Furazolidone

Background & objectives: The resistance of enteropathogenic bacteria to commonly prescribed antibiotics is increasing both in developing as well as in developed countries. Resistance has emerged even to newer, more potent antimicrobial agents. The present study was therefore undertaken to report the current antibiotic resistance in common bacterial enteropathogens isolated in a tertiary care hospital in north India.

Methods: Faecal samples from 1802 patients were cultured for common bacterial enteropathogens and identified by standard methods. Antibiotic susceptibility was done by Stoke's disk diffusion method. The clinical and demographic profile of the patients was noted.

Results: Stool specimens from 119 (88 male, 31 female) patients yielded Shigella, Salmonella, Vibrio cholerae or Aeromonas. Fifty two per cent (62/119) of patients were children and 70 per cent were below the age of 5 yr. Twenty seven patients developed hospital acquired diarrhoea. Among all enteropathogens, Shigella spp. was the commonest followed by non-typhoidal Salmonella (27), K cholerae O1 El tor serotype Ogawa (19), Aeromonas spp. (14), Salmonella Typhi and S. paratyphi A (2 isolates each). Resistance to antimicrobial agents was common among all pathogens. Among shigellae an overall resistance of 63.6, 58.1 and 16.3 per cent was observed for nalidixic acid, cotrimoxazole and furazolidone respectively. Seven isolates of Shigella were resistant to ciprofloxacin, (18.5%) of non-typhoidal salmonellae were resistant to ciprofloxacin. V. cholerae were generally susceptible to tetracycline (only 1 isolate out of 13 resistant) and other drugs except nalidixic acid (89.5% resistance) and cotrimoxazole (77.8% resistance).

Interpretation & conclusion: Enteropathogens have developed high level resistance to first line agents used for empiric treatment of diarrhoea. Progressively increasing resistance to ciprofloxacin is a serious cause of concern.

Key words Antimicrobial resistance - enteropathogens

Infectious diarrhoeal diseases are responsible for considerable morbidity and mortality, especially in developing countries'. In India, one third of total paediatric admissions in hospitals are due to diarrhoeal diseases and 17 per cent of all deaths in indoor paediatric patients are diarrhoea related2. Though fluid and electrolyte replacement either by oral hydration or intravenous fluid therapy is the treatment of choice for acute diarrhoea, antibacterial agents are indicated for treatment of suspected shigellosis, invasive salmonellosis, traveller's diarrhoea and as adjuncts to rehydration in cholera. Since most cases of diarrhoea are treated empirically, it is important to know the susceptibility pattern of prevalent pathogens. In addition, the resistance of enteropathogenic bacteria to commonly prescribed antibiotics is increasing both in developing as well as developed countries. Resistance has emerged even to newer, more potent antimicrobial agents and is commonly seen in organisms like Salmonella, Shigella and Vibrio cholerae3-14. Therefore, the present study was undertaken to assess the current antibiotic resistance in common enteropathogens isolated in a tertiary care hospital in north India. Material & Methods

A total of 1802 faecal samples from the same number of patients suffering from diarrhoea submitted to the Department of Medical Microbiology, PGIMER, Chandigarh from January 2000 to September 2002 were processed for Salmonella, Shigella, V. choleras and Aeromonas spp. by standard bacteriological methods15. Isolates of Salmonella, Shigella and V. cholerae were confirmed by serotyping (Denka-Seiken, Japan).

Antibiotic susceptibility of enteropathogens was done by Stoke's disk diffusion method16. Escherichia coli NCTC 10418 originally obtained from Colindale and being maintained in our laboratory was used as the control strain. Antibiotics tested (concentration per disc in µg) were amoxycillin (100), amikacin (10), cefotaxime (30), chloramphenicol (30), ciprofloxacin (5), cotrimoxazole (25), gentamicin (10), furazolidone(300), nalidixicacid (30) and tetracycline (30). All culture media except thiosulphate citrate bile-salt sucrose (TCBS) and antibiotic discs were obtained from Hi-Media Laboratories, Mum bai, India. TCBS was obtained from Difco Laboratories, Detroit, Michigan.

Patients' clinico-demographic details were noted wherever available. These included age, sex, ward/OPD, presenting clinical features and underlying illness. Diarrhoea was considered to be hospital acquired if it developed after 72 h of admission and patient did not have it at the time of admission.

