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Oseltamivir- Resistant Pandemic (H1N1)

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Oseltamivir- Resistant Pandemic (H1N1) LETTERS ated with hypoxia, edema, or other 8. Sánchez-Torrent L, Triviño-Rodriguez apy with tacrolimus and everolimus. unknown processes. However, the M, Suero-Toledano P, Claret-Teruel G, Thus, a 5-day regimen of oseltamivir Muñoz-Almagro C, Martínez-Sánchez L, patient had no history of hypotensive et al. Novel infl uenza A (H1N1) encepha- treatment was undertaken, and the pa- episodes, hypoxemia, abnormal meta- litis in a 3-month-old infant. Infection. tient’s clinical signs improved. bolic and toxic processes, and other in- 2010;38:227–9. DOI: 10.1007/s15010- However, 3 days after drug treat- fectious disease. In conclusion, IAAE 010-0014-3 ment was suspended, the child had a 9. Amin R, Ford-Jones E, Richardson SE, with pandemic (H1N1) 2009 may be MacGregor D, Tellier R, Heurter H, et relapse and exhibited fever, cough, caused by direct viral infection of the al. Acute childhood encephalitis and en- and mild respiratory distress. The CNS and, although its pathogenesis cephalopathy associated with infl uenza: patient had fi ne crackles in the left is not clear, physicians should remain a prospective 11-year review. Pediatr In- posterior basal lung, normal oxygen fect Dis J. 2008;27:390–5. DOI: 10.1097/ alert to this possibility. INF.0b013e31816507b2 saturation, and an infi ltrate in the 10. Ichiyama T, Isumi H, Ozawa H, Matsubara left basal lung, observed on chest Song Mi Moon, Sung-Han Kim, T, Morishima T, Furukawa S. Cerebrospi- radiograph. Infection with pandemic Min Hee Jeong, Eun Hye Lee, nal fl uid and serum levels of cytokines and (H1N1) 2009 virus was confi rmed. and Tae-Sung Ko soluble tumor necrosis factor receptor in infl uenza virus associated encephalopathy. He was then transferred to an isolated Author affi liation: University of Ulsan Col- Scand J Infect Dis. 2003;35:59–61. DOI: ward of the pediatric department, and lege of Medicine, Seoul, South Korea 10.1080/0036554021000026986 oseltamivir treatment was again initi- DOI: 10.3201/eid1611.100682 ated and dosages of immunosuppres- Address for correspondence: Sung-Han Kim, sive drugs were reduced. However, Department of Infectious Diseases, Asan no clinical or virologic responses References Medical Center, University of Ulsan College were observed during the 3 weeks of 1. Kitcharoen S, Pattapongsin M, Sawan- of Medicine, 388-1 Pungnap-2 dong, Songpa- drug administration. yawisuth K, Angela V, Tiamkao S. Neu- gu, Seoul 138-736, South Korea; email: Over the next month, the oral rologic manifestations of pandemic [email protected] dosage of oseltamivir was increased (H1N1) 2009 virus infection. Emerg In- fect Dis. 2010;16:569–70. DOI: 10.3201/ twice, without substantial effects on eid1603.091699 clinical course and viral clearance 2. Kuiken T, Taubenberger JK. Pathol- of the infection (Figure). Because ogy of human infl uenza revisited. Vac- of persistence of infection, the viral cine. 2008;26(Suppl 4):D59–66. DOI: 10.1016/j.vaccine.2008.07.025 neuraminidase gene was sequenced, 3. Ito Y, Ichiyama T, Kimura H, Shibata M, which showed the H275Y mutation Ishiwada N, Kuroki H, et al. Detection of Oseltamivir- (1). We immediately requested zana- infl uenza virus RNA by reverse transcrip- mivir aqueous solution from GlaxoS- tion PCR and proinfl ammatory cytokines Resistant Pandemic in infl uenza-virusassociated encephal- mithKline (Brentford, UK), and, after opathy. J Med Virol. 1999;58:420–5. (H1N1) 2009 the approval of the hospital’s ethics DOI: 10.1002/(SICI)1096-9071(199908) Treated with committee and parents’ consent were 58:4<420::AID-JMV16>3.0.CO;2-T obtained, nebulized treatment was car- 4. Franková V, Jirásek A, Tumová B. Type Nebulized Zanamivir A infl uenza: postmortem virus isolations ried out for 10 days. Fever and respira- from different organs in human lethal To the Editor: In late November tory symptoms and signs resolved af- cases. Arch Virol. 1977;53:265–8. DOI: 2009, a 3-year-old immunocompro- ter 6 days of treatment and progressive 10.1007/BF01314671 real-time PCR gave negative results. 5. Centers for Disease Control and Preven- mised boy experienced an upper respi- tion. Neurologic complications associ- ratory tract infection caused by infl u- Moreover, at the end of the treatment ated with novel infl uenza A (H1N1) virus enza A pandemic (H1N1) 2009 virus, period, chest radiograph did not show infection in children, Dallas, Texas, May as demonstrated by a positive result for abnormal fi ndings, and results of a he- 2009. MMWR Morb Mortal Wkly Rep. magglutination-inhibition assay were 2009;58:773–8. real-time PCR on a nasal swab speci- 6. Gonzalez BE, Brust DG. Novel infl uenza men. His medical history was notable positive for infl uenza. No zanamivir- A (H1N1) presenting as an acute febrile for a congenital intracardiac tumor; an related adverse events were observed, encephalopathy in a mother and daughter. ABO–incompatible heart transplant except for a mild bronchospasm that Clin Infect Dis. 2009;49:1966–7. DOI: responded to albuterol. 