title: Combination therapy with micafungin and amphotericin B for invasive pulmonary aspergillosis in an immunocompromised mouse model.
abstract: OBJECTIVE
  Antifungal monotherapy with polyenes, azoles or echinocandins is not always effective for invasive pulmonary aspergillosis (IPA). The main purpose of this study was to evaluate the efficacy of a combination of micafungin and amphotericin B for the primary treatment of IPA in an immunocompromised mouse model.
  
  
  METHODS
  Female ICR mice were used in all experiments. An immunosuppressive state was induced in mice by an intraperitoneal injection of cyclophosphamide. Mice were intratracheally inoculated with Aspergillus fumigatus conidia, treated with micafungin, amphotericin B or both for 7 days, and were tested for their survival 20 days after the Aspergillus inoculation. Fungal burden in lungs, serum galactomannan index (GMI) and histopathology of lungs, spleen and kidneys were also evaluated.
  
  
  RESULTS
  Combination therapy with micafungin and amphotericin B gave excellent survival of infected mice compared with monotherapy with micafungin or amphotericin B alone. Combined therapy reduced the fungal burden in the lungs and the serum GM levels compared with monotherapy or untreated controls, resulting in a significant histological improvement with disappearance of fungi in the lungs.
  
  
  CONCLUSIONS
  These findings suggest that combination therapy with micafungin and amphotericin B is more effective compared with monotherapy with either of them alone for IPA treatment.
authors.affiliation: Faculty of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-8582, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagasaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Eriguchi
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Uchida
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Masako
authors.initials: M
authors.lastname: Kadowaki
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimono
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001232:Aspergillus fumigatus / Q000302:isolation & purification; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000627:therapeutic use*; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D016867:Immunocompromised Host; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy*; D007668:Kidney / Q000473:pathology; D055666:Lipopeptides / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008351:Mannans / Q000097:blood; D000077551:Micafungin; D051379:Mice; D008813:Mice, Inbred ICR; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008351:Mannans; C012990:galactomannan; D000666:Amphotericin B; D000077551:Micafungin; D005690:Galactose