title: 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.
  
  
  OBJECTIVE
  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®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 μg/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) μg/mL at 6 hours, 17.1 (13.1) μg/mL at 24 hours, and 6.8 (6.8) μg/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 tobramycin-impregnated bone cement group were 0.3 μg/mL or less for all samples whereas serum concentrations and median (IQR) for the control group were 1.2 (2.6) μg/mL, 1.6 (4.4) μg/mL, and 2.0 (3.3) μg/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).
  
  
  CONCLUSIONS
  Tobramycin-impregnated bone cement provides a way to deliver antibiotics in patients undergoing TKA. This supratherapeutic short-term prophylactic perioperative antibiotic local delivery can be achieved with limited systemic absorption, whereas joint tobramycin levels were less than therapeutic levels when given intravenously alone. In the control group, with only intravenous tobramycin, a subtherapeutic (< 2.0 μg/mL) level of tobramycin was found in all the intraarticular samples at 6, 24, and 48 hours. Based on the evidence obtained in this study, commercially prepared low-dose tobramycin bone cement can be used to obtain short-term supratherapeutic local concentrations in the knee while maintaining serum tobramycin levels at a minimum.
  
  
  METHODS
  Level II, therapeutic study.
authors.affiliation: Department of Orthopaedic Surgery, Akron General Medical Center, 224 W. Exchange Street, Suite 430, Akron, OH, 44302, USA. Gregory.vrabec@akrongeneral.org.
authors.forename: Gregory
authors.initials: G
authors.lastname: Vrabec
authors.affiliation: Department of Orthopaedic Surgery, Akron General Medical Center, 224 W. Exchange Street, Suite 430, Akron, OH, 44302, USA.
authors.forename: Willis
authors.initials: W
authors.lastname: Stevenson
authors.affiliation: Department of Orthopaedic Surgery, Akron General Medical Center, 224 W. Exchange Street, Suite 430, Akron, OH, 44302, USA.
authors.forename: Sameh
authors.initials: S
authors.lastname: Elguizaoui
authors.affiliation: Department of Orthopaedic Surgery, Akron General Medical Center, 224 W. Exchange Street, Suite 430, Akron, OH, 44302, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kirsch
authors.affiliation: Department of Orthopaedic Surgery, Akron General Medical Center, 224 W. Exchange Street, Suite 430, Akron, OH, 44302, USA.
authors.forename: John
authors.initials: J
authors.lastname: Pinkowski
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods; D001843:Bone Cements / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000378:metabolism / Q000601:surgery*; D007720:Knee Prosthesis / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009820:Ohio; D016459:Prosthesis-Related Infections / Q000175:diagnosis / Q000382:microbiology / Q000517:prevention & control*; D014018:Tissue Distribution; D014031:Tobramycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D014031:Tobramycin