This study aimed at determining the in vitro antibacterial activity of a clinically achievable marbofloxacin (MAR) concentration against the clinical isolate S. pseudintermedius in an in vitro dynamic model simulating the in vivo pharmacokinetics of dogs. The in vitro PK/PD (pharmacokinetic/pharmacodynamic) model that mimics the single daily doses of MAR (half-life, 8 h) was simulated. An inoculum (108 cfu/ml) of clinical isolate S. pseudintermedius (MIC = 0.0625 μg/ml) was exposed to monoexponentially decreasing concentrations of MAR with simulated AUC24 h/MIC varied from 34.81 h to 696.15 h. Every two hours, the multiple sample colony forming units were determined. The result of this study demonstrated that the clinically achieved MAR concentrations at AUC24 h/MIC ratios of 348.08 and 696.15 h produced a pronounced reduction in the bacterial counts and prevented the re-growth of the clinical isolate S. pseudintermedius. However, further study, considering the strains with different susceptibility levels, is recommended.
Awji EG, Tassew DD, Lee JS, Lee SJ, Choi MJ, Reza MA, Rhee MH, Kim TH, Park SC. Comparative mutant prevention concentration and mechanism of resistance to veterinary fluoroquinolones in Staphylococcus pseudintermedius. Vet Dermatol. 2012 Aug;23(4):376-80. https://doi.org/10.1111/j.1365-3164.2012.01038.x
Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. Bacterial persistence as a phenotypic switch. Science. 2004 Sep 10;305(5690):1622-5. https://doi.org/10.1126/science.1099390
Beco L, Guaguere E, Mendez CL, Noli C, Nuttall T, Vroom M. Suggested guidelines for using systemic antimicrobials in bacterial skin infections: Part 2 – antimicrobial choice, treatment regimens and compliance. Vet Rec. 2013 Feb 9;172(6):156-60. https://doi.org/10.1136/vr.101070
CLSI – Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Seventeenth informational supplement (M100-S17). Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
Damte D, Lee SJ, Yohannes SB, Hossain MA, Suh JW, Park SC. Comparative activities of selected fluoroquinolones against dynamic populations of Actinobacillus pleuropneumoniae in an in vitro model of time–kill continuous culture experiment. Int J Antimicrob Agents. 2013 Dec 1;42(6):544-52. https://doi.org/10.1016/j.ijantimicag.2013.08.011
Firsov AA, Zinner SH, Lubenko IY, Portnoy YA, Vostrov SN. Simulated in vitro quinolone pharmacodynamics at clinically achievable AUC/MIC ratios: advantage of IE over other integral parameters. Chemotherapy. 2002 Feb; 48(6):275-9. https://doi.org/10.1159/000069709
Firsov AA, Vostrov SN, Lubenko IY, Drlica K, Portnoy YA, Zinner SH. In vitro pharmacodynamic evaluation of the mutant selection window hypothesis using four fluoroquinolones against Staphylococcus aureus. Antimicrob Agents Chemother. 2003 May 1;47(5):1604-13. https://doi.org/10.1128/AAC.47.5.1604-1613.2003
Frazier DL, Thompson L, Trettien A, Evans EI. Comparison of fluoroquinolone pharmacokinetic parameters after treatment with marbofloxacin, enrofloxacin, and difloxacin in dogs. Journal of J Vet Pharmacol Ther. 2000 Oct;23(5):293-302. https://doi.org/10.1046/j.1365-2885.2000.00285.x
Gebru E, Damte D, Choi MJ, Lee SJ, Kim YH, Park SC. Mutant prevention concentration and phenotypic and molecular basis of fluoroquinolone resistance in clinical isolates and in vitro-selected mutants of Escherichia coli from dogs. Vet Microbiol. 2012 Jan 27;154(3-4):384-94. https://doi.org/10.1016/j.vetmic.2011.07.033
Gloede J, Scheerans C, Derendorf H, Kloft C. In vitro pharmacodynamic models to determine the effect of antibacterial drugs. J Antimicrob Chemother. 2010 Feb 1;65(2):186-201. https://doi.org/10.1093/jac/dkp434
Heinen E. Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administration. J Vet Pharmacol Ther. 2002 Feb;25(1):1-5. https://doi.org/10.1046/j.1365-2885.2002.00381.x
Lacy MK, Lu W, Xu X, Tessier PR, Nicolau DP, Quintiliani R, Nightingale CH. Pharmacodynamic comparisons of levofloxacin, ciprofloxacin, and ampicillin against Streptococcus pneumoniae in an in vitro model of infection. Antimicrob Agents Chemother. 1999 Mar 1;43(3):672-7. https://doi.org/10.1128/AAC.43.3.672
Lee SJ, Awji EG, Park NH, Park SC. Using in vitro dynamic models to evaluate fluoroquinolone activity against emergence of resistant Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother. 2017 Feb 1;61(2):1-14.
Martinez MN, Papich MG, Drusano GL. Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target. Antimicrob Agents Chemother. 2012 Jun 1;56(6):2795-805. https://doi.org/10.1128/AAC.05360-11
Morris DO, Loeffler A, Davis MF, Guardabassi L, Weese JS. Recommendations for approaches to meticillin-resistant staphylococcal infections of small animals: Diagnosis, therapeutic considerations and preventative measures. Clinical Consensus Guidelines of the World Association for Veterinary Dermatology. Vet Dermatol. 2017 Jun;28(3):304-69. https://doi.org/10.1111/vde.12444
Tam VH, Nikolaou M. A novel approach to pharmacodynamic assessment of antimicrobial agents: New insights to dosing regimen design. PLoS Comput Biol. 2011 Jan;7(1):e1001043. https://doi.org/10.1371/journal.pcbi.1001043
Van Hoovels L, Vankeerberghen A, Boel A, Van Vaerenbergh K, De Beenhouwer H. First case of Staphylococcus pseudintermedius infection in a human. J Clin Microbiol. 2006 Dec 1;44(12):4609-12. https://doi.org/10.1128/JCM.01308-06
Wetzstein HG. Comparative mutant prevention concentrations of pradofloxacin and other veterinary fluoroquinolones indicate differing potentials in preventing selection of resistance. Antimicrob Agents Chemother. 2005 Oct 1;49(10):4166-73. https://doi.org/10.1128/AAC.49.10.4166-4173.2005
Yoon JW, Lee KJ, Lee SY, Chae MJ, Park JK, Yoo JH, Park HM. Antibiotic resistance profiles of Staphylococcus pseudintermedius isolates from canine patients in Korea. J Microbiol Biotechnol. 2010 Dec 1;20(12):1764-8.
Zinner SH, Lubenko IY, Gilbert D, Simmons K, Zhao X, Drlica K, Firsov AA. Emergence of resistant Streptococcus pneumoniae in an in vitro dynamic model that simulates moxifloxacin concentrations inside and outside the mutant selection window: related changes in susceptibility, resistance frequency and bacterial killing. J Antimicrob Chemother. 2003 Oct 1;52(4):616-22. https://doi.org/10.1093/jac/dkg401