Dynamic distribution of systemically administered antibiotics in orthopeadically relevant target tissues and settings

Abstract

This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English-published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady-state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target.

Keywords: Antibiotics; bone; orthopaedic; penetration; pharmacokinetics.

Fig. 1

PRISMA Flowchart of study selection [31].

Fig. 2

(A) Ultrafiltration relies on vacuum as a driving force to extract interstitial fluid (n = 2/97 studies). (B) Microdialysis relies on continuous concentration‐driven diffusion (n = 95/97 studies).

Fig. 3

Graphical presentation of the number of studies according to antibiotic drug.