Adjunctive Rifampin Is Crucial to Optimizing Daptomycin Efficacy against Rabbit Prosthetic Joint Infection Due to Methicillin-Resistant Staphylococcus aureus
Azzam Saleh-Mghir,Claudette Muller-Serieys,Aurélien Dinh,Laurent Massias,Anne-Claude Crémieux +4 more
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Daptomycin mutant strains were isolated in vivo even without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.Abstract:
Daptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistant Staphylococcus aureus (MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin (22 mg/kg given intravenously [i.v.] once daily [o.d.]; equivalent to 8 mg/kg/day in humans) or vancomycin (60 mg/kg given intramuscularly [i.m.] twice daily [b.i.d.]), both either alone or with adjunctive rifampin (10 mg/kg i.m. b.i.d.). After partial knee replacement with a silicone implant, 10(7) MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Although in vivo mean log(10) CFU/g of daptomycin-treated (4.23 ± 1.44; n = 12) or vancomycin-treated (4.63 ± 1.08; n = 12) crushed bone was significantly lower than that of controls (5.93 ± 1.15; n = 9) (P < 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycin-treated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ± 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ± 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P < 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolated in vivo even without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.read more
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Journal ArticleDOI
Prosthetic Joint Infection
Aaron J. Tande,Robin Patel +1 more
TL;DR: The recently proposed consensus definitions of PJI and approaches to accurate diagnosis are reviewed in detail and an overview of the treatment and prevention of this challenging condition is provided.
Journal ArticleDOI
Propionibacterium acnes: from Commensal to Opportunistic Biofilm-Associated Implant Pathogen
TL;DR: Treatment requires a combination of surgery and a prolonged antibiotic treatment regimen to successfully eliminate the remaining bacteria, and most authors suggest a course of 3 to 6 months of antibiotic treatment, including 2 to 6 weeks of intravenous treatment with a beta-lactam.
Journal ArticleDOI
Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall
TL;DR: Modifications of the cell wall appear to also contribute to DAP‐R, including enhanced expression of the dlt operon (involved in d‐alanylation of CW teichoic acids) and progressive CW thickening.
Journal ArticleDOI
Impact of bacterial biofilm on the treatment of prosthetic joint infections
TL;DR: Considering the complexity of biofilm-related infections, further studies are needed to assess the activity of new therapeutic agents in combination with antibiotics (quorum-sensing inhibitors, biofilm disruptors and specific anti-biofilm molecules).
Journal ArticleDOI
Antimicrobial treatment concepts for orthopaedic device-related infection
TL;DR: In this review, rational arguments for initial parenteral treatment for bone penetration are presented, and data are provided on linezolid and daptomycin, which can potentially be used in bone and joint infections.
References
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Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children
Catherine Liu,Arnold S. Bayer,Sara E. Cosgrove,Robert S. Daum,Scott K. Fridkin,Rachel J. Gorwitz,Sheldon L. Kaplan,Adolf W. Karchmer,Donald P. Levine,Barbara E. Murray,Michael J. Rybak,Henry F. Chambers +11 more
TL;DR: These guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system infections.
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Prosthetic-Joint Infections
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TL;DR: This review summarizes the diagnostic challenges and explains the approaches to managing infections that are associated with various devices, including prosthetic heart valves, vascular grafts, pacemakers and defibrillators, and joint prostheses.
Journal ArticleDOI
Infection Associated with Prosthetic Joints
José Luis del Pozo,Robin Patel +1 more
TL;DR: A 62-year-old woman with osteoarthritis presents with a 7-month history of progressively worsening left hip pain radiating to the groin, 8 months after undergoing total left-hip arthroplasty.
Journal ArticleDOI
The Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin-Structure Infections
Robert D. Arbeit,Dennis G. Maki,Francis P. Tally,Edward Campanaro,Barry I. Eisenstein,Investigators +5 more
TL;DR: The safety and efficacy of daptomycin were comparable with conventional therapy, and the frequency and distribution of adverse events were similar among both treatment groups.
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