Abstract
BackgroundBacterial 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/ObjectivesTo 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/MaterialsBacterial strains collected from dogs with urinary tract infections were studied.Methods and materialsHigh bacterial densities ranging from 106 to 109 colony forming units (cfu)/mL were exposed to minimum inhibitory, mutant prevention, blood and tissue drug concentrations, and the percentages (log10) of viable cells killed following 30 min, 1, 2, 4, 6, 12 and 24 h of drug exposure were quantified.ResultsDoxycycline exhibited bacteriostatic properties with less killing than the other three agents. For example, at a 107 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 importanceDifferences 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.
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