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Infectious Diseases in Clinical Practice:
doi: 10.1097/IPC.0b013e31817e9ab4
Letters to the Editor

Daptomycin Failures in Prosthetic Joint Infections and Bone Infections

Anthony, Suresh Jude MD

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Texas Tech University, Health Sciences Center, Department of Medicine, Section of Infectious Diseases, El Paso, TX

santony@elp.rr.com

To the Editor:

There has been some literature published addressing the use of daptomycin in a variety of clinical situations, including skin and soft tissue infections, prosthetic joint infections, and even in endocarditis.1-4 The failure rates in these articles have varied between 10% and 40% depending on the site of infection treated. We have attempted to address the failures in patients who have been treated for prosthetic and bone infections using daptomycin. At this time, we have treated more than 120 patients with skin and soft tissue infections, including prosthetic joint infections with daptomycin. One hundred six patients were successfully treated with appropriate follow-up for their infections. We present 14 patients in which daptomycin along with appropriate surgical intervention failed, and we have attempted to analysis the reasons for the failure.

In these14 patients, 6 were men and 8 were women, with a mean age of 65.5 years. Infections included methicillin-resistant Staphylococcus aureus (12), methicillin-sensitive S. aureus (1), and culture-negative with gram-positive cocci on the Gram stain (1). Infected sites included vertebra infections with and without hardware (5), prosthesis joint infection (knee, hip, and elbow; 8; all had hardware removed), and were treated with daptomycin but still had recurrence of the infection. There was no increase in the minimal inhibitory concentration (MIC) posttreatment.

Prior antibiotics administered included vancomycin (11 patients), cephazolin (5), linezolid (3), and trimethoprim-sulfamethoxazole (1). Daptomycin was dosed at 6mg/kg for 4 to 6 weeks in 9 patients and 4 mg/kg in 5 patients with renal failure. Underling disease states included diabetes mellitus (7) renal failure (5), rheumatoid arthritis, and cancer (2).

The MIC of daptomycin for the failures versus the successes was similar (≤1 μg/mL). In the 11 patients previously treated with vancomycin, the MICs were 0.5 to 1 μg/mL, and the MICs to daptomycin were 1 μg/mL.

Despite the small number of patients in this observational study, there are some important issues that need to be addressed:

1. What is an acceptable failure rate in patients with prosthesis infections and bone infections despite hardware removal? In the literature, it varies between 10% and 15%.1-3 This difference could be accounted for by the patient selection, dose of daptomycin used, duration of treatment, etc. This seems to be a rather good success rate in this clinical scenario and needs to be authenticated with larger controlled studies.

2. The appropriate dose has yet to be determined at this time, especially for prosthetic and bone infections, and both in vitro bone concentration studies and clinical studies would be useful to address this important issue.

3. The sometimes difficult decision to retain hardware in some patients and the use of suppressive antibiotic regimens need to be addressed, and prolonged use of daptomycin could lead to increasing resistance to daptomycin.

4. Should we be routinely looking at pretreatment MICs and posttreatment MICs in prosthetic and bone infections where a possibility of failure could exist? If so, should this index be tracked?

5. Finally, the issue of combination therapy with other antibiotics in hard-to-treat infections such as recurrent methicillin-resistant S. aureus needs to be addressed because there is scant literature, both in vitro and in vivo, addressing this issue.5

Suresh Jude Anthony, MD

Texas Tech University

Health Sciences Center

Department of Medicine

Section of Infectious Diseases

El Paso, TX

santony@elp.rr.com

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REFERENCES

1. Antony SJ, Angelos E, Stratton CW. Clinical experience with daptomycin in patients with orthopedic-related infections. Infect Dis Clin Pract. 2006;14:144-149.

2. Finney MS, Crank CW, Segreti J. Use os daptomycin to treat drug resistant gram positive bone and joint infections. Curr Med Res Opin. 2005;21:1923-1926.

3. Bernard L, Hoffmeyer P, Assal M, et al. Trends in the treatment of orthopaedic prosthetic infections. J Antimicrob Chemother. 2004;53:127-129.

4. Trampuz A, Zimmerli W. New strategies for the treatment of infections associated with prosthetic joints. Curr Opin Invest Drugs. 2005;6 (2):185-190.

5. Antony S. Combination therapy with daptomycin, vancomycin and rifampin for recurrent severe bone and prosthetic joint infections involving methicillin resistant Staphylococcus aureus. Scand J Infect Dis. 2006;38:293-295.

© 2008 Lippincott Williams & Wilkins, Inc.