title: Viral shedding and susceptibility to oseltamivir in hospitalized immunocompromised patients with influenza in the Influenza Resistance Information Study (IRIS).
abstract: BACKGROUND
  Immunocompromised patients are at greater risk of complicated influenza and may be more likely to develop antiviral resistance. This observational substudy of the Influenza Resistance Information Study (NCT00884117) aimed to study antiviral resistance in immunocompromised patients with influenza and characterize its effect on clinical and virological outcomes.
  
  
  METHODS
  Eligible immunocompromised patients were aged ≥1 year with a local rapid diagnostic or PCR test positive for influenza ≤96 h after diagnosis and with influenza symptoms. Nasal and throat swabs were taken for RT-PCR analysis on day 1 and then every 3 days until patients were virus-free. Resistance was assessed by mutation-specific RT-PCR, phenotypic susceptibility analysis and Sanger sequencing.
  
  
  RESULTS
  Of 42 patients enrolled, 29 (69%) were influenza-positive (RT-PCR) on day 1: 18 adults and 11 children aged 1-12 years. Six patients were severely immunocompromised. On days 3, 6 and 9, most patients tested (18/24, 9/15 and 6/9, respectively) had not cleared the virus. Two of five patients assessed after day 9 continued shedding virus until day 15. H1N1pdm09 viruses harbouring H275Y mutations were detected in post-baseline samples from four patients (aged 52-61 years), one of whom had prolonged viral shedding. No genotypic antiviral resistance was detected in the other 20 treated patients (prevalence of resistance, 17%). Correlation between level of immune compromise and resistance or outcomes could not be assessed. Ten patients (seven influenza-positive) were admitted to intensive care and three died.
  
  
  CONCLUSIONS
  In these patients with mild/moderate immunocompromise, emergence of oseltamivir-resistant viruses was not common. Severity of influenza symptoms ranged from mild to moderate, but correlation with level of compromise could not be determined.
authors: Viroscience, Erasmus MC, Rotterdam, the Netherlands. p.fraaij@erasmusmc.nl.
authors: Pieter L
authors: PL
authors: Fraaij
authors: Martin
authors: M
authors: Schutten
authors: Etienne
authors: E
authors: Javouhey
authors: Laura
authors: L
authors: Burleigh
authors: Russell
authors: R
authors: Outlaw
authors: Deepali
authors: D
authors: Kumar
authors: Charles A
authors: CA
authors: Boucher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053139:Oseltamivir / Q000627:therapeutic use*; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D016019:Survival Analysis; D017201:Virus Shedding / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D053139:Oseltamivir