Daptomycin-loaded static cement spacer: salvage for a failed first-stage revision of a total knee replacement with vancomycin resistance

P rosthetic joint infection (PJI) is a devastating and significant complication of joint arthroplasty. The reported incidence rate is 0.25% to 1.0% for primary hip replacements and 0.4% to 2% in primary total knee replacements. PJI causes significant patient morbidity, is technically difficult to treat, and has a high economic burden. The use of antibiotic-loaded acrylic cement is a proven means of preventing and treating PJI. Antibiotic-loaded cement spacers and beads are well established in the twostage revision strategy to eradicate PJI and are believed to contribute to success rates. For many years, the glycopeptide antibiotic, vancomycin, has been the mainstay in treatment of the majority of drug-resistant, gram-positive, bacterial infections. However, concerns are now developing over the emergence of antimicrobial resistance, concurrent with clinical failures involving apparently vancomycin-susceptible Staphylococcus aureus (VSSA) strains and methacillin-resistant staphylococcus aureus (MRSA). The growing trend of PJI and antibiotic resistance necessitates research into novel strategies and additional antimicrobial agents. The goal is an antibiotic with effective and sustained antimicrobial activity and minimal concerns over resistance, with the ability to be combined safely with other agents and suitability for addition to local delivery materials such as bone cement and calcium sulfate. In a recent review by Gbejuade et al., a number of antimicrobials were suggested as options for use in recalcitrant infections. One such antibiotic is daptomycin. Daptomycin is a 13-member amino acid cyclic lipopeptide antibacterial agent that was first discovered and used in clinical trials in the early 1980s. Its development, which was initially discontinued during the early stages of clinical trials, was rejuvenated in 1997 by Cubist Pharmaceuticals (now Merck) in response to increasing need for bactericidal antibiotics effective against vancomycin-resistant grampositive bacteria. Daptomycin acts by irreversibly inserting its hydrophobic tail into the cytoplasmic membrane of gram-positive bacteria with cell death occurring as a result of membrane depolarization, as well as widespread dysfunction of macromolecular synthesis. Studies have shown daptomycin to be active against a broad spectrum of gram-positive bacteria including MRSA, vancomycin-resistant S. aureus, penicillin-resistant Streptococcus pneumoniae, and ampicillin-resistant and vancomycin-resistant enterococci. Daptomycin also has excellent antimicrobial activity against coagulase negative staphylococci and has superior antibacterial effects to vancomycin and teicoplanin in most situations. Furthermore, daptomycin exhibits synergistic effects when used in combination with other antimicrobials such as gentamicin and rifampicin. In 2011, Sader et al. evaluated the in-vitro activities of daptomycin and comparators (including vancomycin, teicoplanin and clindamycin) against 36,769 contemporary gram positive clinical isolates (including enterococcus faecalis, B-haemolytic streptococci, Streptoccocus pneumoniae and MRSA) that caused infection in 34 medical centers in 13 European countries including the United Kingdom. In their results, daptomycin demonstrated very high potency and wide spectrum against the targeted gram-positive organisms, and its activity remained stable across the 7-year period evaluated. They also showed that resistance to vancomycin or quinupristin/dalfopristin or oxacillin did not compromise the potency of daptomycin against staphylococci or enterococci. We present a case of an infected total knee replacement that failed to respond to a standard two-stage protocol using Financial Disclosure: Dr. Murry has received grants from Smith & Nephew, DePuy, Stryker, and Corin. He has received payment for lectures from Smith & Nephew and Biocomposite. He receives royalties from CUP-A-Z, MSK, and owns stock in Spine Health. Drs. Gbejuade and Warner have no disclosures. Other than the mention of Biocomposite (Keele, UK) the authors report no other conflicts of interest in regard to this work. Correspondence to Herbert Gbejuade, MBBS, MRCS, Trauma and Orthopaedics Department, Southmead Hospital, Southmead Way, 21, Oxted Rise, Oadby, Leicester. LE2 5WG, Avon, Bristol, BS10 5NB UK Tel: þ07957172725; fax: þ01173230902; e-mail: gbej1@yahoo.com. 1940-7041 Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved. C A S E R E P O R T