Effect of feeding on the pharmacokinetics of oral minocycline in healthy adult horses.

Minocycline is commonly used to treat bacterial and rickettsial infections in adult horses but limited information exists regarding the impact of feeding on its oral bioavailability. This study's objective was to compare the pharmacokinetics of minocycline after administration of a single oral dose in horses with feed withheld and with feed provided at the time of drug administration. Six healthy adult horses were administered intravenous (2.2 mg/kg) and oral minocycline (4 mg/kg) with access to hay at the time of oral drug administration (fed) and with access to hay delayed for 2 hr after oral drug administration (fasted), with a 7-day washout between treatments. Plasma concentration versus time data was analyzed based on noncompartmental pharmacokinetics. Mean ± SD bioavailability (fasted: 38.6% ± 4.6; fed: 15.7% ± 2.3) and Cmax (fasted: 1.343 ± 0.418 µg/ml; fed: 0.281 ± 0.157 µg/ml) were greater in fasted horses compared to fed horses (p < .05 both). Median (range) Tmax (hr) in fasted horses was 2.0 (1.5-3.5) and in fed horses was 5.0 (1.0-8.0) and was not significantly different between groups. Overnight fasting and delaying feeding hay 2 hr after oral minocycline administration improve drug bioavailability and thus plasma concentrations.

Comparative pharmacokinetics of minocycline in foals and adult horses.

The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6- to 9-week-old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross-over design. Five additional oral doses were administered at 12-h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry was used to measure minocycline concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar (BAL) cells. After i.v. administration to foals, minocycline had a mean (±SD) elimination half-life of 8.5 ± 2.1 h, a systemic clearance of 113.3 ± 26.1 mL/h/kg, and an apparent volume of distribution of 1.24 ± 0.19 L/kg. Pharmacokinetic variables determined after i.v. administration to adult horses were not significantly different from those determined in foals. Bioavailability was significantly higher in foals (57.8 ± 19.3%) than in adult horses (32.0 ± 18.0%). Minocycline concentrations in PELF were higher than in other body fluids. Oral minocycline dosed at 4 mg/kg every 12 h might be adequate for the treatment of susceptible bacterial infections in foals.

Pharmacokinetics of ceftiofur sodium in equine pregnancy.

Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re-enrolled in the study at least 3 days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 µg/ml (low dose) and 7.45 ± 1.05 µg/ml (high dose). Terminal half-life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 µg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 µg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 µg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.

Disposition of firocoxib in late pregnant and early postpartum mares.

Pregnancy induces several physiologic changes that might impact the bioavailability, distribution, metabolism, and excretion of drugs. The objective of this study was to determine the effects of pregnancy on the disposition of oral firocoxib in mares. Seven pony mares received oral firocoxib paste at a dose of 0.1 mg/kg during late pregnancy and again 12 to 33 days postpartum. Firocoxib concentrations were measured in plasma by HPLC with ultraviolet detection. Maximum plasma concentrations were significantly lower in pregnant (50.0 ± 21.8 ng/mL) than in postpartum (73.7 ± 25.6 ng/mL) mares. Plasma concentrations 24 h after administration, time to maximum plasma concentrations, and area under the plasma concentration versus time curve were not significantly different between late pregnancy and the postpartum period in mares.

Pharmacokinetics of danofloxacin and N-desmethyldanofloxacin in adult horses and their concentration in synovial fluid.

The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half-life of 8.00 ± 0.48 h. Maximum plasma concentration (Cmax ) of N-desmethyldanofloxacin (0.151 ± 0.038 µg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 µg/mL) than after IG administration (0.99 ± 0.1 µg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 µg/mL) and i.m. (0.70 ± 0.35 µg/mL) than after IG (0.20 ± 0.12 µg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 µg/mL for i.v. and i.m. administration and 0.12 µg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.

Disposition of ampicillin trihydrate in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle.

