AcinetobacterProsthetic Joint Infection Treated with Debridement and High-Dose Tigecycline

Abstract

Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline.Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30–60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is probably under-dosed for the treatment of implant and biofilm associated infections.

Spontaneous Knee Hemarthrosis Due to Hypofibrinogenemia Following Tigecycline Treatment for Periprosthetic Joint Infection

“…Its use has been approved by the Food and Drugs Administration (FDA) and the European Medicines Agency (EMA) for complicated intra-abdominal infections, community-acquired pneumonia by sensitive bacteria, and complicated skin and soft tissue infections. However, tigecycline has recently been used in the treatment of periprosthetic joint infections [5][6]. Treating periprosthetic joint infections is a challenge because of the presence of a microbial biofilm.…”

“…Additionally, animal studies show that tigecycline is active against foreign body infections, as monotherapy or in combination with other antimicrobial agents [8][9]. Although there is limited experience in the treatment of periprosthetic joint infection because of the biofilm and the MDRO, the use of high dosage tigecycline administration was chosen to maximize the effectiveness of the drug [6,10].…”

“…MDS could possibly be one of the reasons why leucocytosis was absent, even though, in many cases of chronic musculoskeletal infections, the white blood cell count is normal. The platelet count was normal (PLT: 262 X10 3 /μL) and the red blood cell count (RBC) was 4.25 x10 6 /μL with haemoglobin 11.1 g/dL. No known allergic reactions were reported.…”

Clinical Experience with Tigecycline in the Treatment of Prosthetic Joint Infections

“…Outcome was poor with 2 deaths and the other patient requiring limb amputation. Vila et al reported a series of 3 patients treated for multi-drug resistant Acinetobacter baumannii early PJI with combination high dose tigecycline (100 mg every 12 hours) plus a mean 8.7 days of colistin 9. All patients required at least one additional debridement but remained asymptomatic after a median of 2.5 years.…”

“…To our knowledge, there are only a few case series describing tigecycline's use in the treatment of PJI, each including 3 or 4 patients 8, 9, 10. At our institution, tigecycline is used as a second or third line agent in patients with polymicrobial or culture negative PJI.…”