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ORIGINAL ARTICLE
Year : 2005  |  Volume : 23  |  Issue : 2  |  Page : 125-127
 

Study of Clinical Profile and Antibiotic Response in Typhoid Fever


1 Department of Pharmacology, Kasturba Medical College, Mangalore, India
2 Department of Medicine, Kasturba Medical College, Mangalore - 575 002, India

Correspondence Address:
N K Chowta
Department of Medicine, Kasturba Medical College, Mangalore - 575 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.16054

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 ~ Abstract 

The objective of the present study is to evaluate the clinical profile and pattern of various drugs used in the treatment of typhoid fever. A retrospective analysis of adult patients suffering from typhoid fever was done at Kasturba Medical College hospital, Attavar during the year 1999-2001. Diagnosis of patients was based on clinical features, widal test and blood culture. The sensitivity pattern of isolates from blood culture was recorded. The mode of presentation, clinical course, treatment history, laboratory investigations reports, antibiotic administered, response to therapy and the complications were recorded. Total number of 44 cases of typhoid fever were studied. Out of these 21(47.7%) were males and 23(52.3%) were females. Average age of presentation was 23.9 years. Average duration of hospital stay was 10.8 days. Fever was present in all patients. Resistance of S. typhi to amoxicillin, chloramphenicol, ampicillin and co-trimoxazole were significantly high. Ciprofloxacin also showed resistance in 18.1% of cases. Sensitivity to cephalosporin was 100% in our study. Ciprofloxacin was the most commonly used antibiotic in our study (23 patients). Chloramphenicol alone was used in 2 patients and in 3 patients it was given after 6 days of ciprofloxacin treatment. Third generation cephalosporins(ceftriaxone) alone were used in 16 patients. Indiscriminate use of drugs in typhoid fever should be discouraged. Appropriate antibiotic as indicated by sensitivity tests should be employed to prevent the development of resistant strains of S. typhi.


Keywords: Resistance, S. typhi, clinical profile


How to cite this article:
Chowta M N, Chowta N K. Study of Clinical Profile and Antibiotic Response in Typhoid Fever. Indian J Med Microbiol 2005;23:125-7

How to cite this URL:
Chowta M N, Chowta N K. Study of Clinical Profile and Antibiotic Response in Typhoid Fever. Indian J Med Microbiol [serial online] 2005 [cited 2019 Oct 18];23:125-7. Available from: http://www.ijmm.org/text.asp?2005/23/2/125/16054


Typhoid fever occurs in all parts of the world where there is substandard water supply and sanitation. In India, it is endemic with morbidity ranging from 102 to 2219 per 100,000 population.[1] Today due to its changing modes of presentation, as well as the development of multidrug resistance, typhoid fever is becoming increasingly difficult to diagnose and treat. Improved standards of public health have resulted in a marked decline in the incidence of typhoid fever in developed countries.[2] The emergence of strains of Salmonella typhi resistant to multiple antibiotics poses a serious problem. Chloramphenicol was considered the antimicrobial gold standard for the treatment of typhoid fever till 1948.[3] But in the last two decades there has been increase in the resistance of strains of S. typhi to chloramphenicol. It was first reported in Britain, in 1950[4] and in India in 1972.[5] Gradually, resistance to multiple antibiotics developed.[6] The first major epidemic of multidrug resistant S. typhi was reported in 1972[7] in Mexico. Since then, an increasing frequency of antibiotic resistance has been reported from all parts of the world, but more so from the developing countries.[6] The uses of chloramphenicol, ampicillin and co-trimoxazole have become infrequent and quinolones have become the first line of treatment of typhoid fever. However, over the last few years there has been increase in the defervescence period in patients treated with quinolones. Hence, this study was undertaken to evaluate the clinical profile and antibiotic response in typhoid fever.