The objective of this study was to determine the disposition of ampicillin in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle. Ampicillin trihydrate was administered by intramuscular (i.m.) injection at a dose of 11 mg/kg of body weight every 24 h (n = 6, total of 3 doses) or every 12 h (n = 6, total of 5 doses) for 3 days. Concentrations of ampicillin were measured in plasma, uterine tissue, lochial fluid, and milk using HPLC with ultraviolet absorption. Quantifiable ampicillin concentrations were found in plasma, milk, and lochial fluid of all cattle within 30 min, 4 h, and 4 h of administration of ampicillin trihydrate, respectively. There was no significant effect of dosing interval (every 12 vs. every 24 h) and no significant interactions between dosing interval and sampling site on the pharmacokinetic variable measured or calculated. Median peak ampicillin concentration at steady-state was significantly higher in lochial fluid (5.27 µg/mL after q 24 h dosing) than other body fluids or tissues and significantly higher in plasma (3.11 µg/mL) compared to milk (0.49 µg/mL) or endometrial tissue (1.55 µg/mL). Ampicillin trihydrate administered once daily by the i.m. route at the label dose of 11 mg/kg of body weight achieves therapeutic concentrations in the milk, lochial fluid, and endometrial tissue of healthy postpartum dairy cattle.

Disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (CCFA) to pony mares with placentitis.

The objective of this study was to determine the pharmacokinetics of CCFA in mares with placentitis and evaluate the disposition of the drug in fetal fluids, fetal membranes, colostrum, and serum of foals. A secondary objective was to obtain pilot data regarding the efficacy of CCFA for improving foal survival in mares with placentitis. Twelve pregnant pony mares were enrolled in the study, inoculated with Streptococcus zooepidemicus, intracervically and assigned to one of three groups: CEFT (n = 3; administered CCFA only; 6.6 mg/kg, i.m., q96h); COMBO (n = 6; administered combination therapy of CCFA, altrenogest, and pentoxifylline); UNTREAT (n = 3, no treatment). Treatment was initiated at the onset of clinical signs. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur metabolites, were measured using high-performance liquid chromatography. Maximum and minimum serum concentrations of DCA at steady state in treated mares were 2.40±0.40 µg/mL and 1.06±0.29 µg/mL, respectively. Concentration of DCA in colostrum was 1.51±0.60 µg/mL. DCA concentrations in placenta and fetal tissues were very low (median = 0.03 µg/mL) and below the minimum inhibitory concentration of relevant pathogens. DCA was not detected in amniotic fluid or foal serum. Treatment did not appear to improve foal survival (CEFT: 0/3; COMBO: 2/6; UNTREAT: 2/3). Bacteria were recovered from the uterus of most mares postpartum and from blood cultures of most foals regardless of treatment.

Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals.

The objectives of this study were to determine the plasma and pulmonary disposition of gamithromycin in foals and to investigate the in vitro activity of the drug against Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Rhodococcus equi. A single dose of gamithromycin (6 mg/kg of body weight) was administered intramuscularly. Concentrations of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils were determined using HPLC with tandem mass spectrometry detection. The minimum inhibitory concentration of gamithromycin required for growth inhibition of 90% of R. equi and S. zooepidemicus isolates (MIC(90)) was determined. Additionally, the activity of gamithromycin against intracellular R. equi was measured. Mean peak gamithromycin concentrations were significantly higher in blood neutrophils (8.35±1.77 µg/mL) and BAL cells (8.91±1.65 µg/mL) compared with PELF (2.15±2.78 µg/mL) and plasma (0.33±0.12 µg/mL). Mean terminal half-lives in neutrophils (78.6 h), BAL cells (70.3 h), and PELF (63.6 h) were significantly longer than those in plasma (39.1 h). The MIC(90) for S. zooepidemicus isolates was 0.125 µg/mL. The MIC of gamithromycin for macrolide-resistant R. equi isolates (MIC(90)=128 µg/mL) was significantly higher than that for macrolide-susceptible isolates (1.0 µg/mL). The activity of gamithromycin against intracellular R. equi was similar to that of azithromycin and erythromycin. Intramuscular administration of gamithromycin at a dosage of 6 mg/kg would maintain PELF concentrations above the MIC(90) for S. zooepidemicus and phagocytic cell concentrations above the MIC(90) for R. equi for approximately 7 days.

Plasma and pulmonary disposition of ceftiofur and its metabolites after intramuscular administration of ceftiofur crystalline free acid in weanling foals.

