 CFU, with the exception of tetracycline, which reduced CFU/ml of T. pyogenes by
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Though carbapenems are not licensed for use in food animals in the U.S., carbapenem resistance among Enterobacteriaceae has been identified in farm animals and their environments. The objective of our study was to determine the extent to which older-generation ß-lactam antibiotics approved for use in food animals in the U.S. might differentially select for resistance to antibiotics of critical importance to human health, such as carbapenems. Escherichia coli (E. coli) strains from humans, food animals, or the environment bearing a single ß-lactamase gene (n = 20 each) for blaTEM-1, blaCMY-2, and blaCTX-M-* or else blaKPC/IMP/NDM (due to limited availability, often in combination with other bla genes), were identified, along with 20 E. coli strains lacking any known beta-lactamase genes. Baseline estimates of intrinsic bacterial fitness were derived from the population growth curves. Effects of ampicillin (32 µg/mL), ceftriaxone (4 µg/mL) and meropenem (4 µg/mL) on each strain and resistance-group also were assessed. Further, in vitro batch cultures were prepared by mixing equal concentrations of 10 representative E. coli strains (two from each resistance gene group), and each mixture was incubated at 37°C for 24 hours in non-antibiotic cation-adjusted Mueller-Hinton II (CAMH-2) broth, ampicillin + CAMH-2 broth (at 2, 4, 8, 16, and 32 µg/mL) and ceftiofur + CAMH-2 broth (at 0.5, 1, 2, 4, and 8µg/mL). Relative and absolute abundance of resistance-groups were estimated phenotypically. Line plots of the raw data were generated, and non-linear Gompertz models and multilevel mixed-effect linear regression models were fitted to the data. The observed strain growth rate distributions were significantly different across the groups. AmpC strains (i.e., blaCMY-2) had distinctly less robust (p < 0.05) growth in ceftriaxone (4 µg/mL) compared to extended-spectrum beta-lactamase (ESBL) producers harboring blaCTX-M-*variants. With increasing beta-lactam antibiotic concentrations, relative proportions of ESBLs and CREs were over-represented in the mixed bacterial communities; importantly, this was more pronounced with ceftiofur than with ampicillin. These results indicate that aminopenicillins and extended-spectrum cephalosporins would be expected to propagate carbapenemase-producing Enterobacteriaceae in food animals if and when Enterobacteriaceae from human health care settings enter the food animal environment.
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Carbapenêmicos/farmacologia , Seleção Genética , Resistência beta-Lactâmica , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genéticaRESUMO
BACKGROUND: The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues. RESULTS: Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 µg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 µg/g). Meloxicam was detected in a single liver sample (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g). CONCLUSIONS: These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.
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Anti-Inflamatórios não Esteroides/farmacocinética , Clonixina/análogos & derivados , Meloxicam/farmacocinética , Animais , Clonixina/sangue , Clonixina/farmacocinética , Clonixina/urina , Meia-Vida , Injeções Intramusculares/veterinária , Rim/química , Fígado/química , Masculino , Meloxicam/sangue , Meloxicam/urina , Sus scrofaRESUMO
Critically appraised topics (CATs) are evidence syntheses that provide veterinary professionals with information to rapidly address clinical questions and support the practice of evidence-based veterinary medicine (EBVM). They also have an important role to play in both undergraduate and post-registration education of veterinary professionals, in research and knowledge gap identification, literature scoping, preparing research grants and informing policy. CATs are not without limitations, the primary one relating to the rapid approach used which may lead to selection bias or restrict information identified or retrieved. Furthermore, the narrow focus of CATs may limit applicability of the evidence findings beyond a specific clinical scenario, and infrequently updated CATs may become redundant. Despite these limitations, CATs are fundamental to EBVM in the veterinary profession. Using the example of a dog with osteoarthritis, the five steps involved in creating and applying a CAT to clinical practice are outlined, with an emphasis on clinical relevance and practicalities. Finally, potential future developments for CATs and their role in EBVM, and the education of veterinary professionals are discussed. This review is focused on critically appraised topics (CATs) as a form of evidence synthesis in veterinary medicine. It aims to be a primary guide for veterinarians, from students to clinicians, and for veterinary nurses and technicians (hereafter collectively called veterinary professionals). Additionally, this review provides further information for those with some experience of CATs who would like to better understand the historic context and process, including further detail on more advanced concepts. This more detailed information will appear in pop-out boxes with a double-lined surround to distinguish it from the information core to producing and interpreting CATs, and from the boxes with a single line surround which contain additional resources relevant to the different parts of the review.
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Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid analgesics with prolonged durations of activity could alleviate pain, but associated adverse effects including gastrointestinal ileus, inappetence, and tissue reactions have been reported. In this study, we compared gross tissue reactions at the site of injection, food consumption, and fecal production after single injections of buprenorphine HCl (Bup; n = 7), sustained-release buprenorphine (BupSR; n = 8), and high-concentration buprenorphine (BupHC; n = 7) during the first 3 d after minor survival surgery. We also measured plasma concentrations of the parent drug, buprenorphine, and 3 metabolites (buprenorphine-3-glucuronide (B3G), norbuprenorphine-3ß-glucuronide (N3G), and norbuprenorphine (NB)). Plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for 4 h for Bup and 42 h for BupHC. For BupSR, plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for approximately 77 h, starting 15 h after administration. For all 3 formulations, N3G was the most prominent metabolite in the blood. No injection site reactions were visible grossly in any rabbit. Relative to baseline measures and compared with controls (n = 8), food consumption was suppressed on days 1 through 3 in rabbits that received BupSR and on days 2 through 3 in those given BupHC. Feces production on day 3 was reduced to a greater extent in BupSR rabbits than control animals. Two rabbits in the BupHC group exhibited neurologic signs after drug administration. These adverse effects should be considered when choosing a long-lasting buprenorphine formulation to manage pain in rabbits.
