Daptomycin Therapy for Osteomyelitis: A Retrospective Study
Daptomycin is a rapidly bactericidal agent with broad coverage against Gram-positive organisms, including Staphylococcus aureus, the most frequent cause of osteomyelitis. The objective of this study was to describe the clinical outcome of patients with non-hardware associated osteomyelitis, and the safety profile of daptomycin in the treatment of these infections.
All patients with osteomyelitis, excluding concurrent orthopedic foreign body infections, treated with daptomycin and identified between 2007–2008 in a retrospective, multicenter, observational registry, were included. Investigators assessed patient outcome (cured, improved, failed, non-evaluable) at the end of daptomycin therapy. Patients with a successful outcome at the end of daptomycin therapy were reassessed in 2009. All patients were included in the safety analysis; evaluable patients were included in the efficacy analysis. Data was assessed using descriptive statistics. A Kaplan Meier analysis was used to assess time to clinical failure.
Two-hundred and nine osteomyelitis patients successfully completed daptomycin therapy in 2007–2008, 71 of which (34%) had a follow-up visit in 2009 and had an evaluable clinical outcome. The median (min, max) daptomycin dose and duration were 6 mg/kg (4, 10) and 42 days (1, 88), respectively. Of the 52 patients with a documented pathogen, S. aureus was the most common (42%); primarily methicillin-resistant S. aureus. All patients were included in the safety analysis; evaluable patients were included in the efficacy analysis. Clinical resolution was reported in 94% (CI - 86.2%, 98.44%) of patients. A Kaplan Meier analysis of time to clinical failure showed that approximately 85% (CI – 64%, 95%) of patients had a continued successful outcome at the time of re-evaluation. Eighteen patients (25%) in the safety population experienced an adverse event; 13 patients (18%) had an adverse event that was possibly-related to daptomycin treatment.
Daptomycin appears to be an effective therapeutic choice with an acceptable safety profile in the management of osteomyelitis that does not involve hardware.
- Berbari EF, Steckelberg JM, Osmon DR Osteomyelitis: Principles and practice of infectious diseases, 6th ed. Elsevier Churchill Livingstone: G. L. Mandell, J. E. Bennett, and R Dolin (ed.); 2005.
- Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM, Stellrecht K: Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother 2008, 52:3315–3320. CrossRef
- Soriano A, Marco F, Martínez JA, Pisos E, Almela M, Dimova VP, Alamo D, Ortega M, Lopez J, Mensa J: Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 2008, 46:193–200. CrossRef
- Steinkraus G, White R, Friedrich L: Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001–05. J Antimicrob Chemother 2007, 60:788–794. CrossRef
- Kullar R, Davis SL, Levine DP, Rybak MJ: Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis 2011, 52:975–81. CrossRef
- Tice AD, Hoaglund PA, Shoultz DA: Outcomes of osteomyelitis among patients treated with outpatient parenteral antimicrobial therapy. Am J Med 2003, 114:723–728. CrossRef
- Lamp KC, Rybak MJ, Bailey EM, Kaatz GW: In vitro pharmacodynamic effects of concentration, pH, and growth phase on serum bactericidal activities of daptomycin and vancomycin. Antimicrob Agents Chemother 1992, 36:2709–2714. CrossRef
- Mascio CT, Alder JD, Silverman JA: Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells. Antimicrob Agents Chemother 2007, 51:4255–4260. CrossRef
- Raad I, Hanna H, Jiang Y, Dvorak T, Reitzel R, Chaiban G, Sherertz R, Hachem R: Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrob Agents Chemother 2007, 51:1656–1660. CrossRef
- Cubicin®: (daptomycin for injection) for intravenous use [product information]. Lexington (MA): Cubist Pharmaceuticals, Inc; 2010.
- Yin L-Y, Calhoun JH, Tongchuan LI: Comparative efficacies of vancomycin and cubicin, a novel lipopeptide antibiotic, in the treatment of methicillin-resistant Staphylococcus aureus: studies with a rabbit model. Society of America, San Francisco: Abstracts of the 39th annual meeting of the Infectious Diseases; 2001:358.
