pK/pD of antimicrobials

Assay Development

BCARE personnel have considerable in depth knowledge in the development of new high pressure liquid chromatography (HPLC) and LC/MS assays for antibacterials, antivirals and antifungals. Immunoassay technologies have also been extensively trialled prior to introduction into clinical practice. In recent times the BCARE staff have developed HPLC assays for anti viral and anti fungal agents and we are keen to pursue pharmacokinetic studies on antivirals. Our expertise in HPLC assay has also lead to an active research interest in antimicrobial metabolites and/or breakdown products.

Pharmacokinetics

The staff within BCARE have a considerable expertise in antimicrobial pharmacokinetics both in patients and healthy volunteers. In the recent past pharmacokinetic studies have been performed in ITU patients, patients with severe sepsis (bacteraemia, pulmonary infection, after surgery) and orthopaedics.

These pharmacokinetic interests overlap with our knowledge of antimicrobial assay development and pharmacodynamics. In addition to performing pharmacokinetic studies BCARE supports pharmacokinetic research in other centers by the provision of assay services and external quality assurance.

Pharmacodynamics

Pharmacodynamics is an expanding and well established area, and it complements our strong track record in the basic laboratory aspects of antimicrobial chemotherapy and pharmacokinetic evaluations. All pharmacodynamic activities are laboratory based; animals are not used. Expertise exists to perform simple investigations such as post-antibiotic effect through to complex antimicrobial dose fractionation studies using continuous bacterial culture in-vitro models. These models enable intravenous, intramuscular and oral drug concentration serum profiles to be modelled. Hollow fibre in-vitro pharmacokinetic models are also used in preclinical antibacterial drug evaluation. At present we have experience with β-lactams, quinolones, glycopeptides, aminoglycoside and other antimicrobials classes in our in-vitro model systems.

Many major pathogen groups can be studied using these systems, for example, staphylococci, streptococci, enterobacteriacae, haemophilus, pseudomonas and anaerobes.

Sensitivity Testing:

Techniques

Expertise exists to perform susceptibility tests by agar dilution and micro-and macro-broth dilution techniques, and gradient strips. BSAC, EUCAST, CLSI or ISO methodologies are used. In addition, β-lactamase induction tests can be performed. Determination of GISAs, hGISAs are also available.

Bactericidal-time kill curves can be performed and bacterial killing with single agents and combinations studied, using novel, computer generated curve fitting techniques.

Current work:

• In vitro susceptibility testing.
• Determination of minimum inhibitory concentrations (MICs).
• Bactericidal studies on antimicrobials.
• Antibacterial – antibacterial interactions.