Daptomycin > 6 mg/kg/Day as Salvage Therapy in Patients With Complex Bone and Joint Infection: Cohort Study in a Regionalreference Center

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.

Study Overview

• Status: Completed
• Conditions: Bone and Joint Infection; Treated by Daptomycin

• Study Type: Observational
• Enrollment (Actual): 43

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

• patients having BJI treated by daptomycin at >6 mg/kg/d

Exclusion Criteria:

-

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: July 4, 2017
• First Submitted That Met QC Criteria: July 4, 2017
• First Posted (Actual): July 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 6, 2017
• Last Update Submitted That Met QC Criteria: July 4, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Bone and Joint Infection; Daptomycin; Eosinophilic pneumonia
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Arthritis; Infections; Communicable Diseases; Arthritis, Infectious
• Other Study ID Numbers: 69HCL17_0465

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No