March 27, 2024

To: Rachael Lu
From: Danielle Snyder, PharmD Candidate, Dr. Zachary Fricker, PharmD
Re: Intraosseous Vancomycin for Total Knee Arthroplasty
______________________________________________________________________________________________________________________

In response to your request regarding the use of intraosseous vancomycin in patients undergoing total knee arthroplasty (TKA), the following
information is provided.

Response:
Eight trials were found evaluating the use of intraosseous (IO) vancomycin for antibacterial prophylaxis in TKA patients.1-8 Five trials evaluated IO
vancomycin against a control group, mostly intravenous (IV) vancomycin.1-7 Overall, IO vancomycin lead to significantly higher tissue
(subcutaneous fat and bone) vancomycin concentrations and lower systemic concentrations compared to IV therapy.1-5 Additionally, IO
vancomycin does not result in higher rates of complications than IV vancomycin or no IO therapy.1-7 IO vancomycin also leads to low rates of
recurrent infection, though may not be as preventative in patients with chronic infections with unresectable components. Additional data is
needed to further evaluate IO vancomycin in chronic infections.1-8

Table 1. Literature Evaluating Intraosseous Vancomycin for Antibacterial Prophylaxis in Orthopedic Surgery
Study & Design Patient Population Comparators Outcomes
Wininger AE 20 adults who underwent All patients also received systemic Average systemic vancomycin levels, mcg/mL
20241 primary TKA (mean age 68, BMI antibiotic prophylaxis: ● At the start of procedure: 4.9 vs 27.9, p=0.0004
Design: RCT 30) ● IO Vancomycin 500 mg plus ● At the time of closing: 7.8 vs 19.6, p=0.001
weight-dosed cefazolin (10 patients) Average vancomycin local tissue concentrations, mcg/mL
● IV Vancomycin 15 mg/kg (10 patients) ● Distal femoral: 66.2 vs 61.0, p=0.8
● Proximal tibial: 57.1 vs 52.8, p=0.84
● Suprapatellar synovial tissue: 9.0 vs 10.7, p=0.8
Adverse events
● Compartment syndrome: 0
● Redman syndrome: 0
● AKI: 0

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Study & Design Patient Population Comparators Outcomes
● IV group: 1 reoperation due to superficial infection in the IV group
requiring incision and drainage
Spangehl MJ 24 adults (median 68 years) who Patients either received: Median vancomycin concentrations, mcg/g
20222 underwent primary TKA ● IORA (intraosseous regional ● SQ fat: 33.1 vs 5.2, p <0.001
Design: RCT administration) vancomycin 500 mg ● Bone: 21.8 vs 7.9, p=0.06
after tourniquet inflation ● Blood concentration in recovery: 4.7 vs 20.1, p<0.01
● IV-systemic vancomycin 15 mg/kg with
tourniquet inflated for cementation
Kildow 20218 35 adults (median 67 years) with All patients also received systemic Non-recurrence rate for acute infection:
[abstract only] acute PJI in TKA who underwent antibiotic prophylaxis ● Acute, primary: 92.3%
Design: case DAIR (26 patients with primary ● Vancomycin 500 mg IO with DAIR ● Chronic: 44.4%
series infection, 9 patients with chronic (n=35)
infections)
Klasan 20216 631 adults (mean 68 years) who All patients received perioperative AKI: 3.0% vs 5.0%, p=0.203
Design: underwent primary TKA prophylaxis with 3 doses IV cefazolin PJI within 90 days: 0 vs 0
retrospective ● Vancomycin 500 mg IO (n=331) Readmission rate: p=0.279
cohort ● No IO therapy (n=300) Complication rate: p=0.750
Park 20217 1,060 adults who underwent All patients received prophylaxis with IV 30-day complication rates
Design: TKA cefazolin ● PJI: 0% vs 0.52%, p=0.254
retrospective ● Vancomycin 500 mg IO (n=488) ● AKI: 0.41% vs 0.70%
cohort ● Vancomycin 15 mg/kg IV, starting 60 ● DVT: 0.20% vs 0.70%
min before skin incision (n=572) ● Re-operations: 10 vs 8, p=0.892
90-day complication rates
● PJI: 0.22% vs 1.46%, p=0.047
● AKI: 0.45% vs 0.91%
● DVT: 067% vs 0.91%, p=0.524
● Re-operations: 20 vs 13
1-year complication rates
● PJI: 0.37% vs 2.04%, p=0.070
● Re-operations: 29 vs 18, p=0.742
Chin 20183 22 adults (age 55-85 years) with All patients received preoperative Mean tissue vancomycin concentration, mcg/g
Design: RCT BMI >35 undergoing primary prophylaxis with IV cefazolin ● SC fat: 39.3 vs 4.4, p<0.001
TKA for OA ● Vancomycin 500 mg IO (n not ● Bone: 34.3 vs 6.1, p<0.001
reported) Mean plasma vancomycin concentration, mcg/mL: 1.8 vs 16.6, p<0.001
● Vancomycin 15 mg/kg IV, starting Superficial infections: 0 vs 2
60-120 min prior to skin incision (n not Pulmonary emboli: 1 vs 0
reported)

