In vitro killing of canine strains of Staphylococcus pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and pradofloxacin over a range of bacterial densities

BACKGROUND: Bacterial densities likely fluctuate during infection and may exceed the bacterial density used in susceptibility testing. As such, investigation of bacterial killing by antibiotics over a range of varying bacterial densities may provide important differences between compounds and could impact drug selection for therapy. HYPOTHESIS/OBJECTIVES: To measure killing of clinical isolates of Staphylococcus pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and pradofloxacin at clinically relevant (minimum inhibitory, mutant prevention, maximum serum and maximum tissue) drug concentrations against varying densities of bacteria. ANIMALS/MATERIALS: Bacterial strains collected from dogs with urinary tract infections were studied. METHODS AND MATERIALS: High bacterial densities ranging from 10(6) to 10(9) colony forming units (cfu)/mL were exposed to minimum inhibitory, mutant prevention, blood and tissue drug concentrations, and the percentages (log(10)) of viable cells killed following 30 min, 1, 2, 4, 6, 12 and 24 h of drug exposure were quantified. RESULTS: Doxycycline exhibited bacteriostatic properties with less killing than the other three agents. For example, at a 10(7) cfu/mL density of S. pseudintermedius, more cells were killed by pradofloxacin (P < 0.0001) and cefovecin (P = 0.0014) but not cefazolin when compared to doxycycline at the maximum serum drug concentration following 12 h of drug exposure. CONCLUSIONS AND CLINICAL IMPORTANCE: Differences were seen between some drugs in the speed and extent of bacterial killing; this could be clinically important and may impact drug selection and length of therapy.