Clinical experience with daptomycin for the treatment of patients with knee and hip periprosthetic joint infections

Department of Orthopaedic Surgery, Reconstructive and Septic Surgery Division, Hospital Universitario Vall d'Hebron, Universitat Autónoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.31). 04/2012; 67(7):1749-54. DOI: 10.1093/jac/dks119
Source: PubMed


To investigate the clinical efficacy and safety of daptomycin in the treatment of hip and knee periprosthetic joint infections (PJIs).
We completed a retrospective review of all patients in our institution (n=20) who were treated with daptomycin for hip or knee PJI, over the 36 month period from January 2008 until December 2010.
Infection types included eight cases with acute infections, nine cases of chronic infection and three cases of positive intraoperative cultures. Methicillin-resistant coagulase-negative Staphylococcus was the most frequent microorganism found in surgical cultures (40%). Our patients, on average, received daptomycin as salvage therapy at a dose of 6.6 mg/kg/day for 44.9 days. The overall success rate was 78.6% after a median follow-up period of 20 months. In the subgroup of patients with acute PJIs, treatment with daptomycin, debridement and implant retention was successful in all cases. We found two cases of severe side effects (one case of acute renal failure due to massive rhabdomyolysis and one of eosinophilic pneumonia) and two cases of asymptomatic transient creatine phosphokinase (CPK) level elevation.
The combination of high daptomycin doses with an adequate surgical approach could be a viable alternative in cases of difficult-to-treat Gram-positive PJIs. Due to the risk of potentially serious adverse events, serum CPK level should be closely monitored.

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Available from: Pablo S Corona, Dec 05, 2015
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    • "Significantly, the combination also avoided the emergence of resistance (Garrigos et al., 2010; Saleh-Mghir et al., 2011). There is little clinical information regarding the efficacy and safety of high doses of daptomycin in combination with rifampin in the setting of PJI due to methicillin-resistant Staphylococcus managed with DAIR (Corona Pérez Cardona et al., 2012; Jogun et al., 2013). We aimed to assess the efficacy and safety of daptomycin (10 mg/kg/d) plus rifampin in this clinical setting. "
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    ABSTRACT: We aimed to analyze the efficacy and safety of high doses of daptomycin (10 mg/kg/d) plus rifampin (D10R) for prosthetic joint infection (PJI). This was an observational retrospective multicenter study (2010-12) including all patients with acute PJI by fluoroquinolone-resistant staphylococci managed with implant retention and D10 + R. Twenty cases were included: two (10%) were withdrawn due to toxicity, leaving 18 cases for efficacy evaluation: 13 (72%) women, age 79 years (range 58-90). Clinical failure was observed in nine (50%) patients: in five cases staphylococci were recovered (28% of microbiologicalfailures); no modification of daptomycin-MIC was observed. These 18 cases were compared with 44 matched historical cases: failure rates were similar, but whereas in the historical series failure occurred fundamentally during therapy, in the present series it was recorded after discontinuation of antibiotics. In summary, D10 + R may be the initial treatment of choice for PJI by fluoroquinolone-resistant staphylococci managed with implant retention.
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    • "Spanish colleagues recently reported that combination treatment with rifampicin and linezolid showed a 69.4% success rate (34 of 49 patients) for prosthetic joint infection with retention of the implant after two years.71 Recently, daptomycin has also been recommended as a new option for the treatment of implant infections,68 due to its good effect systemically and locally against methicillin-resistant staphylococci and enterococci in patients with implant-associated infections.72,73 By using such antibiotic treatment, prosthetic knee-associated infections in many patients could be well controlled.42 "
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    ABSTRACT: Prosthesis-related infection is a serious complication for patients after orthopedic joint replacement, which is currently difficult to treat with antibiotic therapy. Consequently, in most cases, removal of the infected prosthesis is the only solution to cure the infection. It is, therefore, important to understand the comprehensive interaction between the microbiological situation and the host immune responses that lead to prosthesis infections. Evidence indicates that prosthesis infections are actually biofilm-correlated infections that are highly resistant to antibiotic treatment and the host immune responses. The authors reviewed the related literature in the context of their clinical experience, and discussed the possible etiology and mechanism leading to the infections, especially problems related to bacterial biofilm, and prophylaxis and treatment of infection, including both microbiological and surgical measures. Recent progress in research into bacterial biofilm and possible future treatment options of prosthesis-related infections are discussed.
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    ABSTRACT: Purpose: Treatment of Gram-positive osteoarticular infections requires an adequate surgical approach combined with intensive antimicrobial therapy. The aim of this study was to evaluate the safety and efficacy of a combined regimen of high-dose daptomycin and rifampicin, in patients with various types of Gram-positive osteoarticular infections. Methods: This single centre, non-comparative, prospective study evaluated the safety and efficacy of a combined regimen of intravenous daptomycin (8 mg/kg/day) and oral rifampicin (600 mg/day) in patients with Gram-positive osteoarticular infections, with a minimal follow-up of one year. Creatine phosphokinase, transaminases, bilirubinaemia, and serum creatinine, were measured at baseline and regular intervals. Results: The median daily doses of daptomycin and rifampicin, administered for a median duration of 21 (range, 10-122) days to 16 patients (median age, 63.5 years; 11 males, five females) presenting with staphylococcal (n = 15) or streptococcal (n = 1) osteoarticular infections, were 8.15 (range, 6.6-8.9) mg/kg/day and 600 (range, 600-900) mg/day, respectively. The combined regimen of daptomycin and rifampicin was well tolerated by all except one patient, without requiring treatment adjustment or discontinuation. One patient developed allergic responses probably due to rifampicin after 42 days. Fifteen (94 %) patients showed favourable clinical and microbiological outcomes. Conclusions: The combined regimen of high-dose daptomycin and rifampicin was well tolerated and may provide a useful alternative to standard glycopeptide therapy for Gram-positive osteoarticular infections.
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