Community-based parenteral anti-infective therapy (CoPAT). Pharmacokinetic and monitoring issues

Abstract

Community-based parenteral anti-infective therapy (CoPAT) has, over the past 20 years, increased rapidly in many parts of the world including North America, Europe, South America and Australia. CoPAT is a multidisciplinary activity demanding close cooperation between nurses, pharmacists and physicians, as well as with the patient. The selection of an anti-infective drug for use outside the hospital setting must take into account not only the therapeutic effectiveness, cost effectiveness and safety of the drug, but also pharmacological factors such as the dosage schedule and the stability of the drug. Dosage schedules vary with pharmacokinetic factors (e.g. the use of drugs with long half-lives are favoured by CoPAT programmes) and pharmacodynamic features (e.g. once daily gentamicin therapy is attractive and practical because of concentration-dependent bactericidal killing and prolonged post-antibiotic effect). With selected drugs, the renal and, to a lesser degree, liver function of the patient will influence the dosage schedule. The mode of intravenous (i.v.) drugs administration will vary with volume considerations (limiting the use of syringe-infusion therapy for some drugs), stability issues (prevents drugs that are stable at room temperature for less than 24 hours from being used in multidose computerised delivery systems), as well as patient factors (ability to self administer an i.v. drug). Monitoring serum anti-microbial concentrations is undertaken to assure effectiveness and avoid toxicity, and is indicated for drugs with a narrow therapeutic window, such as the aminoglycosides. With the advent of the single daily dose administration of aminoglycosides, checking serum concentrations at the mid-point, i.e. 6 to 14 hours following administration of the first dose, is one approach. Because the toxic effects of vancomycin have been overstated, serum concentrations should only be obtained for defined indications primarily to assure therapeutic effectiveness.