Above is the message which is being circulated around the world regarding the trial of Gatifloxacin on 390 typhoid patients in Patan Hospital by a team of our Nepali Doctors.

But I am horrified to read about Gatifloxacin and its side effects. This drug was withdrawn from the USA...

We didn't stop the trail. It was independent DATA Safety Monitoring board which advised us to stop the trial. They figured out following two points

achievment of clinical significance before target sample size
adverse effents (Mortality) in cefixime arm.


I am really saddened that not a single reader has brought up the issue that there was a MORTALITY in cefixime group. One of the reason why trial was stopped.

To the question of not measuring blood glucose level. The evidence before NEJM article in 2006 regarding dysglycemia was meagre (few case reports). By the time the NEJM article got published, the trial was already over and there was no point doing blood sugar level because most of the patients in the study had already compeleted six month follow up too. However , none of the followed up patients in gatifloxacin arm got admitted as they say gatifloxacin has serious dysglycemia requiring hospitalization.

We have 1000 patients' prospective data in which gatifloxacin is used (Nepal and Veit Nam combined) and none of them have dysglycemia which will be hopefully published soon.

Every one is focussing on gatifloxacin. I agree there are many questions to be answered regarding gatifloxacin. Another important hit of this study is showing the failure of cefixime which many of trust to work and have knee jerk reflex of prescribing it to the typhoid patients and the WHO still continues to recommend it. We got about 37.2% failure rate!!!!


It is very sensible to be concerned about clinical trail being done in countries like Nepal. However, Britol Mayer Squib or any other companies had no role whatsoever in conduct, design, interpretation and the conclusions of the study. It was funded by the Welcome Trust.

To the question of trial being done in the UK, whereelse would you expect to do trail of typhoid ? UK doesn't have very many typhoid patients to do a trail neither does the US. In the US there are 400 typhoid patients in a year seen in travellers only. It is our disease, we have the disease , we need the research , we need newer treatment as other flouroquinolones are failing. We didn't do this study to advocate on behalf of gatifloxacin. We were not compensated by the drug company for doing research either. There are few people who try to do greater good, sacrificing their own time and energy expecting that their work will fruit the help to many people around them need.

After this issue of dyglycemia came up, we have been following up patients treated with gatifloxacin with blood sugar level (another trail on the way), we didn't find any dysglycemia in any of the patients. We are equally concerned as you all are about the safety of the patients. If we were not, we would have continued the trail because stopping of trail is not considered favourable for the researchers.

I would love to answer any of the questions put forth if the questions are genuine.

About the drug being registered in the NEpal, we registered the drug in Department of Drug Administration for the trial purpose. It is upto DDA to approve it or not for commercial use. It is approved and widely used in INDIA and other countries for other purposes.

Anil Pandit, MD
Maryland General Hospital
University of Maryland Medical System
Baltimore, Maryland
USA

OVERALL WHAT WE WANT IS BETTER FOR HUMANKIND. SO, WE ALL ARE HERE FOR DISCUSSION SO THAT WE COULD LEARN SOMETHING FROM OUR SENIORS, DISCUSS THE MATTERS AND ENFORCE OURSELVES FOR THE QUALITY.

Though Most of my quires were underlooked by the author, i am happy that he is here for discussion.

Still... want to ask many things, but for the timebeing, Is this dysglycemia due to GATI is only during the treatment course ? or if somebody has , then is it lifelong ?

Professor Nicholas J White has posted his comment about the study in the PLos One web site with following link.
PLoS ONE : Publishing science, accelerating research

For those of you who want to know about Dr White, please visit following web link.
Nicholas J White

Have not read your article but will do as soon as I find time. But, reading your last reply, it is saddening to see a person 'who made such a big sacrifice for people around him' saddened when mortality issue was not addressed. I had a look around and found that Dr. AP need not be so sad. Rbeeneta had already brought up the issue.

