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Use of second generation quinolones in Poultry
Abstract
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... Second generation fluoroquinolones are antimicrobial resources used to control enteric and respiratory infectious diseases in birds [1,2], result by its spectrum towards Gram negative germs and mycoplasmas, their bactericidal activity blocking DNA gyrase A subunit and/or topoisomerase IV enzymes, essential for DNA duplication [2,3] and also because fluoroquinolones can be administered in drinking water, making it possible to dose a large number of birds in a short time [4]. ...
... In order to protect the food consumer, the administration of fluoroquinolones in animals destined for human consumption is subject to regulation; maximum residue limits (MRLs) were established in birds for different tissues and for several members of the group [2,5], in order to limit residues impact, for each drug and animal species treated, a withdrawal period estimated at 5-7 days was stipulated for fluoroquinolones and its application in laying birds is not allowed [1]. ...
... The established withdrawal values exceed those suggested for the set of fluoroquinolones for their application in poultry [1] and in particular for eggs with enrofloxacin and its metabolite ciprofloxacin [38] and are significantly lower than those estimated for danofloxacin [36], although too extensive to discourage the poultry producers from using marbofloxacin in producing birds. ...
Marbofloxacin belongs to the group of fluoroquinolones, used exclusively in domestic animals. This study was carried out with the purpose of studying the temporal disposition of marbofloxacin in edible compartments of the egg after administration of 1, 52 mg/kg of marbofloxacin in drinking water for 11 consecutive days in hens in posture peak and average weight of 1,91±0,25 kg. Birds were housed in individual cages under controlled light conditions, ambient temperature, relative humidity, water and balanced feed ad libitum. After the administration, eggs were collected daily and immediately separated into albumen and yolk, identified per bird/day and stored at-20°C until analysis. The preparative assay consisted in extraction of the analyte using 200 mg of yolk or albumen, as appropriate, in deionized water, homogenizing solution and enrofloxacin solution as internal standard. Separation and quantification were performed by HPLC by reverse phase isocratic elution with fluorescence detector, mobile phase composed of water, acetonitrile and triethylamine adjusted to pH 3. According to the peak areas of known concentrations, the concentrations of the test samples were calculated by simple linear regression. The established marbofloxacin levels are higher and more persistent in the yolk than in albumen, reaching 8 and 9 days, respectively. The disposition characteristics observed with marbofloxacin are compatible with the physico-chemical properties of the antimicrobial with the respective compartments of the egg and the time required for its formation. Data obtained from marbofloxacin depletion in egg compartments were analyzed using the EMEA WT 1.4 software and conjecturing a rigorous MRL (0,001 µg/kg), a withdrawal period of 13 and 17 days was estimated, for albumen and yolk, respectively.
... En avicultura comercial, incluido el sector ovícola, el empleo rutinario de antimicrobianos representa un riesgo potencial para los consumidores ( Löhren et al. 2008;Gouvea et al. 2015), por la posibilidad de generar residuos en tejidos o productos animales que impliquen riesgos enfocados en dos aspectos: la manifestación de resistencia en bacterias que pueden ser transmitidas al humano, y la posibilidad que provoquen reacciones tóxicas específicas y/o alteren la microbiota intestinal humana ( Jensen et al. 2008;Reig & Toldrá 2009). En avicultura es habitual la aplicación de fluoroquinolonas de segunda generación para controlar enfermedades infecciosas entéricas y respiratorias ( Anjum & Rizvi 1998;Löhren et al. 2008). El empleo fue fomentado por el espectro, orientado hacia Gram negativas y micoplasmas, la actividad bactericida por el bloqueo de la subnidad A de la enzima ADNgirasa o topoisomerasa II, esencial para la duplicación del ADN ( González & Nieto 2007;Gouvea et al. 2015). ...
... Se establecieron límites máximos de residuos (LMRs) en aves para distintos tejidos y para varios integrantes del grupo y para el conjunto del grupo y especie animal tratada se estipuló un periodo de resguardo (Pr) estimado en 5-7 días. Actualmente la FDA no autoriza el uso de fluoroquinolonas en animales en postura por el incremento de cepas hospitalarias resistentes, aspecto vinculado con la aplicación oral y el temor de inefectividad de estos fármacos para tratar infecciones en humanos causadas por los géneros Campylobacter spp y Salmonella ( Anjum & Rizvi 1998;Jensen et al. 2008;Gouvea et al. 2015). En el caso particular de huevos, cuando se usan antimicrobianos en gallinas en postura, la transferencia y acumulación de residuos de estos fármacos está estrechamente relacionada con su fisiología y los procesos de la formación del huevo ( Donoghue & Myers 2000;Kan & Petz 2000;Goetting et al. 2011), aunque también influyen las características físico químicas de los fármacos utilizados, sobre todo cuando las sustancias son muy liposolubles ( Donoghue 2005). ...