Results & Discussion

Stool specimens from 119 (88 males, 31 females) of 1802 patients yielded Shigella, Salmonella, V. cholerae or Aeromonas. Children (62/119) and adults (57/119) were equally affected. Of the 62 children, 32 (52%) were below the age of 2 yr and 49 (70%) were less than 5 yr old. The ward : OPD ratio was 3.1:1. Presenting clinical features were available only for 93 patients. Fifty two presented with acute watery diarrhoea; 11 had dysentery; one patient each presented with chronic diarrhoea, recurrent diarrhoea and acute exacerbation of ulcerative colitis, and 27 developed hospital acquired diarrhoea (HAD). Of these 27 patients, 12 had haematological malignancies, 4 were post renal transplant patients, 4 had renal failure, 2 each had hepatitis and congenital anomalies of the gastrointestinal tract, 1 each had sepsis, meningitis and pyoderma. The isolates from patients with HAD were Aeromonas spp. (9), non-typhi Salmonella (8), S. flexneri (8), S. dysenteriae (1) and S. sonnei (1). There was a small outbreak of Aeromonas spp. in the Haematoncology unit involving 6 patients. The outbreak was due to cross-infection from the index case. Apart from this, there was no clustering of cases. Therefore it was difficult to trace the source of infection in rest of patients with HAD.

Among all enteropathogens, Shigella spp. (55) was the commonest followed by non-typhoidal Salmonella (27), V. cholerae O1 El tor, serotype Ogawa (19) and Aeromonas spp. (14). Salmonella Typhi and S. Paratyphi A were isolated from 2 patients each. Among shigellae, S. flexneri was the most common serogroup (65.5% of all shigellae) followed by S. boydii and S. dysenteriae (12.7% each) and S. sonnei (9.1%) (Table). Serogroup distribution can vary according to geographic region and at the same centre over a period of time17. At our centre, a decrease in isolation of S. dysenteriae has been noticed from 57 per cent in 1991-94(17) to 12.7 percent in the present study. Isolation of S. flexneri has increased from 35.8 per cent in 1991-94(17) to 65.5 per cent at present. In a recent study conducted at Vellore13 S. flexneri followed by S. sonnei were the commonest serogroups.

Resistance to antimicrobial agents was common among all pathogens (Table). Fifty one isolates (42.9%) were multi-drug resistant (resistant to 3 or more commonly used antibiotics). Among shigellae, an overall resistance of 63.6, 58.1 and 16.3 per cent was observed for nalidixic acid, cotrimoxazole and furazolidone. Resistance to nalidixic acid has increased from 7.4 per cent during 1994-98(18) to the present 63.3 per cent whereas resistance to furazolidone has decreased over the years. This is due to widespread use of nalidixic acid as the first line agent for empiric treatment of infectious diarrhoea in children and ever decreasing use of furoxone. Seven strains (S. flexneri 5, S. dysenteriae T) were resistant to ciprofloxacin. Ciprofloxacin resistance, though uncommon in shigellae has also been reported from other parts of India14,19,20.

Multi-drug resistant non-typhoidal Salmonella spp. are widespread all over the world12,21,22. In the present study resistance to amoxycillin, nalidixic acid, cotrimoxazole, cefotaxime, chloramphenicol and ciprofloxacin was 62.5, 66.7, 34.6, 48.1, 37 and 18.5 per cent respectively. In a multicentric study, proportion of Salmonella spp. resistant to chloramphenicol, cotrimoxazole, furazolidone and tetracycline was higher in Goa, India as compared to Kenya and Jamaica8. In the present study though the antimicrobial resistance in various isolates is still high, a decrease from previous study (1994-98)'8 was noted except for ciprofloxacin which has increased from 13 per cent (1994-98)18 to 18 per cent in the present study.

V. cholerae isolates were generally susceptible to tetracycline (only 1 of 13 isolates resistant) and other drugs except nalidixic acid (89.5% resistance) and cotrimoxazole (77.8% resistance). Resistance pattern of V. cholerae Ol at our centre was different from that reported from other parts of India as none of our isolates were resistant to amoxycillin23,24. A study from Calcutta23 reported an increase in resistance to ampicillin, cotrimoxazole and nalidixic acid from 1994 onwards and all isolates of V. cholerae Ol were uniformly resistant to furazolidone and streptomycin. However, similar to findings from our centre, isolates were largely susceptible to gentamicin and tetracycline. Intermediate level resistance to ciprofloxacin reported from Calcutta23, was not seen in our isolates. Drug resistance observed in isolates ofAeromonas spp. was similar to a study from Goa, India where resistance to ampicillin, cotrimoxazole and nalidixic acid was 98, 91 and 197 .7 per cent respectively25.

To conclude, enteropathogens have developed high level of resistance to first line agents used for empiric treatment of diarrhoea. Progressively increasing resistance to ciprofloxacin is a serious cause of concern. There is a great need to reduce the indiscriminate use of this potent antibiotic, the drug of choice for serious endemic infections like enteric fever. Some degree of regulation of antimicrobial use is necessary as most of antibiotics are available over the counter and can be bought without any prescription. There is a need to educate both the general public and the health practitioners that most diarrhoeas do not require antibiotics. Periodic monitoring of drug resistance in enteropathogens should be carried out in different geographic areas so that an appropriate agent can be chosen for empiric therapy.

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Neelam Taneja, Balvinder Mohan, Sumeeta Khurana & Meera Sharma

Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

Received August 11, 2003

Reprint requests : DrNeelam Taneja, Assistant Professor, Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India

e-mail: drneelampgi@yahoo.com

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