- Lamp KC, Friedrich LV, Mendez-Vigo L, Russo R: Clinical experience with daptomycin for the treatment of patients with osteomyelitis. Am J Med 2007,120(10 Suppl 1):S13–20. CrossRef
- Moise PA, Hershberger E, Amodio-Groton MI, Lamp KC: Safety and clinical outcomes when utilizing high-dose (> or =8 mg/kg) daptomycin therapy. Ann Pharmacother 2009, 43:1211–1219. CrossRef
- Rolston KV, Segreti J, Lamp KC, Friedrich LV: Cubicin Outcomes Registry and Experience (CORE) methodology. Am J Med 2007,120(10 Suppl 1):S4–5. CrossRef
- Finney MS, Crank CW, Segreti J: Use of daptomycin to treat drug resistant Gram-positive bone and joint infections. Curr Med Res Opin 2005, 21:1923–1926. CrossRef
- Antony SJ, Angelos E, Stratton C: Clinical experience with daptomycin in patients with orthopedic-related infections. Infect Dis Clin Pract 2006, 14:144–149. CrossRef
- Shipton LK, Pillai S, Gold H, McCoy C, Kirby JE, Karchmer AW, Eliopoulos G, Chimienti S: Experience With Daptomycin in Staphylococcus Bone and Joint Infections: Case Series and Emergence of Nonsusceptibility. Infect Dis Clin Pract 2007, 15:324–329. CrossRef
- Licitra C, Crespo A, Licitra D, Wallis-Crespo M: Daptomycin for the Treatment of Osteomyelitis and Prosthetic Joint Infection: Retrospective Analysis of Efficacy and Safety in an Outpatient Infusion Center. J Infect Dis: Internet; 2011:9.
- Rao N, Regalla DM: Uncertain efficacy of daptomycin for prosthetic joint infections: a prospective case series. Clin Orthop Relat Res 2006, 451:34–37. CrossRef
- Byren I, Wheeler A, Campanaro E, Yankelev S, Anastasiou D, Kuropatkin G, Evans R, Osmon D: Phase 2 prospective randomised study investigating daptomycin 6 and 8 mg/kg versus standard antibiotic therapy in the treatment of staphylococcal prosthetic joint infections. Abstracts of the 21st ECCMID/27th ICC, Milan, Italy, 7–10 May 2011, Abstract number: R2726. Abstracts accepted for publication only. Clin Microbiol Infect 2011, 17:821–822. CrossRef
- Crompton JA, North DS, McConnell SA, Lamp KC: Safety and efficacy of daptomycin in the treatment of osteomyelitis: results from the CORE registry. J Chemother 2009, 21:414–420.
- Hayden MK, Rezai K, Hayes RA, Lolans K, Quinn JP, Weinstein RA: Development of daptomycin resistance in vivo in methicillin-resistant Staphylococcus aureus. J Clin Microbiol 2005, 43:5285–5287. CrossRef
- Vikram H, Havill NL, Koeth L, Boyce JM: Clinical progression of methicillin-resistant Staphylococcus aureus vertebral osteomyelitis associated with reduced susceptibility to daptomycin. J Clin Microbiol 2005, 43:5384–5387. CrossRef
- Hernandez C, Antony N, Antony S: An Observational Study using Daptomycin to treat Osteomyelitis. J Infect Dis: A Pilot Study. Internet; 2009:7.
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/12/133/prepub
- Daptomycin Therapy for Osteomyelitis: A Retrospective Study
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BMC Infectious Diseases
- Online Date
- June 2012
- Online ISSN
- BioMed Central
- Additional Links
- Author Affiliations
- 1. School of Pharmacy, Temple University, 3307 N Broad St, Philadelphia, PA, 19140, USA
- 2. Cubist Pharmaceuticals, Inc, 65 Hayden Ave, Lexington, MA, 02421, USA
- 3. Department of Medicine, Division of Infectious Diseases, Mayo Clinic College of Medicine, 200 1st St, SW, Rochester, MN, 55905, USA