Antimicrobial properties and elution kinetics of linezolid from polymethylmethacrylate.

Polymethylmethacrylate (PMMA) impregnated with antibiotics is widely used in the treatment of osteomyelitis and infected arthroplasties. With the emergence of resistant bacterial strains, linezolid, which is active against gram-positive bacteria and toward which resistance has been scarce, has been suggested as an alternative. In the current in vitro study, the authors sought to determine and compare the efficacy and elution kinetics of linezolid from PMMA. Polymethylmethacrylate beads impregnated with linezolid, vancomycin, or gentamicin alone and in combinations were placed in suspensions of vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus epidermidis. The leaching out concentrations of antibiotics and growth inhibitory time in days were recorded. The mechanical strength of cement beads was evaluated in accordance with International Standard 5833. The growth inhibitory time of linezolid was significantly longer than that of vancomycin and gentamicin for methicillin-resistant S aureus, vancomycin-resistant enterococci, and S epidermidis. The combination of linezolid with gentamicin and vancomycin significantly increased the growth inhibitory time compared with either antibiotic used alone. Linezolid alone or in combination with vancomycin and gentamicin showed satisfactory elution kinetics and antimicrobial activity in vitro without compromising the mechanical strength of PMMA. Future research evaluating the in vivo profile of linezolid-loaded PMMA in experimental animals is needed before it can be considered for human use.

[1]  W. Rui,et al.  Linezolid versus vancomycin for the treatment of gram-positive bacterial infections: meta-analysis of randomised controlled trials. , 2010, International journal of antimicrobial agents.

[2]  J. Kelm,et al.  Antimicrobial properties and elution kinetics of linezolid-loaded hip spacers in vitro. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[3]  Khaled J Saleh,et al.  Antibiotic-impregnated cement spacers for the treatment of infection associated with total hip or knee arthroplasty. , 2007, The Journal of bone and joint surgery. American volume.

[4]  M. Falagas,et al.  Linezolid for the treatment of adults with bone and joint infections. , 2007, International journal of antimicrobial agents.

[5]  A. Sosna,et al.  [Linezolid in the treatment of antibiotic-resistant gram-positive infections of the musculoskeletal system]. , 2006, Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca.

[6]  T. Shim,et al.  Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. , 2006, The Journal of antimicrobial chemotherapy.

[7]  B. von der Lippe,et al.  Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)--a report of ten cases. , 2006, The Journal of infection.

[8]  D. Jacofsky,et al.  Comparative Study of Antimicrobial Release Kinetics from Polymethylmethacrylate , 2006, Clinical orthopaedics and related research.

[9]  A. Hofmann,et al.  Treatment of Infected Total Knee Arthroplasty Using an Articulating Spacer: 2- to 12-Year Experience , 2005, Clinical orthopaedics and related research.

[10]  D. Jacofsky,et al.  Systemic Safety of High-Dose Antibiotic-Loaded Cement Spacers after Resection of an Infected Total Knee Arthroplasty , 2004, Clinical orthopaedics and related research.

[11]  C. Nelson.  The Current Status of Material Used for Depot Delivery of Drugs , 2004, Clinical orthopaedics and related research.

[12]  A. Hanssen,et al.  Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. , 2004, Clinical orthopaedics and related research.

[13]  R. Uhl,et al.  Spacer endoprosthesis for the treatment of infected total hip arthroplasty. , 2004, The Journal of arthroplasty.

[14]  A. Hanssen,et al.  Treatment of the infected hip replacement. , 2004, Clinical orthopaedics and related research.

[15]  M. Köller,et al.  Linezolid Penetration into Bone and Joint Tissues Infected with Methicillin-Resistant Staphylococci , 2003, Antimicrobial Agents and Chemotherapy.

[16]  P. D. Di Cesare,et al.  Use of Antibiotic‐Impregnated Cement in Total Joint Arthroplasty , 2003, The Journal of the American Academy of Orthopaedic Surgeons.

[17]  B. Masri,et al.  Hip Prosthesis of Antibiotic-Loaded Acrylic Cement for the Treatment of Infections Following Total Hip Arthroplasty , 2002, The Journal of bone and joint surgery. American volume.

[18]  G. Bannister,et al.  Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement. , 2002, The Journal of antimicrobial chemotherapy.

[19]  Ronald N. Jones,et al.  Spectrum and potency evaluation of a new oxazolidinone, linezolid: report from the SENTRY Antimicrobial Surveillance Program, 1998-2000. , 2002, Diagnostic microbiology and infectious disease.

[20]  Ronald N. Jones,et al.  Multi-laboratory assessment of the linezolid spectrum of activity using the Kirby-Bauer disk diffusion method: Report of the Zyvox Antimicrobial Potency Study (ZAPS) in the United States. , 2001, Diagnostic microbiology and infectious disease.

[21]  Michael J. Rybak,et al.  In Vitro Activities of Daptomycin, Vancomycin, Linezolid, and Quinupristin-Dalfopristin against Staphylococci and Enterococci, Including Vancomycin- Intermediate and -Resistant Strains , 2000, Antimicrobial Agents and Chemotherapy.

[22]  S. Dekel,et al.  Prolonged leaching time of peptide antibiotics from acrylic bone cement. , 1999, Clinical orthopaedics and related research.

[23]  B. Masri,et al.  Long-term elution of antibiotics from bone-cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system. , 1998, The Journal of arthroplasty.

[24]  K. Marotti,et al.  Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions , 1997, Antimicrobial agents and chemotherapy.

[25]  B. Masri,et al.  Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement. , 1996, The Journal of arthroplasty.

[26]  J. Kilburn,et al.  In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents , 1996, Antimicrobial agents and chemotherapy.

[27]  D. Seligson,et al.  Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases. , 1995, The Journal of bone and joint surgery. British volume.

[28]  J. Quale,et al.  In vitro elution of ciprofloxacin from polymethylmethacrylate cement beads , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[29]  S. Stern,et al.  Antibiotic impregnated bone cement in total hip arthroplasty. An in vivo comparison of the elution properties of tobramycin and vancomycin. , 1993, Clinical orthopaedics and related research.

[30]  D. Musher,et al.  Elution of vancomycin, daptomycin, and amikacin from acrylic bone cement. , 1991, Clinical orthopaedics and related research.

[31]  H. Buchholz,et al.  [Depot effects of various antibiotics mixed with Palacos resins]. , 1970, Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen.