The Pharmacodynamics of Prolonged Infusion ß-Lactams for the Treatment of Pseudomonas aeruginosa Infections: A Systematic Review.

ABSTRACT

PURPOSE: Pseudomonas aeruginosa is a commonly isolated nosocomial pathogen for which treatment options are often limited for multidrug-resistant isolates. In addition to newer available antimicrobial agents active against P. aeruginosa, strategies such as extended (eg, prolonged or continuous) infusion have been suggested to optimize the pharmacokinetic and pharmacodynamic profiles of ß-lactams. Literature regarding clinical outcomes for extended infusion ß-lactams has been controversial; however, this use seems most beneficial in patients with severe illness. Prolonged infusion of ß-lactams (eg, 3- to 4-hour infusion) can enhance the pharmacodynamic target attainment via increasing the amount of time throughout the dosing interval to which the free drug concentration remains above the MIC (minimum inhibitory concentration) of the organism (fT > MIC). This systematic review summarizes current literature related to the probability of target attainment (PTA) of various antipseudomonal ß-lactam regimens administered as prolonged infusions in an effort to provide guidance in selecting optimal dosing regimens and infusion times for the treatment of P. aeruginosa infections. METHODS: A literature search for all pertinent studies was performed by using the PubMed database (with no year limit) through March 31, 2019. FINDINGS: Thirty-nine studies were included. Although many standard antipseudomonal ß-lactam intermittent infusion regimens can provide adequate PTA against most susceptible isolates, prolonged infusion may enhance percent fT > MIC for organisms with higher MICs (eg, nonsusceptible) or patients with altered pharmacokinetic profiles (eg, obese, critically ill, those with febrile neutropenia). IMPLICATIONS Prolonged infusion ß-lactam regimens can enhance PTA against nonsusceptible P. aeruginosa isolates and may provide a potential therapeutic option for multidrug-resistant infections. Before implementing prolonged infusion antipseudomonal ß-lactams, institutions should consider the half-life of the antibiotic, local incidence of P. aeruginosa infections, antibiotic MIC distributions or MICs isolated from individual patients, individual patient characteristics that may alter pharmacokinetic variables, and PTA (eg, critically ill), as well as implementation challenges.