copy and nasal wash specimens from patient 4 also were negative for such antigens on laboratory testing. This underscores the limitations of current testing and that the sensitivity of pandemic (H1N1) 2009 diagnostic testing remains poor and needs further improvement. Thus, in patients suspected of having pandemic (H1N1) 2009 or in those who are critically ill, lower tract respiratory specimens should tested to improve diagnostic sensitivity, and clinicians should consider using immunoassay and culture methods. All 4 patients described in this case series had viral isolates containing H275Y mutation in the neuraminidase gene of pandemic (H1N1) 2009 virus, which is specifi cally associated with high-level resistance to oseltamivir. Increasing data show that immunocompromised patients are at increased risk for development of drug-resistant infl uenza infections after oseltamivir prophylaxis or while receiving oseltamivir treatment (6). Fortunately, this resistance trait remains rare. Existing evidence suggests oseltamivir-resistant pandemic (H1N1) 2009 virus is stable and retains similar transmissibility and virulence as the wild-type virus (7). Therefore, in immunosuppressed patients, in which the infl uenza mortality rate is high, clinicians should also suspect drug-resistant infl uenza infection if the patient does not improve. Before she died of underlying hematologic illness, patient 2 clinically improved after treatment with intravenous zanamivir (obtained through an emergency application for an investigational–new drug). As reported in other studies, pandemic (H1N1) 2009 virus was found in her nasal washes, 1 week after she received zanamivir for 10 days (8). Some data suggest that pandemic (H1N1) 2009 virus has a predilection to affect the lower respiratory tract and is associated with more illness and death than is seasonal infl uenza (9). All 4 case-patients with in this series developed dyspnea, and 3 of the 4 ultimately died of refractory respiratory failure. Our observations suggest that oseltamivir-resistant pandemic (H1N1) 2009 virus is also associated with poor prognosis and may retain the same tropism for lower respiratory tract involvement as wild type. These case-patients illustrated the complexity of the diagnosis and management of such infections in hospitalized immunocompromised patients. Vigilance and heightened clinical suspicion are needed to facilitate early diagnosis, treatment and prevention measures to limit transmission of pandemic (H1N1) 2009 virus or similar viral pathogens.