Tuesday, May 28, 2013

The Lancet: Antiviral Resistance In Two H7N9 Patients



# 7328


On Sunday, in The Taiwan H7N9 Patient & Antiviral Resistance, we looked at Taiwan’s only H7N9 patient, who spend more than a month in the hospital, and who developed resistance to oseltamivir while undergoing treatment.


Today, the Lancet carries a report of two more cases (out of 14 studied) – this time in Shanghai – who developed resistance to our first line antivirals during their course of treatment for the H7N9 virus.


The authors found that a mutation R292K (Arginine to Lysine at position 292 in the NA) – also known as Arg292Lys – already known to confer antiviral resistance to seasonal flu (see Resistant influenza A viruses in children treated with oseltamivir: descriptive study), appeared in two patients after several days of oseltamivir therapy.


The article, which is available as a PDF file, is called:


Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance

Yunwen Hu, Shuihua Lu, Zhigang Song, Wei Wang, Pei Hao, Jianhua Li, Xiaonan Zhang, Hui-Ling Yen, Bisheng Shi, Tao Li, Wencai Guan, Lei Xu, Yi Liu, Sen Wang, Xiaoling Zhang, Di Tian, Zhaoqin Zhu, Jing He, Kai Huang, Huijie Chen, Lulu Zheng, Xuan Li, Jie Ping, Bin Kang, Xiuhong Xi, Lijun Zha,Yixue Li, Zhiyong Zhang, Malik Peiris, Zhenghong Yuan

Interpretation: Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of  NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor  clinical outcome.


The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning.



While most of the H7N9 patients we’ve had information about appear to have benefited from oseltamivir treatment, we have seen a worrying number of failures.


Helen Branswell has more on this in her article:


Study warns drug resistance develops easily with new H7N9 bird flu

By: Helen Branswell, The Canadian Press

Tuesday, May. 28, 2013 at 8:01 AM |

TORONTO - A new study warns that resistance to the main flu drug Tamiflu seems to develop easily in infections with the new H7N9 bird flu.


The authors say early treatment with Tamiflu or other drugs in that class is still the best approach for treating these cases when they arise.

(Continue . . . )




Of note, both patients received relatively low-dose corticosteroid treatment (40mg/day) during part of their hospitalization, and researchers question whether this might have contributed to their development of resistance.


Higher dose steroid treatment (250-500+ mg/day) has been tried for both H5N1 and SARS in the past. While patients often showed showed short-term improvement, long-term survival rates were less than encouraging. 


The good news here is we are getting patient treatment and outcome data on these H7N9 infections from China with remarkable speed, and in far greater detail, than we ever did for H5N1 or SARS.


Which means that if this virus does manage to spread beyond the Chinese mainland, doctors around the world will have a much better idea of what they will be dealing with.

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