Dianne I. Mawby

Mycobacterium tuberculosis transmission from human to canine.

A 71-year-old woman from Tennessee, USA with a 3-week history of a productive, nonbloody cough was evaluated. Chest radiograph showed infiltrates and atelectasis in the upper lobe of the right lung. A tuberculosis (TB) skin test resulted in a 14-mm area of induration. Sputum stained positive for acid-fast bacilli (AFB) and was positive for Mycobacterium tuberculosis by DNA probe and culture. Treatment was initiated with isoniazid, rifampicin, and pyrazinamide. After 14 days of daily, directly …

Bioequivalence of Orally Administered Generic, Compounded, and Innovator‐Formulated Itraconazole in Healthy Dogs

Background Itraconazole is commonly used to treat systemic fungal infections in dogs, but problems exist with absorption and cost. Objective To determine oral bioequivalence of generic and compounded itraconazole compared to original innovator (brand name) itraconazole in healthy dogs. Animals Nine healthy, adult research Beagle dogs. Methods A randomized, 3‐way, 3‐period, crossover design with an 8‐day washout period. After a 12‐hour fast, each dog received 100 mg (average: 10.5 mg/kg) of either innovator itraconazole, an approved human generic capsule, or compounded itraconazole (compounded using a commercially available compounding vehicle) with a small meal. Plasma was collected at predetermined intervals for high pressure liquid chromatography analysis. Concentration data were analyzed using noncompartmental pharmacokinetics to determine area under the curve (AUC), peak concentration (CMAX), and terminal half‐life. Bioequivalence tests compared generic and compounded itraconazole to the reference formulation. Results Average ratios of compounded and generic formulations to the reference formulation of itraconazole for AUC were 5.52% and 104.2%, respectively, and for CMAX were 4.14% and 86.34%, respectively. A test of bioequivalence using 2 one‐sided tests and 90% confidence intervals did not meet bioequivalence criteria for either formulation. Conclusion and Clinical Importance Neither generic nor compounded itraconazole is bioequivalent to the reference formulation in dogs. However, pharmacokinetic data for generic formulation were similar enough that therapeutic concentrations could be achieved. Compounded itraconazole produced such low plasma concentrations, it is unlikely to be effective; therefore, compounded itraconazole should not be used in dogs.

Associations among albuminuria, C-reactive protein concentrations, survival predictor index scores, and survival in 78 critically ill dogs.

BACKGROUND Microalbuminuria and C-reactive protein (CRP) are predictors of morbidity and survival in critically ill human patients. HYPOTHESIS/OBJECTIVES To evaluate results of microalbuminuria assays (untimed single-sample urine albumin concentration [U-ALB] and the urine albumin:creatinine ratio [UACR]), serum CRP, and survival predictor index (SPI2) scores as predictors of survival in critically ill dogs. ANIMALS Seventy-eight dogs admitted to intensive care units at University of Tennessee (UT) and Colorado State University (CSU). METHODS Prospective observational study. Critically ill dogs were eligible for enrollment, unless euthanized because of financial constraints. Samples were collected within 3 hours of admission. Spearmans rank-correlation coefficients were determined for U-ALB, UACR, CRP, and SPI2. U-ALB, UACR, CRP, and SPI2 were assessed for associations with 7- and 30-day survival by Mann-Whitney U-tests and receiver operating characteristic (ROC) curves. P-values < .0125 were considered significant. RESULTS UT (n = 49) and CSU (n = 29) patients did not differ significantly. Forty percent (31/78) of dogs died. SPI2 was inversely correlated with U-ALB (r(s) = -0.39, P < .001) and UACR (r(s) = -0.41, P < .001). CRP was not correlated with SPI2 (P = .019), U-ALB (P > .1), or UACR (P > .1). U-ALB and UACR had very high correlation (r(s) = 0.95, P < .001). SPI2, U-ALB, and UACR differed significantly for survivors and nonsurvivors. SPI2, U-ALB, and UACR had areas under the ROC curve (AUC) from 0.68 to 0.74 for survival prediction. CONCLUSIONS AND CLINICAL IMPORTANCE Albuminuria and SPI2, but not CRP, are associated with survival in critically ill dogs. Suboptimal AUCs limit the value of microalbuminuria testing for clinical risk assessment. Additional studies are necessary to determine the usefulness of microalbuminuria testing in patient risk stratification for prospective research.

