Oseltamivir for treatment and prophylaxis of influenza infection

Schirmer, Patricia; Holodniy, Mark

doi:10.1517/14740330902840519

Cited by 46 publications

(23 citation statements)

References 152 publications

(121 reference statements)

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“…Seasonal influenza viruses cause between 250,000 and 500,000 deaths annually (17). Among the various types and subtypes of influenza viruses circulating every year, the A/H3N2 subtype is associated with the most severe epidemics (8).…”

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confidence: 99%

The I222V Neuraminidase Mutation Has a Compensatory Role in Replication of an Oseltamivir-Resistant Influenza Virus A/H3N2 E119V Mutant

et al. 2011

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confidence: 99%

The I222V Neuraminidase Mutation Has a Compensatory Role in Replication of an Oseltamivir-Resistant Influenza Virus A/H3N2 E119V Mutant

et al. 2011

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“…Oseltamivir is administered orally, whereas zanamivir is inhaled (9) and is not recommended for use in severely ill patients and young children (15). An investigational NAI, peramivir, is currently undergoing phase II studies (33). NAIs mimic the natural substrate of neuraminidase (NA), sialic acid (N-acetylneuraminic acid), and competitively bind to the highly conserved NA active site, inhibiting the enzyme's key function of destroying the neuraminic acid-containing receptors, thus preventing the release of progeny virions from infected cells and dissemination to neighboring cells (28).…”

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confidence: 99%

Detection of E119V and E119I Mutations in Influenza A (H3N2) Viruses Isolated from an Immunocompromised Patient: Challenges in Diagnosis of Oseltamivir Resistance

Okomo-Adhiambo

Demmler-Harrison

Deyde

et al. 2010

Antimicrob Agents Chemother

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The clinical use of the neuraminidase inhibitor (NAI) oseltamivir is associated with the emergence of drug resistance resulting from subtype-specific neuraminidase (NA) mutations. The influenza A/Texas/12/2007 (H3N2) virus isolated from an oseltamivir-treated immunocompromised patient exhibited reduced susceptibility to oseltamivir in the chemiluminescent neuraminidase inhibition (NI) assay (ϳ60-fold increase in its 50% inhibitory concentration [IC 50 ] compared to that for a control virus). When further propagated in cell culture, the isolate maintained reduced susceptibility to oseltamivir in both chemiluminescent and fluorescent NI assays (ϳ50-and 350-fold increases in IC 50 , respectively). Sequencing analysis of the isolate revealed a mix of nucleotides coding for amino acids at position 119 of the NA [E119(V/I)]. Plaque purification of the isolate yielded E119V and E119I variants, both exhibiting reduced susceptibility to oseltamivir. The E119I variant also showed decreased susceptibility to zanamivir and the investigational NAIs peramivir and A-315675. The emergence of E119V variants in oseltamivir-treated patients has been previously reported; however, the E119I mutation detected here is a novel one which reduces susceptibility to several NAIs. Both mutations were not detected in unpropagated original clinical specimens using either conventional sequencing or pyrosequencing, suggesting that these variants were present in very low proportions (<10%) in clinical specimens and gained dominance after virus propagation in MDCK cells. All virus isolates recovered from the patient were resistant to adamantanes. Our findings highlight the potential for emergence and persistence of multidrug-resistant influenza viruses in oseltamivir-treated immunocompromised subjects and also highlight challenges for drug resistance diagnosis due to the genetic instability of the virus population upon propagation in cell culture.

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“…Decisions concerning antiviral therapy and quarantine measures require rapid results, since antiviral therapy should preferably be initiated within 24 h after the appearance of the patient's first clinical symptoms [1]. Historically, RT-PCR based on readout agarose gel techniques with subsequent hybridization for specificity, is labor intensive and not suited for generating data on large numbers of samples on a daily basis.…”

Section: Satisfying the Need For Rapid Diagnosis Of New Variant Influmentioning

confidence: 99%

Satisfying the need for rapid diagnosis of new variant influenza A H1N1

Vries

Schutten

2010

Expert Review of Molecular Diagnostics

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Oseltamivir for treatment and prophylaxis of influenza infection

Cited by 46 publications

References 152 publications

The I222V Neuraminidase Mutation Has a Compensatory Role in Replication of an Oseltamivir-Resistant Influenza Virus A/H3N2 E119V Mutant

The I222V Neuraminidase Mutation Has a Compensatory Role in Replication of an Oseltamivir-Resistant Influenza Virus A/H3N2 E119V Mutant

Detection of E119V and E119I Mutations in Influenza A (H3N2) Viruses Isolated from an Immunocompromised Patient: Challenges in Diagnosis of Oseltamivir Resistance

Satisfying the need for rapid diagnosis of new variant influenza A H1N1

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