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  • Author or Editor: A. S. J. P. A. M. van Miert x
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SUMMARY

The in vitro antimicrobial activities of aditoprim (ap), a new dihydrofolate reductase (dhfr) inhibitor, trimethoprim (tmp), sulfadimethoxine (sdm), sulfamethoxazole (smx), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (mic) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia.

All B bronchiseptica strains were resistant to ap and tmp. The mic 50 values of ap and tmp for P multocida were 0.25 and 0.06 μg/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 μg/ml, respectively. The mic 50 values of sdm and smx for B bronchiseptica were 4 and 1 μg/ml, respectively; for P multocida, 16 and 8 μg/ml, respectively; and for A pleuropneumoniae, 16 and 8 μg/ml, respectively.

The investigated combinations of the dhfr inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the mic 90 values of the combinations were ≤ 0.06 μg/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The mic of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the dhfr inhibitors in the combinations.

For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type - 9 strains to ap and tmp as well as to sdm and smx (at least a fourfold difference in mic between the 2 types of strains). The mic of the combinations were similar for the 2 types of strains.

Free access
in American Journal of Veterinary Research

Abstract

Objectives

To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5).

Design

A crossover design to administer the 4 drugs orally, and ampicillin IV, to all horses in the study.

Animals

4 healthy adult horses.

Procedure

The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered IV at the same dosage. Blood samples were taken up to 12 hours after drug administration, and ampicillin concentrations in plasma were determined. For the in vitro study, the ampicillin esters were incubated at 37 C in ileal contents obtained from ponies with cecal fistulas. After incubation, the remaining intact ester and the formed ampicillin were measured.

Results

Absolute oral bioavailability was 31, 39, 23, and 2% for pivampicillin, bacampicillin, talampicillin, and ampicillin sodium, respectively. In the in vitro study, 90% decomposition of the ester took place in 30, 60, and 5 minutes, for pivampicillin, bacampicillin, and talampicillin, respectively.

Conclusions

Pivampicillin and bacampicillin are promising candidates for oral antibiotic treatment of horses. The rapid decomposition of ampicillin esters is caused by chemical hydrolysis at the high pH of equine ileal contents. (Am J Vet Res 1996;57:1021–1024)

Free access
in American Journal of Veterinary Research

Summary

The in vitro activity of trimethoprim (tmp) and 9 sulfonamides and their combinations in 6 concentration ratios was tested against 62 Salmonella strains isolated from horses over a 3-year period in the Netherlands, using the agar-dilution method. Most of the isolates were S typhimurium strains (n = 52); the others were S heidelberg (n = 3), S hadar (n = 2), S thompson (n = 2), S enteritidis (n = 1), S infantis (n = 1), and S derby (n = 1). The minimal TMP concentration at which 50% of the Salmonella strains were inhibited (mic 50) was 0.12 |ig/ml. Sulfachlorpyridazine (scp; mic 50, 16 fig/ml), sulfamethoxazole (smx; mic 50, 32 μg/ml), and sulfadiazine (sdz; mic 50; 32 μg/ ml) were the most potent of the sulfonamides tested. The antimicrobial effect of the sulfonamides, in combination with tmp (additive, synergistic, or antagonistic), was expressed by the fractional inhibitory concentration (fic) index. Concentrations of sdz and scp with tmp had marked synergism at all tested tmp-to-sulfonamide concentration ratios (1:1 to 1: 160; fic index, 0.10 to 0.50); smx had synergy with tmp at all ratios, except 1:1 (fic index, 0.10 to 0.27). Sulfamethazine, sulfamerazine, sulfadoxine (sdx), sulfatroxazole, sulfadimethoxine, and sulfacetamide had mic 50 greater than their breakpoint mic value and are, therefore, less potent drugs. However, synergy with TMP was found for these less potent sulfonamides at certain concentration ratios, depending on the sulfonamide used. Sixteen Salmonella strains were resistant to tmp, all sulfonamides, and tmp-sulfonamide combinations; 14 of these strains were S typhimurium phage type 200, 1 was S typhimurium phage type 61, and 1 was S typhimurium phage type 10. Four additional Salmonella strains were resistant to the sulfonamides alone (1 S typhimurium phage type 171 and 3 S typhimurium strains that could not be biotyped). Results of this study indicate that sdz, scp, and smx are the best sulfonamides to combine with tmp for treatment of salmonellosis in equids, because they are the most potent sulfonamides and have strong synergism with tmp at a wide range of tmp-to-sulfonamide concentration ratios.

