Pharmacoeconomics of continuous versus intermittent infusion of piperacillin–tazobactam for the treatment of complicated intraabdominal infection

Piperacillin sodium–tazobactam sodium, a β-lactam antimicrobial, is extensively used because of its broad-spectrum activity against many enteric gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa; gram-positive pathogens, such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus species; and anaerobes such as Bacteroides fragilis.1 The drug’s activity against these pathogens and its reliable safety profile make it an appealing choice for the monotherapy of complicated intraabdominal infections. Applying pharmacodynamic principles to antimicrobial dosing regimens has been shown to be an effective way to optimize the probability of clinical success while potentially limiting the toxicity and costs associated with the administration of these agents.2 In theory, the clinical efficacy of piperacillin–tazobactam, as well as the other β-lactam antimicrobials, could be maximized with increases in the time that the antimicrobial concentrations remain above the minimum inhibitory concentration (MIC) (t>MIC).3 Strategies used to increase t>MIC include increasing the amount of drug given per dose or giving more doses per day. However, the short half-lives of β-lactam antimicrobials make these inefficient and costly ways to increase drug exposure over time. More efficient ways to increase the t>MIC involve prolonging the infusion time of β-lactam antimicrobials, including administration as a continuous infusion over 24 hours. This practice allows the drug’s concentration to remain above the MIC for a longer period of time while potentially allowing less drug to be given daily. This practice is theoretically sound because no greater benefit is observed with time-dependent bactericidal agents when the concentration at the site of infection increases beyond four times the initial MIC.3,4