• PDF / 142,646 Bytes
• 1 Pages / 595.245 x 841.846 pts (A4) Page_size
• 25 Downloads / 162 Views

DOWNLOAD

REPORT

---

1

S

Development of oseltamivir and peramivir resistance in influenza A infection, in immunocompromised patients: 2 case reports Two immunocompromised patients developed Influenza A H1N1 infections that became resistant to oseltamivir and peramivir during treatment. Patient 1, a 24-year-old woman, presented with fever, coryza, myalgias, loose stools and a productive cough with clear sputum. She had an HR of 120 beats/minute, tachypnoea, an oxygen saturation of 89%, slight lymphopenia, and a right-sided infiltrate on chest x-ray. She received treatment including empirical oseltamivir 75mg twice daily [route not stated]. Tests were positive for influenza A virus. Chest CT on day 6 showed patchy infiltrates bilaterally. She remained symptomatic despite 30 continuous days of oseltamivir administration; however, her respiratory symptoms began improving after day 21 of therapy. All nasopharyngeal wash samples remained positive until 44 days after the initial diagnosis. Viral isolates collected on day 0 and day 5 showed wildtype histidine at position 275 of the NA gene; however, all isolates after day 9 had the H275Y mutation. The H275Ycontaining isolates had a > 200-fold increase in 50% inhibitory concentration (IC50) to oseltamivir and 50-fold increase in IC50 to peramivir. Patient 2, a 49-year-old man, presented with lymphopenia and symptoms of a mild upper respiratory tract infection. Respiratory virus culture was positive for Influenza A virus, and he began oseltamivir 75mg twice daily [route not stated]. After 14 days of oseltamivir therapy, he was hospitalised with worsening fatigue, cough, sinus pressure and lower extremity oedema. Chest CT revealed extensive patchy infiltrates bilaterally, and nasal wash and bronchoalveolar lavage cultures were exclusively positive for influenza A. Oseltamivir was continued, and empirical levofloxacin was added. After 24 days of continuous oseltamivir therapy, he developed respiratory distress and was transferred to the ICU, where he received noninvasive ventilation. Cultures remained positive for influenza A; further empirical antibiotics were added, and he received 10 days of IV peramivir [dosage not stated]. His severe symptoms stabilised 31 days after diagnosis; however, he remained symptomatic and nasopharyngeal washes remained positive on day 40. He received zanamivir, and, by day 46, nasopharyngeal wash was negative; his overall symptoms improved. Viral isolates on day 0 had wild-type NA; however, all subsequent isolates (day 14 thereafter) possessed the H275Y mutation. The H275Y-containing isolates had a > 200-fold increase in IC50 to oseltamivir and 50-fold increase in IC50 to peramivir. Author comment: "In both cases, these individuals were significantly immunocompromised at the time of infection, which likely contributed to the failure of the antivirals." Memoli MJ, et al. Rapid selection of oseltamivir and peramivir-resistant pandemic H1N1 virus during therapy in 2 immunocompromised hosts. Clinical Infectious Diseases 50: 1252-1255, No. 9, 1 May 2010. Available from: