What is the Intraarticular Concentration of Tobramycin Using Low-dose Tobramycin Bone Cement in TKA: An In Vivo Analysis?

Abstract

Background Antibiotic-impregnated bone cement has increased in popularity as an effort to reduce the risk of infection in high-risk TKAs. However, limited data has been reported regarding antibiotic levels achieved when using tobramycin-impregnated bone cement after implanting total knee components. Questions/Purposes We asked: (1) What is the tobramycin serum and knee intraarticular levels in patients undergoing primary TKA using tobramycin cement? (2) What is the intraarticular tobramycin level for patients receiving only intravenous tobramycin? Methods All patients undergoing primary TKA by one of the two study surgeons (GV, JP) during a 6-month period were evaluated for inclusion and invited to participate. The study enrolled 15 patients undergoing primary TKA by one of two surgeons (GV, JP) who met inclusion criteria; treatment allocation was assigned randomly through blinded envelope. The study group consisted of 10 patients whose components were implanted using a commercially prepared low-dose tobramycin bone cement mixture (1 g/ 40 g). The control group consisted of five patients who received standard weight-based dose intravenous tobramycin. Samples of serum and Hemovac 1 drain-collected intraarticular hematoma were analyzed at 6, 24, and 48 hours postoperatively. Tobramycin levels were measured using an immunoassay technique with a low-end sensitivity of 0.28 lg/mL. Mann-Whitney U tests were performed to compare the serum and intraarticular tobramycin concentrations at each time in the independent variable of group (Control and Study). Results The median (interquartile range [IQR]) intraarticular tobramycin concentrations for the study group, with tobramycin-impregnated bone cement, was 31.8 (29.0) lg/ mL at 6 hours, 17.1 (13.1) lg/mL at 24 hours, and 6.8 (6.8) lg/mL at 48 hours. The intraarticular tobramycin concentrations of this study group were larger than those for the control group at 6 hours (median = 1.3; IQR = 0.7; p = 0.002), 24 hours (median = 1.3, IQR = 1.0; p = 0.002), and 48 hours (median = 1.4; IQR = 1.0; p = 0.02). The serum concentrations for the tobramycinimpregnated bone cement group were 0.3 lg/mL or less for all samples whereas serum concentrations and median (IQR) for the control group were 1.2 (2.6) lg/mL, 1.6 (4.4) lg/mL, and 2.0 (3.3) lg/mL at 6, 24, and 48 hours respectively. The serum levels for the tobramycin-impregnated cement group were less than those for the control group at 6 hours (p = 0.001), 24 (p = 0.001), and 48 hours (p \ 0.001).

Antibiotic bone cement’s effect on infection rates in primary and revision total knee arthroplasties

“…In one study[ 27 ], the revision TKAs were done because of previous infection. Four of the studies did not report such data on the patient population used[ 19 , 20 , 23 , 26 ]. In all of the studies, systemic antibiotics were used in conjunction with AIBC to facilitate recovery and prevent reinfection.…”

“…Vrabec et al[ 23 ] described that local concentrations of antibiotics from AIBC not only had supratherapeutic concentrations in the joint fluid, but also achieved therapeutic concentrations locally within the first 48 h postoperatively. Systemic antibiotics, on the other hand, only achieved subtherapeutic levels locally, not in the joint fluid.…”

“…That systematic review had articles published up until 2013 and used four RCTs[ 19 - 22 ] that were used in this analysis paper. With the goal of including the most recent published results in the field, this study included two papers[ 23 , 24 ] published after 2013. This study also included seven other RCTs that the previous meta-analysis[ 7 ] did not (five extra primary TKA RCTs and two revision TKA RCTs).…”

Acute kidney injury after hip or knee replacement: Can we lower the risk?

“…Some American authors propose antibiotic-loaded cement prophylaxis for patients at high risk, eg, those with immunosuppression, infl ammatory cause of arthritis, or diabetes. 54 Vrabec et al, 55 in a study of low-dose tobramycin-loaded cement used for primary total knee arthroplasty, found a peak median intra-articular tobramycin concentration of 32 mg/L at 6 hours, declining to 6 mg/L at 48 hours with all serum levels 0.3 mg/L or less (unmeasureable) at similar time points.…”

Renal failure after placement of an articulating, antibiotic impregnated polymethylmethacrlyate hip spacer

“…During surgical management of acute septic arthritis with concomitant osteomyelitis, antibiotic impregnated cement (AIC) may be used both as a spacer and to control long-term joint infections [19] . Studies show that AIC leads to local concentrations above the minimum inhibitory concentration for most pathogens, whereas systemic concentrations remain relatively below levels associated with nephrotoxicity [20] , [21] , thus conferring an advantage over intravenous antibiotic administration.…”