Diagnosis and antimicrobial therapy of pulmonary infiltrates in febrile neutropenic patients

Patients with severe neutropenia lasting for more than 10 days, who develop fever and pulmonary infiltrates, are at high risk of treatment failure and infection-related death, under conventional broad-spectrum antibiotics. Early supplementation by a systemic antifungal therapy active against Aspergillus spp. has been shown to markedly improve their clinical outcome. Prognosis is significantly influenced by early identification of lung infiltrates by means of high-resolution thoracic computed tomography. Non-culture based diagnostic procedures using a highly sensitive Sandwich ELISA assay to detect circulating galactomannan, or PCR techniques to amplify circulating fungal DNA, may facilitate the diagnosis of invasive pulmonary aspergillosis. CT-directed bronchoscopy and bronchoalveolar lavage using standardized procedures are useful in order to identify causative microorganisms such as filamentous fungi or Pneumocystis carinii. The standard antifungal agent in the treatment of these patients, amphotericin B deoxycholate, has been challenged recently by newly developed antifungals such as voriconazole. It seems important to continue antifungal treatment for at least 14 days before first response assessment. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their etiological relevance for pulmonary infiltrates, to avoid inadequate antimicrobial treatment modification.