Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Klebsiella pneumoniae-authors' response.

We read the comments by Giry et al.1 on our study ‘Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Klebsiella pneumoniae’ with interest. Although piperacillin and tazobactam are hydrophilic molecules,2,3 the authors hypothesized that, like lipophilic drugs, they may exhibit non-specific binding to polysulfone fibres, contrary to previous reports of negligible binding of hydrophilic drugs.1,4 Their concern seems related to our reported concentrations being measured from the central compartment rather than the extracellular compartment of a hollow-fibre infection model (HFIM). We agree that verifying the equilibration of antibiotic concentration between central and extracellular compartment is important when establishing the model set-up. Equilibration can be achieved by using an appropriate flow rate between the central and extracellular compartment, relative to the selected volume of the central compartment and that of the cartridge used, as we did in our model establishment. The second reason for concern seems related to the perception that we have used polysulfone cartridges for the first time to study piperacillin/tazobactam.1 However, this is uncertain given the fact that the information on the type of cartridge used has not been reported in the majority (71.3% according to Sadouki et al.5) of published HFIM studies including those investigating piperacillin/tazobactam.6