Tissue Pharmacokinetics of Cefazolin in Patients with Lower Limb Infections

Abstract

c Cefazolin, a first-generation cephalosporin with activity against methicillin-susceptible Staphylococcus aureus and streptococci, is often used to treat lower limb infections caused by these pathogens. Antimicrobial penetration is often limited in these patients due to compromised vasculature. Therefore, we sought to evaluate the exposure profile of cefazolin in serum and tissue in patients with lower limb infections. An in vivo microdialysis catheter was inserted into the tissue near the margin of the wound and constantly perfused with lactated Ringer's solution. Steady-state serum and tissue samples were simultaneously collected over a dosing interval. Serum protein binding was also assessed. Serum concentrations were analyzed by noncompartmental analysis. Tissue concentrations were corrected for percent in vivo recovery by using the retrodialysis technique. Seven patients with a mean weight of 95.45 ؎ 18.51 kg and a mean age of 54 ؎ 19 years were enrolled. Six patients received 1 g every 8 h, and one patient received 2 g every 24 h due to acute kidney injury. The free area under the curve from 0 to 8 h (fAUC 0 -8 ) values for serum and wound were 48.0 ؎ 18.66 and 56.35 ؎ 41.17 g · h/ml, respectively, for the patients receiving 1 g every 8 h. The fAUC 0 -24 values for serum and wound were 1,326.1 and 253.9 g · h/ml, respectively, for the single patient receiving 2 g every 24 h. The mean tissue penetration ratio (tissue/serum fAUC ratio) was 1.06. These data suggest that the amount of time that free-drug concentrations remain above the MIC (fT>MIC) for cefazolin in wound tissue is adequate to treat patients with lower limb infections.

Pharmacokinetics and Tissue Penetration of Ceftolozane-Tazobactam in Diabetic Patients with Lower Limb Infections and Healthy Adult Volunteers

“…Tazobactam also demonstrated excellent penetration into the soft tissue of these healthy volunteers and patients with DFI with median penetration ratios of 0.85 (range, 0.63 to 2.05) and 1.18 (range, 0.54 to 1.44), respectively. While diabetic patients are known to suffer from peripheral vascular disease, the penetration of ceftolozane and tazobactam into the target site was not compromised, similar to findings for other ␤-lactam antibiotics, cefepime and cefazolin (19,20).…”

“…Microdialysis procedure. The microdialysis procedure was performed as previously described (19,20,(29)(30)(31). Following the local injection of a 0.5% lidocaine solution near the site of insertion, a microdialysis probe (63 microdialysis catheter; M Dialysis, Inc., North Chelmsford, MA) with a membrane length of 30 mm and a molecular mass cutoff of 20 kDa was inserted within 10 cm of the wound margin in the patients or in the thigh tissue in healthy volunteers.…”

Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery

“…Cefazolin concentration in serum and AT for each regimen were simulated every 15 minutes after dosing. A fraction unbound of 15% (ie, 85% protein binding) was applied to correct all serum concentrations to free drug concentrations . AT concentrations were assumed to be unbound during the calculation of area under the curve (AUC) and free time above the MIC (ƒT>MIC) in AT.…”

“…A fraction unbound of 15% (ie, 85% protein binding) was applied to correct all serum concentrations to free drug concentrations. 20 AT concentrations were assumed to be unbound during the calculation of area under the curve (AUC) and free time above the MIC (ƒT>MIC) in AT. The AUC for a 2-hour interval (AUC 0-2 ), reflecting the duration of the time period that samples were collected, was estimated in serum and AT after simulation to calculate the penetration into AT as AUC AT /ƒAUC serum .…”

Limitations of ceftriaxone compared with cefazolin against MSSA: an integrated pharmacodynamic analysis

“…A consistent infusion time of 0.5 h was applied to all doses. Using established one-compartment PK models for ceftriaxone 13,17 and cefazolin, [18][19][20][21] free plasma concentration profiles were simulated for each dosing regimen in each subject. Unlike the IPDM studies, Monte Carlo simulations were conducted for the more relevant cefazolin therapy alone (not co-administered with probenecid).…”