Safety and Efficacy of High-Dose Daptomycin Therapy for Prosthetic Joint Infection

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Authors: Reid JJ, Rubin ZA, Leibowitz MR, Oakes DA.
UCLA / Orthopaedic Hospital, Santa Monica, CA

Title: Safety and Efficacy of High-Dose Daptomycin Therapy for Prosthetic Joint Infection

Background: Combination antimicrobial therapy with vancomycin is considered the standard of care for severe methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRSE) infection. Vancomycin bacteriostatic activity induces increasing cell wall thickness, a mechanism associated with resistance. Daptomycin has concentration-dependent bactericidal activity and lasting post-antibiotic effects. It has been clinically shown to have microbiological activity in prosthetic joint infections (PJI), including those caused by MRSA and vancomycin-resistant Enterococcus (VRE).

Hypothesis/Purpose: Is high-dose daptomycin a safe and effective antimicrobial in PJI?

Methods: We conducted a retrospective review of PJI treated by a single fellowship-trained arthroplasty surgeon at a tertiary referral center. Fourteen patients diagnosed with 15 PJI underwent a standard 2-stage protocol and received high-dose daptomycin (>8mg/kg/day) for 6 weeks. Serum white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), wound exam, ambulatory status, and re-operation were assessed. The mean follow-up was 21 months (range 3-66).

Post-antimicrobial cultures were taken of joint aspirates. Measured adverse effects included peak CK level >10-fold above pre-treatment level, myositis, hyperkalemia, and interstitial pneumonitis.

Results: Microorganism isolates included 4 MRSA, 3 MSSA, 3 MRSE, and 3 VRE. Two patients failed to grow a pathogen in culture. Post-therapy cultures were negative in 13/15 (87%) joints. WBC, ESR, and CRP normalized in most cases. Three patients required re-operation: delayed complex closure for wound dehiscence, constrained revision for late instability, and revision 2-stage protocol for refractory MRSA infection. 13/14 (93%) patients were ambulatory at last follow-up. All patients completed 6 weeks of high-dose daptomycin therapy, and five patients required a second 6-week course. Three patients had CK elevation. No patients developed myositis, hyperkalemia, or pneumonitis associated with daptomycin.

Discussion: PJI treated by a standard two-stage protocol with high-dose daptomycin therapy are eradicable. Adverse effects were rare in an elderly patient cohort with multiple comorbidities.

Conclusion: High-dose daptomycin is a safe and effective antimicrobial for PJI with resistant organisms.