Dr. Santhosh Kumar in his present letter as well as in earlier four publications in this Joumal(1-4) wanted to establish his hypothesis that furazolidone is mainly a non-absorbable drug. Furazolidone does not attain significant serum concentration, therefore, it is not expected to be effective for the treatment of bacteriologically confirmed typhoid fever. He also hypothesized that bactericidal effect of furazolidone is limited only to the intestinal tract and it has the capacity to eradicate Salmonella' typhi when the organisms return back to the intestine during the second week of illness and thus resists re-entry of the organisms to the circulation which results in cure in some patients(1-4). Insignificant results of an open. trial of furazolidone for the treatment of bacteriologically confirmed typhoid fever is the genesis of his hypothesis(1). It is a fact that many of the clinical trials fail to show the desirable results if they are not properly designed (without inclusion and exclusion criteria, inclusion of patients of proper age group, favorable nutritional status of the study population, selection of patients in proper stage of illness). A referred clinical trial(1) falls under this category. Furthermore, inspite of observing insignificant results with furazolidone, another open clinical trial was also conducted by the same group of investigators which showed 40% cure rate(2) which was a little higher (7%) than the previous study(1). One should not expect good results if clinically severe cases (toxic, delirious, obtunded, stuporous, shock) and malnourished children are included in the study population.

Dr. Santosh Kumar referred to the review article of White(5) in all his five communications indicating the negligible serum level of furazolidone which does not have much capacity to eradicate S. typhi from the circulation. Without referring to the pharmacokinetic details, I would like to inform that White(5) mentioned just the re- verse view about serum concentration of furazolidone, i.e., it is well absorbed and achieves a significant level in blood and urine. Others also reported these favorable views(6,7).

In this context, I would also like to refer the results of some well designed, controlled, clinical trials of furazolidone for the treatment of typhoid fever which showed excellent clinical response as compared to chloramphenicol or trimethoprim-sulphamethoxazole(8-11). Gilman in his review also described that furazolidone has many of the characteristics of an ideal drug for treating typhoid fever(12).

To ignore the efficacy of furazolidone, Dr. Santhosh Kumar referred to low case fatality rate (around 12%) even in the pre- antibiotic era(1,3,4). Indirectly, he probably wanted to express that majority of the typhoid fever cases who were claimed to be cured by furazolidone actually. were cured automatically as typhoid fever is a self limiting disease. This opinion is not appropriate for therapeutic evaluation of drug which actually shows the shortening of the disease process. The referred clinical trials(8-11) showed that furazolidone had. the capacity to shorten the duration of illness.

Dr. Santhosh Kumar also mentioned that furazolidone therapy is not documented in reputed text books, I would like to refer Harrison's Principles of Internal Medicine(13) where it is mentioned that furazolidone is one of the drugs which can be used for the treatment of typhoid fever.

I personally believe that the patients should be treated according to the clinical judgement of the physicians. Simple clinically suspected, uncomplicated and short duration enteric fever may be treated with furazolidone.
 

P. Dutta,
Deputy Director and Head,
Division of Clinical Medicine,
National Institute of Cholera
and Enteric Diseases,
P-33, C.I.T. Road, Scheme XM,
Beliaghata, Calcutta 700010,
India.
E-mail: [email protected]
 

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