Table 1.
Clinical isolates of influenza B virus with NA mutations resulting in decreased susceptibility to FDA-approved NAIs.
| NA mutation and function a |
Method of testing b |
Susceptibility to NAIs (range fold difference) c |
Patient information |
||||
|---|---|---|---|---|---|---|---|
| Oseltamivir | Zanamivir | Age (years) |
Immune status |
NAI treatment (days of treatment prior to resistance) |
Reference | ||
| Catalytic mutation | |||||||
| R152K | FL | 100-187 | 28-70 | 1.5 | IC | zanamivir (14) | Gubareva et al., 1998, 2001 |
| Framework mutation | |||||||
| D198N | FL | 9.2 | 9.4 | 2 | IC | oseltamivir (27) | Ison et al., 2006 |
| D198N d | FL | 2.8 - 3.5 | 7.2 - 9.3 | 1, 6, 8 | -- | oseltamivir (0) | Hatakeyama et al., 2007 |
| I222T d | FL | 6.1 - 7.1 | 3.4 - 4.5 | 3, 5, 6 | -- | oseltamivir (0) | Hatakeyama et al., 2007 |
| H274Y | CL | 11.4 | 1 | 33 | -- | no treatment (0) | Higgins et al., 2012 |
| N294S | FL | 23 | S | 7 | IC | oseltamivir (0) | Carr et al., 2011 |
| Other mutation | |||||||
| G109E | CL | 5.5 | 3.6 | 87 | -- | oseltamivir (3) | Bastien et al., 2011 |
| E105K | CL | 4.2 | 14.6 | 35 | -- | no treatment (0) | Fujisaki et al., 2012 |
| S250G | FL | 0.7 | 29 | 22 | -- | no treatment (0) | Hatakeyama et al., 2007 |
| G402S | FL | 3.9 | 7.1 | 7 | -- | oseltamivir (3) | Hatakeyama et al., 2007 |
a
The function of NA mutation is based on Colman et al. (1989), N2 numbering.
b
Fold difference in mean IC50 values derived from FL, fluorescence-based or CL, chemiluminescence-based assay.
c
Fold difference as compared to mean IC50 value of susceptible isolates.
d
Cluster of 3 patients.
Abbreviations: S, susceptible; IC, immunocompromised patient (leukemia); -- immunocompetent patient.