Purpose:

In critically ill patients, changes in the pharmacokinetics (PK) of β-lactams can lead to significant variations in serum concentrations, with possibly detrimental effects on outcomes. The utilization of individually calculated doses, extended infusion regimen, and therapeutic drug monitoring (TDM)-guided dose adjustments can mitigate the PK changes and help to achieve and attain an individual PK target.

Methods:

We reviewed relevant literature from 2004 to 2021 using 4 search engines (PubMed, Web of Science, Scopus, and Google Scholar). Unpublished clinical data were also examined.

Results:

TDM-guided, individualized dosing strategies facilitated PK target attainment and improved patient outcomes. TDM-guided therapy is a core concept of individualized dosing that increases PK target attainment and identifies possible toxic β-lactam concentrations.

Conclusions:

Individualized dosing and TDM facilitate the rational use of β-lactams and are integral for antibiotic stewardship interventions in critical care, affording the optimal exposure of both pathogen and drugs, along with enhanced treatment efficacy and reduced emergence of antimicrobial resistance.

BACKGROUND

Sepsis is a leading cause of morbidity and mortality in intensive care units (ICUs). 1–3 In addition to patient comorbidities and intrinsic pathogen virulence, the emergence of antimicrobial resistance (AMR) has evolved as a major determinant of outcome in critically ill patients suffering from severe infections and sepsis, respectively. 4 According to the World Health Organization (WHO), antimicrobial prescription patterns and misuse are the main drivers of AMR with an estimated burden of 700,000 deaths. 5 Interprofessional antibiotic stewardship (ABS) programs have been implemented in clinical routine to rationalize antibiotic use in patients, helping clinicians to make informed decisions and counteract the emergence of AMR locally and globally. Although ABS measures are sometimes still erroneously perceived as the arbitrary rationing of a critical resource, they are ultimately aimed at increasing the adequacy of treatment 6 in an environment where the highest per-capita consumers of antimicrobials are known to accumulate: the ICU. 7–9 The American Thoracic Society (ATS) recently published a collaborative ABS guideline 6 comprising the major challenges of ABS in the ICU. The ATS guideline 6 addresses the “[…] fear of inadequate (empirical) treatment” and emphasizes the need for “individualized approaches to antibiotic therapy […]” in the ICU. The present article outlines the integral role of ABS providers in implementing individualized antimicrobial therapy using modern pharmacokinetic (PK) and pharmacodynamic (PD) concepts and therapeutic drug monitoring (TDM), especially in critically ill patients with sepsis or septic shock. The first section focuses on basic PK/PD considerations. Section 2 addresses individualized β-lactam therapy in clinical practice.

MATERIALS AND METHODS

The authors conducted a literature review of prospective and retrospective studies, review articles, and consensus statements, covering reports published from 2000 to 2021 using PubMed, Web of Science, Scopus, and Google Scholar. Searches were performed with different combinations of keywords: β-lactams, therapeutic drug monitoring, toxicity, antibiotic harm/toxicity, extended infusion, continuous infusion, and critical care. The search was limited to adult and critically ill/ICU patients. The search results were assessed for publication date, enrolled study cohort, and relevance to the topic. In addition, the authors included unpublished clinical data.

RESULTS

PK and PD Considerations …