The efficacy and tolerability of a marbofloxacin-clotrimazole-dexamethasone otic suspension (MCD) was compared with a standard topical treatment using a phase III clinical trial protocol. In a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion to identify the causative pathogen; a further sample was collected in the event of failure or relapse, and from dogs (at day 14) for which Pseudomonas species had been isolated at inclusion. One group received MCD (10 drops per affected ear) once daily and a second received Surolan (containing polymyxin B, miconazole and prednisolone) (5 drops per affected ear), twice daily. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Efficacy and tolerability were evaluated on days 7, 14 and, if necessary, 28 for dogs treated for 14 days. The trial demonstrated equivalence of both treatments in terms of efficacy, with a cure rate of 58.3% for MCD and 41.2% for Surolan. Both medications were equally well tolerated by dogs, but MCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator's assessment on day 14.

The plasma and milk pharmacokinetics of marbofloxacin, a fluoroquinolone antibacterial compound, were evaluated in dairy cows, as well as its pharmacodynamic characteristics against mastitis-isolated pathogens. Marbofloxacin was given intramuscularly as a 10% aqueous solution to dairy cows either at a single dose or at repeated doses of 2 mg/kg once daily for 3 d. Blood and milk samples were collected for the determination of the concentration of marbofloxacin and of its putative metabolites: N-desmethyl-marbofloxacin and N-oxide-marbofloxacin. Bacterial field isolates were from milk samples collected from dairy cows suspected of having an intramammary infection. After identification, the minimal inhibitory concentration (MIC) was determined against the isolated strains. The maximal marbofloxacin concentration (Cmax) observed in milk after the first administration was 1.024 microg/mL, and the area under the curve during the first dosing interval was 6.513 microg/h per milliliter. After the third administration, these parameters were slightly increased (about 20% at most). Both metabolites were detected in the milk, but their concentrations were below the limit of quantification. The MIC against 90% of the population (MIC90) of Escherichia coli was 0.016 microg/mL, and it was 0.229 microg/mL against Staphylococcus aureus. The following surrogate clinical outcome markers were obtained against E. coli strains: a Cmax/MIC ratio of 67 and an area under the curve/MIC ratio of 407 h. Hence, a possible efficacy of marbofloxacin in the treatment of E. coli-induced mastitis could be expected as the endpoints of 10 and 250 h, respectively, are reached.

The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl®). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4–16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively.

MCR-1 was detected yearly in European food-producing animal since 2004 with a high diversity of pulsotypes supporting the dissemination of mcr-1 via plasmids.

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