Serum chloramphenicol levels and the intramuscular bioavailability of several parenteral formulations of chloramphenicol in ruminants

Summary

Serum chloramphenicol concentrations were determined by microbiological and chemical assay methods in cows, ewes, and goats treated parenterally with seven different veterinary parenteral chloramphenicol products, including the water soluble sodium succinate ester of chloramphenicol and solutions of 20%, 25% and 50% of chloramphenicol base in various organic solvents. Serum drug concentrations were analyzed for the effect of product formulation differences, dosage, whether the drug was administered i.m. at a single body site or to two sites, and the method of assay, on the absorption from the injection site, peak drug levels, and the persistence in serum of effective concentrations of the drug i.e. 5 to 10 ug / ml. Although differences were observed among the 6 products containing chloramphenicol base in respect to absorption rate and peak serum drug levels, and although these differences significantly influenced the persistence of microbiologically‐active serum drug concentrations at the level of ≥ 10 μg / ml, they did not at the level of ≥ 5 μg / ml.

In the animal species examined, injections given at 2 sites appeared to influence the duration of predetermined serum drug levels more than the differences among the products in respect of the absorption and elimination rates from serum, the peak serum concentrations, and the dose. The shapes of the concentration‐to‐time curves in cows and ewes injected with the same dose of a given product were essentially the same, but they were different in goats. Serum chloramphenicol concentrations measured chemically after treatment with chloramphenicol base were 20% to 46% higher than those measured microbiologically.

For 60 minutes after the sodium succinate ester had been administered i.v. and i.m. to ewes, the chemically determined chloramphenicol levels were more than twice as high as the respective concentrations determined by microbiological assay, but thereafter, the magnitude of those differences was not greater than observed after treatment with chloramphenicol base.

Intramuscular bioavailability of the products containing chloramphenicol base injected at 2 sites was rather poor (51% to 80.5%ofthe dose) and even lower values were calculated after injection at a single site.

Results are briefly discussed of the effect of dosage form on the persistence of microbiologically effective serum drug levels. A dose of at least 50 mg / kg to be administered i.m. at two sites are essential prerequisits for chloramphenicol therapy in ruminants.     

Effect of glucocorticoids on cows suspected of subclinical infection with M. paratuberculosis

Summary

Glucocorticoids were administered to 10 heifers suspected of subclinical infection with Mycobacterium paratuberculosis. Three animals remained untreated.

M. paratuberculosis was isolated from the internal organs of 2 animals after this treatment but not from any of the control group. Delayed type hypersensitivity and lymphocyte reactivity towards Johnin and purified protein derivates of M. avium and M. bovis were depressed. A sharp increase in total leucocyte count, due loan increase in neutrophil numbers, occurred. In the three untreated animals these parameters did not change during the experiment.

A decrease of specific immunological reactivity towards M. paratuberculosis occurred, but not to such an extent that clinical disease developed.     

Relationship between latency of brainstem auditory‐evoked potentials and head size in dogs

Summary

Cranium and brainstem dimensions were measured in 32 postmortem dog heads. Positive correlations were found between cranium length (CL) and brainstem length (BL) (r=0.87), between cranium width (CW) and brainstem width (BW) (r=0.83), and between cranium distance (CD = CL CW/2) and brainstem distance (BD = BL+BW/2) (r=0.91). Positive correlation coefficients were also found between CL and CW (r=0.90), and between BL and BW (r=0.85). It was concluded that head size accurately reflected brainstem size. A least squares estimation of the brainstem distance (BD) from CL and CW values was BD = 10.9 + 0.16 (CL CW/2) (BD, CL and CW in mm).

