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Antimicrobial Agents and Chemotherapy, March 2008, p. 954-961, Vol. 52, No. 3
0066-4804/08/$08.00+0 doi:10.1128/AAC.00575-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Induction of the Carrier State in Pigeons Infected with Salmonella enterica Subspecies enterica Serovar Typhimurium PT99 by Treatment with Florfenicol: a Matter of Pharmacokinetics
Frank Pasmans,1*
Kris Baert,2
An Martel,1
Alain Bousquet-Melou,3
Ruben Lanckriet,1
Sandra De Boever,2
Filip Van Immerseel,1
Venessa Eeckhaut,1
Patrick de Backer,2 and
Freddy Haesebrouck1
Department of Pathology, Bacteriology and Avian Diseases,1 Department of Pharmacology, Toxicology, Biochemistry and Organ Physiology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium,2 UMR 181 de Physiopathologie et Toxicologie Expérimentales INRA, ENVT, Ecole Nationale Vétérinaire, 23 Chemin des Capelles, 31076 Toulouse, France3
Received 2 May 2007/ Returned for modification 9 October 2007/ Accepted 25 December 2007
Paratyphoid caused by Salmonella enterica subsp. enterica serovar Typhimurium is the main bacterial disease in pigeons. The ability of Salmonella serovar Typhimurium to persist intracellularly inside pigeon macrophages results in the development of chronic carriers, which maintain the infection in the flock. In this study, the effect of drinking-water medication with florfenicol on Salmonella infection in pigeons was examined. The pharmacokinetics of florfenicol in pigeons revealed a relatively high volume of distribution of 2.02 liters/kg of body weight and maximum concentrations in plasma higher than the MICs for the Salmonella strain used (4 µg/ml) but quick clearance of florfenicol due to a short half-life of 1.73 h. Together with highly variable bioavailability and erratic drinking-water uptake, these parameters resulted in the inability to reach a steady-state concentration through the continuous administration of florfenicol in the drinking water. Florfenicol was capable of reducing only moderately the number of intracellular salmonellae in infected pigeon macrophages in vitro. Only at high extracellular concentrations (>16 µg/ml) was a more-than-10-fold reduction of the number of intracellular bacteria noticed. Florfenicol treatment of pigeons via the drinking water from 2 days after experimental inoculation with Salmonella serovar Typhimurium until euthanasia at 16 days postinoculation resulted in a reduction of Salmonella shedding and an improvement in the fecal consistency. However, internal organs in florfenicol-treated pigeons were significantly more heavily colonized than those in untreated pigeons. In conclusion, the oral application of florfenicol for the treatment of pigeon paratyphoid contributes to the development of carrier animals through sub-MIC concentrations in plasma that do not inhibit intracellular persistency.
* Corresponding author. Mailing address: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. Phone: 32 (0)9 264 7444. Fax: 32 (0)9 264 7494. E-mail: frank.pasmans{at}ugent.be
Published ahead of print on 7 January 2008.
Antimicrobial Agents and Chemotherapy, March 2008, p. 954-961, Vol. 52, No. 3
0066-4804/08/$08.00+0 doi:10.1128/AAC.00575-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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