title: A prospective intervention study on higher-dose oseltamivir treatment in adults hospitalized with influenza a and B infections.
abstract: BACKGROUND
  It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization.
  
  
  METHODS
  A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated.
  
  
  CONCLUSIONS
  We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT01052961.
authors.affiliation: Department of Medicine and Therapeutics.
authors.forename: N
authors.initials: N
authors.lastname: Lee
authors.forename: D S C
authors.initials: DS
authors.lastname: Hui
authors.forename: Z
authors.initials: Z
authors.lastname: Zuo
authors.forename: K L K
authors.initials: KL
authors.lastname: Ngai
authors.forename: G C Y
authors.initials: GC
authors.lastname: Lui
authors.forename: S K
authors.initials: SK
authors.lastname: Wo
authors.forename: W W S
authors.initials: WW
authors.lastname: Tam
authors.forename: M C W
authors.initials: MC
authors.lastname: Chan
authors.forename: B C K
authors.initials: BC
authors.lastname: Wong
authors.forename: R Y K
authors.initials: RY
authors.lastname: Wong
authors.forename: K W
authors.initials: KW
authors.lastname: Choi
authors.forename: W W Y
authors.initials: WW
authors.lastname: Sin
authors.forename: E L Y
authors.initials: EL
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Tomlinson
authors.forename: F G
authors.initials: FG
authors.lastname: Hayden
authors.forename: P K S
authors.initials: PK
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006723:Hong Kong / Q000453:epidemiology; D006760:Hospitalization; D006801:Humans; D009980:Influenza A virus / Q000302:isolation & purification*; D009981:Influenza B virus / Q000302:isolation & purification*; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000821:virology; D053139:Oseltamivir / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011446:Prospective Studies; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir
keywords: high dose; influenza; oseltamivir; treatment; viral clearance