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MULTIDRUG RESISTANCE INSALMONELLA TYPHI

Sweta Chomal, Lina Deodhar
Department of Microbiology, Bombay Hospital and Medical Research Centre, Mumbai 400 020.

Out of 3279 blood cultures processed in the Microbiology department, over a period of 1 1/2 years, 109 strains of Salmonella typhi (S. typhi) were isolated out of 558 positive blood cultures. Processing of the blood cultures was done by a Semi-automated machine, BACTEC 9050. 60.8 per cent strains were multi drug resistant and ampicillin, chloramphenicol, co-trimoxazole and tetracycline (ACCoT) was the commonest pattern of drug resistance. 66 per cent strains were resistant to nalidixic acid (NA), the first member of quinolone class of antimicrobial agents. Though none of the S. typhi strains showed resistance to ciprofloxacin, when tested by Kirby-Bauer disc diffusion method, it was observed that S. typhi resistant to NA showed increased Minimum Inhibiting Concentration (MIC) for ciprofloxacin.

Typhoid fever is endemic in India. Though the disease occurs throughout the year, there is a definite increase in the incidence during the rainy season (June to September).

Specific antimicrobial therapy for enteric fever became available in 1948 with the introduction of chloramphenicol. Chloramphenicol was the drug of choice for the treatment of typhoid fever till recently. Resistance to this drug was observed in England in 1950 and later on reported from Mexico, Vietnam and Kerala, India. Of late, there has been an emergence of multi drug resistant S. typhi (MDRST) strains throughout the world.[1]

An outbreak of enteric fever called ‘Dombivali Fever’ was reported from Mumbai in 1990[2] and the causative organism was MDRST. Due to the development of multi drug resistance and atypical presentation of the disease, typhoid fever is becoming difficult to diagnose unless aided by blood culture studies.

Most of the laboratories in India use conventional blood culture techniques for detecting bacteraemia. However, semi automated machines like BACTEC system, which are designed for rapid detection of bacteria in blood and sterile body fluids, are now available. With this system, identification of blood stream pathogen and results of antimicrobial susceptibility test can be made available to the clinicians in 48 hours.[3]

MATERIAL AND METHODS

3279 blood culture samples collected in BACTEC culture media were processed in the microbiology department, over a period of 1 1/2 years. Positive blood cultures (shown by a signal in BACTEC machine) were processed and the isolates were identified as S. typhi by standard biochemical methods and confirmed by slide agglutination with specific antisera. The antimicrobial susceptibility testing was carried out according to Kirby-Bauer method. The antimicrobial agents used for testing included ampicillin, chloramphenicol, cotrimoxazole, tetracycline, ciprofloxacin, nalidixic acid (NA) and ceftriaxone (third generation cephalosporin). Minimum Inhibitory Concentration (MIC) for ciprofloxacin was determined for the strains resistant to NA by agar dilution method.[4]

RESULTS

Out of 3279 blood culture samples, 558 blood cultures were positive and a total of 109 strains of S. typhi were isolated. All the strains were sensitive to ciprofloxacin and ceftriaxone while 60.8 per cent strains were multi drug resistant. Ampicillin, chloramphenicol co-trimoxazole and tetracycline (ACCoT) was the commonest pattern of drug resistance. 66 per cent strains were resistant to NA. The MIC range for ciprofloxacin was between 0.5-1 mcg/ml and 0.03 to 0.25 mcg/ml for S. typhi strains resistant and sensitive to NA respectively.

DISCUSSION

Multi drug resistance (MDR) in Salmonella typhi i.e. resistance to 3 or more antibiotics was observed in 60.8 per cent strains in the present study. Sanghavi et al from Pune[5] have reported 60 per cent MDRST and in their study 9.3 per cent strains were resistant to ciprofloxacin. Nadgir et al6 have reported 3 isolates (5.3 per cent) resistant to ciprofloxacin.

Though, none of the S. typhi strains showed resistance to ciprofloxacin in sensitivity pattern, 66 per cent strains were resistant to nalidixic acid (NA) and it was observed that for these strains MIC for ciprofloxacin was increased.

Several reports indicate multi drug resistant S. typhi with plasmid mediated block resistance to chloramphenicol, ampicillin and cotrimoxazole thriving in Mumbai.[2],[7] It is also evident now, that there is a gradual increase in the incidence of resistance to newer drugs like quinolones.[5],[6] Thus, when the sensitivity pattern indicates resistance to nalidixic acid which is a marker for delayed clinical response to fluoroquinolones, it is necessary to increase the oral dose of ciprofloxacin or treat the patient with third generation cephalosporin like ceftriaxone.[7],[8] In the present study, all the S. typhi strains were sensitive to ceftriaxone.


REFERENCES
  1. Ananthanarayan R, Panicker CKJ. ‘Text book of Microbiology’ Chapter 32, 4th Edition. Orient Longman Ltd. 1990; 277-92.
  2. Deodhar L, Bhave S, Agarwal A. ‘Bacteriophage typing of multi drug resistant Salmonella typhi in paediatric patients’. Bombay Hospital Journal 1993; 35 (4) : 114-15.
  3. Deodhar Lina. ‘Rapid detection of blood stream infections by BACTEC 9050’. Bombay Hospital Journal 1998; 40 : 573-74.
  4. Alex C, Leonard J. Gradwohl’s Clinical Laboratory methods and diagnosis, Chapter 75, 8th Edition. 1980; 2 : 1554.
  5. Sanghavi SK, Mane MP, Niphadkar KB. ‘Multidrug resistance in Salmonella serotypes’. Indian Journal of Medical Microbiology 1999; 17 (2) : 88-90.
  6. Nadgir S, Krishna BVS, Halesh LH, Tallur SS. ‘Multidrug resistant Salmonella typhi in Hubli.’ Indian Journal of Medical Microbiology 1998; 16 (4) : 185.
  7. Rodrigues C, Mehta A, Joshi VR. Quinolone resistant enteric fever - problems and remedies. JAPI 1998; 46 (8) : 751-52.
  8. Miller SI, Hohmann E, Pagues DA. Chapter 200 on Salmonella (including Salmonella typhi) in ‘Infectious Diseases’ Editors : GL Mandell, JE Bennett, R Dolin, Churchill Livingstone, 4th Edition. 1995; 2013-33.

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