Comparative in vitro killing of canine strains of Staphylococcus pseudintermedius and Escherichia coli by cefovecin, cefazolin, doxycycline and pradofloxacin.

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.

Bactericidal effects of various concentrations of enrofloxacin, florfenicol, tilmicosin phosphate, and tulathromycin on clinical isolates of Mannheimia haemolytica.

OBJECTIVE: To determine bactericidal effects of enrofloxacin, florfenicol, tilmicosin, and tulathromycin on clinical isolates of Mannheimia haemolytica at various bacterial densities and drug concentrations. SAMPLE: 4 unique isolates of M haemolytica recovered from clinically infected cattle. PROCEDURES: Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined for each drug and isolate. Mannheimia haemolytica suspensions (10(6) to 10(9) CFUs/mL) were exposed to the determined MIC and MPC and preestablished maximum serum and tissue concentrations of each drug. Log10 reduction in viable cells (percentage of cells killed) was measured at various points. RESULTS: Bacterial killing at the MIC was slow and incomplete. After 2 hours of isolate exposure to the MPC and maximum serum and tissue concentrations of the tested drugs, 91% to almost 100% cell killing was achieved with enrofloxacin, compared with 8% growth to 93% cell killing with florfenicol, 199% growth to 63% cell killing with tilmicosin, and 128% growth to 43% cell killing with tulathromycin over the range of inoculum tested. For all drugs, killing of viable organisms was evident at all bacterial densities tested; however, killing was more substantial at the MPC and maximum serum and tissue drug concentrations than at the MIC and increased with duration of drug exposure. Rank order of drugs by killing potency was enrofloxacin, florfenicol, tilmicosin, and tulathromycin. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that antimicrobial doses that equaled or exceeded the MPC provided rapid killing of M haemolytica by the tested drugs, decreasing opportunities for antimicrobial-resistant subpopulations of bacteria to develop during drug exposure.