Are Bone and Serum Cefazolin Concentrations Adequate for Antimicrobial Prophylaxis?

Abstract

Background Antimicrobial prophylaxis is considered beneficial for preventing surgical-site infections in clean orthopaedic surgery. However, whether tissue concentrations of cefazolin achieve the minimum inhibitory concentration for the targeted contaminants have yet to be clarified. Questions/purposes We asked whether 2 g of cefazolin would enable effective serum and bone concentrations relative to the current minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococci and methicillin-sensitive Staphylococcus aureus. Patients and Methods We enrolled 43 patients (THA, n = 16; TKA, n = 27) scheduled for primary THAs and primary TKAs. Subjects were given 2 g of cefazolin intravenously before incision. One blood sample and two bone samples were collected from each subject before tourniquet deflation before any additional dose. All samples were assayed at the same laboratory. Minimum inhibitory concentration values were defined based on nationwide surveys. Results Mean (± standard deviation) serum concentration was 170.3 ± 51.3 lg/mL (range, 99.3-370.3 lg/mL). Mean bone concentration was 32.3 ± 15.2 lg/g (range, 11.4-70.0 lg/g) in THA, and 16.0 ± 10.4 lg/g (range, 6.3-46.3 lg/g) in TKA. All serum and bone concentrations exceeded the minimum inhibitory concentration for methicillin-sensitive S. aureus, but some serum levels were marginal and no bone levels exceeded the minimum inhibitory concentration for cefazolin-resistant coagulasenegative Staphylococcus. Conclusions Our data suggest intravenous administration of 2 g of cefazolin achieves the minimum inhibitory concentration for methicillin-sensitive S. aureus in serum and bone, but not the minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococcus in bone, resulting in a potential risk of deep surgical site infections in THAs and TKAs.

Higher Cefazolin Concentrations with Intraosseous Regional Prophylaxis in TKA

“…Over recent decades, however, resistance to cephalosporins among CoNS has increased markedly, and current MIC 90 is as high as 100 ug/mL in half of reported species [28]. This increase in resistance coincides with clinical data reporting a rise in the number of CoNS deep prosthetic infections [20].…”

“…Because we used a relatively high cutoff of BMI [ 35 kg/m 2 , some of our systemic patients may have been underdosed. However, in patients undergoing TKA (mean BMI 25 kg/m 2 ) given 2 g cefazolin systemically, Yamada [28] found a mean bone concentration of only 16 ug/g suggesting a higher systemic dose would be unlikely to alter our findings. A higher intraosseous dose could be considered for obese patients, but given the smaller volume of distribution in regional administration, 1 g is still likely to provide extremely high tissue levels.…”

“…The tissue concentrations of cephalosporins in our study are comparable to those seen with intravenous regional administration [15], suggesting the two routes are similar. Second, we excluded patients with high BMIs to minimize the effect of this variable and because many authors recommend a higher systemic cefazolin dose in heavier patients [28]. Because we used a relatively high cutoff of BMI [ 35 kg/m 2 , some of our systemic patients may have been underdosed.…”

“…Coagulase-negative staphylococci (CoNS), one of the most common causes of infection post-TKA, have relatively high MICs against cephalosporins [28]. Conventional systemic dosing of prophylactic cephalosporins may therefore lead to inadequate tissue concentrations against these organisms [8,28].…”

Staphylococcal Persistence Due to Biofilm Formation in Synovial Fluid Containing Prophylactic Cefazolin

“…Antibiotic penetration is thought to determine the effectiveness of prophylaxis (13,(27)(28)(29). Because CFZ is bactericidal, obtains high levels within the synovial fluid within 30 to 60 min, and has a broad spectrum of coverage, it is recommended for preoperative prophylaxis in procedures that breach the joint capsule (33).…”