title: Failure of combination oral oseltamivir and inhaled zanamivir antiviral treatment in ventilator- and ECMO-treated critically ill patients with pandemic influenza A (H1N1)v.
abstract: OBJECTIVE
  The objective of this study was to describe the clinical course of severe and complicated pandemic (H1N1)v infection treated with oral oseltamivir and inhaled zanamivir in a series of intensive care patients.
  
  
  METHODS
  We investigated a case series of patients with respiratory failure and a positive (H1N1)v real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Treatment consisted of oseltamivir tablets 75 mg × 4 daily in a nasogastric tube plus zanamivir intravenous (i.v.) solution 25 mg × 4 daily as inhalation. Ventilator inspiratory plateau airway pressure in the ventilator was kept below 30 cmH₂O, PaO₂ above 8 kPa and pH above 7.30. If this could not be achieved, inhalational nitric oxide (NO) was added or extracorporeal membrane oxygenation (ECMO) was initiated.
  
  
  RESULTS
  Twenty-one patients were admitted, with a median age of 50 y (range 6-69 y). Five patients (23.8%) died in the intensive care unit (ICU) and 1 patient died 2 weeks after ICU discharge. Nine patients received ECMO treatment, of whom 3 died during ECMO (33.3%; 3/9) and 1 at 2 weeks after. The mortality in patients not receiving ECMO treatment was 16.6% (2/12). Sixteen patients (76%) were influenza PCR-positive on day 7 after the start of antiviral treatment. Irreversible presumed lung fibrosis complicated with pneumothorax was common. A high Murray score at admission was significantly associated with a fatal outcome.
  
  
  CONCLUSIONS
  The mortality in these patients was high despite combined antiviral treatment with oseltamivir and zanamivir. Patients shed virus for a long time despite intensive therapy. Optimal management of patients with bilateral pneumonia and respiratory failure caused by (H1N1)v still needs to be determined.
authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital, Skejby, DK-8200 Aarhus, Denmark. joepeter@rm.dk
authors.forename: Eskild
authors.initials: E
authors.lastname: Petersen
authors.forename: Dorte B
authors.initials: DB
authors.lastname: Keld
authors.forename: Svend
authors.initials: S
authors.lastname: Ellermann-Eriksen
authors.forename: Sophie
authors.initials: S
authors.lastname: Gubbels
authors.forename: Susanne
authors.initials: S
authors.lastname: Ilkjær
authors.forename: Søren
authors.initials: S
authors.lastname: Jensen-Fangel
authors.forename: Christian
authors.initials: C
authors.lastname: Lindskov
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D002648:Child; D016638:Critical Illness; D004359:Drug Therapy, Combination / Q000379:methods; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification*; D007251:Influenza, Human / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000008:administration & dosage*; D012121:Respiration, Artificial; D013997:Time Factors; D017211:Treatment Failure; D017201:Virus Shedding; D053243:Zanamivir / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D053243:Zanamivir