Pharmacokinetics of ceftazidime in Northern leopard frogs (Lithobates pipiens) at two different doses and administration routes.

OBJECTIVE: To determine an optimal ceftazidime dosing strategy in Northern leopard frogs (Lithobates pipiens) by evaluation of 2 different doses administered SC and 1 dose administered transcutaneously. ANIMALS: 44 Northern leopard frogs (including 10 that were replaced). PROCEDURES: Ceftazidime was administered to frogs SC in a forelimb at 20 mg/kg (n = 10; SC20 group) and 40 mg/kg (10; SC40 group) or transcutaneously on the cranial dorsum at 20 mg/kg (10; TC20 group). Two frogs in each ceftazidime group were euthanized 12, 24, 48, 72, and 96 hours after drug administration. Plasma, renal, and skin concentrations of ceftazidime were measured by means of reversed-phase high-performance liquid chromatography. Four control frogs were used for assay validation. RESULTS: Mean plasma half-life of ceftazidime in the SC20, SC40, and TC20 groups was 9.01 hours, 14.49 hours, and too low to determine, respectively. Mean maximum plasma ceftazidime concentration was 92.9, 96.0, and 1.3 µg/mL, respectively. For 24 hours after drug administration in the SC20 and SC40 groups, plasma ceftazidime concentration exceeded 8 µg/mL. Renal and skin concentrations were detectable at both doses and routes of administration; however, skin concentrations were significantly lower than renal and plasma concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that ceftazidime administration to Northern leopard frogs at 20 mg/kg, SC, every 24 hours would achieve a plasma concentration exceeding the value considered effective against common amphibian pathogens. Transcutaneous administration of the injectable ceftazidime formulation at 20 mg/kg warrants further investigation but is not currently recommended because of a potential lack of efficacy.

Diagnostic evaluation of fatal Balamuthia mandrillaris meningoencephalitis in a captive Bornean orangutan (Pongo pygmaeus) with identification of potential environmental source and evidence of chronic exposure.

A female Bornean orangutan (Pongo pygmaeus) aged 11 years and 6 months was examined by veterinarians after caretakers observed lethargy and facial grimacing. Within 72 h the primate had left-sided hemiparesis that worsened over the next week. An MRI revealed a focal right-sided cerebral mass suspected to be a neoplasm. Ten days after onset of clinical signs, the orangutan died. On postmortem exam, the medial right parietal lobe was replaced by a 7 × 4 × 3.5 cm focus of neuromalacia and hemorrhage that displaced the lateral ventricle and abutted the corpus callosum. Histopathology of the cerebral lesion revealed pyogranulomatous meningoencephalitis with intralesional amoeba trophozoites and rare cysts. Fresh parietal lobe was submitted to the Centers for Disease Control and Prevention lab for multiplex free-living amoebae real-time PCR and detected Balamuthia mandrillaris DNA at a high burden. Mitochondrial DNA was sequenced, and a 760-bp locus 19443F/20251R was compared to several human infections of B. mandrillaris and shown to be identical to the isolates from four human cases of encephalitis: 1998 in Australia, 1999 in California, 2000 in New York, and 2010 in Arizona. Indirect immunofluorescent antibody testing of stored serum samples indicated exposure to B. mandrillaris for at least 2 years prior to death. Within 1 week of the orangutan's death, water from the exhibit was analyzed and identified the presence of B. mandrillaris DNA, elucidating a possible source of exposure. B. mandrillaris, first reported in a mandrill in 1986, has since occurred in humans and animals and is now considered an important emerging pathogen.

Evaluation of subcutaneous administration of alfaxalone-midazolam and ketamine-midazolam as sedation protocols in African pygmy hedgehogs (Atelerix albiventris).