Canine Pancreatic-Specific Lipase Concentrations in Clinically Healthy Dogs and Dogs with Naturally Occurring Hyperadrenocorticism

Background Specificity of canine pancreatic lipase immunoreactivity (cPLI) assays in dogs with hyperadrenocorticism (HAC) is unknown. Hypothesis Results of cPLI assays differ for clinically healthy dogs and dogs with HAC. Animals Seventeen healthy dogs and 20 dogs with HAC diagnosed by ACTH stimulation test results without evidence of clinical pancreatitis. Methods Dogs were enrolled between December 2009 and November 2010. Serum cPLI concentrations were determined by quantitative (Spec cPL test, SPEC) and semiquantitative (SNAP cPL test, SNAP) assays. Results were categorized as normal, equivocal, or abnormal (SPEC) or negative or positive (SNAP). Associations between group and cPLI were assessed using Fishers exact test or the Mann–Whitney U‐test. Spearman rank correlation coefficients (ρ) were determined for SNAP and SPEC results. Significance was set at P < .05. Results Spec cPL test concentrations were significantly (P < .001) higher in dogs with HAC (491.1 μg/L) than in healthy dogs (75.2 μg/L), with more abnormal SPEC results in HAC dogs (P < .001). There were more (P = .002) positive SNAP results in dogs with HAC (55%) than in healthy dogs (6%). SNAP and SPEC results were highly correlated (ρ = 0.85; P < .001). Conclusions and Clinical Importance Dogs with HAC had higher SPEC concentrations and more positive SNAP results than clinically healthy dogs with normal ACTH stimulation test results. Specificity of SPEC and SNAP assays in HAC dogs without clinical pancreatitis were 65 and 45%, respectively. Pending further study, SNAP and SPEC results should be interpreted cautiously in dogs with HAC to avoid false diagnosis of concurrent pancreatitis.

Serum Cortisol Concentrations in Dogs with Pituitary‐Dependent Hyperadrenocorticism and Atypical Hyperadrenocorticism

Background Atypical hyperadrenocorticism (AHAC) is considered when dogs have clinical signs of hypercortisolemia with normal hyperadrenocorticism screening tests. Hypothesis/Objectives To compare cortisol concentrations and adrenal gland size among dogs with pituitary‐dependent hyperadrenocorticism (PDH), atypical hyperadrenocorticism (AHAC), and healthy controls. Animals Ten healthy dogs, 7 dogs with PDH, and 8 dogs with AHAC. Method Dogs were prospectively enrolled between November 2011 and January 2013. Dogs were diagnosed with PDH or AHAC based on clinical signs and positive screening test results (PDH) or abnormal extended adrenal hormone panel results (AHAC). Transverse adrenal gland measurements were obtained by abdominal ultrasound. Hourly mean cortisol (9 samplings), sum of hourly cortisol measurements and adrenal gland sizes were compared among the 3 groups. Results Hourly (control, 1.4 ± 0.6 μg/dL; AHAC, 2.9 ± 1.3; PDH, 4.3 ± 1.5) (mean, SD) and sum (control, 11.3 ± 3.3; AHAC, 23.2 ± 7.7; PDH, 34.7 ± 9.9) cortisol concentrations differed significantly between the controls and AHAC (P < .01) and PDH (P < .01) groups. Hourly (P < .01) but not sum (P = .27) cortisol concentrations differed between AHAC and PDH dogs. Average transverse adrenal gland diameter of control dogs (5.3 ± 1.2 mm) was significantly less than dogs with PDH (6.4 ± 1.4; P = .02) and AHAC (7.2 ± 1.5; P < .01); adrenal gland diameter did not differ (P = .18) between dogs with AHAC and PDH. Conclusions and Clinical Importance Serum cortisol concentrations in dogs with AHAC were increased compared to controls but less than dogs with PDH, while adrenal gland diameter was similar between dogs with AHAC and PDH. These findings suggest cortisol excess could contribute to the pathophysiology of AHAC.

Effects of various factors on Doppler ultrasonographic measurements of radial and coccygeal arterial blood pressure in privately owned, conscious cats

OBJECTIVE To assess the effects of age, body condition score (BCS), and muscle condition score (MCS) on radial and coccygeal systolic arterial blood pressure (SAP) in cats. DESIGN Prospective randomized trial. ANIMALS 66 privately owned cats enrolled between May and December 2010. PROCEDURES BCS and MCS of cats were assessed by 2 investigators; SAP was measured via Doppler ultrasonic flow detector, with cats positioned in right lateral or sternal recumbency for measurements at the radial or coccygeal artery, respectively, with order of site randomized. Associations among variables were assessed through correlation coefficients, partial correlation coefficients, and ANCOVA. RESULTS Interrater reliability for BCS and MCS assessment was high (correlation coefficients, 0.95 and 0.83, respectively). No significant effect was identified for order of SAP measurement sites. Coccygeal and radial SAP were positively correlated (ρ = 0.45). The median difference in coccygeal versus radial SAP was 19 mm Hg, but differences were not consistently positive or negative. Radial SAP was positively correlated with age (ρ = 0.48) and negatively correlated with MCS (ρ = -0.30). On the basis of the correlation analysis, the association between radial SAP and MCS reflected the confounding influence of age. Coccygeal SAP was not significantly correlated with age, BCS, or MCS. CONCLUSIONS AND CLINICAL RELEVANCE Use of the coccygeal artery is recommended to reduce the confounding effects of age and sarcopenia on Doppler ultrasonographic SAP measurements in cats. Additionally, monitoring for changes in MCS is recommended for cats undergoing serial SAP measurement.