REA TEMÁTICA. REQUISITOS TÉCNICOS RESUMEN. En la avicultura una herramienta farmacológica habitual es la aplicación de fluoroquinolonas de segunda generación dentro de esta se encuentra marbofloxacina. Se desarrolló un método analítico sencillo y preciso para la extracción, determinación y cuantificación de este antibiótico en los distintos compartimentos del huevo (clara y yema) a través de HPLC usando detección por fluorescencia. La preparación de la muestras consistió en añadir yema o clara, concentraciones conocidas de marbofloxacina, estándar interno, solución homogeneizadora. Las condiciones del estudio fueron el detector de fluorecencia a una λ ex 295 y λ em : 500 nm, una fase móvil compuesta por agua deionizada, acetonitrilo y trietilamina ajustada a pH 3.0. Para ambas matrices se mostró que el método era lineal (r 2 0,99) para las concentraciones de marbofloxacina (0,0024 a 1,25 µg/g), con un tiempo de retención del analito de estudio a los 5,57 ± 0,17 minutos. El límite de detección en clara fue de 0,012 µg/g y en yema de 0,010 µg/g, mientras que el porcentaje recuperación de ambas matrices supero el 90% y los coeficientes de variación en los ensayos de precisión no fueron mayores al 2,5%. Determinando que esta metodología presenta precisión, es eficiente, sensible y confiable para las futuras determinaciones de residuos y estudios farmacocinéticos de marbofloxacina en huevos.
... Various forms of quinolones available in Pakistan including ciprofloxacin, norfloxacin and enrofloxacin etc are extensively used in poultry sector to overcome the infectious bacterial maladies (Anjum and Rizvi, 1998). For the control of early chick mortality, for prophylaxis and treatment of respiratory, renal and digestive infections, enrofloxacin has undergone growth in poultry enterprises. ...
... Las fluoroquinolonas son agentes sintéticos con notable desarrollo en avicultura, particularmente en los integrantes de segunda generación (1,2). Ejercen actividad bactericida de tipo concentración dependiente, mediante el bloqueo de las enzimas ADN girasa y topoisomerasa IV, que intervienen en el plegamiento de la doble hélice de ADN, fundamentales para la estructura tridimensional del material genético (3)(4)(5). ...
This paper aimed to study the disposition of danofloxacin in broiler chickens in order to establish pharmacokinetic parameters in plasma and tissues and to estimate a withdrawal period. 42 adult chickens were divided into 14 groups of 3 individuals each, who received a single oral dose of 5 mg/kg of danofloxacin after a fasting period of 12 h before and 3 h post-administration. Each batch was sacrificed at pre-established times, and blood, muscle, and liver samples were obtained over a period of up to 120 h post-application. The assay consisted of the liquid-liquid extraction of analyte and its separation and quantification by high-performance liquid chromatography (HPLC). Time averages for plasma and tissue concentration were analyzed using the PK Solution software. Withdrawal period was calculated using the WT 1.4 program, based on maximum residue limits (MRL) of 200 and 400 μg/kg, established for chicken muscle and liver, respectively. Danofloxacin exhibits a rapid absorption, resulting in a Cmax of 1.1 μg/ml with a Tmax of 1 h; t½β (h) was 7.64; 6.16 and 12.77 in plasma, liver, and muscle, respectively; a Vd of 5.51 L/kg; tissue/plasma ratios of 0.48 and 6.61 in muscle and liver, respectively, and levels up to 72 h. Based on residual concentration analysis, a withdrawal period of 1.4 and 3.34 d was estimated for muscle and liver, respectively.
Aims:
Quinolone-resistant nontyphoidal Salmonella having serine replaced by isoleucine at the 83rd amino acid in GyrA (GyrA-Ser83Ile) has recently been found in Asian countries. In this study, we aimed to examine the direct effect of substitution Ser83Ile on DNA gyrase activity and/or resistance to quinolones.
Materials and Methods:
Using 50% of the maximal inhibitory concentrations (IC50s) of quinolones, recombinant wild type (WT) and seven mutant DNA gyrases having amino acid substitutions, including Ser83Ile, were screened for enzymatic activity that causes supercoils in relaxed plasmid DNA and resistance to quinolones.
Results:
Little differences in supercoiling activity were observed between WT and mutant DNA gyrases. By contrast, the IC50s of ciprofloxacin and norfloxacin against GyrA-Ser83Ile/GyrB-WT were 11.6 and 73.3 μg/mL, respectively, which were the highest used against the DNA gyrases examined in this study.
Conclusion:
Ser83Ile in GyrA was shown to confer high-level quinolone resistance to DNA gyrases of nontyphoidal Salmonella, with no loss of supercoiling activity. Salmonella strain carrying GyrA with Ser83Ile may emerge under a high-concentration pressure of quinolones and easily spread even with no selection bias by quinolones. Hence, avoiding the overuse of quinolones is needed to prevent the spread of Salmonella with Ser83Ile in GyrA.
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