10.1086/649014 at 2 months of age; and an Epstein- 7. Webster RI, Hazelton B, Suleiman J, Mac- Barr virus–related humoral rejection Another notable point is that the artney K, Kesson A, Dale RC. Severe en- 20 months later that was treated with clinical course of the disease was not cephalopathy with swine origin infl uenza anti-CD20 and plasmapheresis and severe, although the child was immu- A H1N1 infection in childhood: case re- nocompromised and the infection per- ports. Neurology. 2010;74:1077–8. DOI: continuous immunosuppressive ther- 10.1212/WNL.0b013e3181d6b113 sisted for almost 2 months. However, Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 11, November 2010 1813 LETTERS infl uenza virus persistence, possibly and as compassionate therapy in 2 im- infection, emergence of resistant viral caused by inability of the child’s im- munocompromised adult patients who strains should be strictly monitored. mune system to clear the infection, underwent mechanical ventilation for In this context, recently developed and prolonged treatment with osel- severe pneumonia (4,5). Moreover, real-time PCRs for rapid screening of tamivir, led to the appearance of the successful use of intravenous zana- H275Y could be useful (8). Moreover, H275Y mutation. H275Y has been de- mivir in a critically ill child, who was although a direct cause and effect has scribed as the most common mutation immunosuppressed after allogenic not been confi rmed, this case suggests that confers oseltamivir resistance in stem cell transplantation and infected that aerosolized zanamivir solution pandemic (H1N1) 2009 infection and with oseltamivir-resistant pandemic can be considered as a therapeutic op- has been found in all the resistant iso- (H1N1) 2009 virus, has been reported tion in young children with mild re- lates reported worldwide (1). Consis- (6). In this latter case, the regimen was spiratory symptoms who are infected tent with previous reports (2), in the well tolerated and was associated with with oseltamivir-resistant infl uenza patient described here, antiviral drug a decrease in viral load. viruses. Additional studies should resistance arose early in the treatment Despite these results showing the be conducted in young patients with course. Retrospective analysis dem- effi cacy of zanamivir intravenous ad- more severe disease. onstrated the appearance of a mixed ministration, the inhalatory route for population after ≈2 weeks of drug use infl uenza virus–specifi c drugs should Financial support was provided to with a slow progression toward a pure be the fi rst choice, whenever pos- G.P. from Regione Veneto (Centro Re- H275Y variant. This latter fi nding may sible, because it delivers therapeutic gionale Specializzato per la genofenotip- be explained by other virologic char- molecules directly to the site of viral izzazione ed epidemiologia molecolare acteristics of this viral isolate, which replication, resulting in low systemic degli agenti da infezione per la diagnostica is currently undergoing deep sequenc- exposure. For this reason and because microbiologica e virale. Dgr n. 448 del ing of the full genome. of the mild severity of the patient’s 24.02.2009). Zanamivir represents the thera- disease, we decided to use zanamivir peutic option for patients infected solution nebulized by aerosol. The with the H275Y mutation of pandemic compliance to this treatment was eas- Liviana Da Dalt, (H1N1) 2009 virus. Its licensed for- ily achieved, and the therapy showed Arianna Calistri, mulation as a dry powder is suitable good effi cacy and was well tolerated Chiara Chillemi, only for patients who can actively use by the child. The minor side effect Riccardo Cusinato, inhaled drugs and thus cannot be used observed has already been reported in Elisa Franchin, Cristiano Salata, in children <7 years of age (3). Intra- the literature (7). Dino Sgarabotto, venous zanamivir solution has been In conclusion, our experience Giuseppe Toscano, reported to be safe and effective in ex- supports the view that in immuno- Antonio Gambino, perimental infl uenza A virus infection compromised patients with persistent and Giorgio Palù Author affi liations: University of Padova, Padova, Italy (L. Da Dalt, A. Calistri, C. Chil- lemi, E. Franchin, C. Salata, G. Palù); and Azienda Ospedaliera di Padova, Padova (R. Cusinato, E. Franchin, D. Sgarabotto, G. Toscano, A. Gambino) DOI: 10.3201/eid1611.100789 References 1. Centers for Disease Control and Preven- tion. World Health Organization. Pandem- ic (H1N1) 2009, update 91. 2010 Mar 12 [cited 2010 Mar 23]. http://www.who.int/ csr/don/2010_03_12/en/index.html. 2. Centers for Disease Control and Preven- tion. Oseltamivir-resistant novel infl uenza Figure. Schematic showing events surrounding oseltamivir-resistant pandemic (H1N1) A (H1N1) virus infection in two immuno- 2009 virus infection in 3-year-old immunocrompromised child, Italy, in relation to viremia suppressed patients.
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