 ~ Materials and Methods Top


A retrospective analysis of adult patients suffering from typhoid fever was done at Kasturba Medical College hospital, Attavar during the year 1999-2001. Both males and females were included in the study. Diagnosis of patients was based on clinical features, widal test and blood culture. The sensitivity pattern of blood culture was recorded. The mode of presentation, clinical course, treatment history, laboratory investigations reports, antibiotic administered response to therapy and the complications were recorded. Defervescence was defined as the number of days required for abatement of fever after starting the antibiotics.


 ~ Results Top


A total number of 44 cases of typhoid fever were studied. Out of these 21(47.7%) were males and 23(52.3%) were females. Average age of presentation was 23.9 years. Average duration of hospital stay was 10.8 days. Fever was present in all patients (100%). Vomiting was present in 20.4% patients. Diarrhoea was seen in 20.4% patients. 11.3% patients had pain abdomen. Constipation was present in 9.09% patients. Hepatomegaly was detected in 18% patients and splenomegaly was present in 34.09% patients [Table - 1].

Myocarditis was observed in two patients and bleeding per rectum was seen in one patient. One of the patients died due to disseminated intravascular coagulation [Table - 2]. A single estimation of widal test was suggestive of enteric fever in significant titres in 88.6% cases (O titre of 1:160 or more). Blood culture was positive in 25% of cases. Malarial smear was positive in one of the patients and dengue antibody was positive in one patient. There was no luecopenia or thrombocytopenia in any patient.

Antibiotic sensitivity pattern in culture proven cases

[Table - 3] shows that resistance of S. typhi to amoxycillin, chloramphenicol, ampicillin and co-trimoxazole was significantly high. Ciprofloxacin also showed resistance in 18.1% of cases. Sensitivity to cephalosporin (ceftriaxone) was 100% in our study. In one of the patients, even though there was in vitro sensitivity to ciprofloxacin, patient did not respond to it, suggesting in vivo resistance.

Pattern of drug response

[Table - 4] shows pattern of drug response. Ciprofloxacin was the most commonly used antibiotic in our study (23 patients). Chloramphenicol alone was used in two patients and in three patients it was given after six days of ciprofloxacin treatment. Third generation cephalosporins (ceftriaxone) alone were used in 16 patients. In nine patients it was given after six days of ciprofloxacin treatment as there was no clinical response. Average duration of treatment was 12 days with ciprofloxacin, 14 days with chloramphenicol and 10 days with third generation cephalosporins. Steroids were given in two patients for myocarditis. Defervescence period was eight days with ciprofloxacin, 10 days with chloramphenicol and six days with third generation cephalosporins.


 ~ Discussion Top


Drug resistance in typhoid fever is considered as one of the important factors in the morbidity and mortality of the disease. Since the introduction of chloramphenicol in 1948, it has been the drug of choice in the treatment of typhoid fever in most parts of the world. But the indiscriminate use of the drug and acquisition of plasmid mediated R factor has led to the development of resistance to S. typhi against this drug.[8] Various reports from India and other tropical countries have shown widespread distribution of chloramphenicol resistant strains of S. typhi, the incidence varying from 38.6% to 83%.[9],[10] The emergence of chloramphenicol resistance posed a big problem regarding the treatment of patients with typhoid fever. Alternative drugs suggested included co-trimoxazole, ampicillin and amoxycillin. During 1990, drug resistant S. typhi not responding to chloramphenicol, ampicillin and co-trimoxazole appeared in various parts of the country, the incidence varying from 50 to 52.9%.[10] In our study, incidence of chloramphenicol resistance was found to be 63.6%. Resistance to amoxycillin, ampicillin and co-trimoxazole was also present in significant number of patients.

The quinolone group of drugs emerged as useful drugs for the treatment of multiple drug resistant cases of S. typhi . But unfortunately, the same factors of indiscriminate antibiotic use and cross resistance within the antibiotic group which led to the emergence of chloramphenicol resistant organisms are still operative. The resistance to quinolone is not plasmid coded but due to an altered DNA gyrase subunit. Resistance to ciprofloxacin is now being reported both from the Indian subcontinent and West.[11],[12] In the present study also S. typhi has shown resistance to ciprofloxacin in 18.1% of cases.