Free access
in American Journal of Veterinary Research

Summary

The influence of infection with Ehrlichia phagocytophila (ep) on serum thyroid hormone concentrations and on antipyrine (25 mg/kg of body weight, iv) plasma elimination and urinary metabolite excretion was studied in castrated male dwarf goats. Mean thyroid hormone concentrations moderately decreased in ep-infected goats, with maximal decrease in total and free triiodothyronine and thyroxine serum concentrations of 56, 64, 23, and 19%, respectively. The estimated pharmacokinetic values of antipyrine (ap) in ep-infected goats were similar to those in the goats when healthy. However, glucuronidation of the ap-metabolites 3-hydroxymethyl-ap, 4,4′-dihydroxy-ap, and 4-hydroxy-ap was reduced during the febrile episode of the acute-phase response to ep infection.

Free access
in American Journal of Veterinary Research

Summary

The influence of triiodothyronine (5 μg/kg of body weight, sc, q 12 h for 7 days) on antipyrine (ap, 25 mg/kg, iv) plasma elimination and urinary metabolite excretion was studied in castrated male dwarf goats. After triiodothyronine treatment, a significant increase in ap elimination was found. However, the observed changes in clearances for production of ap metabolites (nor-ap, 3-hydroxymethyl-ap; 4-hydroxy-ap, and 4,4′-dihydroxy-ap) do not suggest a clear selectivity of triiodothyronine toward any of the metabolic pathways of ap.

Free access
in American Journal of Veterinary Research

SUMMARY

Plasma disposition and urinary recovery of sulfamethazine (smz), its N4-acetylated metabolite (N4AcSMZ), and 2 of its hydroxylated metabolites—5-hydroxysulfamethazine (5OHSMZ) and 6-hydroxymethylsulfamethazine (6CH2OHSMZ)—were determined in either sex of 4 animal species: rats, dwarf goats, rabbits, and cattle. Rats, rabbits, and dwarf goats had significant (P < 0.01) sex difference in smz plasma clearance. Male rats had higher plasma clearance than did female rats, and excreted higher amounts of the hydroxy metabolites and lower amounts of N4AcSMZ. The N4AcSMZ metabolite was predominant in plasma and urine of rabbits. Male rabbits had higher plasma clearance than did female rabbits, but differences in metabolite profile were not apparent. With regard to plasma smz elimination, the situation in goats was opposite to that in rats. Male goats had considerably lower clearance than did female goats. This was associated with a lower hydroxylation rate in males. Plasma half-life of smz in cows was lower than that in bulls, probably because of a smaller distribution volume in cows. Compared with elimination via urine, elimination via milk was negligible in cows. Significant differences in metabolite profiles were not found between bulls and cows. Similar to those in rats and mice, hormone-dependent xenobiotic metabolic pathways may exist in other species. Depending on species and xenobiotic compound residue concentrations of xenobiotics, their metabolites, or both may differ with sex of the animal, or may be altered after treatment with anabolic hormones.

Free access
in American Journal of Veterinary Research

Summary

Plasma disposition of aditoprim, a new dihydrofolate reductase inhibitor, was studied in healthy cows and cows with endotoxin-induced mastitis. A single dose of 5 mg of aditoprim/kg of body weight was administered iv to 5 healthy cows and to the same cows 3 weeks later at 2 hours after intramammary infusion of 0.1 mg of endotoxin into the rear quarters.

Mastitis developed in all endotoxin-infused quarters and cows had systemic signs of disease (fever, tachycardia, depression) from 2 to 10 hours after infusion of endotoxin.

Pharmacokinetic characteristics of aditoprim in healthy cows were a large volume of distribution (6.28 L/kg), a systemic clearance of 0.82 L/h/kg, and an elimination halflife of 7.26 hours. In cows with mastitis, plasma concentrations of aditoprim were lower between 5 and 26 hours after injection. The systemic clearance (1.00 L/h/kg) and the volume of distribution (12.25 L/kg) were significantly higher in cows with mastitis, but elimination half-life was not significantly different.

The lower plasma concentrations of aditoprim between 5 and 26 hours after injection in cows with mastitis are explained by fluid compartment shifts and/or blood flow changes induced by mastitis, although increased elimination of aditoprim in cows with mastitis cannot completely be ruled out.

The antibacterial activity of aditoprim is nearly the same as that of trimethoprim. The longer elimination half-life time of aditoprim, however, indicates that it may have a practical pharmacotherapeutic advantage over trimethoprim.

Free access
in American Journal of Veterinary Research