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 Study & Design Patient Population Comparators
Young 20184 20 adults undergoing unilateral All patients received preoperative
Design: RCT revision TKA prophylaxis with IV cefazolin
● Vancomycin 500 mg IO (n=10)
● Vancomycin 1 g IV, starting 60 min
before skin incision (n=10)
Young 20145 30 adults (<90 years) undergoing All patients received preoperative
Design: RCT primary TKA for OA prophylaxis with IV cefazolin
● Vancomycin 250 mg IO (n=10)
● Vancomycin 500 mg IO (n=10)
● Vancomycin 15 mg/kg IV, starting
60-120 min prior to skin incision
(n=10)
Bolded indicates statistical significance; outcomes listed in order of intervention; AKI = acute kidney injury; BMI = body mass index, in kg/m2; DAIR = debridement, antibiotics, and implant retention;
DVT = deep vein thrombosis; IO = intraosseous; IV = intravenous; OA = osteoarthritis; PJI = prosthetic joint infection; POD = post-operative day; RCT = randomized controlled trial; SBP = systolic blood
pressure; SC = subcutaneous; TKA = total knee arthroplasty
Outcomes
Mean tissue vancomycin concentration, mcg/g
● SC fat: 49.3 vs 3.7, p<0.001
● Bone: 77.1 vs 6.4, p<0.001
Mean intraarticular vancomycin concentration on POD 1, mcg/L: 6.6 vs 4.6,
p=0.08
Infections: 0 vs 0
Thromboembolism: 0 vs 0
Mean tissue vancomycin concentration, mcg/g
● SC fat: 14.0 vs 44.0 vs 3.2, p<0.001 for both IO vs IV and 500 IO vs 250 IO
● Bone: 16.0 vs 38.0 vs 4.0, p<0.001 for both IO vs IV and 500 IO vs 250 IO
Mean plasma vancomycin concentration: lower in both IO groups vs IV
group
Red man syndrome: 0 vs 0 vs 1
Minor transient SBP drops (5-30 mmHg): 6 vs 5 vs 7
Infections: 0 vs 0 v 0
DVT: 0 vs 1 vs 0

Secondary and tertiary resources were queried for information. Medline was searched with combinations of the following MeSH terms (MH) and
keywords: keyword “vancomycin,” MH “arthroplasty, replacement, knee,” keyword “total knee arthroplasty,” MH “infusions, intraosseous,” and
“intraosseous.” Embase was searched with combinations of the following Emtree terms and keywords: Emtree “vancomycin,” keyword
“vancomycin,” Emtree “total knee arthroplasty,” keyword “total knee arthroplasty,” Emtree “intraosseous drug administration,” and keyword
“intraosseous.”

Thank you for contacting the HealthTrust Clinical Pharmacy Drug Information Team; please contact us through customer service
(hpgsvc@healthtrustpg.com) with any additional requests. The Drug Information Request Form can be found at
https://members.healthtrustpg.com/pharmacy/drug-information/drug-information-request-form.

References:
1. Wininger AE, Gurusamy P, Sullivan TC, et al. Intraosseous versus intravenous vancomycin in tourniquetless primary total knee arthroplasty: a
randomized trial. J Arthroplasty. Published online March 8, 2024. doi:10.1016/j.arth.2024.02.083

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2. Spangehl MJ, Clarke HD, Moore GA, Zhang M, Probst NE, Young SW. Higher tissue concentrations of vancomycin achieved with low-dose intraosseous
injection versus intravenous despite limited tourniquet duration in primary total knee arthroplasty: a randomized trial. J Arthroplasty.
2022;37(5):857-863. doi:10.1016/j.arth.2022.01.057
3. Chin SJ, Moore GA, Zhang M, et al. The AAHKS Clinical Research Award: Intraosseous regional prophylaxis provides higher tissue concentrations in high
BMI patients in total knee arthroplasty: a randomized trial. J Arthroplasty. 2018;33:S13-8. doi:10.1016/j.arth.2018.03.013
4. Young SW, Zhang M, Moore GA, et al. The John N. Insall Award: Higher tissue concentrations of vancomycin achieved with intraosseous regional
prophylaxis in revision TKA: a randomized controlled trial. Clin Orthop Relat Res. 2018;746:66-74. doi:10.1007/s11999.0000000000000013
5. Young SW, Zhang M, Freeman JT, et al. The Mark Coventry Award: Higher tissue concentrations of vancomycin with low-dose intraosseous regional
versus systemic prophylaxis in TKA: a randomized trial. Clin Orthop Relat Res. 2014;472:57-65. doi:10.1007/s11999-013-3038-z
6. Klasan A, Patel CK, Young SW. Intraosseous regional administration of vancomycin in primary total knee arthroplasty does not increase the risk of
vancomycin-associated complications. J Arthroplasty. 2021;36:1633-7. doi:10.1016/j.arth.2020.12.034
7. Park KJ, Chapleau J, Sullivan TC, Clyburn TA, Invaco SJ. 2021 Chitranjan S. Ranawat Award: Intraosseous vancomycin reduces periprosthetic joint
infection in primary total knee arthroplasty at 90-day follow-up. Bone Joint J. 2021;103-B(6 Suppl A):13-7.
doi:10.1302/0301-620X.103B6.BJJ-2020-2401.R1
8. Kildow BJ, Patel SP, Otero JE, et al. Results of debridement, antibiotics, and implant retention for periprosthetic knee joint infection supplemented with
the use of intraosseous antibiotics. Bone Joint J. 2021;103-B(6 Suppl A). doi:10.1302/0301-620X.103B6.BJJ-2020-2278.R1 [abstract only]