title: Triple-combination antiviral drug for pandemic H1N1 influenza virus infection in critically ill patients on mechanical ventilation.
abstract: A recent in vitro study showed that the three compounds of antiviral drugs with different mechanisms of action (amantadine, ribavirin, and oseltamivir) could result in synergistic antiviral activity against influenza virus. However, no clinical studies have evaluated the efficacy and safety of combination antiviral therapy in patients with severe influenza illness. A total of 245 adult patients who were critically ill with confirmed pandemic influenza A/H1N1 2009 (pH1N1) virus infection and were admitted to one of the intensive care units of 28 hospitals in Korea were reviewed. Patients who required ventilator support and received either triple-combination antiviral drug (TCAD) therapy or oseltamivir monotherapy were analyzed. A total of 127 patients were included in our analysis. Among them, 24 patients received TCAD therapy, and 103 patients received oseltamivir monotherapy. The 14-day mortality was 17% in the TCAD group and 35% in the oseltamivir group (P = 0.08), and the 90-day mortality was 46% in the TCAD group and 59% in the oseltamivir group (P = 0.23). None of the toxicities attributable to antiviral drugs occurred in either group of our study, including hemolytic anemia and hepatic toxicities related to the use of ribavirin. Logistic regression analysis indicated that the odds ratio for the association of TCAD with 90-day mortality was 0.58 (95% confidence interval, 0.24 to 1.42; P = 0.24). Although this study was retrospective and did not provide virologic outcomes, our results suggest that the treatment outcome of the triple combination of amantadine, ribavirin, and oseltamivir was comparable to that of oseltamivir monotherapy.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul 138-736, Republic of Korea. sbh
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Gee
authors.initials: G
authors.lastname: Young Suh
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Huh
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Kim
authors.forename: Min-ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yun Seong
authors.initials: YS
authors.lastname: Kim
authors.forename: Hye-Ryoun
authors.initials: HR
authors.lastname: Kim
authors.forename: Yon Ju
authors.initials: YJ
authors.lastname: Ryu
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Han
authors.forename: Young Gwan
authors.initials: YG
authors.lastname: Ko
authors.forename: Gyu Rak
authors.initials: GR
authors.lastname: Chon
authors.forename: Kwan Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Sang-Bum
authors.initials: SB
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000547:Amantadine / Q000008:administration & dosage / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D016638:Critical Illness; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology / Q000821:virology; D007723:Korea; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000008:administration & dosage / Q000627:therapeutic use*; D058873:Pandemics; D012121:Respiration, Artificial; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D012254:Ribavirin; D000547:Amantadine