title: Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study.
abstract: BACKGROUND
  Empirical antifungal therapy is the standard treatment for persistent or relapsing antibiotic-resistant neutropenic fever. However, overtreatment resulting in increased toxicity and treatment-related cost is a major shortcoming of such therapy. We assessed the feasibility of a "preemptive" approach based on the incorporation of sensitive, noninvasive diagnostic tests for consecutive high-risk neutropenic patients who had received fluconazole prophylaxis while avoiding empirical therapy.
  
  
  METHODS
  A total of 136 treatment episodes for persons who were at risk of acquiring invasive fungal infection (IFI) were screened for the presence of galactomannan with an enzyme immunoassay. A diagnostic evaluation, which included thoracic computed tomography scanning (HRCT) and bronchoscopy with lavage, was performed on the basis of well-defined clinical, radiological, and microbiological criteria. Only seropositive patients and patients with a positive microbiological test result plus supportive radiological findings received liposomal amphotericin B.
  
  
  RESULTS
  Neutropenic fever developed in 117 episodes, of which at least 41 episodes (35%) satisfied existing criteria for empirical antifungal therapy. However, our protocol-driven preemptive approach reduced the rate of antifungal use for these episodes from 35% to 7.7% (a 78% reduction) and led to the early initiation of antifungal therapy in 10 episodes (7.3%) that were clinically not suspected of being IFI. No undetected cases of invasive aspergillosis were identified; 1 case of zygomycosis was missed. Breakthrough candidemia was diagnosed by conventional culture techniques and was treated successfully. With use of a preemptive approach, the 12-week survival rate for patients with IFI was 63.6% (it was 63.1% for those with invasive aspergillosis).
  
  
  CONCLUSIONS
  Preemptive therapy based on enzyme immunoassay and HRCT reduced the exposure to expensive and potentially toxic drugs and offered effective antifungal control, but it failed to detect non-Aspergillus IFI.
authors.affiliation: Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium. johan.maertens@uz.kuleuven.ac.be
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Koen
authors.initials: K
authors.lastname: Theunissen
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: Johnny
authors.initials: J
authors.lastname: Verschakelen
authors.forename: Katrien
authors.initials: K
authors.lastname: Lagrou
authors.forename: Eric
authors.initials: E
authors.lastname: Verbeken
authors.forename: Alexander
authors.initials: A
authors.lastname: Wilmer
authors.forename: Jan
authors.initials: J
authors.lastname: Verhaegen
authors.forename: Marc
authors.initials: M
authors.lastname: Boogaerts
authors.forename: Johan
authors.initials: J
authors.lastname: Van Eldere
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control; D005240:Feasibility Studies; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D008172:Lung Diseases, Fungal / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control; D008297:Male; D008351:Mannans / Q000097:blood*; D008875:Middle Aged; D009181:Mycoses / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000517:prevention & control*; D009503:Neutropenia / Q000150:complications*; D011446:Prospective Studies; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
chemical_list: D000935:Antifungal Agents; D008351:Mannans; C012990:galactomannan; D000666:Amphotericin B; D005690:Galactose