Induction of the carrier state in pigeons infected with Salmonella enterica subspecies enterica serovar typhimurium PT99 by treatment with florfenicol: a matter of pharmacokinetics.
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 microg/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 microg/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.
Pasmans
Frank
F
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. frank.pasmans@ugent.be
Baert
Kris
K
Martel
An
A
Bousquet-Melou
Alain
A
Lanckriet
Ruben
R
De Boever
Sandra
S
Van Immerseel
Filip
F
Eeckhaut
Venessa
V
de Backer
Patrick
P
Haesebrouck
Freddy
F
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002353:Carrier State / Q000188:drug therapy* / Q000382:microbiology; D010856:Columbidae / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000302:isolation & purification* / Q000472:pathogenicity; D013839:Thiamphenicol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; C035534:florfenicol; D013839:Thiamphenicol