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Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Buprenorfina/administração & dosagem , Buprenorfina/farmacologia , Medição da Dor/veterinária , Dor/veterinária , Coelhos , Animais , Animais de Laboratório , Buprenorfina/análogos & derivados , Buprenorfina/sangue , Buprenorfina/metabolismo , Preparações de Ação Retardada/administração & dosagem , Masculino , Dor/tratamento farmacológico , Manejo da DorRESUMO
OBJECTIVE: To compare analgesic efficacy and fetal effects between transdermal administration of fentanyl and IM administration of buprenorphine in pregnant sheep. ANIMALS: 12 healthy pregnant ewes. PROCEDURES: Before study initiation, each ewe was confirmed pregnant with a single fetus between 113 and 117 days of gestation. Ewes were randomly assigned to receive buprenorphine (0.01 mg/kg, IM, q 8 h for 48 hours beginning 1 hour before anesthesia induction; n = 6) or fentanyl (a combination of transdermal fentanyl patches sufficient to deliver a dose of 2 µg of fentanyl/kg/h applied between the dorsal borders of the scapulae 24 hours before anesthesia induction; 6). Ewes were anesthetized and underwent a surgical procedure to instrument the fetus with an arterial catheter and place a catheter in utero for collection of amniotic fluid samples. Physiologic variables and behavioral changes indicative of pain were assessed, and amniotic fluid and blood samples from ewes and fetuses were collected for determination of drug concentrations at predetermined times. RESULTS: Both protocols provided acceptable postoperative analgesia with no adverse effects observed in the ewes or fetuses. Compared with the buprenorphine protocol, the fentanyl protocol induced more profound analgesia, decreased the requirement for isoflurane during surgery, and was associated with a shorter anesthesia recovery time. Fetal indices did not differ significantly between the 2 analgesic protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that both protocols provided acceptable analgesia. However, the fentanyl protocol was superior in regard to the extent of analgesia induced, inhalant-sparing effects, and anesthesia recovery time.
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Buprenorfina , Fentanila , Dor Pós-Operatória , Administração Cutânea , Analgésicos , Analgésicos Opioides , Animais , Feminino , Feto , Dor Pós-Operatória/veterinária , Gravidez , OvinosRESUMO
Flunixin meglumine, a nonsteroidal anti-inflammatory medication, has been used in rhinoceros species at doses extrapolated from domestic animals. There is increasing evidence to suggest significant variations exist in metabolism of drugs in exotic species. Due to the differences in drug metabolism, dose extrapolation from domestic animals may not be appropriate for exotic species. The objective of this study was to investigate the pharmacokinetics of flunixin meglumine in five white rhinoceroses (Ceratotherium simum) administered a single (1 mg/kg) oral dose of a commercial equine flunixin meglumine paste. Concentrations of flunixin and its metabolite 5-OH flunixin were analyzed, and pharmacokinetic parameters were estimated for each animal. Mean observed plasma concentrations peaked at 1,207 ± 601 ng/ml and occurred at 3 ± 1 hr. The geometric mean of the apparent elimination half-life after oral administration was 8.3 ± 1.2 hr. This data suggests that flunixin meglumine appears to be slowly metabolized or slowly absorbed in this species. No adverse clinical effects were observed during the study period. A single dose of 1 mg/kg appears safe for use in the white rhinoceros. Multidose studies are needed to determine if plasma accumulation of flunixin meglumine occurs and to evaluate safety.
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Anti-Inflamatórios não Esteroides/farmacocinética , Clonixina/análogos & derivados , Perissodáctilos/sangue , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Área Sob a Curva , Clonixina/administração & dosagem , Clonixina/sangue , Clonixina/farmacocinética , Feminino , Meia-Vida , MasculinoRESUMO
OBJECTIVE: To determine oxytetracycline concentrations in plasma and in fluid from Corynebacterium pseudotuberculosis (CPT)-inoculated tissue chambers (used as experimental abscess models) and uninoculated (control) tissue chambers in sheep after IM or local administration of the drug and to investigate whether CPT growth was reduced or eliminated by these treatments. ANIMALS: 10 clinically normal female sheep. PROCEDURES: Sterile tissue chambers were surgically implanted in both paralumbar fossae of each sheep; ≥ 2 weeks later (day -6), 1 randomly selected chamber was inoculated with CPT, and the opposite chamber was injected with sterile growth medium. Sheep received oxytetracycline IM (n = 5) or by percutaneous injection into CPT-inoculated (4) or uninoculated (1) chambers on day 0. Tissue fluid from each chamber and venous blood samples for plasma collection were obtained at predetermined times over 6 days for bacterial counts (tissue chambers) and analysis of oxytetracycline concentrations (tissue chambers and plasma). Sheep were euthanized on day 6. Regional lymph nodes were collected bilaterally from each sheep for culture. RESULTS: Measurable concentrations of oxytetracycline were present in each chamber throughout the study, regardless of administration route or presence of CPT. No CPT growth was detected after the 48-hour time point in inoculated chambers injected with oxytetracycline; however, CPT was isolated from all inoculated chambers throughout the study after IM drug administration. One regional lymph node (ipsilateral to a CPT-inoculated, oxytetracycline-injected chamber with no CPT growth after 48 hours) was culture positive for CPT. CONCLUSIONS AND CLINICAL RELEVANCE: Intralesional administration of oxytetracycline may eliminate growth of CPT locally, but complete elimination of the organism remains difficult.