Pharmacotherapeutic Group: Antibacterials for systemic use, Flouroquinolones.
ATC Vet Code: QJ01MA93
Pharmacodynamic properties
Marbofloxacin is a synthetic, broad spectrum antimicrobial, belonging to the fluoroquinolone group of antibiotics. Marbofloxacin is bactericidal with efficacy against a wide range of Gram-negative bacteria, Gram-positive bacteria and Mycoplasma species. The mechanism of action of marbofloxacin is based on the inhibition of type II topoisomerases, DNA gyrase and topoisomerase IV.
A 6 year pan European study by Kroemer, S et al 2012, reviewed marbofloxacin efficacy against indicated pathogens isolated from cases of bovine respiratory disease. In this study, 751 isolates of P. multocida were identified, over 99% of which were determined to be highly susceptible to marbofloxacin with MIC ranging from 0.004 to 1μg/ml. MIC50 was identified as 0.015μg/ml and MIC90 was 0.120μg/ml. This study also assessed 514 isolates of M. haemolytica with >98% of isolates determined to be highly susceptible with a MIC range of 0.008 to 1µg/ml, MIC50 value of 0.03μg/ml and MIC90 value of 0.25μg/ml. 171 isolates of M. bovis were identified with 74% demonstrating susceptibility with MIC ranging from 0.5 to 1μg/ml, 25% exhibiting intermediate susceptibility with MIC of 2μg/ml and 1% demonstrating resistance with MIC of 4 μg/ml. MIC50 was 1μg/ml and MIC90 was 2μg/ml; however these were deemed to be irrelevant due to the low number of isolates. This study also reviewed marbofloxacin efficacy in E. coli mastitis which analysed 617 isolates and demonstrated over 98% susceptibility with MIC of these susceptible organisms ranging from 0.008 to 1μg/ml. MIC50 and MIC90 were both determined to be 0.03μg/ml. In a pan European study by El Garch et al 2017, 369 E. Coli isolates from porcine metritis identified 92.7% susceptibility to marbofloxacin with a MIC ranging from 0.008 to 1 μg/ml. 0.3% of isolates exhibited intermediate susceptibility with a MIC of 2 and 7% exhibited resistance with a MIC of >4. MIC50 was determined to be 0.03μg/ml and MIC90 was 0.5μg/ml.
The pan European studies by Kroemer, S et al 2012 and El Garch, F., et al 2017, established clinical breakpoints for marbofloxacin use in P. multocida and M. haemolytica associated bovine respiratory disease and E. Coli in bovine mastitis and porcine metritis. Resistant strains were determined to have a MIC of ≥4 μg/ml, intermediate strains a MIC=2 μg/ml and susceptible strains, a MIC≤1 μg/ml. No clinical breakpoints have been established for Mycoplasma species.
Resistance to fluoroquinolones mainly occurs by chromosomal mutations with three mechanisms: decrease of the bacterial cell wall permeability, change in expression of efflux pump genes or mutation within genes coding for target enzymes. Plasmid mediated quinolone resistance is a separate mechanism by which resistance may develop. This may occur via three different mechanisms: through plasmid genes coding for proteins which protect DNA gyrase and topoisomerase IV from quinolone inhibition, through acetylation of certain quinolones by a variant of acetyltransferase AAC(6′)-Ib or through plasmid genes coding for enhanced efflux pumps. Whilst the low-level resistance this confers should not exceed the clinical breakpoints for susceptibility, it may enable selection of higher level resistance.
Pharmacokinetic properties
After subcutaneous or intramuscular administration in cattle and pigs, at the recommended dose of 2 mg/kg bodyweight, marbofloxacin is readily absorbed and reaches peak plasma concentrations of 1.5 μg/ml within 1 hour. The bioavailability of marbofloxacin is almost 100%.
Marbofloxacin is weakly bound to plasma proteins (less than 10% in pigs and 30 % in cattle), extensively distributed and achieves a higher concentration in most tissues, (liver, kidney, skin, lung, bladder, uterus and digestive tract) than in plasma.
In cattle, marbofloxacin is eliminated slowly in pre-ruminant calves but faster in ruminant cattle (t1/2 = 5-9 hours and 4 – 7 hours respectively). In pre-ruminant calves elimination of the active form is predominantly via urine, (¾ urine, ¼ faeces). In ruminant cattle the active form is eliminated equally in urine and faeces.
In pigs, the active form of marbofloxacin is eliminated slowly (t1/2= 8 – 10 hours) predominantly via urine (2/3) and faeces (1/3).