title: Virus load kinetics and resistance development during oseltamivir treatment in infants and children infected with Influenza A(H1N1) 2009 and Influenza B viruses.
abstract: BACKGROUND
  Infants and small children are the most effective transmitters of influenza, while bearing a high risk of hospitalization and adverse disease outcomes. This study aims to investigate virus load kinetics and resistance development during oseltamivir therapy in infants and children infected with influenza A(H1N1) 2009 and influenza B viruses.
  
  
  METHODS
  Virus load in nasopharyngeal samples and phenotypic/genotypic neuraminidase inhibitor resistance were determined at baseline, at day 5 and in additional follow-up samples, if available. Patient-specific viral clearance indices CLν(i) were determined along with estimates of the time required to achieve nondetectable virus load.
  
  
  RESULTS
  No evidence of baseline oseltamivir resistance was detected in 36 patients infected with influenza A(H1N1) 2009 (n = 27) or influenza B (Victoria, Yamagata; n = 9) before oseltamivir therapy. On average, viral loads were lower for influenza type B (median = 5.9·10/mL) than for drug-resistant (median = 2.6·10/mL) and sensitive A(H1N1) 2009 (median = 4.8·10/mL), P = 0.04 and P = 0.09, respectively. Time required to achieve nondetectable virus load was significantly longer in drug-resistant A(H1N1) 2009 (median 15.4 days) compared with drug-sensitive A(H1N1) 2009 (P = 0.003; median 7.7 days) and drug-sensitive influenza B (P = 0.001; median 5 days). No evidence of viral rebound was observed once viral clearance was achieved.
  
  
  CONCLUSIONS
  Our data indicate that influenza subtyping in combination with baseline viral load measurements might help to optimize the duration of antiviral therapy in the individual child. Lower than expected virologic response rates in patients without malabsorption or compliance issues may suggest resistance development.
authors.affiliation: Department of Pediatrics, Division of Pneumonology-Immunology, Charité University Medical Center, Augustenburger Platz 1, 13353 Berlin, Germany. Barbara.Rath@gmail.com
authors.forename: Barbara
authors.initials: B
authors.lastname: Rath
authors.forename: Max
authors.initials: M
authors.lastname: von Kleist
authors.forename: Franziska
authors.initials: F
authors.lastname: Tief
authors.forename: Katharina
authors.initials: K
authors.lastname: Karsch
authors.forename: Ewelina
authors.initials: E
authors.lastname: Tuerk
authors.forename: Susann
authors.initials: S
authors.lastname: Muehlhans
authors.forename: Florian
authors.initials: F
authors.lastname: Louis
authors.forename: Heino
authors.initials: H
authors.lastname: Skopnik
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Schweiger
authors.forename: Susanne
authors.initials: S
authors.lastname: Duwe
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D005334:Fever / Q000821:virology; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000254:growth & development*; D009981:Influenza B virus / Q000187:drug effects / Q000254:growth & development*; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D053208:Kaplan-Meier Estimate; D008297:Male; D053139:Oseltamivir / Q000627:therapeutic use*; D011446:Prospective Studies; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir