Plasma disposition of ceftazidime in healthy neonatal foals following intravenous and intramuscular administration.

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.

Pharmacokinetics and pharmacodynamics of meperidine after intramuscular and subcutaneous administration in horses.

OBJECTIVE: To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. STUDY DESIGN: prospective, randomized, blinded, crossover trial. ANIMALS: Six adult horses weighing 494 ± 33 kg. METHODS: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at .05. RESULTS: Meperidine terminal half-life (T1/2 ), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P > .2 for all). CONCLUSION: Maximum meperidine concentrations were achieved quickly with a short T1/2 in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables. CLINICAL SIGNIFICANCE: The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.

Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses.

OBJECTIVE: To compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration. STUDY DESIGN: Randomized, masked, crossover design. ANIMALS: A total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg. METHODS: Horses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (fR), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant. RESULTS: The mean ± SD hydromorphone terminal half-life (t1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute⁻1 kg⁻1 and 1125 ± 309 mL kg⁻1. The t1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: IM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration. IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.

Cladophialophora encephalitis in an alpaca.

A 4-year-old Huacaya hembra was evaluated for acute neurologic signs including recumbency and a left head tilt. Cranial nerve examination revealed a left ear droop, muzzle deviation to the right, mydriasis of the left eye, an absent menace response, bilateral absent pupillary light reflex when light was directed into the left eye, and bilateral horizontal nystagmus with fast phase to the right. Multifocal intracranial lesions were suspected. Computed tomography revealed an intracranial mass. Postmortem examination, histopathology, and sequencing of a polymerase chain reaction product confirmed a diagnosis of phaeohyphomycotic meningoencephalitis caused by Cladophialophora bantiana. Key clinical message: Advanced diagnostic imaging (computed tomography) was useful in achieving a diagnosis of an intracranial mass in an alpaca with acute neurological signs, later confirmed to be central nervous system (CNS) phaeohyphomycosis. Although uncommon, intracranial fungal infection should be considered as a differential diagnosis in camelid patients exhibiting CNS signs, particularly if they do not respond to initial antimicrobial and anthelmintic therapy.

Encéphalite à Cladophialophora chez un alpaga. Une femelle alpaga de race Huacaya âgée de 4 ans fut évaluée pour des signes neurologiques aigus incluant un décubitus et une inclinaison de la tête à gauche. L'examen des nerfs crâniens a révélé un affaissement de l'oreille gauche, une déviation vers la droite du museau, une mydriase de l'oeil gauche, une absence de réponse à la menace, l'absence bilatérale de réflexe pupillaire lorsqu'une lumière était pointée dans l'oeil gauche, et un nystagmus horizontal bilatéral avec phase rapide vers la droite. Des lésions intra-crâniales multifocales étaient suspectées. Un examen par tomodensitométrie révéla une masse intra-crâniale. L'examen post-mortem, l'histopathologie et le séquençage d'un produit de réaction d'amplification en chaîne par la polymérase confirmèrent un diagnostic de méningo-encéphalite phaeohyphomycotique causée par Cladophialophora bantiana.Message clinique clé :L'examen par imagerie diagnostique de pointe (tomodensitométrie) fut utile afin d'arriver à un diagnostic de masse intra-crâniale chez un alpaga avec des signes neurologiques aigus, plus tard confirmé par une phaeohyphomycose du système nerveux central (CNS). Bien que peu fréquente, une infection fongique intra-crâniale devrait être considérée comme un diagnostic différentiel chez des camélidés présentant des signes du CNS, particulièrement s'ils ne répondent pas à un traitement initial avec des antimicrobiens et des anthelmintiques.(Traduit par Dr Serge Messier).

Ceftiofur use and antimicrobial stewardship in the horse.

Equine practitioners require recommendations that support antimicrobial stewardship and avoid generating resistance to medically important antibiotics. This review examines current inadequacies in antimicrobial stewardship standards within the veterinary community, related to antimicrobial categorisation and prescribing practices. Resistance to cephalosporin antibiotics in horses is also described. Properties of cephalosporin antibiotics are outlined and equine-specific studies of ceftiofur, a third-generation cephalosporin antibiotic with medical importance, are detailed. Readers are provided with recommendations that encourage appropriate use of ceftiofur, citing the evidence available in horses.

Plasma UCHL-1 as a Biomarker of Brain Injury in Hospitalized Foals With Neonatal Encephalopathy.