The defervescence period for ciprofloxacin is about 3- 5 days[13] according to the literature and for cephalosporin is about three days. But in the present study we have observed that the defervescence period was comparatively longer; about eight days for ciprofloxacin and about six days for cephalosporins. In one patient, although there was in vitro sensitivity to ciprofloxacin patient did not respond to the drug. These findings suggest that sensitivity of S. typhi to ciprofloxacin is gradually decreasing. Indiscriminate use of drugs is one of the important factors leading to drug resistance and in case of ciprofloxacin, moderate cost, advantage of oral route, tolerability, convenient dosage schedule have contributed towards its indiscriminate use. In our study, sensitivity to third generation cephalosporins was 100%, although study done by Ranju et al[14] has shown significant decrease in the in vitro sensitivity to cephalosporins. High cost of cephalosporins may not permit its indiscriminate use for minor infection.

To conclude, the indiscriminate use of drugs in typhoid fever should be discouraged. Appropriate antibiotic indicated by sensitivity tests should be employed to prevent the development of resistant strains of S. typhi.

 
 ~ References Top

1.Mehta PJ, Hakim A, Kamath S. The changing faces of salmonellosis. J Assoc Physicians India 1992:40 ;713.  Back to cited text no. 1    
2.Gulati PD, Saxena SN, Gupta PS, Chuttani HK. Changing pattern of typhoid fever. Am J Med 1968;45 ;544-8.  Back to cited text no. 2    
3.Wood Ward TE, Smadel JE, Ley HL, Green R. Preliminary report on beneficial effects of chloromycetin in treatment of typhoid fever. Ann Int Med 1948;29 ;131-4.  Back to cited text no. 3    
4.Calquhoun J, Weetch RS. Resistance to chloramphenicol developing during treatment of typhoid fever. Lancet 1950;2 :621.  Back to cited text no. 4    
5.Panicker CK, Vimla KM. Transferable chloramphenicol resistance in salmonella typhi. Nature 1973;239 :109.   Back to cited text no. 5    
6.Samantray SK. Typhoid fever resistant to furazolidine, Ampicillin, chloramphenicol and co-trimoxazole. Indian J Med Sci 1979;33 ;1-3.  Back to cited text no. 6    
7.Edelman R, Levine MM. Summary of an international workshop on typhoid fever. Rev Infect Dis 1986;8 :329-49.  Back to cited text no. 7  [PUBMED]  
8.Agarwal KC, PanHotra BR, Mahanta J. Typhoid fever due to chloramphenicol resistant S.typhi associated with 'r' plasmid. Indian J Med Res 1981;73 :484-8.  Back to cited text no. 8    
9.Anand AC, Kataria VK, Singh W. Epidemic of multiresistant enteric fever in eastern India. Lancet 1990;335 ;352.  Back to cited text no. 9    
10.Khosla SN, Samar A, Khosla P, Sabharwal U, Khosla A. Drug resistant typhoid fever. Trop Doc 1998:28 ;235-7.  Back to cited text no. 10    
11.Rowe B, Ward LR, Threlfall EJ. Ciprofloxacin resistant salmonella typhi in the UK. Lancet 1995;346 :1302.  Back to cited text no. 11  [PUBMED]  
12.Piddock LJ, Whale K, Wise R. Quinolone resistance in salmonella: Clinical experience. Lancet 1990;335 :1459.  Back to cited text no. 12  [PUBMED]  
13.Mandal BK. Salmonella infections. In : Cook G editor. Manson's tropical diseases. 20th Ed. London: WB. Saunders Company; 2001. p. 849-63.  Back to cited text no. 13    
14.Ranju C, Pais P, Ravindran GD, Singh G. Changing pattern of antibiotic sensitivity of salmonella typhi. Natl Med J Ind 1998;11 ;266-7.  Back to cited text no. 14    


Tables

[Table - 1], [Table - 2], [Table - 3], [Table - 4]

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