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The choice of antimicrobial therapy to treat complex bone and joint infections (BJI) is challenging, requiring consideration of: (i) the problem of bone diffusion; (ii) the necessity of using antimicrobials active against bacterial biofilms; (iii) the growing incidence of antibiotic resistance; and (iv) the high risk of severe adverse events (SAE) in response to first-line antimicrobials in these patients.
Consequently, off-label use of recently developed antimicrobials, such as daptomycin, is frequently required as salvage therapy in complex BJI. Even if daptomycin does not have approval for the treatment of BJI, the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients as bone penetration of daptomycin is limited.
The present cohort study aimed to assess the safety and efficacy of prolonged high-dose (>6 mg/kg/d) daptomycin salvage therapy in patients with complex BJI.
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| Measure | Description | Time Frame |
|---|---|---|
| Measure of daptomycin through plasma concentration (Cmin) | The approximal maximal treatment duration is 300 days. Daptomycin trough plasma concentration (Cmin) is determined monthly to detect any patients with daptomycin trough levels (Cmin) over 24 mg/L. Cmin is determined 24 h after daptomycin injection (just before reinjection, if performed) using a validated HPLC process developed in the laboratory and a diode array UV detector. Cmin > 24 mg/L was considered an overdose, as the risk of high CPK levels (with or without symptoms of myopathy) is greater above this threshold | 300 days |
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Inclusion Criteria:
Exclusion Criteria:
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patients who received daptomycin >6 mg/kg/d as an alternative therapy for complex BJI from January 2011 to July 2013 in a French regional reference center.
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| ID | Term |
|---|---|
| D011657 | Pulmonary Eosinophilia |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D017681 | Hypereosinophilic Syndrome |
| D004802 | Eosinophilia |
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| D007960 |
| Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |