title: Micafungin plus fluconazole in an infected knee with retained hardware due to Candida albicans.
abstract: OBJECTIVE
  To describe the use of micafungin and fluconazole in the management of a fungal prosthetic joint infection caused by Candida albicans.
  
  
  METHODS
  A 55-year-old female who had undergone total left knee arthroplasty due to rheumatoid arthritis presented with symptoms of a left knee infection. Intravenous vancomycin 1 g every 12 hours and intravenous ampicillin/sulbactam 1.5 g every 6 hours were initiated. Arthrocentesis produced cloudy synovial fluid with a white blood cell (WBC) count of 5.995 x 10(3)/microL. C-reactive protein (CRP) was 19.8 mg/dL and erythrocyte sediment rate (ESR) was greater than 120 mm/h. Gram stain was negative, but intraoperative cultures grew C. albicans. Four days later the patient's condition worsened and repeat arthrocentesis showed WBC count of 16.8 x 10(3)/microL with budding yeast in the synovial fluid. Antibiotics were stopped and liposomal amphotericin B 5 mg/kg once daily was started but was stopped after a few doses due to renal failure. Intravenous micafungin 100 mg daily was initiated; intravenous fluconazole 400 mg daily was added 2 days later and subsequently changed to oral fluconazole after 2 days of therapy. The patient received combination micafungin/fluconazole therapy for 8 weeks. After approximately 8 weeks of therapy, the CRP level and ESR had decreased from 19.8 to 7.1 mg/dL and greater than 120 to 81 mm/h, respectively. The patient's pain and range of motion in her knee had returned to baseline levels at last follow-up after the total knee arthroplasty. After 8 weeks of combination therapy, micafungin was discontinued but oral fluconazole was continued; approximately 8 weeks later the patient relapsed, requiring removal of the prosthetic knee hardware.
  
  
  CONCLUSIONS
  Fungal prosthetic joint infections are rare, but definitive data regarding appropriate treatment are lacking. Echinocandins are an attractive treatment option due to their enhanced biofilm penetration. In our patient, treatment with micafungin plus fluconazole for 8 weeks followed by fluconazole monotherapy was associated with an initial good outcome in the treatment of a C. albicans prosthetic knee infection with retained hardware. This was, to our knowledge, the first case using micafungin in a prosthetic joint infection.
  
  
  CONCLUSIONS
  Although micafungin plus fluconazole showed positive results in our patient, more data are needed regarding combination therapy for fungal prosthetic joint infections.
authors.affiliation: Department of Clinical Pharmacy, Dwight D Eisenhower Army Medical Center, Fort Gordon, GA 30905, USA. chris.bland@us.army.mil
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bland
authors.forename: Sanil
authors.initials: S
authors.lastname: Thomas
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D018441:Biofilms; D002177:Candidiasis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage*; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage*; D006801:Humans; D007720:Knee Prosthesis / Q000009:adverse effects*; D055666:Lipopeptides / Q000008:administration & dosage*; D000077551:Micafungin; D008875:Middle Aged; D016459:Prosthesis-Related Infections / Q000188:drug therapy*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D015725:Fluconazole; D000077551:Micafungin