Treatment of canine pyoderma with ibafloxacin and marbofloxacin – fluoroquinolones with different pharmacokinetic profiles

The objective of the present study was to determine the antimicrobial susceptibility of 136 canine isolates of Staphylococcus intermedius and 10 canine isolates of S. schleiferi subspecies coagulans to 16 fluoroquinolones (FQs), and to investigate the mechanisms of resistance in the nonsusceptible isolates. Of the 136 of S. intermedius tested 98.5% were susceptible to all 16 FQs whereas only 40% of the 10 isolates of S. schleiferi subspecies coagulans were susceptible. Two isolates of S. intermedius and six isolates of S. schleiferi, were found to be resistant to 13 out of 16 FQs, while they retained their susceptibility to fourth generation FQs such as gatifloxacin, moxifloxacin and trovafloxacin. Sequencing of the quinolone-resistance determining regions of gyrA and grlA genes showed that in S. intermedius, dichotomous resistance to FQs was associated with the occurrence of one alteration in GyrA-84 and one in GrlA-80, while in S. schleiferi the same pattern of resistance was observed in isolates showing these changes only in gyrA. This study is the first to screen FQs of the second, third and fourth generation for antimicrobial resistance in clinical isolates of S. intermedius and S. schleiferi of canine origin, and to describe mutations in gyrA and grlA associated with FQ resistance in these bacterial species.

“…, 2006). The use of fluoroquinolones (FQs) for the treatment of canine pyoderma is well documented (Heinen, 2002; Horspool et al. , 2004).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antimicrobial susceptibility and mechanism of resistance to fluoroquinolones in Staphylococcus intermedius and Staphylococcus schleiferi

Intorre

Vanni

Bello

et al. 2007

“…MAR at a dosage of 2 mg/kg once daily has been shown to be clinically effective in the treatment for canine pyoderma (Horspool et al. , 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Treatment for both pyoderma forms involves antibiotic therapy in which lesions associated with deep pyoderma require longterm oral antibiotic therapy (DeBoer, 1990). Established fluoroquinolones (FQ) have been considered to be appropriate drugs for treatment for canine pyoderma owing to their favourable pharmacokinetic and pharmacodynamic properties (Horspool et al, 2004). However, successful outcome of treatment has been threatened by the emergence of FQ resistance among staphylococcal isolates (Morris et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Comparative activity of pradofloxacin and marbofloxacin against coagulase‐positive staphylococci in a pharmacokinetic–pharmacodynamic model based on canine pharmacokinetics

Körber-Irrgang

Wetzstein

Bagel‐Trah

et al. 2012

Pradofloxacin (PRA), a novel veterinary 8-cyano-fluoroquinolone (FQ), is active against Staphylococcus pseudintermedius, the primary cause of canine pyoderma. An in vitro pharmacokinetic-pharmacodynamic model was used to compare the activities of PRA and marbofloxacin (MAR) against three clinical isolates of S. pseudintermedius and reference strain Staphylococcus aureus ATCC 6538. Experiments were performed involving populations of 10(10) CFU corresponding to an inoculum density of approximately 5 × 10(7) CFU/mL. The time course of free drug concentrations in canine serum was modelled, resulting from once daily standard oral dosing of 3 mg of PRA/kg and 2 mg of MAR/kg. In addition, experimentally high doses of 6 mg of PRA/kg and 16 mg of MAR/kg were tested against the least susceptible strain. Viable counts were monitored over 24 h. At concentrations associated with standard doses, PRA caused a faster and more sustained killing than MAR of all strains. The ratios of free drug under the concentration-time curve for 24 h over MIC and the maximum concentration of free drug over MIC were at least 90 and 26, and 8.5 and 2.1 for PRA and MAR, respectively. At experimentally high doses, PRA was superior to MAR in terms of immediate killing. Subpopulations with reduced susceptibility to either FQ did not emerge. We conclude that PRA is likely to be an efficacious therapy of canine staphylococcal infections.

“…Until now, data published for dogs were based on HPLC assay (Coulet et al. , 2002b; Horspool et al. , 2004).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of ibafloxacin in healthy cats

Coulet¹,

Morello²,

Cox³

et al. 2005

The pharmacokinetics of ibafloxacin following single and repeated administration of an oral gel formulation and the effect of food intake were investigated in cats. Ibafloxacin is a chiral fluoroquinolone available for clinical use as a racemic mixture of the R- and S-enantiomers. Plasma concentrations of ibafloxacin and its metabolites were determined using microbiological, LC-MS-MS and enantioselective capillary zone electrophoresis assays. Ibafloxacin was absorbed rapidly [time of maximum concentration (tmax) 2-3 h], reaching a mean maximum concentration (Cmax) of approximately 2.1 and 1.6 microg/mL for R- and S-ibafloxacin, respectively, following a single oral administration of the racemate at 15 mg/kg. Once absorbed, ibafloxacin was metabolized to 7-hydroxy-ibafloxacin and mainly to 8-hydroxy-ibafloxacin. Following repeated oral administration, significant increases in Cmax and AUC of ibafloxacin and its less active metabolites (racemic or enantiomers) were observed between the first and the tenth day of treatment. This twofold exposure increase in concentrations of ibafloxacin and its metabolites may contribute additionally to the efficacy of this drug in the treatment of feline bacterial infections. Single and repeated doses of ibafloxacin were well tolerated by cats. Food promoted the absorption of ibafloxacin, doubling Cmax and increasing AUC and slightly delaying tmax. High concentrations of the metabolites, mainly 8-hydroxy- and 7-hydroxy-ibafloxacin were excreted in urine, either unchanged or as glucurono-conjugates.