Bone and subcutaneous adipose tissue pharmacokinetics of vancomycin in total knee replacement patients

Abstract

Background and purposeThe incidence of orthopedic methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. Vancomycin may therefore play an increasingly important role in orthopedic perioperative antimicrobial prophylaxis. Studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. We assessed single-dose plasma, subcutaneous adipose tissue (SCT) and bone concentrations of vancomycin using microdialysis in male patients undergoing total knee replacement.Methods1,000 mg of vancomycin was administered postoperatively intravenously over 100 minutes to 10 male patients undergoing primary total knee replacement. Vancomycin concentrations in plasma, SCT, cancellous, and cortical bone were measured over the following 8 hours. Microdialysis was applied for sampling in solid tissues.ResultsFor all solid tissues, tissue penetration of vancomycin was significantly impaired. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 2 mg/L was 3, 36, 27, and 110 min for plasma, SCT, cancellous, and cortical bone, respectively. As opposed to the other compartments, a mean MIC of 4 mg/L could not be reached in cortical bone. The area under the concentration-time curve from 0 to the last measured value and peak drug concentrations (Cmax) for SCT, cancellous, and cortical bone was lower than that of free plasma. The time to Cmax was higher for all tissues compared with free plasma.InterpretationPostoperative penetration of vancomycin to bone and SCT was impaired and delayed in male patients undergoing total knee replacement surgery. Adequate perioperative vancomycin concentrations may not be reached using standard prophylactic dosage.

Antibiotic penetration into bone and joints: An updated review

“…This good penetration profile was also seen in sternal bone after administration of 15 mg/kg to patients undergoing cardiac surgery (Martin et al, 1994). Conversely, a study in TKA 10 patients given 1 g of vancomycin showed a weaker penetration pattern where mean concentration in cancellous and cortical bones were 0.1 AE 0.3 and 0.1 AE 0.1 mg/mL, respectively (Bue et al, 2018). In a study of lower limb ischemia, mean concentrations were 17 mg/mL in serum and 11.6, 13.7, and 8.8 mg/mL in bones with low, moderate, and high levels of ischemia, respectively (Lozano-Alonso et al, 2016).…”

Local Vancomycin Concentrations after Intra-articular Injection into the Knee Joint: An Experimental Porcine Study

“…2,4 Moreover, vancomycin may not provide adequate target-site concentrations after intravenous administration in some orthopaedic settings. [5][6][7] Various perioperative local vancomycin applications have been employed, given its potential to reach high target-site concentrations and at the same time lowering the systemic toxic side effects due to lower systemic concentrations. 3,8,9 Especially when implants are involved, local vancomycin application may be promising, given the increasing bacterial virulence.…”

“…11,13 Opposed to these methods, microdialysis has evolved as a promising pharmacokinetic tool for dynamic in vivo sampling of the unbound and microbiologically active extracellular concentrations of vancomycin simultaneously from multiple orthopaedic relevant compartments. [5][6][7]14 The objective of this study was to investigate the prophylactic effectiveness of an intra-articular injection of vancomycin into the knee joint.…”

Can systemically administered antibiotics be detected in wound tissues and surfaces under negative pressure wound therapy?

“…Antibiotic concentrations have been measured in wound fluid from Redon drains with regard to short time effectiveness in orthopaedic surgery, indicating that antibiotic concentrations at therapeutic levels can be reached for a short period perioperatively . Bone samples in joint replacement have also shown that systemically administered drugs can be found within the bone . In the context of colorectal surgery, attempts have been made to clarify the pharmacokinetics of prophylactically administered antibiotic in serum, intestinal tissue, and subcutaneous adipose tissue in patients who underwent surgery for colorectal cancer, but in subcutaneous tissue, the concentrations were found to be low at the time of measurement .…”

“…15,16 Bone samples in joint replacement have also shown that systemically administered drugs can be found within the bone. 17 In the context of colorectal surgery, attempts have been made to clarify the pharmacokinetics of prophylactically administered antibiotic in serum, intestinal tissue, and subcutaneous adipose tissue in patients who underwent surgery for colorectal cancer, but in subcutaneous tissue, the concentrations were found to be low at the time of measurement. 18 This has repeatedly led surgeons to administer antibiotics locally into wounds with the aim of reaching effective dosages.…”