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Secondary Prophylaxis With Voriconazole in a Leukemic Patient With Pulmonary Aspergillosis

2007; Lippincott Williams & Wilkins; Volume: 26; Issue: 10 Linguagem: Inglês

10.1097/inf.0b013e318149e369

1532-0987

Javier Úriz, Nagore García de Andoín, Cristina Calvo, Joseba Landa, Eider Oñate, A E Nogues, Rafael Guerrero,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

To the Editors: Antifungal secondary prophylaxis in immunocompromised children is often a handicap when treating their underlying disease. Secondary prophylaxis was first demonstrated in a series of pediatric oncology patients in management of hepatosplenic candidiasis through repeated cycles of neutropenia, where both infection and neoplastic disease were successfully treated.1 In recent years, voriconazole effectiveness and safety have been demonstrated in the treatment of Aspergillus infections in immunosuppressed children.2,3 However, the use of voriconazole as secondary prophylaxis is not well described.4,5 We present the case of a 3-year-old girl who received voriconazole for the treatment of invasive pulmonary aspergillosis and the subsequent secondary prophylaxis for 260 days. She was diagnosed with acute lymphoblastic leukemia (LLA pre-B, L2 of FAB) and treated with the low-risk PETHEMA-2001 protocol [induction cycle: prednisone iv 60 mg · m−2 · d−1, intrathecal therapy (methrotrexate, hydrocortisone, and cytarabine), asparaginase im, vincristine iv, daunorubicin iv, and cyclophosphamide iv]. From day 2, because of febrile neutropenia, with negative cultures, the patient received antibiotic therapy (cefepime) for 13 days. On day 21, still neutropenic, she was treated with vancomycin and cefepime for a new fever episode with negative cultures. From day 28, she experienced progressive worsening and was diagnosed with typhlitis requiring parenteral nutrition, analgesia with morphine, imipenem, vancomycin, liposomal amphotericin B, dopamine, and G-CSF. On day 30, the patient presented a bilateral pulmonary infiltrate, and trimethoprim-sulfamethoxazole plus erythromycin were added to treatment. After 4 days, A. fumigatus was isolated from an endotracheal tube, and liposomal amphotericin B was replaced with voriconazole iv (loading dose 6 mg/kg every 12 hours for 1 day, maintenance dose 4 mg/kg every 12 hours). Thoracic computed tomography (CT) scan showed diffuse alveolar damage. After day 36, she recovered from neutropenia with slow clinical improvement. The CT, 1 month later, showed improvement of the alveolar damage without signs of cavitation. After clinical recovery and complete bone marrow remission, consolidation treatment, according to the protocol, was maintained. After 30 days of treatment with voriconazole iv, she was given oral voriconazole. Subsequent radiographic studies showed improvement, and after 260 days, had the last maintenance reinduction, with a normal thoracic CT and a negative galactomannan test, voriconazole treatment was stopped (Fig. 1).FIGURE 1.: High-resolution CT series at level of middle lobe bronchus. (A) Day 35: bronchopneumonia alveolar pattern in middle lobe, posterior segment of right lower lobe, and lingula. (B) Day 65: minimal changes in lung pattern. (C) Day 260: total resolution of alveolar diffuse pattern.During treatment she experienced 4 episodes of profound neutropenia with an average length of 26 days. Secondary effects were monitored but no relevant alterations were observed. After 12 months without antifungal treatment the patient is totally asymptomatic and the disease shows complete remission. We consider this case to be illustrative of the alternative that voriconazole offers to pediatric oncology patients after a fungal infection, and how voriconazole can successfully treat established invasive aspergillosis through repeated cycles of neutropenia.5 Javier Úriz, MD Nagore Garcia de Andoin, MD Cristina Calvo, MD Joseba Landa, MD Eider Onate, MD Agustín Nogues, MD Rafael Guerrero, MD Hospital Donostia San Sebastian, Spain