• Barbara Rath, Max von Kleist, Franziska Tief, Katharina Karsch, Ewelina Tuerk, Susann Muehlhans, Florian Louis, Heino Skopnik, Brunhilde Schweiger, and Susanne Duwe.
• Department of Pediatrics, Division of Pneumonology-Immunology, Charité University Medical Center, Augustenburger Platz 1, 13353 Berlin, Germany. Barbara.Rath@gmail.com
• Pediatr. Infect. Dis. J. 2012 Sep 1; 31 (9): 899-905.

BackgroundInfants 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.MethodsVirus 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.ResultsNo 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.ConclusionsOur 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.

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