Pharmacokinetics of Cefuroxime in Synovial Fluid

Abstract

Cefuroxime is frequently used as preoperative antibiotic prophylaxis and may be used for the treatment of septic arthritis. A prerequisite for successful treatment of septic arthritis is the ability of an antibiotic agent to penetrate into the target site. Therefore, the concentration of cefuroxime in synovial fluid was evaluated. Ten patients who underwent elective knee arthroscopy were included in this study. Patients were treated with a single dose of 1,500 mg cefuroxime intravenously, and subsequently, the concentrations in plasma, the interstitial fluid of muscle tissue, and synovial fluid were measured by using microdialysis. Pharmacokinetic/pharmacodynamic calculations to predict bacterial killing were performed using the epidemiologically defined MIC for clinical isolates and CLSI breakpoints. Cefuroxime penetrated excellently into muscle tissue (ratio of the area under the concentration-time curve [AUC] for muscle tissue/AUC for free plasma, 1.79) and synovial fluid (ratio of the AUC for synovial fluid/AUC for free plasma, 1.94). The cefuroxime concentration was greater than the MIC for and strains (≤2 mg/liter) over the complete dosing interval (the percentage of the dosing interval during which the free cefuroxime concentration exceeded the MIC for the pathogen []). CLSI defines staphylococci with MICs of ≤8 mg/liter to be susceptible to cefuroxime. For staphylococci with MICs of ≤8 mg/liter, the in plasma was 52.5%, while the in muscle tissue and synovial fluid was 93.6% and 96.3%, respectively. Cefuroxime may be used to treat septic arthritis caused by susceptible bacterial strains (MIC ≤ 8 mg/liter). The activity of cefuroxime in septic arthritis might be underestimated when relying exclusively on plasma concentrations.

Pharmacokinetic Assessment of Staphylococcal Phage K Following Parenteral and Intra-articular Administration in Rabbits

“…The literature describing drug access to the joint space generally addresses small-molecule antibiotics and non-steroidal antiinflammatory drugs, corticosteroids, or biomolecular precursors administered for the treatment of infection and arthritis ( Evans et al, 2014 ). Antibiotics (amphenicols, macrolides, fluoroquinolones, and β-lactams) and antiinflammatory drugs access the synovial compartment when administered systemically to both healthy ( Depenbrock et al, 2017 ; Knych et al, 2017 ; Schwameis et al, 2017 ; Uney et al, 2017 ; Langston et al, 2019 ; Krueger et al, 2020 ) and unhealthy (defined as having one or more infected or inflamed joints) subjects ( Porter et al, 1970 ; Thomas et al, 1975 ; Kennedy, 1976 ; Caruso et al, 1980 ; Kennedy, 1983 ; Hinderling et al, 1988 ; Kraml et al, 1988 ; Brown et al, 1991 ; Day et al, 1991 ; Scott et al, 2004 ; Rodrigues et al, 2010 ). An isotope clearance study in healthy and rheumatoid arthritis (RA) patients demonstrated a longer isotope half-life—defined as the length of time required for the decay of one-half of administered atoms—in healthy individuals and in clinically uninvolved knees in RA cases as compared with diseased knees.…”

Predictive Performance of Physiologically Based Pharmacokinetic Modelling of Beta-Lactam Antibiotic Concentrations in Adipose, Bone, and Muscle Tissues

“…the model assumption) implies that the ratio of the AUC of uISF to the AUC of unbound plasma approaches unity. This was not the case in multiple studies, with ratios ranging between 0.3 ) and 1.8 (Schwameis et al, 2017). The limited dataset and large variability of uISF concentrations between and within studies does not allow for any statement to be made on whether this can be seen as evidence against the free drug hypothesis.…”

“…Half of the simulated concentration-time profiles in uISF of tissue (6/12) did not pass the model performance criteria (AFE and AAFE within twofold) (Table 2). Two of those studies had AFE and AAFE outside the 3 fold criteria (Brunner et al, 2000;Schwameis et al, 2017). The overall AFE and AAFE were 1.52 and 2.32, respectively, indicating that the models were mostly inaccurate and tended to overpredict the observed uISF concentration profiles (+52%) (Figure 3C).…”