The objectives of this study were to determine the plasma and pulmonary disposition of ceftiofur crystalline free acid (CCFA) in weanling foals and to compare the plasma pharmacokinetic profile of weanling foals to that of adult horses. A single dose of CCFA was administered intramuscularly to six weanling foals and six adult horses at a dose of 6.6 mg/kg of body weight. Concentrations of desfuroylceftiofur acetamide (DCA) were determined in the plasma of all animals, and in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells of foals. After intramuscular (IM) administration to foals, median time to maximum plasma and PELF concentrations was 24 h (12-48 h). Mean (± SD) peak DCA concentration in plasma (1.44 ± 0.46 µg/mL) was significantly higher than that in PELF (0.46 ± 0.03 µg/mL) and BAL cells (0.024 ± 0.011 µg/mL). Time above the therapeutic target of 0.2 µg/mL was significantly longer in plasma (185 ± 20 h) than in PELF (107 ± 31 h). The concentration of DCA in BAL cells did not reach the therapeutic level. Adult horses had significantly lower peak plasma concentrations and area under the curve compared to foals. Based on the results of this study, CCFA administered IM at 6.6 mg/kg in weanling foals provided plasma and PELF concentrations above the therapeutic target of 0.2 µg/mL for at least 4 days and would be expected to be an effective treatment for pneumonia caused by Streptococcus equi subsp. zooepidemicus at doses similar to the adult label.

The effects of deferoxamine mesylate on iron elimination after blood transfusion in neonatal foals.

BACKGROUND: Hepatic failure is one of the more common complications in foals requiring blood transfusion to treat neonatal isoerythrolysis. Iron intoxication is likely the cause of hepatic injury. OBJECTIVES: To determine the effects of deferoxamine on iron elimination in normal foals. ANIMALS: Thirteen neonatal foals. METHODS: Randomized-controlled trial. At 1-3 days of age, foals received either 3 L of washed packed dam's red blood cells (RBC) or 3 L of saline IV once. Foals were treated with deferoxamine (1 g) or saline (5 mL) SC twice daily for 14 days. Foals were randomly assigned to 1 of 3 groups: RBC/deferoxamine (deferoxamine), RBC/saline (placebo), or saline/saline (control). Blood and urine samples and liver biopsy specimens were collected for measurement of hematological, biochemical, and iron metabolism variables. RESULTS: There was a significant (P<.05) increase in hematocrit, RBC count, and hemoglobin in the groups transfused with packed RBC as compared with controls at all times. Biochemical variables and liver biopsy scores were not significantly different between groups at any time. Urine iron concentrations and fractional excretion of iron were significantly higher in deferoxamine treated foals. By 14 days after transfusion, liver iron concentrations in foals treated with deferoxamine (79.9±30.9 ppm) were significantly lower than that of foals receiving placebo (145±53.0 ppm) and similar to that of controls (44.8±4.09 ppm). CONCLUSIONS AND CLINICAL IMPORTANCE: Deferoxamine enhances urinary iron elimination and decreases hepatic iron accumulation after blood transfusion in foals.

Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates.

The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6-10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean +/- SD time to peak serum telithromycin activity (T(max)) was 1.75 +/- 0.76 h, maximum serum activity (C(max)) was 1.43 +/- 0.37 microg/mL, and terminal half-life (t(1/2)) was 3.81 +/- 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 +/- 14.5 microg/mL) than in PELF (5.07 +/- 2.64 microg/mL), and plasma (0.84 +/- 0.25 microg/mL). The MIC(90) of telithromycin for macrolide-resistant R. equi isolates (8 microg/mL) was significantly higher than that of macrolide-susceptible isolates (0.25 microg/mL). The MIC of telithromycin for macrolide-resistant isolates (MIC(50)=4.0 microg/mL) was significantly lower than that of clarithromycin (MIC(50)=24.0 microg/mL), azithromycin (MIC(50)=256 microg/mL) and erythromycin (MIC(50)=24 microg/mL).

Pharmacokinetics of intravenous and oral administration of enrofloxacin to the late-term pregnant and non-pregnant mares.

