Treatment of Bovine Leptospirosis with Enrofloxacin HCl 2H2O (Enro-C): A Clinical Trial.

Pharmacokinetics/pharmacodynamics ratios of enrofloxacin HCl-2H2O (enro-C) in cows to treat bovine leptospirosis prompted this clinical trial in the highlands (HL) and the tropics (TL) in Mexico. In the HL, 111 Holstein-Friesian cows were included and 38 F1 Zebu-Holstein/Friesians in the TL. Affected cows were randomly divided into two treatment groups, both in the HL and TL. PCR and MAT tests were performed before and after treatment. Treatments in both groups were administered for 5 d with either IM injections of enro-C or streptomycin/penicillin-G. Reproductive performance data were gathered for 90 d. The cows treated with enro-C became PCR negative: 87.5% and 78.94% on day 5, 92.85% and 94.73% on day 28 (in the HL and TL, respectively). For streptomycin/penicillin-G, the same values were 65.45% and 70.90% on day 5, and 73.68% twice on day 28 in the HL and TL, respectively. In both groups and geographical settings, the MAT titers dropped on day 28 but remained above reference values usually considered negative. The gestation rates were: 86.53% and 79.06% and 88.88% and 87.5% for the HL and TL, either with enro-C or streptomycin/penicillin-G, respectively. This is the first report of successful treatment with a fluoroquinolone derivative in treating bovine leptospirosis with a high bacteriological cure rate.

Tilmicosin modulates the innate immune response and preserves casein production in bovine mammary alveolar cells during Staphylococcus aureus infection.

Tilmicosin is an antimicrobial agent used to treat intramammary infections against Staphylococcus aureus and has clinical anti-inflammatory effects. However, the mechanism by which it modulates the inflammatory process in the mammary gland is unknown. We evaluated the effect of tilmicosin treatment on the modulation of the mammary innate immune response after S. aureus infection and its effect on casein production in mammary epithelial cells. To achieve this goal, we used immortalized mammary epithelial cells (MAC-T), pretreated for 12 h or treated with tilmicosin after infection with S. aureus (ATCC 27543). Our data showed that tilmicosin decreases intracellular infection (P < 0.01) and had a protective effect on MAC-T reducing apoptosis after infection by 80% (P < 0.01). Furthermore, tilmicosin reduced reactive oxygen species (ROS) (P < 0.01), IL-1ß (P < 0.01), IL-6 (P < 0.01), and TNF-α (P < 0.05) production. In an attempt to investigate the signaling pathways involved in the immunomodulatory effect of tilmicosin, mitogen-activated protein kinase (MAPK) phosphorylation was measured by fluorescent-activated cell sorting. Pretreatment with tilmicosin increased ERK1/2 (P < 0.05) but decreased P38 phosphorylation (P < 0.01). In addition, the anti-inflammatory effect of tilmicosin helped to preserve casein synthesis in mammary epithelial cells (P < 0.01). This result indicates that tilmicosin could be an effective modulator inflammation in the mammary gland. Through regulation of MAPK phosphorylation, ROS production and pro-inflammatory cytokine secretion tilmicosin can provide protection from cellular damage due to S. aureus infection and help to maintain normal physiological functions of the bovine mammary epithelial cell.

Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical trial.

Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid-polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic-pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment.

Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations.

To test if capsaicin could improve the bioavailability of ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, CAS 85721-33-1, Bay q 3939) in rats, 0.01, 0.1, 0.5 and 1% capsaicin ((E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonenamide, trans-8-methyl-N-vanillyl-6-nonenamide, CAS 404-86-4) dissolved in ethanol and mixed with 20 mg/kg of ciprofloxacin were orally administered to groups of 10 rats each. Control groups were dosed with capsaicin-free, ethanol-containing or ethanol-free ciprofloxacin. Reference intravenous pharmacokinetics of ciprofloxacin was also established. The results revealed that capsaicin increased ciprofloxacin bioavailability by approximately 70% in groups receiving preparations containing capsaicin at a rate of 0.01, 0.1 and 0.5%. Higher concentrations failed to further increase bioavailability. However, capsaicin appears to have little or no impact on the rate of absorption or clearance of ciprofloxacin. Considering that 0.01% or 0.1% capsaicin are unlikely to upset the gastrointestinal tract, it may be worth attempting to study if a similar effect occurs in man, and to evaluate if the addition of capsaicin can be used as a method to increase the area under the curve/minimum inhibitory concentration rate, a key variable to improve clinical efficacy of ciprofloxacin.

