Carbadox

Carbadox is a drug that combats bacterial infection in swine, particularly swine dysentery.

Carbadox has both temporary and lasting effects on the swine gut microbiota.[Pubmed:24959163]

Front Microbiol. 2014 Jun 10;5:276.

Antibiotics are used in livestock and poultry production to treat and prevent disease as well as to promote animal growth. Carbadox is an in-feed antibiotic that is widely used in swine production to prevent dysentery and to improve feed efficiency. The goal of this study was to characterize the effects of Carbadox and its withdrawal on the swine gut microbiota. Six pigs (initially 3-weeks old) received feed containing Carbadox and six received unamended feed. After 3-weeks of continuous Carbadox administration, all pigs were switched to a maintenance diet without Carbadox. DNA was extracted from feces (n = 142) taken before, during, and following (6-week withdrawal) Carbadox treatment. Phylotype analysis using 16S rRNA sequences showed the gradual development of the non-medicated swine gut microbiota over the 8-week study, and that the Carbadox-treated pigs had significant differences in bacterial membership relative to non-medicated pigs. Enumeration of fecal Escherichia coli showed that a diet change concurrent with Carbadox withdrawal was associated with an increase in the E. coli in the non-medicated pigs, suggesting that Carbadox pre-treatment prevented an increase of E. coli populations. In-feed Carbadox caused striking effects within 4 days of administration, with significant alterations in both community structure and bacterial membership, notably a large relative increase in Prevotella populations in medicated pigs. Digital PCR was used to show that the absolute abundance of Prevotella was unchanged between the medicated and non-medicated pigs despite the relative increase shown in the phylotype analysis. Carbadox therefore caused a decrease in the abundance of other gut bacteria but did not affect the absolute abundance of Prevotella. The pending regulation on antibiotics used in animal production underscores the importance of understanding how they modulate the microbiota and impact animal health, which will inform the search for antibiotic alternatives.

Dual-label quantum dot-based immunoassay for simultaneous determination of Carbadox and Olaquindox metabolites in animal tissues.[Pubmed:26775945]

Food Chem. 2016 May 15;199:70-4.

A novel and reliable dual-label direct competitive fluorescence-linked immunosorbent assay (dc-FLISA) based on quantum dots (QDs) was developed for the simultaneous determination of the major metabolites of Carbadox and Olaquindox residues in animal tissues, using anti-QCA monoclonal antibodies and anti-MQCA polyclonal antibodies labeled with QD520 and QD635, respectively. The limits of detection for QCA and MQCA were 0.05 and 0.07ng/ml, respectively. The method was used to analyze fortified samples and analyte recoveries ranged from 81.5% to 98.2% (QCA) and 84.2% to 95.7% (MQCA). Good correlations between the dc-FLISA method and HPLC were demonstrated for the determination of QCA and MQCA residues in swine tissue samples, confirming the reliability of the proposed method.

HPLC-MS/MS method validation for the detection of carbadox and olaquindox in poultry and swine feedingstuffs.[Pubmed:26452885]

Talanta. 2015 Nov 1;144:740-4.

Carbadox (CBX) and olaquindox (OLA) were used in poultry and swine feed for growth promotion, to improve feed efficiency and increase the rate of weight gain. However, the use of these agents in feedingstuffs was prohibited because of concerns about their toxicity. Regulatory laboratories are required to have suitably validated analytical methods to ensure compliance with the ban. A quantitative and confirmatory method for determining the presence of CBX and OLA in poultry and swine feed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed, optimized, and validated. The analytes extraction was performed with a mixture of water and acetonitrile (1:1v/v) and cleanup with hexane and C18 (dispersive phase). The method was evaluated by the following parameters: specificity, linearity, matrix effect, decision limits (CCalpha), detection capability (CCbeta), accuracy, precision, limits of detection (LoD), limits of quantification (LoQ) and measurement uncertainty. The validated method presented a broad linear study range and no significant matrix effect. The limit of detection (LoD) was defined at 9 mug kg(-1) for CBX and 80 mug kg(-1) for OLA, and the limit of quantification (LoQ) was defined at 12 mug kg(-1) and 110 mug kg(-1) for CBX and OLA, respectively. The accuracy of the method was adequate for CBX and OLA. The recovery values found in the repeatability conditions were 99.41% for CBX and 104.62% for OLA. Under intralaboratory reproducibility conditions, the values were 98.63% for CBX and 95.07% for OLA. It was concluded that the performance parameters demonstrated total method adequacy for the detection and quantification of CBX and OLA in poultry and swine feedingstuffs.

In vivo studies to highlight possible illegal treatments of rabbits with carbadox and olaquindox.[Pubmed:26400201]

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2015;32(12):1976-91.

For the treatment of rabbit dysentery and bacterial enteritis, veterinary practitioners often adopt veterinary medicinal products authorised for other food-producing species, but in some cases non-authorised drugs frequently used in the past, such as Carbadox and olaquindox, might be illegally adopted. To verify the Carbadox and olaquindox distribution and persistence in rabbit tissues, two independent in vivo studies were carried out. In the first study, 24 healthy rabbits received water medicated with Carbadox at 100 mg l(-1) over a period 28 days, whereas in the second one, 24 healthy rabbits were administered water containing olaquindox at 100 mg l(-1). In each study rabbits were randomly assigned to four groups to be sacrificed respectively at 0, 5, 10 and 20 days from treatment withdrawal, for depletion studies. A control group of six animals was adopted for control and as a reservoir of blank tissues. Muscle and liver samples collected from each treated animal were stored at -20 degrees C pending the analysis. Sensitive and robust liquid chromatography-tandem mass spectrometry analytical methods were set up for the parent compounds and their main metabolites quinoxaline-2-carboxylic acid, desoxyCarbadox and 3-methylquinoxaline-2-carboxylic acid to verify their residual. Data collected demonstrate that the combination of liver as target matrix, quinoxaline-2-carboxylic acid and 3-methylquinoxaline-2-carboxylic acid as marker residue and enzymatic digestion is strategic to evidence Carbadox and/or olaquindox illegal treatments in rabbits, even 20 days after treatment withdrawal at concentration levels higher than 0.5 microg kg(-1). This findings suggests that liver should be proposed as target matrix for official control in national monitoring plan.

Carbadox is a quinoxaline-di-N-oxide antibiotic compound which is widely fed to nursery-age pigs to control enteric diseases and improve feed efficiency.

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