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Dose optimisation of enrofloxacin for use in chickens against Salmonella enterica serovar Typhimurium DT104 to improve efficacy and minimise selection of resistance

Abstract number: p1555

Randall  L.P., Cooles  S.W., Stapleton  K., Coldham  N.G., Piddock  L.J.V., Woodward  M.J.

Objectives: 

Optimal antimicrobial dosage regimens aim to achieve successful clinical outcomes without drug toxicity or emergence of bacterial resistance. For concentration dependent antibiotics, such as the fluoroquinolones, in humans a Cmax:MIC ratio of >10 is considered more important for efficacy and reduced selection of resistance than prolonged antibiotic concentrations just above the MIC. Fluoroquinolone resistance in zoonotic bacteria is a matter of public health concern, and fluoroquinolone treatment of poultry can rapidly select for bacteria with reduced fluoroquinolone susceptibility. In this study we compared basic pharmacokinetic parameters for the recommended dose of Baytril (enrofloxacin) 10% oral solution in poultry to 2.5x this dose for birds dosed by continuous water (standard) compared to pulsed water treatments and dosing by gavage.

Methods. For the pulsed versus continuous water treatments, groups of chickens received Baytril 10% oral solution at 50 (recommended) or 125 ppm continuously in the water or at 10 (recommended) or 25 mg/kg pulsed in the water. For each group, three birds were killed at 0, 2, 4, 6, 8, 10 and 24 hours after start of antibiotic treatment and caecal contents, liver, lung and sera were taken and the concentration of fluoroquinolone determined by fluorescence HPLC. For gavage treatment, dosing was at 10 and 25 mg/kg by crop intubation and four birds were killed in each group at 2, 6 and 24 hours after gavage; caecal contents, liver and sera were taken and analysed as above. Basic pharmacokinetic parameters were determined using PK solutions software.

Results: 

The mean fluoroquinolone Cmax in caecal contents (and sera) for gavage, pulsed water and continuous water treatments respectively was 78.01 (1.81), 53.19 (1.17) and 24.73 (0.73) mg/ml after the recommended dose and 115.86 (3.86), 115.63 (2.74) and 68.02 (1.17) mg/ml after 2.5x the recommended dose. Cmax of antibiotic in liver and lung was increased by the modified regimens in similar proportions to above. Both pulsed water and gavage treatment not only resulted in higher Cmax values, but also a faster rate of fluoroquinolone clearance than continuous water treatment (Figure 1).

Conclusion: 

Dosing by gavage is not practical for thousands of chickens. However, pulsed dosing at 2.5x the recommended dose can increase Cmax values about fourfold and so could improve efficacy and reduce selection of resistance, compared to the current recommended treatment regime.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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