BACKGROUND: Enrofloxacin may be an alternative antimicrobial for unresponsive cases of severe bacterial infections in pregnant mares. As pregnancy may affect drug bioavailability, distribution, metabolism and excretion, dose adjustment might be necessary. OBJECTIVES: To determine the disposition of orally and intravenously administered enrofloxacin in pregnant and non-pregnant mares. STUDY DESIGN: Randomised cross-over experiment. METHODS: Six light-breed, healthy pregnant mares (260 days gestation) were given a single dose of either intravenous (5 mg/kg bwt) or oral compounded (7.5 mg/kg bwt) enrofloxacin, with the opposite dose administered after a 7-day washout. The protocol was repeated 45-60 days post-partum, 15-30 days after foals were weaned. Plasma samples were obtained via venepuncture at 0, 5, 10, 20, 30, 45, 60, 90 min, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h after enrofloxacin administration. Enrofloxacin and ciprofloxacin concentrations were measured by LC-MS/MS. Concentration versus time data were analysed based on non-compartmental pharmacokinetics. RESULTS: Enrofloxacin AUC0-∞ was significantly higher in pregnant mares than non-pregnant mares after PO administration and tended to be higher after i.v. administration. Ciprofloxacin maximum plasma concentration (Cmax ) and concentration at 24 h (C24h ) were higher, and half-life of the terminal phase (t½λz ) was longer in pregnant mares than non-pregnant mares after oral administration. Similarly, ciprofloxacin C24h was higher in pregnant mares with intravenous administration. Oral bioavailability did not differ based on pregnancy status. MAIN LIMITATIONS: Only six healthy light breed mares were assessed. Disease or horse breed may affect the endpoints evaluated. A lack of established enrofloxacin AUC/MIC targets for equine pathogens limits pharmacokinetic-pharmacodynamic conclusions. CONCLUSIONS: The oral form of enrofloxacin was well absorbed, and oral bioavailability was comparable to previous studies. While differences in enrofloxacin and ciprofloxacin pharmacokinetics were seen between pregnant and non-pregnant mares, the recommended drug dose and dose intervals are appropriate for MIC <0.25 µg/mL. Dosages may need to be adjusted for bacteria with a MIC >0.25 µg/mL.

A Common Practice of Widespread Antimicrobial Use in Horse Production Promotes Multi-Drug Resistance.

The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of R. equi resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR. In silico and in vitro analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (GaM; n = 19) and 19 untreated controls was performed. Treatment with MaR, but not GaM, significantly decreased fecal microbiota abundance and diversity, and expanded the abundance and diversity of antimicrobial resistance genes in feces. Soil plots experimentally infected with Rhodococcus equi (R. equi) and treated with MaR selected for MaR-resistant R. equi, whereas MaR-susceptible R. equi out-competed resistant isolates in GaM-treated or untreated plots. Our results indicate that MaR use promotes multi-drug resistance in R. equi and commensals that are shed into their environment where they can persist and potentially infect or colonize horses and other animals.

Infectious agents detected in the feces of diarrheic foals: a retrospective study of 233 cases (2003-2008).

BACKGROUND: Diarrhea is common in foals but there are no studies investigating the relative prevalence of common infectious agents in a population of hospitalized diarrheic foals. OBJECTIVES: To determine the frequency of detection of infectious agents in a population of hospitalized foals with diarrhea and to determine if detection of specific pathogens is associated with age, outcome, or clinicopathologic data. ANIMALS: Two hundred and thirty-three foals < or = 10 months of age with diarrhea examined at a referral institution. METHODS: Retrospective case series. Each foal was examined for Salmonella spp., viruses, Clostridium difficile toxins, Clostridium perfringens culture, C. perfringens enterotoxin, Cryptosporidium spp., and metazoan parasites in feces collected at admission or at the onset of diarrhea. RESULTS: At least 1 infectious agent was detected in 122 foals (55%). Rotavirus was most frequently detected (20%) followed by C. perfringens (18%), Salmonella spp. (12%), and C. difficile (5%). Foals < 1 month of age were significantly more likely to be positive for C. perfringens (odds ratio [OR] = 15, 95% confidence interval [CI] = 3.5-66) or to have negative fecal diagnostic results (OR = 3.0, 95% CI = 1.7-5.2) than older foals. Foals > 1 month of age were significantly more likely to have Salmonella spp. (OR = 2.6, 95% CI = 1.2-6.0), rotavirus (OR = 13.3, 95% CI = 5.3-33), and parasites (OR = 23, 95% CI = 3.1-185) detected compared with younger foals. Overall 191 of the 223 foals (87%) survived. The type of infectious agent identified in the feces or bacteremia was not significantly associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: In the population studied, foals with diarrhea had a good prognosis regardless of which infectious agent was identified in the feces.

Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foals.

