Selecting antibacterials for outpatient parenteral antimicrobial therapy : pharmacokinetic-pharmacodynamic considerations

Abstract

Some infectious diseases require management with parenteral therapy, although the patient may not need hospitalisation. Consequently, the administration of intravenous antimicrobials in a home or infusion clinic setting has now become commonplace. Outpatient parenteral antimicrobial therapy (OPAT) is considered safe, therapeutically effective and economical. A broad range of infections can be successfully managed with OPAT, although this form of treatment is unnecessary when oral therapy can be used. Many antimicrobials can be employed for OPAT and the choice of agent(s) and regimen should be based upon sound clinical and microbiological evidence. Assessments of cost and convenience should be made subsequent to these primary treatment outcome determinants. When designing an OPAT treatment regimen, the pharmacokinetic and pharmacodynamic characteristics of the individual agents should also be considered. Pharmacokinetics (PK) is the study of the time course of absorption, distribution, metabolism and elimination of drugs (what the body does to the drug). Clinical pharmacokinetic monitoring has been used to overcome the pharmacokinetic variability of antimicrobials and enable individualised dosing regimens that attain desirable antimicrobial serum concentrations. Pharmacodynamics (PD) is the study of the relationship between the serum concentration of a drug and the clinical response observed in a patient (what the drug does to the body). By combining pharmacokinetic properties (peak [C(max)] or trough [C(min)] serum concentrations, half-life, area under the curve) and pharmacodynamic properties (susceptibility results, minimum inhibitory concentrations [MIC] or minimum bactericidal concentrations [MBC], bactericidal or bacteriostatic killing, post-antibiotic effects), unique PK/PD parameters or indices (t > MIC, C(max)/MIC, AUC(24)/MIC) can be defined. Depending on the killing characteristics of a given class of antimicrobials (concentration-dependent or time-dependent), specific PK/PD parameters may predict in vitro bacterial eradication rates and correlate with in vivo microbiologic and clinical cures. An understanding of these principles will enable the clinician to vary dosing schemes and design individualised dosing regimens to achieve optimal PK/PD parameters and potentially improve patient outcomes. This paper will review basic principles of useful PK/PD parameters for various classes of antimicrobials as they may relate to OPAT. In summary, OPAT has become an important treatment option for the management of infectious diseases in the community setting. To optimise treatment course outcomes, pharmacokinetic and pharmacodynamic properties of the individual agents should be carefully considered when designing OPAT treatment regimens.