Posaconazole Pharmacokinetics in Healthy Cats after Oral and Intravenous Administration.

Background Posaconazole is the most active available azole antifungal drug, but absorption and pharmacokinetics are not available to guide dosing regimens in cats. Objective To determine the pharmacokinetics of posaconazole in cats given an IV solution and PO suspension. Animals Six healthy, adult research cats. Methods After a 12‐hour fast, each cat received 15 mg/kg of posaconazole PO suspension with food. Four cats also received 3 mg/kg IV posaconazole after a 7‐day washout period. Plasma was collected at predetermined intervals for analysis using high‐pressure liquid chromatography (HPLC). Concentration data were analyzed using a 2‐compartment pharmacokinetic analysis for IV administration data and a 1‐compartment analysis with first‐order input for PO administration data using Phoenix® software.5 Results After IV dosing, volume of distribution (V SS) was 1.9 (0.3) L/kg (mean, standard deviation), terminal half‐life (T ½) was 57.7 (28.4) hours, and clearance was 28.1 (17.3) mL/kg/h. After PO dosing, peak concentration (C MAX) was 1.2 (0.5) μg/mL and T ½ was 38.1 (15.0) hours. Bioavailability of PO suspension was 15.9% (8.6). No adverse effects were observed with either route of administration. Conclusion and Clinical Importance Despite low PO absorption, these data allow for simulation of PO dosage regimens that could be explored in clinical studies. Two regimens can be considered to maintain targeted trough concentrations of 0.5–0.7 μg/mL as extrapolated from studies in humans: (1) 30 mg/kg PO loading dose followed by 15 mg/kg q48h, or (2) 15 mg/kg PO loading dose followed by 7.5 mg/kg q24h.

Comparison of absorption characteristics of oral reference and compounded itraconazole formulations in healthy cats

OBJECTIVE To compare absorption characteristics of orally administered compounded itraconazole capsules and suspension with those of reference (brand-name) formulations in healthy cats. DESIGN Randomized crossover study. ANIMALS 8 healthy adult cats. PROCEDURES After 12 hours of food withholding, cats received 50 mg of itraconazole (reference capsule, reference solution, compounded capsule, and compounded suspension) in a randomized crossover design, with a 21-day washout period. Capsules were administered with a small meal. Blood samples were collected at predetermined intervals for high-pressure liquid chromatography analysis of plasma itraconazole concentrations. Area under the concentration-time curve, maximum concentration, and terminal half-life of itraconazole were determined and compared among formulations. RESULTS 7 cats completed the study. Mean half-life of itraconazole in reference formulations was 18 to 26 hours. Absorption of the reference solution was 3 times that of the reference capsule. Compounded formulations were absorbed poorly and inconsistently. Complete pharmacokinetic results for the compounded capsule were obtained for only 3 of 6 cats and for the compounded suspension for only 1 of 5 cats, precluding bioequivalence analysis. Relative absorption of compounded formulations was only 2% to 8% of reference formulation values. CONCLUSIONS AND CLINICAL RELEVANCE Compounded oral formulations of itraconazole should not be used for cats because of poor absorption. The differences in absorption between the 2 reference formulations suggested that doses required to meet human target serum concentrations in cats are markedly different (capsules, 12.5 mg/kg [5.7 mg/lb], q 24 h, with food; solution, 4 mg/kg [1.8 mg/lb], q 24 h, without food).

Effects of various factors on Doppler flow ultrasonic radial and coccygeal artery systolic blood pressure measurements in privately-owned, conscious dogs

Objective The purpose of this study was to assess the effects of age, body condition score (BCS) and muscle condition score (MCS) on indirect radial and coccygeal Doppler systolic arterial blood pressure (SAP) measurements in dogs. Methods Sixty-two privately-owned dogs were enrolled between June and July 2016. The BCS and MCS were determined by two investigators. Blood pressure was measured per published guidelines and using headphones, and the order of measurement site was randomized. Dogs were positioned in right lateral recumbency for radial measurements and sternal recumbency or standing for coccygeal measurements. Associations between SAP and other variables were assessed by correlation coefficients and analysis of covariance. Results Radial and coccygeal SAP measurements were moderately correlated (r = 0.45, P < 0.01). Radial SAP measurements were higher than coccygeal SAP measurements (mean difference 9 mmHg, P < 0.01), but discordance occurred in both directions. No difference was observed between the first measurement taken, the average of measurements 2–6, or the average of all 6 measurements for either the radial (128, 129, and 129 mmHg; P = 0.36) or coccygeal (121, 122, and 122 mmHg; P = 0.82) site. Associations were not found between SAP measurements for either site and age, weight, BCS, MCS, anxiety score, or cuff size. Heart rate decreased significantly from the start of acclimation to the end of the first data collection series regardless of site (P < 0.01). Conclusions and Clinical Relevance Initial measurement site can be based on patient and operator preference given lack of associations with patient variables, but the same site should be used for serial SAP measurements given discordant results between sites.