Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against Staphylococcus aureus Isolated from Caprine Clinical Mastitis.

Staphylococcus aureus (S. aureus) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against S. aureus. However, the studies developed to evaluate the bacterial drug interaction only have used the MIC as a single reference point with artificial growth media. The aims of this study were to describe the effect of marbofloxacin on S. aureus isolated from mastitis goats' milk by different approaches as the minimum inhibitory and bactericidal concentrations (MIC and MBC) in cation adjusted Mueller-Hinton broth (CAMHB), serum and milk of goats at two inoculum sizes of 105 and 108 CFU/mL, the determination and analysis of the time kill curves (TKC) by non-linear mixed effect models in each growth medium and inoculum size, as well as the estimation of their pharmacokinetics/pharmacodynamics (PK/PD) cutoff values. The results obtained indicate that MIC values were higher and increases 2,4-fold in serum and 3,6-fold in milk at high inoculum, as well as the EC50 values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC24/MIC ratios to achieve clinical efficacy were highly dependent on inoculum and growth medium, with median values of 60-180, especially at high inoculum in milk, suggesting that further studies are necessary to evaluate and optimize the best therapeutic strategies for treating S. aureus in lactating goats.

Comparative pharmacokinetics and pharmacokinetic/pharmacodynamic analysis by nonlinear mixed-effects modeling of cefquinome in nonpregnant, pregnant, and lactating goats after intravenous and intramuscular administration.

Cefquinome is a fourth-generation cephalosporin that is used empirically in goats. Different physiologic factors like pregnancy or lactation could determine the pharmacokinetic behavior of drugs in the organism. The objectives of this study are to (a) compare the pharmacokinetics of cefquinome after intravenous and intramuscular administration in adult nonpregnant (n = 6), pregnant (n = 6), and lactating goats (n = 6), at a dose of 2 mg/kg, with rich sampling by nonlinear mixed-effects modeling, (b) conduct a pharmacokinetic/pharmacodynamic analysis to evaluate the efficacy of the recommended posology in goats with different physiological states, and (c) determine the optimal posology that achieve a PTA value ≥ 90%, taking into account a T > MIC ≥ 60% of a MIC value ≤ 0.25 µg/ml, in the different subpopulations of goats for both routes. Gestation significantly increased Ka and V1, while reduced F0, Cl, and Q. On the other hand, lactation significantly increased V1 and reduced Tk0. Cefquinome concentrations achieved in placental cotyledon, amniotic fluid, and fetal serum indicate a minimal penetration across the placental barrier. Moreover, milk penetration of cefquinome was minimal. The total body clearance of cefquinome for goats was 0.29 L kg-1  hr-1 , that is apparently higher than the reported for cows (0.13 L kg-1  hr-1 ) and pigs (0.16 L kg-1  hr-1 ). So, the optimal dose regimen for cefquinome after intravenous and intramuscular administration required higher dose and frequency of administration compared with recommendations for cows or pigs. Therefore, 2 mg kg-1  8 hr-1 and 5 mg kg-1  12 hr-1 could be used for IV and IM routes, respectively, for the treatment of respiratory infections caused by P. multocida and M. haemolytica, but only 5 mg kg-1  12 hr-1 by both routes should be recommended for Escherichia coli infections.

Ricobendazole nanocrystals obtained by media milling and spray drying: Pharmacokinetic comparison with the micronized form of the drug.

Helminthic infections are produced by different types of worms and affect millions of people worldwide. Benzimidazole compounds such as ricobendazole (RBZ) are widely used to treat helminthiasis. However, their low aqueous solubility leads to poor gastrointestinal dissolution, absorption and potential lack of efficacy. The formulation of nanocrystals (NCs) have become the strategy of preference for hydrophobic drugs. In this work, we prepared RBZ NCs (RBZ-NCs) by an optimized combination of bead milling and spray-drying. Following the physicochemical characterization, a comparative pharmacokinetic evaluation of RBZ-NCs was performed in dogs using as controls a micronized powdered form of RBZ (mRBZ) and a physical mixture of drug and stabilizer 1:1 (PM). The particle size of the redispersed RBZ-NCs was 181.30 ± 5.93 nm, whereas DSC, PXRD and FTIR analyses demonstrated that the active ingredient RBZ remained physicochemically unchanged after the manufacture process. RBZ-NCs exhibited improved in vitro biopharmaceutical behaviour when compared to mRBZ. Consequently, the pharmacokinetic trial demonstrated a significant increase in the drug oral absorption, with an AUC0-∞ 1.9-fold higher in comparison to that obtained in animals treated with mRBZ. This novel formulation holds substantial potential for the development of new/alternative treatments for helminth infections both in human and veterinary medicine.

[Epidemiological study of recorded trichinosis cases in Santa Fe Province, Argentina, 1998-2009]. / Estudio epidemiológico de los casos de triquinelosis registrados en la provincia de Santa Fe, Argentina, 1998-2009.