The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration (MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1-2 days-of-age and 4-5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six additional foals between 1 and 5 days of age at a dose of 5 mg/kg q 12 h. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur-related metabolites were measured in plasma, synovial fluid, urine, and CSF by use of UPLC-MS/MS. A microbiologic assay was used to measure ceftiofur activity for a subset of plasma samples. Following i.v. administration of ceftiofur at a dose of 5 mg/kg to 1-2 day-old foals, DCA had a t(1/2) of 7.8 +/- 0.1 h, a body clearance of 74.4 +/- 8.4 mL/h/kg, and an apparent volume of distribution of 0.83 +/- 0.09 L/kg. After multiple i.v. doses at 5 mg/kg, DCA concentrations in CSF were significantly lower than concurrent plasma concentrations. Ceftiofur activity using a microbiologic assay significantly underestimated plasma concentrations of DCA. The MIC of ceftiofur required to inhibit growth of 90% of isolates of Escherichia coli, Pasteurella spp, Klebsiella spp, and beta-hemolytic streptococci was <0.5 microg/mL. Intravenous administration of ceftiofur sodium at the rate of 5 mg/kg every 12 h would provide sufficient coverage for the treatment of susceptible bacterial isolates.

Factors associated with long-term athletic outcome in Thoroughbred neonates admitted to an intensive care unit.

BACKGROUND: Limited information exists on the long-term outcome of foals that survive following hospitalisation for disease as a neonate. Significant financial investment is required to raise foals to racing age, therefore improved understanding of factors that affect long-term outcome and future athletic performance is important. OBJECTIVES: To analyse racing performance in Thoroughbred foals hospitalised as neonates, compared with their maternal siblings and to determine factors associated with failure to race and racing performance. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of Thoroughbred foals admitted to a neonatal intensive care unit between 1982 and 2008 were reviewed. Surviving foals of registered mares were included. Data including the foal's primary and concurrent diseases were extracted from the medical record. Racing records for foals and maternal siblings were evaluated. Multivariable logistic regression was used to identify disorders associated with failure to race and decreased racing performance. RESULTS: Two-hundred and sixty-nine of 454 previously hospitalised foals (59%) raced. Sixty-eight percent (269/394) of registered foals raced, compared with 79% (697/880) of registered siblings. Foals with prematurity/dysmaturity (P = 0.002) and those with orthopaedic disease (P = 0.007) were significantly less likely to race than their siblings. Premature/dysmature foals also had significantly fewer starts and wins and lower earnings than siblings. Foals with orthopaedic disorders had a lower percentage of wins, relative to their siblings. There was no significant association between racing performance and other disease categories. MAIN LIMITATIONS: Small sample size in some disease categories and retrospective nature of study. CONCLUSIONS: Foals hospitalised due to prematurity/dysmaturity or orthopaedic disorders were less likely to race than their maternal siblings and those that did race had decreased performance.

Identification of macrolide- and rifampicin-resistant Rhodococcus equi in environmental samples from equine breeding farms in central Kentucky during 2018.

Rhodococcus equi causes severe pneumonia in foals and is most often recognized in people as an opportunistic pathogen. Longitudinal studies examining antimicrobial-resistant R. equi from environmental samples are lacking. We hypothesized that antimicrobial-resistant R. equi would be detectable in the ground (pasture soil or stall bedding) and air at breeding farms with previous documentation of foals infected with resistant isolates, and that concentrations of resistant isolates would increase over time during the foaling season. In this prospective cohort study, ground and air samples were collected from stalls and paddocks in January, March, May and July of 2018 at 10 horse-breeding farms with history of foal pneumonia attributed to macrolide- or Rifampicin-resistant R. equi. Environmental samples were cultured in the presence and absence of macrolides and Rifampicin to select for resistant organisms. Data were analyzed with linear mixed-effects and Hurdle models. Concentrations of total R. equi in bedding or air of stalls were significantly (P < 0.05) higher in January than other months. The proportion of resistant R. equi in soil samples from paddocks was significantly (P < 0.05) higher than stall bedding during all months. For each month, air samples from paddocks had a significantly (P < 0.05) higher proportion of resistant isolates than those from stalls. Fifty-five percent of resistant soil isolates and 34% of resistant air isolates were considered virulent by identification of the vapA gene. Concentrations of resistant R. equi isolates did not increase over time during the foaling season. Antimicrobial-resistant R. equi can persist in the environment at farms with a history of pneumonia caused by resistant R. equi infections, and exposure to resistant isolates in paddocks and stalls appears stable during the foaling season. Resistant isolates in the environment not only pose a risk for disease but also can serve as a repository for dissemination of resistance genes.

Retrospective comparison of caffeine and doxapram for the treatment of hypercapnia in foals with hypoxic-ischemic encephalopathy.

