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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

Main Article

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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Page created: March 09, 2011
Page updated: March 09, 2011
Page reviewed: March 09, 2011
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