OBJECTIVE: To characterize recorded trichinosis cases and outbreaks in Santa Fe Province, Argentina, from 1998 to 2009 from epidemiological, clinical, and laboratory viewpoints. METHODS: An analysis was conducted of 1 519 epidemiological records of persons who had signs and symptoms compatible with trichinosis in Santa Fe Province in the period 1998-2009. A descriptive statistical analysis of information in epidemiological records and of clinical and laboratory results, as well as a bifactorial analysis of possible associations with epidemiological and environmental factors were also carried out. RESULTS: Trichinosis symptoms were found in 1 276 cases; 372 met the clinical case definition and 224 samples were positive by indirect immunofluorescence, independent of their clinical case classification. There were 27 outbreaks that involved 1 157 cases identified in eight departments, with greater frequency in the province's center and south. Annual distribution of epidemiologically associated cases was heterogeneous, with greater frequency in the period 2000-2003 and in the months of August to October. Probability of becoming sick was greater with consumption of products from informal sources (OR = 3.69; P = 0.014) and in rural areas (OR = 1.799; P = 0.011). Disease incubation period (median) was 12 days. The risk of becoming sick was 2.06 times greater in persons who ate meat or ate pork by-products than in those who did not. CONCLUSIONS: The greatest number of outbreaks occurred in departments that were more populous and where pork production was greater. Specific actions should be designed for prevention and control of the disease in those departments. Epidemiological risk analysis should be considered in evaluating, managing, and communicating trichinosis health risks.

Estudio epidemiológico de los casos de triquinelosis registrados en la provincia de Santa Fe, Argentina, 1998-2009 / Epidemiological study of recorded trichinosis cases in Santa Fe Province, Argentina, 1998-2009

OBJETIVO: Caracterizar desde los puntos de vista epidemiológico, clínico y de laboratorio los casos y brotes de triquinelosis que se registraron en la provincia de Santa Fe, Argentina, entre 1998 y 2009. MÉTODOS: Se analizaron 1 519 fichas epidemiológicas de personas que presentaron síntomas y signos compatibles con triquinelosis en la provincia de Santa Fe en el período 1998-2009. Se realizó el análisis estadístico descriptivo de la información contenida en las fichas epidemiológicas y los resultados clínicos y de laboratorio; se aplicó el análisis bifactorial para determinar las posibles asociaciones con factores epidemiológicos y ambientales. RESULTADOS: Se encontraron síntomas de triquinelosis en 1 276 casos; 372 cumplían la definición de caso clínico y 224 muestras resultaron positivas por inmunofluorescencia indirecta, independientemente de su clasificación como caso clínico. Se identificaron 27 brotes que involucraron a 1 157 casos en ocho departamentos, con mayor frecuencia en el centro y el sur de la provincia. La distribución anual de los casos asociados epidemiológicamente entre sí fue heterogénea, con una mayor frecuencia en el período 2000-2003 y en los meses de agosto a octubre. Hubo mayor probabilidad de enfermar cuando se consumieron productos de fuentes informales (OR = 3,69; P = 0,014) y en las áreas rurales (OR = 1,799; P = 0,011). El período de incubación de la enfermedad (mediana) fue de 12 días. Las personas que consumieron carne de cerdo o sus derivados tuvieron 2,06 veces más riesgo de enfermar que las que no la consumieron. CONCLUSIONES: El mayor número de brotes ocurrió en los departamentos más poblados y con mayor producción porcina. Se deben diseñar acciones específicas de prevención y control de la enfermedad en esos departamentos. Se debe considerar el análisis epidemiológico de riesgos al evaluar, gestionar y comunicar los riesgos sanitarios de triquinelosis.

OBJECTIVE: To characterize recorded trichinosis cases and outbreaks in Santa Fe Province, Argentina, from 1998 to 2009 from epidemiological, clinical, and laboratory viewpoints. METHODS: An analysis was conducted of 1 519 epidemiological records of persons who had signs and symptoms compatible with trichinosis in Santa Fe Province in the period 1998-2009. A descriptive statistical analysis of information in epidemiological records and of clinical and laboratory results, as well as a bifactorial analysis of possible associations with epidemiological and environmental factors were also carried out. RESULTS: Trichinosis symptoms were found in 1 276 cases; 372 met the clinical case definition and 224 samples were positive by indirect immunofluorescence, independent of their clinical case classification. There were 27 outbreaks that involved 1 157 cases identified in eight departments, with greater frequency in the province's center and south. Annual distribution of epidemiologically associated cases was heterogeneous, with greater frequency in the period 2000-2003 and in the months of August to October. Probability of becoming sick was greater with consumption of products from informal sources (OR = 3.69; P = 0.014) and in rural areas (OR = 1.799; P = 0.011). Disease incubation period (median) was 12 days. The risk of becoming sick was 2.06 times greater in persons who ate meat or ate pork by-products than in those who did not. CONCLUSIONS: The greatest number of outbreaks occurred in departments that were more populous and where pork production was greater. Specific actions should be designed for prevention and control of the disease in those departments. Epidemiological risk analysis should be considered in evaluating, managing, and communicating trichinosis health risks.