Intraosseous cefuroxime (Ceftin) may improve tissue delivery compared to intravenous administration during total knee arthroplasty

1. In adult patients undergoing robotic-assisted total knee arthroplasty (RA-TKA) for knee osteoarthritis, intraosseous cefuroxime (Ceftin) was significantly associated with higher concentrations of local tissue cefuroxime compared to intravenous administration.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Prosthetic joint infection (PJI) prevention after TKA is a significant challenge and major cause of consequent morbidity and mortality. Prophylactic antibiotics are the current mainstay of prevention, with cefazolin and cefuroxime primarily used to target coagulase-negative staphylococci (CONS) and Staphylococcus aureus, which cause up to two-thirds of global PJIs. However, CONS resistance to cephalosporins has risen significantly, with one study showing a potential near-100-fold increase in cephalosporin minimum inhibitory concentrations (MICs). Preoperative intravenous antibiotic administration is unable to reach these MICs, and subtherapeutic levels will further drive resistance. Previous research has validated intraosseous regional administration (IORA) of vancomycin for TKA, and a dual-antibiotic approach of IORA of cefuroxime in combination with intravenous cefuroxime. A previous study showed preoperative stand-alone IORA of cefuroxime produced higher periarticular concentrations than intravenous administration. However, it is unclear if the same relationship exists in RA-TKA.

This prospective, randomized, single-blind, controlled study was conducted at one center in China between July 2024 and August 2024, and included adult patients aged 18 years or older diagnosed with knee osteoarthritis who underwent MAKO RA-TKA. Patients were randomly assigned in a 1:1:1 ratio to receive cefuroxime 750 mg intraosseous (R750IO group), cefuroxime 1 500 mg intraosseous (R1500IO group), or cefuroxime 1500 mg intravenous (R1500IV group). During the surgical procedure, nine tissue samples (three each of adipose tissue, synovium, and cancellous bone) and two blood samples were taken. The primary outcome was local tissue cefuroxime concentration. Secondary outcomes included blood cefuroxime concentration, inflammatory markers, and adverse events. Overall, the study found that both doses of intraosseous cefuroxime significantly increased local tissue cefuroxime concentrations compared to intravenous administration, but no significant differences were noted between 750 mg and 1500 mg doses of intraosseous cefuroxime.

Click here to read this study in JAMA Network Open

Relevant reading: Superior Clinical Results With Intraosseous Vancomycin in Primary Total Knee Arthroplasty

In-Depth [randomized clinical trial]:

PJI after TKA is increasingly becoming a challenge with rising rates of antibiotic resistance and the need for higher MICs. IORA has been shown to achieve higher local tissue concentrations than intravenous administration in conventional TKA. It is unclear if the same relationship exists in RA-TKA, and what the optimal dose is. This prospective, randomized trial compared local tissue cefuroxime concentrations in adult patients undergoing RA-TKA or knee osteoarthritis.

39 patients were randomized to the R750IO (n = 13; mean [range] age, 64 [49-73] years; 76.9% female), R1500IO (n = 13; mean [range] age, 63 [55-72] years; 69.2% female), and R1500IV groups (n = 13; mean [range] age; 67 [60-74] years; 83.3% female). Both the R750IO and the R1500IO groups had significantly higher tissue concentrations (p < 0.05) and lower blood concentrations (p < 0.05) in all samples compared to the R1500IV group. The R1500IO group had a significantly higher post-tourniquet-release blood concentration compared to the R750IO group. There were no other significant differences in tissue and blood concentrations between the R750IO and R1500IO groups. The authors used a prespecified exploratory tissue-concentration benchmark of 16 μg/g, defined as four times the cefuroxime epidemiological cutoff value. In the R1500IV, R750IO, and R1500IO groups, 41.7% (44/108), 95.7% (112/117), and 99.1% (116/117) of tissue samples were above this benchmark, respectively. There were also no significant differences between the three groups in respiration rate, heart rate, systolic blood pressure, diastolic blood pressure, and laboratory findings (including C-reactive protein, erythrocyte sedimentation rate, and interleukin-6) on postoperative days 1 and 3.

Citation: Liu T, Zhang H, Guo M, Zhao R, Tao Y, Zhang Z, et al. Higher tissue concentrations of cefuroxime achieved with preoperative stand-alone intraosseous regional prophylaxis in robotic-assisted total knee arthroplasty: a randomized controlled trial. Arthroplasty. 2026 Oct 19;8(1):81. doi: 10.1186/s42836-026-00436-0. PMID: 42894257; PMCID: PMC13678901.

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