A plasma biomarker such as ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) to distinguish neonatal encephalopathy (NE) from other disorders and provide prognostic information would be useful for equine practitioners. In this prospective study, plasma UCHL-1 was measured in 331 hospitalized foals ≤4 days of age. Clinical diagnoses of neonatal encephalopathy only (NE group, n = 77), sepsis only (Sepsis group, n = 34), concurrent sepsis and NE (NE+Sepsis group, n = 85), or neither sepsis nor NE (Other group, n = 101) were made by the attending veterinarian. Plasma UCHL-1 concentrations were measured by ELISA. Differences between clinical diagnoses groups were evaluated and receiver operator curve (ROC) analysis was performed to assess diagnostic and prognostic performance. Median admission UCHL-1 concentration was significantly higher for NE (18.22 ng/mL; 7.93-37.43) and NE+Sepsis (17.42 ng/mL; 7.67-36.24) groups than Other foals (7.77 ng/mL; 3.92-22.76). Admission UCHL-1 was significantly higher in nonsurvivors (16.66 ng/mL; 6.89-34.84) than survivors (10.27 ng/mL; 5.82-29.94). Overall diagnostic performance of admission UCHL-1 concentration for NE diagnosis was determined (AUC 0.61; 95% confidence interval [CI] = 0.55-0.68); sensitivity and specificity for predicting NE were 73% and 49% respectively. Overall prognostic performance of time to lowest UCHL-1 concentration for predicting nonsurvival was determined (AUC 0.72; 95% CI = 0.65-0.79); sensitivity and specificity were 86% and 43% respectively. In this foal population, differences in plasma UCHL-1 concentrations were observed between foals with NE or NE with sepsis, and other diagnoses. The diagnostic and prognostic value of admission UCHL-1 concentration was limited.

Evaluation of transpalpebral ultrasonographic measurement of optic nerve sheath diameter for indirect assessment of intracranial pressure in anesthetized and standing healthy adult horses.

OBJECTIVE: To determine whether an association exists between direct intracranial pressure (ICP) measurement and ultrasonographic measurement of optic nerve sheath diameter (ONSD) in anesthetized and standing horses. DESIGN: Cross-sectional study performed on a convenience sample of healthy adult horses. SETTING: University teaching hospital. ANIMALS: Eight adult horses donated to the University. Enrolled horses were free of abnormalities on physical examination, CBC, neurological evaluation, and ophthalmological examination. MEASUREMENTS AND MAIN RESULTS: Horses were anesthetized in lateral recumbency for placement of an ICP transducer. Three head positions (neutral, elevated, and lowered) were used to alter ICP. ICP and ONSD in 2 directions (D1 and D2) were recorded at 5 and 10 minutes after position change to elevated and lowered. ICP and ONSD measurements were repeated in standing sedated horses 24-36 hours after recovery from anesthesia. Linear regressions were performed with ICP as the dependent variable and ONSD as the independent variable by head position and times. Linear regressions were also performed for change from neutral under anesthesia, with ONSD as the independent variable and ICP as the dependent variable, by head position and times. Significance was set at P < 0.05. There was a moderate association between ICP and ONSD in horses with head lowered at 5 and 10 minutes (R2 values = 63%-78%) and weak association in head elevated at 10 minutes (R2 values = 56%-63%). There was a weak association between change from neutral ICP and change from neutral ONSD in the elevated anesthetized position at 10 minutes for summed D1 + D2 (R2  = 33%). CONCLUSIONS: Consistent associations between direct ICP and ONSD in anesthetized or standing horses were not observed. This inconsistency limits the clinically utility of transpalpebral ultrasonographic ONSD measurement for ICP monitoring in horses.

The effect of xylazine on intracranial pressure in anesthetized and standing horses.

OBJECTIVE: To determine the effect of xylazine on intracranial pressure (ICP) in standing compared to isoflurane-anesthetized horses. DESIGN: Prospective, crossover study design. SETTING: University Teaching Hospital. ANIMALS: Six adult horses donated to the University. Horses were determined to be healthy via physical examination, complete blood count, and neurological evaluation. INTERVENTIONS: Horses were anesthetized, maintained on isoflurane in oxygen in left lateral recumbency, and ventilated to normocapnia. Horses were instrumented for intraparenchymal measurement of ICP, invasive blood pressure, pulse oximetry, and end tidal gas analyzer. Xylazine 1 mg/kg was administered IV and ICP, systolic arterial pressure, mean arterial pressure (MAP), diastolic arterial pressure, and heart rate were recorded and cerebral perfusion pressure (CPP) was calculated for the following 15 minutes. Twenty-four to 36 hours following anesthetic recovery, xylazine 1 mg/kg was administered IV and ICP, heart rate, and Doppler blood pressure (BPdop) on the tail were monitored for 15 minutes. MEASUREMENTS AND MAIN RESULTS: There was a decrease in ICP following administration of xylazine in anesthetized horses (P < 0.003) but not standing horses (P = 0.227). There was an increase in systolic arterial pressure, MAP, diastolic arterial pressure (P < 0.001), and BPdop (P = 0.001) following administration of xylazine. As a result, CPP increased in anesthetized horses (P < 0.03). There was a negative association between ICP and MAP in anesthetized horses (P = 0.007) but not ICP and BPdop conscious horses (P = 0.379). CONCLUSIONS: Administration of xylazine to anesthetized horses resulted in an increased CPP due to decreased ICP with concurrent increased MAP. Administration of xylazine to standing horses did not result in a change in ICP. However, with the increase in BPdop found in awake horses, it is likely that CPP would also increase in awake horses following xylazine administration.

