A pilot study on the comparative minimum inhibitory and mutant prevention concentration values for moxifloxacin and pradofloxacin against canine and human isolates of Staphylococcus pseudintermedius and S. schleiferi

Abstract

Background -Moxifloxacin is a fourth-generation fluoroquinolone (FQ) that is approved for use in people to treat a variety of infections. Some veterinary microbiology laboratories report moxifloxacin in culture and sensitivity profiles for Staphylococcus pseudintermedius and S. schleiferi albeit using Clinical & Laboratory Standards Institute (CLSI) breakpoints for S. aureus. Previous studies have shown that S. aureus breakpoints can mischaracterize S. pseudintermedius susceptibility to various drugs. Pradofloxacin is a third generation veterinary FQ with a similar mechanism of action and spectrum of activity to moxifloxacin; however, the dose format (25 mg/mL solution) available in the USA may limit its practical use in large dogs.Objective -To determine the minimum inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant selection window (MSW) of moxifloxacin and pradofloxacin for isolates of S. pseudintermedius and S. schleiferi.Methods and materials -Pulsed-field gel electrophoresis was performed to establish that each bacterial isolate selected for testing represented an unique strain. The MIC, MPC and MSW for moxifloxacin and pradofloxacin were determined from 60 strains of S. pseudintermedius and seven strains of S. schleiferi.Results -The MIC and MPC ranges of moxifloxacin and pradofloxacin for meticillin-susceptible S. pseudintermedius were similar. However, MIC and MPC ranges were much wider and resistance to both drugs was more common for meticillin-resistant strains of S. pseudintermedius and S. schleiferi.Conclusions and Clinical Importance -The narrow MSW of these drugs may reduce the risk of selecting for antibiotic-resistant subpopulations. Pharmacokinetic, pharmacodynamic and safety studies are needed.

Investigation of In Vitro Susceptibility and Resistance Mechanisms in Skin Pathogens: Perspectives for Fluoroquinolone Therapy in Canine Pyoderma

“…Our data indicate that pradofloxacin and moxifloxacin overall show low MICs with bactericidal effect both in staphylococci and E. coli , compared to earlier generation veterinary and human FQs. The results are compatible with and expand those previously published on MICs [ 31 , 38 , 40 , 42 , 51 , 55 , 56 , 57 ], in isolates collected from canine skin infections. However, this is the first veterinary study that examined a substantial number of MS and MR staphylococci in canine pyoderma.…”

“…As other authors have highlighted, this addresses the need for harmonized guidelines across countries [ 76 ]. Moreover, CBPs were not available for S. pseudintermedius and were extrapolated from S. aureus as adopted by previous investigators [ 51 ].…”

“…Moxifloxacin clinical breakpoints for E. coli were obtained from EUCAST guidelines (2022) [ 86 ]. For S. pseudintermedius , moxifloxacin and ciprofloxacin CBPs were adopted from CLSI for S. aureus as previously described in a veterinary study [ 51 ]. Clinical breakpoints are listed in Table S2 .…”

“…However, their primary targets are specific for bacterial species: DNA gyrase for Gram-negative and Topoisomerase IV for Gram-positive bacteria, respectively [ 47 , 48 , 49 ]. In comparison, newer generation pradofloxacin and moxifloxacin may represent an advantage in reducing the likelihood of resistance development as the drugs target both bacterial topoisomerases with increased affinity, conferring low minimum inhibitory concentrations (MIC) and mutant prevention concentrations (MPC) [ 50 , 51 ].…”