Brainstem auditory evoked potentials (BAEPs) and cranium dimensions were measured in 43 dogs (86 ears) with different head size, body size, sex and age. Wave form, absolute and interpeak latencies and correlation coefficients, relating latencies to cranium dimensions and body weight, were analysed CL, CW, and CD were positively correlated with body weight (r=0.93, 0.70 and 0.93, respectively), and CL, CW, and CD were correlated with age (r=0.33, 0.52 and 0.40, respectively). BAEPs consisted of five distinct positive peaks (I to V). Secondary positive peaks following peaks I and II were seen in 60% (I') and 90% (II') of the recordings. Late waves were recorded in 90% (VI), 50% (VII), and 25% (VIII) of the recordings. Latencies increased with decreasing stimulus intensity level (from 90 dB to 10 dB hearing level, HL),especially for peaks I, II, V, and the I‐V interpeak interval Absolute and interpeak latencies were positively correlated with cranium distance and body weight. Correlation coefficients increased as wave latencies increased At 90 dB HL, the highest correlation coefficients, relating cranium distance to peak V and the I‐V interpeak latency, were 0.55 and 0.53 (P < 0.00001), respectively. Regression analysis showed that each 1 cm increase in cranium distance was accompanied by an increase of 0.006 ms in the latency of wave I, 0.03 ms for wave III, 0.05 ms for wave V, and 0.05 ms for the I‐V interpeak interval Regression analysis showed that an increase of 1 kg in body weight was accompanied by an increase of 0.001 ms in the latency of wave I, 0.005 ms for wave III, 0.011 ms for wave V, and 0.01 ms for the I‐V interpeak interval. It is concluded that head size, which accurately reflects brain size, is a relevant source (25%) of intersubject variance of BAEP latencies in the dog.     

Equine proliferative enteropathy – a review of recent developments

Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This emerging disease affects mainly weanling foals and causes fever, lethargy, peripheral oedema, diarrhoea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinaemia, thickening of segments of the small intestinal wall observed upon abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in faeces. Although the clinical entity, diagnostic approach and treatment of EPE are well established and described, the epidemiology for this disease has remained largely unaddressed. This article focuses on new developments in the field of EPE, including epidemiology, pathophysiology, clinical signs, diagnosis, treatment and prevention. The Summary is available in Chinese – see Supporting information.     

Bodyweight and serum copper concentrations of farmed red deer stags following oral copper oxide wire administration

A diagnosis of secondary copper deficiency was established on a deer farm with a peat soil type, on the basis of confirmed enzootic ataxia in hinds, liver and serum copper concentrations and pasture and soil element analyses. Seventy-four weaner stags were selected for a trial to investigate a growth response to copper supplementation.

Thirty-seven red and red x wapiti type stags were treated with 4g copper oxide wire particles at four months of age (April). A further 8g copper oxide wire was given in June. Thirty-seven untreated animals acted as controls. Body weights were measured on five occasions, from April 24 to November 26. Serum copper analyses were undertaken on ten deer prior to commencement of the trial, and on seven treated and eight control deer in June, July and October.

Serum copper concentrations ranged from 2.0 to 19.3μmol/l prior to the trial. In June, July and October serum copper ranged from 0.1–6.7, 0.6–5.0, and 1.3–6.3μmol/l respectively, in control deer. In treated deer concentrations ranged from 7.2–14.7, 5.2–10.8, and 6.9–13.7µmoM in June, July and October respectively. The difference between mean copper concentration at each post-treatment sampling date was highly significant, (P<0.001). At the conclusion of the trial (November 26) the treated deer averaged 3.lkg heavier than controls, but this difference was not statistically significant.

In view of these results and the variation in growth response trials in other species, further investigation of the effects of copper on the growth of young deer is warranted.     

Analysis of horse movements from non-commercial horse properties in New Zealand

AIMS: To investigate property-level factors associated with the movement of horses from non-commercial horse properties, including the size and location of the property, number and reason for keeping horses.

METHODS: Using a cross-sectional survey 2,912 questionnaires were posted to randomly selected non-commercial horse properties listed in a rural property database. The survey collected information about the number of horses, and reasons for keeping horses on the property, and any movement of horses in the previous 12 months. Three property-level outcomes were investigated; the movement status of the property, the frequency of movement events, and the median distance travelled from a property. Associations were examined using logistic regression and Kruskal-Wallis analysis of variance.

RESULTS: In total 62.0% (488/791) of respondents reported at least one movement event in the year prior to the survey, for a total of 22,050 movement events. The number of movement events from a property varied significantly by the number of horses on the property (p<0.02), while the median distance travelled per property varied significantly by both region (p<0.03) and property size (p<0.01). Region, property size, the number of horses kept, and keeping horses for competition, recreation, racing or as pets were all significantly associated with movement status in the multivariable analyses (p<0.001).

CONCLUSION AND CLINICAL RELEVANCE: This study showed that there are characteristics of non-commercial horse properties that influence movement behaviour. During an exotic disease outbreak the ability to identify properties with these characteristics for targeted control will enhance the effectiveness of control measures.