Efectividad clínica de mallas de alginato de sodio para el control de la diseminación de infección con Escherichia coli y Staphylococcus epidermidis en heridas cavitadas con cierre primario en ratas / Clinical efficacy of sodium alginate meshes for the control of infectious dissemination by Escherichia coli and Staphylococcus epidermidis in cavitated wounds with primary healing

The potential wound healing ability of sodium alginate (SA) meshes was determined in cavitated rat wounds infected either with Escherichia coli or Staphylococcus epidermidis. Wound progress was evaluated macroscopically and histopathologically to assess dissemination of the induced infection through evaluation of granuloma formation and adjacent tissue irritation. Five groups of 24 female Wistar rats weighing 280 ± 34 g were formed as follows: control group with SA mesh without inoculum, control group with Escherichia coli inoculum without SA mesh, control group with Staphylococcus epidermidis inoculum without mesh, group with SA mesh + Escherichia coli inoculum and group with SA mesh + Staphylococcus epidermidis inoculum. Abdominal flank incisions were performed under anaesthesia and groups were formed. Both macroscopic and histopathological follow up were carried out and results indicated that the presence of SA meshes avoids or greatly diminishes bacteria dissemination and adjacent tissue irritation. This reaction occurs even in the presence of Escherichia coli or Staphylococcus epidermidis. In the control groups with SA mesh without inoculum and in the groups with Escherichia coli inoculum without SA mesh, and control group with Staphylococcus epidermis inoculum without mesh and group with SA mesh + Escherichia coli inoculum re-epithelialization and wound healing aspect were better than in groups inoculated with Staphylococcus epidermidis, the general odd ratios showed that the dissemination risk was 58 times greater in treatment with SA mesh and E. coli as infectious agent (IC 95% 6.2-210). These results indicate that SA mesh is capable of providing adequate conditions to allow granulation of cavitated wounds, without irritation to adjacent tissues and avoiding dissemination of the infection by E. coli and Staphylococcus epidermidis in rats. However, presence of granuloma can be a healing or esthetic disadvantage, as observed in control group with SA mesh without inoculum.

Se determinó el efecto potencial de cicatrización de mallas de alginato de sodio (AS) en heridas cavitadas infectadas con Escherichia coli y Staphylococcus epidermidis, y se evaluó histopatológica y macroscópicamente la diseminación del proceso infeccioso, formación de granuloma e irritación de los tejidos adyacentes. Se formaron 5 grupos de 24 ratas Wistar hembras de 280 ± 34 g de la siguiente manera: grupo testigo con malla de AS sin inóculo; testigo con inóculo de Escherichia coli sin malla; otro grupo testigo con inóculo de Staphylococcus epidermidis, sin malla; grupo con malla de AS + inóculo de Escherichia coli; grupo con malla de AS + inóculo de Staphylococcus epidermidis. Bajo anestesia se realizaron las incisiones en los flancos absominales y se formaron los grupos. Se realizó un seguimiento macroscópico e histopatológico de la zona afectada y se encontró que la presencia de mallas de AS evita o disminuye drásticamente, tanto la diseminación de la infección a tejidos adyacentes como su irritación. Ello ocurre aun en presencia de Escherichia coli o de Staphylococcus epidermidis. En los grupos testigo con malla de AS sin inóculo, testigo con inóculo de Escherichia coli sin malla, otro grupo testigo con inóculo de Staphylococcus epidermidis sin malla y el grupo con malla de AS + inóculo de Escherichia coli, la reepitelización y la reducción en la herida fueron superiores a los grupos que fueron inoculados con Staphylococcus epidermidis. Los odd ratios generales mostraron que el riesgo de diseminación fue 58 veces menor con el uso de malla de AS y E. coli como organismo infectante (IC 95% 6.2-210). Los resultados encontrados indican que la malla de AS es capaz de proporcionar condiciones adecuadas para la formación de tejido de granulación, sin irritación en los tejidos adyacentes y evitando la diseminación de la infección en heridas cavitadas y contaminadas por E. coli y por Staphylococcus epidermidis en ratas. Sin embargo, la presencia de granuloma puede significar una desventaja cicatrizal o estética, como se observó en el grupo testigo con malla de AS sin inóculo.

Problemática del uso de enrofloxacina en la avicultura en México / The use of enrofloxacin in poultry medicine in Mexico an overview

Hace más de dos décadas se introdujo a México y a gran parte de Latinoamérica la enrofloxacina, un derivado fluorínico, considerado el antibacteriano más potente descubierto a la fecha en medicina veterinaria. Su uso, inicialmente a dosis de 5 mg/kg/día de una presentación al 5 por ciento y más recientemente a dosis de 10 mg/kg/día de una presentación al 10 por ciento, sugiere el inicio de la aparición de resistencias bacterianas y de reducción de su eficacia clínica. Sin embargo, la proliferación de presentaciones similares de dudosa calidad, así como el uso clínico descuidado, en campo, de este antibacteriano puede contribuir, aún más que las resistencias bacterianas, a la disminución de la eficacia percibida (no demostrada) por el clínico. En este artículo se presenta un punto de vista sobre el uso y abuso de uno de los medicamentos de más valor en la historia de la medicina veterinaria, en particular para la industria avícola, la enrofloxacina. El principal objetivo este trabajo es revisar aspectos farmacológicos básicos de la enrofloxacina y orienta al clínico para que haga buen uso del medicamento, al tiempo que se compara el estado actual del uso de este antibacteriano en otras partes del mundo.