Please answer her too. We will be grateful to you for that

You can view the article from the followin link
PLoS ONE: An Open Randomized Comparison of Gatifloxacin versus Cefixime for the Treatment of Uncomplicated Enteric Fever

You can view the comment on the article from the followin link
PLoS ONE : Publishing science, accelerating research

Ongoing discussion:-


Response by Nicholas White, Data and safety monitorin committee of this research

Thanks Angel for posting my reply to Prof. White on this thread before I could post it here.

The evidence available so far suggests that dysglycaemic effects are seen during the treatment and for first few weeks of treatment.

Reference:
Frothingham R. Glucose homeostasis abnormalities associated with the use of gatifloxacin. CID 2005; 41: 1269-76.
Zvonar R. Gatifloxacin induced dysglycemia. Am J Health Syst Pharm 2006; 63:2087-92.

I have been following the debate and discussion about Gatifloxacin trail for Enteric fever in Patan, Nepal.
At a face value, the article gives an impression of having a breakthrough in the management of Enteric Fever by this trial. I sincerely hope that this will prove to be far superior to other drugs currently available. However, there are many questions raised in this forum which have not been clarified and satisfactorily answered. Many people have contributed in this forum, but the bulk of discussion seems to be between Dr Anil Tuladhar (UK), and two authors: Dr Basnyat and Dr Pandit. Among others rbineeta (UK) has also raised some interesting points. As I am also working in UK, I would like to emphasize that this debate is not between the authors and some Nepalese doctors in the UK. The issues are not only about the results and outcomes, but they are also about how the trail is conducted. Regarding dysglycemia, I still struggle to understand why the investigators were so happy that they didn’t feel that blood glucose monitoring was warranted in these patients. I feel, although these patients were not diabetic, such an important side effect highlighted in the literature with severe consequences, should have been monitored. The question raised by Dr Pandit regarding one mortality in Cefixime group is already mentioned by rbineeta in the discussion.There are few more authors/investigators in this study, who are actually from UK. One author has much wider association with Vietnam, Oxford, and Manchester and also with Wellcome Trust. It would also be useful to read their views on Gatifloxacin, its safety, the limitations put on their marketing and use in the West. You may also be interested to read the press release by Wellcome Trust on 27 June 2007.
http://www.wellcome.ac.uk/doc_WTX038509.html
Let’s not forget that any drug or intervention carries risk of side effects and complications.
I hope that the decision of using any drug should be based on risk/benefit ratio, efficacy, and availability of particular drugs, and their safety record. I will be only too pleased to see if Gatifloxacin meets these criteria and can save many lives. But we need a robust evidence before we draw any firm conclusions. Finally, I am very pleased that so much of interest has been generated in this scientific discussion and I would like to thank everyone for their contribution in this healthy debate.

Following Dr Acharya's posting, I happened to surf Wellcome Trust website.

It is very interesting to see that one of the authors is the director of the Vietnam Unit and the replier to my posting in PLoS website is the director of the Southeast Asia Unit of Wellcome Trust.

You may recall that this study was funded by the Wellcome Trust.

Now, I will leave this to the readers to decide whether this amounts to Professional Conflict of Interest, which is not declared and repeatedly refuted by the Principal Investigators.

Read attached file which was published in the BMJ. Visit following section of PLoS website on "Conflict of Interest" too.

Attached Files

	conflict-of-interest.ppt (77.5 KB, 6 views)

I request readers to give input in the PLoS one website so that they can be formally addressed.

Anil Pandit

Has the discussion on the topic ended or has it been abandonded?

Thank you Dr. Anil Tuladhar for bringing to our attention to this topic and to the authors of the research for their answers but still, there are many issues that have not been adequately answered.

I have been following the discussion in PLoS One Website too but I cannot see answers to Dr. Tuladhar's queries. Or, am I looking at wrong site? Dr. Tuladhar was only once answered by NJ White but on further questioning, neither NJ White nor the authors posted any replies.

Can someone tell us what we are to expect next?