BACKGROUND: Despite a lack of data regarding their efficacy, both caffeine and doxapram have been recommended for treatment of hypercapnia in equine neonates with central nervous system damage. HYPOTHESIS: Caffeine and doxapram alleviate hypercapnia in foals with hypoxic-ischemic encephalopathy. ANIMALS: Sixteen foals treated with either caffeine (n = 8) or doxapram (n = 8). METHODS: Information on age, body temperature, heart rate, respiratory rate, arterial blood gas parameters, duration of therapy, and outcome was abstracted from each medical record. RESULTS: Therapy with doxapram resulted in a significant decrease in partial pressure of carbon dioxide (PaCO2 [P= .004]), bicarbonate concentration (P= .002), and base excess (P= .005) compared with baseline values but failed to correct acidemia. In contrast, administration of caffeine did not result in significant changes from baseline values. The percentage decrease in PaCO2 and bicarbonate concentration was significantly greater in foals treated with doxapram than in foals treated with caffeine (P= .004). The proportions of foals that achieved the targeted PaCO2 (< or = 50 mmHg) were significantly higher in foals treated with doxapram than in foals treated with caffeine (P= .029). The proportion of survivors in the 2 treatment groups was not significantly different. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxapram is more effective than caffeine for rapid correction of hypercapnia in foals with hypoxic-ischemic encephalopathy.

Factors associated with outcome in foals with neonatal isoerythrolysis (72 cases, 1988-2003).

BACKGROUND: Neonatal foals with isoerythrolysis (NI) often die, but the risk factors for death have not been identified. OBJECTIVES: To identify factors associated with outcome in foals with NI and to identify factors associated with death from liver failure or kernicterus in the same population. ANIMALS: Seventy-two foals with NI examined at referral institutions. METHODS: Retrospective case series. Information on signalment, clinical examination findings, laboratory testing, treatment, complications, outcome, and necropsy results were obtained. RESULTS: The overall survival rate was 75% (54 of 72). Liver failure (n=7), kernicterus (n=6), and complications related to bacterial sepsis (n=3) were the 3 most common reasons for death or euthanasia. The number of transfusions with blood products was the factor most strongly associated with nonsurvival in a multivariate logistic regression model. The odds of liver failure developing in foals receiving a total volume of blood products >or= 4.0 L were 19.5 (95% confidence intervals [CI]: 2.13-178) times higher than that of foals receiving a lower volume (P= .009). The odds of kernicterus developing in foals with a total bilirubin >or= 27.0 mg/dL were 17.0 (95% CI: 1.77-165) times higher than that of foals with a lower total bilirubin (P= .014). CONCLUSIONS AND CLINICAL IMPORTANCE: Development of liver failure, kernicterus, and complications related to bacterial sepsis are the most common causes of death in foals with NI. Foals administered a large volume of blood products are at greater risk for developing liver failure.

Effect of age, feeding, and omeprazole administration on gastric tonometry in healthy neonatal foals.

BACKGROUND: Gastric tonometry is commonly used in humans as an assessment of intestinal mucosal perfusion. Values in healthy foals are currently unknown. HYPOTHESIS: Age, enteral feeding, and omeprazole administration would significantly alter gastric tonometry measurements in neonatal foals. ANIMALS: Nine clinically normal foals were used to assess the effect of age and feeding, and 8 similar foals were used to assess the effect of omeprazole. METHODS: At 1, 7, and 14 days of age, gastric intramucosal PCO2 (PgCO2) and arterial blood gas samples were obtained at baseline, immediately after feeding milk, and 1 and 2 hours after fasting for calculation of the intramucosal-arterial PCO2 difference (DeltaCO2). To evaluate the effect of omeprazole, foals were evaluated twice as above, 2 hours after fasting, comparing administration of omeprazole to no drug. RESULTS: There was a significant effect of age and feeding on PgCO2 and DeltaCO2, whereas arterial PCO2 was not significantly affected by these factors. Postfeeding DeltaCO2 values were significantly lower than fasted values. Baseline and postfeeding DeltaCO2 increased with age. There was no significant effect of age on data collected after 1 or 2 hours of fasting. The 90% reference interval for DeltaCO2 data collected after fasting was 0-54 mmHg. Foals had a significantly higher mean gastric pH and significantly higher DeltaCO2 and PgCO2 following omeprazole relative to no treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Because of the high and variable DeltaCO2, which is exacerbated by omeprazole administration, the reference interval in foals is extremely wide.