Joseph M Blondeau1,2, Shantelle D Shebelski1. 1. Division of Clinical Microbiology, Royal University Hospital and Saskatoon Health Region, 103 Hospital Drive, Saskatoon, Saskatchewan, S7N 0W8, Canada. 2. Departments of Microbiology and Immunology, Pathology and Ophthalmology, University of Saskatchewan, 103 Hospital Drive, Saskatoon, Saskatchewan, S7N 0W8, Canada.
Abstract
BACKGROUND: Bacterial eradication is necessary for clinical cure of infections and antimicrobial agents are important adjunctive therapies for inhibiting the growth of or killing bacteria. Pre-existing skin diseases predispose animals to infection by Staphylococcus pseudintermedius and, more rarely, by Gram-negative bacilli. The property of rapid killing of bacteria may influence drug selection and duration of therapy in the setting of infection. OBJECTIVES: To test the killing of canine isolates of S. pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and pradofloxacin at the minimum inhibitory, mutant prevention, maximum serum and maximum tissue drug concentrations. METHODS: Under standard conditions, bacterial cells were exposed to clinically relevant drug concentrations in vitro and the log10 reduction (and % kill) of viable cells measured at 5, 10, 15, 20, 25, 30, 60, 120 and 180 min after drug exposure. RESULTS: Statistically significant differences were seen between killing efficiencies by pradofloxacin versus the other agents, whereby pradofloxacin killed cells more rapidly than the others. For example, against the S. pseudintermedius strains, significantly more cells were killed by pradofloxacin following 15 min of maximum tissue drug concentration exposure than for cefazolin (P = 0.0002), cefovecin (P = 0.0007) and doxycycline (P ≤ 0.0001). CONCLUSION AND CLINICAL IMPORTANCE: The rank order of potency based on these kill experiments was pradofloxacin > cefazolin > cefovecin > doxycycline. Rapid killing of bacteria affects the speed of clinical resolution and may influence drug selection and duration of therapy for skin infections.
BACKGROUND: Bacterial eradication is necessary for clinical cure of infections and antimicrobial agents are important adjunctive therapies for inhibiting the growth of or killing bacteria. Pre-existing skin diseases predispose animals to infection by Staphylococcus pseudintermedius and, more rarely, by Gram-negative bacilli. The property of rapid killing of bacteria may influence drug selection and duration of therapy in the setting of infection. OBJECTIVES: To test the killing of canine isolates of S. pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and pradofloxacin at the minimum inhibitory, mutant prevention, maximum serum and maximum tissue drug concentrations. METHODS: Under standard conditions, bacterial cells were exposed to clinically relevant drug concentrations in vitro and the log10 reduction (and % kill) of viable cells measured at 5, 10, 15, 20, 25, 30, 60, 120 and 180 min after drug exposure. RESULTS: Statistically significant differences were seen between killing efficiencies by pradofloxacin versus the other agents, whereby pradofloxacin killed cells more rapidly than the others. For example, against the S. pseudintermedius strains, significantly more cells were killed by pradofloxacin following 15 min of maximum tissue drug concentration exposure than for cefazolin (P = 0.0002), cefovecin (P = 0.0007) and doxycycline (P ≤ 0.0001). CONCLUSION AND CLINICAL IMPORTANCE: The rank order of potency based on these kill experiments was pradofloxacin > cefazolin > cefovecin > doxycycline. Rapid killing of bacteria affects the speed of clinical resolution and may influence drug selection and duration of therapy for skin infections.