title: Nosocomial outbreak of the pandemic Influenza A (H1N1) 2009 in critical hematologic patients during seasonal influenza 2010-2011: detection of oseltamivir resistant variant viruses.
abstract: BACKGROUND
  The pandemic influenza A (H1N1) 2009 (H1N1pdm09) virus infection caused illness and death among people worldwide, particularly in hematologic/oncologic patients because influenza infected individuals can shed virus for prolonged periods, thus increasing the chances for the development of drug-resistant strains such as oseltamivir-resistant (OST-r) variant.
  
  
  METHODS
  The aim of our study was to retrospectively evaluate the clinical importance of OST-r variant in circulating strains of the pandemic H1N1pdm09 virus. By means of RT-PCR and Sanger sequencing we analysed the presence of OST-r variant in 76 H1N1pdm09 laboratory-confirmed cases, hospitalized at the hematologic/oncologic ward at Spedali Civili of Brescia -Italy.
  
  
  RESULTS
  Out of 76 hospitalized hematologic/oncologic patients, 23 patients (30.2%) were infected by H1N1pdm09 virus. Further investigation revealed that 3 patients were positive for the OST-r variant carrying the H275Y mutation. All the 23 infected patients were immuno-compromised, and were under treatment or had been treated previously with oseltamivir. Three patients died (13%) after admission to intensive care unit and only one of them developed H275Y mutation.
  
  
  CONCLUSIONS
  Our retrospective observational study shows that pandemic influenza A (H1N1) 2009 virus can cause significant morbidity and even mortality in hematologic/oncologic patients and confirms the high rate of nosocomial transmission of pandemic H1N1pdm09 virus in these critical subjects. Indeed, the reduction in host defences in these hospitalized patients favoured the prolonged use of antiviral therapy and permitted the development of OST-r strain. Strategies as diagnostic vigilance, early isolation of patients and seasonal influenza A(H1N1) vaccination may prevent transmission of influenza in high risk individuals.
authors.affiliation: Laboratory of Microbiology and Virology, A, O, Spedali Civili, Brescia, University of Brescia, Brescia, Italy. patriziapollara@libero.it
authors.forename: Caterina P
authors.initials: CP
authors.lastname: Pollara
authors.forename: Giorgio
authors.initials: G
authors.lastname: Piccinelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Chiara
authors.initials: C
authors.lastname: Cattaneo
authors.forename: Francesca
authors.initials: F
authors.lastname: Perandin
authors.forename: Silvia
authors.initials: S
authors.lastname: Corbellini
authors.forename: Dolores De
authors.initials: DD
authors.lastname: Tomasi
authors.forename: Carlo
authors.initials: C
authors.lastname: Bonfanti
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003428:Cross Infection / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D004196:Disease Outbreaks; D024882:Drug Resistance, Viral; D005260:Female; D019337:Hematologic Neoplasms / Q000821:virology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D007251:Influenza, Human / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir