Enrofloxacin-based therapy to prevent endometritis in embryo transfer mares

GONZALEZ, C.; MORENO, L.; FUMUSO, E.; CONFALONIERI, A.; SPARO M ,; SANCHEZ BRUNI SF

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 33 p. 267 - 294

0140-7783

Gonza´lez, C., Moreno, L., Fumuso, E., Garcý´a, J., Rivulgo, M., Confalonieri, A., Sparo, M., Sanchez Bruni, S. Enrofloxacin-based therapeutic strategy for the prevention of endometritis in susceptible mares. J. vet. Pharmacol. Therap. 33, 287–294. Enrofloxacin (EFX) is often used empirically to prevent uterine infections in mares in order to improve efficiency on Commercial Embryo Transfer Farms. This study investigated the uterine distribution of EFX and its metabolite ciprofloxacin (CFX) in mares and assessed the minimal inhibitory concentrations (MIC) of EFX against various common pathogens as a basis for establishing a rational dosing schedule. Plasma and uterine pharmacokinetic (PK) studies were performed in two groups (n = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg⁄ kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (b-haemolytic streptococci) ranged from 0.25–2 and 1.5–3.0 lg ⁄ mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MICJ. vet. Pharmacol. Therap. 33, 287–294. Enrofloxacin (EFX) is often used empirically to prevent uterine infections in mares in order to improve efficiency on Commercial Embryo Transfer Farms. This study investigated the uterine distribution of EFX and its metabolite ciprofloxacin (CFX) in mares and assessed the minimal inhibitory concentrations (MIC) of EFX against various common pathogens as a basis for establishing a rational dosing schedule. Plasma and uterine pharmacokinetic (PK) studies were performed in two groups (n = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg⁄ kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (b-haemolytic streptococci) ranged from 0.25–2 and 1.5–3.0 lg ⁄ mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MICn = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg⁄ kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (b-haemolytic streptococci) ranged from 0.25–2 and 1.5–3.0 lg ⁄ mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MIC⁄ kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (b-haemolytic streptococci) ranged from 0.25–2 and 1.5–3.0 lg ⁄ mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MICMIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (b-haemolytic streptococci) ranged from 0.25–2 and 1.5–3.0 lg ⁄ mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MICEscherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (b-haemolytic streptococci) ranged from 0.25–2 and 1.5–3.0 lg ⁄ mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MICb-haemolytic streptococci) ranged from 0.25–2 and 1.5–3.0 lg ⁄ mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MICAUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MIC⁄ kg respectively. After i.v. treatment with EFX at 5 mg⁄ kg, endometrial concentrations of EFX and CFX above the MIC⁄ kg, endometrial concentrations of EFX and CFX above the MIC value were detected for 36–48 and 22–43 h posttreatment for Gram-negative and -positive isolates respectively. Concentrations above MIC were maintained for much shorter periods at the lower (2.5 mg⁄ kg) treatment dose. Based on these results, a conventional dose (5 mg⁄ kg) of EFX given prebreeding followed by two further doses at 36–48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis. (Paper received 20 May 2009; accepted for publication 31 August 2009)MIC were maintained for much shorter periods at the lower (2.5 mg⁄ kg) treatment dose. Based on these results, a conventional dose (5 mg⁄ kg) of EFX given prebreeding followed by two further doses at 36–48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis. (Paper received 20 May 2009; accepted for publication 31 August 2009)⁄ kg) treatment dose. Based on these results, a conventional dose (5 mg⁄ kg) of EFX given prebreeding followed by two further doses at 36–48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis. (Paper received 20 May 2009; accepted for publication 31 August 2009)⁄ kg) of EFX given prebreeding followed by two further doses at 36–48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis. (Paper received 20 May 2009; accepted for publication 31 August 2009) Prof. Sergio Sa´nchez Bruni, Laboratory of Pharmacology, Faculty of Veterinary Medicine, Sergio, UNCPBA, Tandil (7000)-Argentina. E-mail: ssanchez@vet. unicen.edu.ar INTRODUCTION Embryo transfer is a management technique used to facilitate the production of foals from older breeding mares suffering persistent chronic or non-responsive, mating-induced endometritis and ⁄ or repeated early embryonic death or abortion (Hurtgen, 2006). On Commercial Embryo Transfer Farms (CETFs) decreasing of fertility in older mares is often a based on their inability to eliminate the uterine fluid accumulation after breeding, and the adherence of bacteria resulting in the development of chronic bacterial endometritis (Watson, 2000). Moreover, practices such as repeated examinations and repeated breeding can lead to uterine contamination such mares, although this problem can be alleviated⁄ or repeated early embryonic death or abortion (Hurtgen, 2006). On Commercial Embryo Transfer Farms (CETFs) decreasing of fertility in older mares is often a based on their inability to eliminate the uterine fluid accumulation after breeding, and the adherence of bacteria resulting in the development of chronic bacterial endometritis (Watson, 2000). Moreover, practices such as repeated examinations and repeated breeding can lead to uterine contamination such mares, although this problem can be alleviated