Kinetics of bacterial killing

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The rate of bacterial killing has been considered to have high therapeutic relevance. Bactericidal activity was determined by assessing the kinetics of bacterial killing over a 24 h incubation period for the aerobes and 48 h for the anaerobes, and defined as a ≥3 log10 reduction (≥99.9% reduction) in viable bacterial count (compared with the initial inoculum) after the incubation period.

The graphs below are some examples of the lowest concentration over time at which pradofloxacin exerted bactericidal activity against specific pathogens.

a) Canine pyoderma: Kill kinetics of pradofloxacin (PRA) against Staphylococcus pseudintermedius

b) Canine periodontal disease: Kill kinetics of pradofloxacin against Prevotella corporis

The data shows that when the antibiotic concentration in the test system was increased a faster rate of killing was generally observed and bactericidal effects were observed.

As this data relates to clinical isolates the true significance of the kill rates must be considered relative to serum concentrations of pradofloxacin following administration of the drug at anticipated in use dose levels. In such cases serum pradofloxacin exceeds 1.5 mg/mL in dogs and cats and will be considerably higher at sites of infection, for example in urine, bronchial secretions and skin. It is expected that such a rapid rate of kill will play a significant role in clinical efficacy 30.

The kill-kinetic data has shown some interesting differences between the aerobic and anaerobic strains: Of greatest significance was the complete absence of grow-back: for aerobes this was after 24h and for the anaerobes after 48 h. At concentrations as low as 0.125mg/mL, there was complete kill of oral isolates of Porphyromona gingivalis and Prevotella corporis 30.

Pradofloxacin exhibits clear bactericidal activity in terms of kill kinetics against aerobic and anaerobic clinical isolates from dogs and cats.

This is important because, due to the increasing development of resistance of anaerobic bacteria to antimicrobial agents, there is a need to find effective agents against anaerobes. Additionally, it is of benefit to have oral antimicrobial agents with activity against both aerobes and anaerobes as currently available fluoroquinolones in veterinary medicine only have modest activity against anaerobes 30.

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