title: β-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review.
abstract: 1. Infections and related sepsis are two of the most prevalent issues in the care of critically ill patients, with mortality as high as 70%. Appropriate antibiotic selection, as well as adequate dosing, is important to improve the clinical outcome for these patients. 2. β-Lactams are the most common antibiotic class used in critically ill sepsis patients because of their broad spectrum of activity and high tolerability. β-Lactams exhibit time-dependent antibacterial activity. Therefore, concentrations need to be maintained above the minimum inhibitory concentration (MIC) of pathogenic bacteria. β-Lactams are hydrophilic antibiotics with small distribution volumes similar to extracellular water and are predominantly excreted through the renal system. 3. Critically ill patients experience a myriad of physiological changes that result in changes in the pharmacokinetics (PK) of hydrophilic drugs such as β-lactams. A different approach to dosing with β-lactams may increase the likelihood of positive outcomes considering the pharmacodynamics (PD) of β-lactams, as well as the changes in PK in critically ill patients. 4. The present review describes the strategies for dose optimization of β-lactams in critically ill patients in line with the PK and PD of these drugs.
authors.affiliation: Pharmacy Department, The Queen Elizabeth Hospital, Adelaide, SA, Australia.
authors.forename: Mahipal G
authors.initials: MG
authors.lastname: Sinnollareddy
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D016638:Critical Illness / Q000453:epidemiology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D018805:Sepsis / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism; D018440:beta-Lactam Resistance / Q000187:drug effects / Q000502:physiology; D047090:beta-Lactams / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D047090:beta-Lactams