OBJECTIVE: To evaluate SC administration of 2 sedation protocols, ketamine-midazolam (KM) and alfaxalone-midazolam (AM), in African pygmy hedgehogs (Atelerix albiventris). ANIMALS: 9 healthy adult hedgehogs (5 males, 4 females). PROCEDURES: A randomized, blinded, complete crossover study was performed. Sedation was induced by SC administration of either ketamine (30 mg/kg [14 mg/lb]) with midazolam (1 mg/kg [0.45 mg/lb]) or alfaxalone (3 mg/kg [1.4 mg/lb]) with midazolam (1 mg/kg), including a 2-week washout period between treatments. Flumazenil (0.05 mg/kg [0.02 mg/lb], SC) was administered 45 minutes after administration of either protocol to reverse the effects of midazolam. Physiologic variables, reflexes, and behaviors were monitored. Food intake and body weight were measured before and after sedation. RESULTS: Deep sedation characterized by complete loss of the righting reflex, decreased jaw tone, decreased pelvic limb withdrawal reflex, and preservation of the palpebral reflex was produced in 7 of 9 hedgehogs after KM administration and all 9 hedgehogs after AM administration. Mean ± SD time to loss of righting reflex was 6.4 ± 2.4 minutes after KM administration and 10 ± 4.0 minutes after AM administration. Following flumazenil administration, no significant difference was found in recovery time between sedation with KM (18.8 ± 12.7 minutes) and AM (14.4 ± 7.8 minutes). No significant differences were found in respiratory rate, oxygen saturation, or body temperature between protocols, whereas heart rate was higher for sedation with KM. Both sedation protocols resulted in a transient reduction in food intake. CONCLUSIONS AND CLINICAL RELEVANCE: Subcutaneous administration of KM and AM provided deep sedation that might be useful to facilitate routine, noninvasive procedures in hedgehogs.

Pharmacokinetics of subcutaneously administered hydromorphone in bearded dragons (Pogona vitticeps) and red-eared slider turtles (Trachemys scripta elegans).

OBJECTIVE: To determine pharmacokinetic dosing strategy in bearded dragons (Pogona vitticeps) and red-eared sliders (Trachemys scripta elegans) based on two subcutaneously (SC) administered doses of hydromorphone (0.5 and 1.0 mg kg-1). STUDY DESIGN: Randomized crossover study. ANIMALS: Six healthy adult bearded dragons, seven healthy adult red-eared slider turtles. METHODS: Hydromorphone (0.5 and 1.0 mg kg-1; 2 mg mL-1) was administered SC dorsolateral to the scapulae in the bearded dragons and between the head and thoracic limb of the red-eared slider turtles. Blood was collected for hydromorphone plasma concentration analysis from the ventral tail vein in bearded dragons and subcarapacial sinus in turtles before (time 0) hydromorphone administration and at 0.5, 1, 6, 12 and 24 hours. RESULTS: The half-life of hydromorphone administered at 0.5 and 1.0 mg kg-1 was 2.54 and 3.05 hours in bearded dragons and 2.67 and 2.01 hours in red-eared sliders, respectively. The maximum plasma concentrations for 0.5 and 1.0 mg kg-1 were 142 and 369 ng mL-1 in bearded dragons and 1610 and 5142 ng mL-1 in red-eared sliders, respectively. Peak plasma concentrations were detected at 30 minutes for both species. Hydromorphone administered at both dosages provided plasma concentrations of 13-14 ng mL-1 for at least 24 hours in bearded dragons and of 5-6 ng mL-1 for at least 12 hours in red-eared sliders. Clinical sedation was observed for up to 1 hour posthydromorphone (1.0 mg kg-1) administration for five of six bearded dragons characterized by low body carriage and decreased response to stimuli. No evidence of clinical sedation was observed in red-eared sliders at either dose. CONCLUSIONS AND CLINICAL RELEVANCE: Recommended dosing strategy for hydromorphone is 0.5 mg kg-1 administered SC every 24 hours in bearded dragons and every 12-24 hours in red-eared sliders.