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Volume 16, Number 11—November 2010

Letter

Pandemic (H1N1) 2009 and Oseltamivir Resistance in Hematology/Oncology Patients

Cameron WolfeComments to Author , Ian Greenwald, and Luke Chen
Author affiliations: Duke University Medical Center, Durham, North Carolina, USA

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Table

Clinical, diagnostic, and therapeutic patient information for 4 patients hospitalized for hematologic and oncologic conditions, North Carolina, USA, 2009*

Patient information Patient no./age, y/sex
1/43/F 2/58/F 3/67/F 4/61/M
Underlying disease
Relapsed acute myelogenous leukemia
Refractory mycosis fungoides
Recurrent metastatic thymoma
B-cell acute lyphoblastic lymphoma
Reason for admission
Scheduled consolidative chemotherapy
Staphylococcal sepsis; recent interferon-α; malnutrition
Progressive fevers and hypoxia; diffuse; infiltrates shown on chest radiograph
Fevers and respiratory compromise at home, after recent chemotherapy
Signs/symptoms on admission
Intermittent fever during early admission; d 14† cough, persistent fevers; d 24 progressive hypoxia
Intermittent fevers; d 27, cough; persistent fevers, progressive hypoxia
Fever for 5 d; hypoxia, widespread pulmonary infiltrates
Daily fevers for 5 d, cough, hypoxia, fatigue, generalized weakness; diffuse infiltrates on radiograph
Use of oseltamivir
Yes, for 10 d; 75 mg daily prophylaxis after known exposure 2 d prior
No
No
No
Diagnostic information
d 14, nasal wash PCR negative‡; d 25, BAL positive for pandemic (H1N1) 2009 virus; d 37, BAL remained positive, H275Y mutation
d 27 nasal wash positive for pandemic (H1N1) 2009 virus; d 44, H275Y mutation confirmed on d 27 specimen; medication modified
d 1, nasal wash positive for pandemic (H1N1) 2009 virus; d 4, d 9, bronchoscopy results positive; d 12, bronchoscopy results negative for influenza on culture and PCR; H275Y mutation detected on all positive specimens§
d 23 bronchoscopy and d 27 nasal wash results negative; d 28 bronchoscopic viral culture positive for pandemic (H1N1) 2009 virus, 1 d after patient’s death; H275Y mutation detected by CDC
Factors confounding pandemic (H1N1) 2009 diagnosis
Consolidation chemotherapy; Escherichia coli bacteremia, presumptive fungal pneumonia, persistent leukopenia neutropenia postchemotherapy
Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae bacteremia; recent interferon-α therapy; salvage chemotherapy; persistent leukopenia and neutropenia at discharge
Recent thoracic radiotherapy; catheter-associated Staphylococcus aureus bloodstream infection.
Consolidative chemotherapy with prolonged neutropenia; significant emphysema; catheter-associated pseudomonal bloodstream infection
Treatment
Oseltamivir,75 mg 2×/d for 5 d; then, 150 mg 2×/d until death; mechanical ventilation for 15 d
Oseltamivir, 75 mg 2×/d for 9 d; then 150 mg 2×/d for 8 d; modified to renally adjusted IV zanamivir for 10 d, when mutation detected
Oseltamivir, 75 mg 2×/d for 12 d; mechanical ventilation for 16 d
Broad-spectrum antibacterial agents; antiviral agents (not influenza agents), and antifungal agents; mechanical ventilation for 48 h
Clinical outcome Died 38 d postadmission; refractory respiratory failure and progressive ARDS Improvement in respiratory status following zanamivir treatment; ultimately, failure of bone marrow recovery; died 4 d after discharge to hospice Refractory respiratory failure; septic shock; decision to withdraw care Refractory respiratory failure and elective withdrawal of care

*BAL, bronchoalveolar lavage; ARDS, acute respiratory disease syndrome; IV, intravenous; CDC, Centers for Disease Control and Prevention.
†Days postadmission.
‡All specimens, unless otherwise stated, were tested with proFlu Plus PCR (Prodesse, Waukesha, WI, USA) for influenza viruses A and B and respiratory syncytial virus. No quantitative tests were available.
§Mutation genotype confirmed at CDC. Results were available posthumously for patients 1, 3, and 4. No mutation that conferred zanamivir resistance was detected.

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