Administration of pilocarpine by microneedle patch as a novel method for cystic fibrosis sweat testing.

The sweat test is the gold standard for the diagnosis of cystic fibrosis (CF). The test utilizes iontophoresis to administer pilocarpine to the skin to induce sweating for measurement of chloride concentration in sweat. However, the sweat test procedure needs to be conducted in an accredited lab with dedicated instrumentation, and it can lead to inadequate sweat samples being collected in newborn babies and young children due to variable sweat production with pilocarpine iontophoresis. We tested the feasibility of using microneedle (MN) patches as an alternative to iontophoresis to administer pilocarpine to induce sweating. Pilocarpine-loaded MN patches were developed. Both MN patches and iontophoresis were applied on horses to induce sweating. The sweat was collected to compare the sweat volume and chloride concentration. The patches contained an array of 100 MNs measuring 600 µm long that were made of water-soluble materials encapsulating pilocarpine nitrate. When manually pressed to the skin, the MN patches delivered >0.5 mg/cm2 pilocarpine, which was double that administered by iontophoresis. When administered to horses, MN patches generated the same volume of sweat when normalized to drug dose and more sweat when normalized to skin area compared to iontophoresis using a commercial device. Moreover, both MN patches and iontophoresis generated sweat with comparable chloride concentration. These results suggest that administration of pilocarpine by MN patches may provide a simpler and more-accessible alternative to iontophoresis for performing a sweat test for the diagnosis of CF.

Effect of Meperidine on Equine Blood Histamine, Tryptase, and Immunoglobulin-E Concentrations.

Objectives: To evaluate changes in immunological parameters following subcutaneous (SC) and intramuscular (IM) administration of meperidine in horses through quantitative analysis of plasma tryptase, histamine, and IgE levels. Methods: Six adult horses were enrolled in a prospective randomized crossover design. Horses were administered one treatment per day, with a seven day washout period: (a) meperidine 1 mg/kg IM, saline 6 mL SC; (b) saline 6 mL IM, meperidine 1 mg/kg SC; (c) saline 6 mL SC, saline 6 mL IM. Blood samples were obtained for plasmatic histamine (baseline, 5, 10, 15, 30, and 60 min) via LC-MS/MS and plasmatic tryptase (baseline, 15, 30, 60, 120, and 240 min) quantification with enzyme-linked immunoabsorbent assays. Serum immunoglobulin E (IgE) concentrations prior to any meperidine treatment and 7-14 days following the first meperidine treatment were evaluated with enzyme-linked immunoabsorbent assays. Histamine and tryptase concentrations were evaluated with a mixed-effect analysis of variance. The levels of IgE at baseline (before the administration of the first dose of meperidine) were compared with the IgE values at 60 min following the second meperidine administration with the Paired t test. Biopsies of localized injection site reactions from subcutaneous meperidine administration were collected from two horses. Results: No statistically significant elevations from baseline in histamine (p = 0.595), tryptase (p = 0.836), or IgE (p = 0.844) were found in any of the horses in this study. There were no differences between treatment groups. Administration of SC meperidine caused a localized vasculitis and thrombosis with regional edema and hemorrhage. Conclusion: No evidence of anaphylactoid or anaphylactic type reactions occurred following IM or SC meperidine administration.

Nondiarrheal disorders of the gastrointestinal tract in neonatal foals.

Neonates can have a variety of gastrointestinal disorders, primary and secondary in nature. Important primary disorders include con-genital abnormalities and meconium retention. One of the most important secondary lesions is generalized ileus. Gastric ulceration can occur as a primary or secondary event. This article addresses the pathophysiology, diagnosis, and treatment of gastrointestinal problems commonly observed in neonatal foals.