Ciprofloxacin resistance in typhoid fever

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ASTNAIK S., BARIK B.K., ORAM G,, PADHAN P.

Abstract: Typhoid fever is widely prevalent in this part of Orissa. After multidrug resistance against the first line drugs chlormphenicol, ampicillin and co-trimoxazole, the emergence of chromosomally mediated quinolone resistance in typhoid fever has become a major concern in its treatment. Treatment failures with ciprofloxacin are being increasingly reported. 156 cases of Typhoid fever were admitted, out of them 802 cases were culture positive i.e. responded to ciprofloxacin. 18 cases did not responded to ciprofloxacin, as chloramphenicol was given in the dose of 50mg/kg for further 7 days. 10 cases responded to chloramphericol. 4 cases each responded to certriaxone and cefixime.

Key Word:  Ciprofloxacin, Salmonella typhi, Typoid fever.

Introduction:

Thyphoid fever is endemic in most developing regions, especially the Indian sub continent, South and Central America and Asia.

Thyphoid fever continues to be global health problem, with an estimated 13 to 17 million cases worldwide resulting in approximately 600,000 deaths per year ³. Children <1 year of age appear to be most susceptible to initial infection and to the development of severe disease. The increasing trend in the mortality and morbidity is due to factors like poor nutrition, poor environmental sanitation and inadequate treatment set-up. The standard textbook picture to typhoid fever is an exception rather than the rule. Typhoid fever is a common illness in this part of the state. The high incidence of typhoid fever is a common illness in this part of the state. The high incidence of typhoid fever acquired greater significance because of various spectrum of presentation and emergence of multidrug resistance led us to carry out a detailed study of typhoid fever cases.

Material and method:

            All the cases of fever (high grade) admitted to the medical wards of V.S.S. Medical College/Hospital, Burla with a provisional diagnosis of Typhoid fever, during the period of (January 20021 to December 2002) were taken up for the study.

            Patients with continuous fever for (more than 40⁰C) for at least 5 days were screened as potential cases for typhoid fever and subjected to thorough clinical and laboratory examination and those satifying at least 4 of the following criteria were taken up as study:

1.                  Splenomegaly.

2.                  Relative bradycardia (if within first week)

3.                  TLC<10,000/cubic mm)

4.                  Positive Culture (one or more)

a.                  Blood culture

b.                  Stool Culture

c.                  Urine culture

5.                  Serology

Positive Widal test ‘O’ titre (³ 320) or rising ‘O’ titre.

Observation:

            In the present study, diagnosis was made by isolation of Salmonella typhi in 54 cases. Half of the cases who had positive stool culture and all the three cases having positive urine culture had positive blood culture also.

            The various complications seen were as follows:

1.                  Typhoid encephalopathy (12.5%)

2.                  Pnemonia (2.5%)

3.                  Myocarditis (2.5%)

4.                  Gastrointestinal complications in the form of paralytic ileus (5%)

Response to treatment is indicated as follows:

                                    CIPROFLOXACIN (80 CASES)

                        Response                                          No response

(62 cases)                                          (18 cases)

                        Chloramphenicol       Ceftriaxone / Cefixime

                                         (10 cases)    (4 cases)     (4 caaes)

            The response to treatment of Salmonella typhi positive in 80 cases were

(a)               62 cases responded to ciprofloxacin

(b)               10 cases responded to chloramphenico.

(c)               4 cases each responded to ceftriaxone / cefixime

Discussion:

            Out of 80 cases, 56 were males and 24 were females. Most cases are reported among males than females, probably as a result of increased exposure to infection. Maximum number of cases were seen in the age group of 21 to 30 years. The epidemiological pattern confirm to the pattern found in the present study i.e. occurrence of maximal number of cases in the late summer and early rainy season when sources of water get contaminated by the still prevalent habit of open air defeacation by the side of ponds.

            Pyrexia is the sine-qua-non of typhoid. The duration of fever prior to enrolment was 5-30 days. Contrary to the text book picture of stepladder pyrexia, most of our patients had either continuous (47.5%) or intermittent (30%). 45% of cases had modereate grade of fever and 57.5% had associated chills and rigor. The next common presenting symptoms in order of frequency was headache (42.5%), vomiting (27.5%), loose motion (15%), altered sensorium (12.5) and cough (10%).

            4 patients presented with features of acute intestinal obstruction, who improved with conservative management contrary to what Patel and Panda had observed in 3.8% of cases ^16.

            Twenty two cases had moderate anaemia, while six cases had severe anaemia (<6 gn%). Total leucocyte count was within the normal range in most of our series (77.5). Only 8 cases had leucopenia and 16.5% of our cases showed leucocytosis, which signified complications like intestinal perforation and the other was pneumonia.

            Widal test was done in all cases of fever. 42.5% of cases showed an initial TO titre of 1:160, 31.2% showed that of 1:320m 23.7% of cases showed titre of 1:80 and 2.5% cases showed low titre 1:40. Out of the 18 cases, where repeat widal test was done, which showed 3 patients having the same titre, while rest patients showed fall in titre.

            Out of the 156 cases, isolation of S. typhi was positive in 80 cases including blood, stool and urine culture.

            With emergence to multi – dryg resistance to chloramphenicol , ampicillin and co-trimoxazole,drugs like fouoroquinolone and third generation cephalosporins gained importance. In fact, ciprofloxacin became synonymous with typhoid fever. However, a very disturbing trend surfaced in 1992, when news of ciprofloxacin resistance btoke out for the first time in Ukin a one –year old child who acquired the infiction from,India¹⁷. In UK, decreased sensitivity against S.typhi i.e MICs ( minimum in hibitory concentrations )of >0.25mg/ml  for ciprofloxacin was reported to have risen from 2.7%in 1995 to 1998.^7­­­

            Most clinician in India now believe that efficacy of ciprofloxacin had reduced over the years. In the light of currently available information, the positive fall out of indiscriminate use of ciprofloxacin is return of suspectibility to primary drugs like chloramphenicol.

            Out of 80 cultured positive cases, all cases were given ciprofloxacin in the dose of 750 mg twice daily for 10-14 days in adults or 200 mg intravenously twice for 7 days. 62 cases responded and became afebrile on 4-5^th day and the test 18 cases did not respond and subsequently changed to chloramphenical ( 50mg/kg )for further 7 days and were afebrile sithin 3-5 days. 4 caseseach responded to third generation cephalosporin (eg. Ceftriaxone, cefixime ).

Conclusion

            Typhoid fever remains a common cause of prolonged pyrexial illness in this part of the country. The classical picture given in standard textbooks of m,edicine has become very rare these days. A high index of suspicion is usually necessary to clinch the diagnosis in the absence of culture facilities.

            However, in the setting of inappropriate and inadequate treatment with antibiotics in the peripheral hospital, there is increased resistance to MDR strains and also to ciprofloxin. Therefore, close onservation is needed and proper antibiotic should be prescribed to prevent relapse as well as outbreak.

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