J Med Microbiol 54 (2005), 997-998; DOI: 10.1099/jmm.0.45993-0
© 2005 Society for General Microbiology
ISSN 0022-2615
Haemolytic uraemic syndrome due to ciprofloxacin-resistant Shigella dysenteriae serotype 1
Neelam Taneja,
Valarie W Lyngdoh and
Meera Sharma
Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
Correspondence Neelam Taneja drneelampgi{at}yahoo.com
Received December 22, 2002
Accepted July 3, 2005
A case of haemolytic uraemic syndrome following dysentery due to ciprofloxacin-resistant Shigella dysenteriae serotype 1 is reported for the first time. The increasing resistance of S. dysenteriae serotype 1 to many commonly available antimicrobial agents has implications for the management of dysentery. The choice of antimicrobial treatment for S. dysenteriae serotype 1 infections should take into account widespread drug resistance and the risk of haemolytic uraemic syndrome.
Abbreviations: HUS, haemolytic uraemic syndrome; STEC, Shiga-toxin-producing Escherichia coli.
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Introduction
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Shigellosis is an important cause of bloody diarrhoea in all age groups, especially in children. Of all serotypes of shigellae, Shigella dysenteriae type 1 attracts special attention for its epidemic-causing potential and its association with most serious dysentery cases, with a high attack rate, high case fatality rate and various complications (Bennish et al., 1990). Haemolytic uraemic syndrome (HUS) can be a sequela of infection with S. dysenteriae serotype 1, which characteristically expresses the Shiga cytotoxin (Raghupathy et al., 1978; Lopez et al., 1989).
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Case report
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A 2-year-old female child had fever and loose stools with mucus and blood beginning on 15 March 2004 in Chandigarh, North India. The child received ciprofloxacin in a peripheral hospital. However, there was no decrease in the severity of the symptoms, and subsequently on 20 March, the patient developed oliguria and haematuria. She was referred to the Advanced Paediatrics Centre in the Post Graduate Institute of Medical Education and Research, Chandigarh, on 21 March 2004 with a clinical diagnosis of acute renal failure.
On physical examination, the child was anaemic and irritable. Pedal oedema with petechial rash on the lower limbs was present. Laboratory tests at admission revealed abnormal renal functions (blood urea, 70 mg dl–1; creatinine, 2.5 mg dl–1), severe anaemia, thrombocytopenia and leukocytosis. A peripheral blood smear showed the presence of schistocytes. HUS was diagnosed based on findings of micro-angiopathic haemolytic anaemia, thrombocytopenia and renal failure. Peritoneal dialysis was done and ciprofloxacin was supplemented with amikacin. Stool samples for bacteriological culture were sent on 21 March 2004.
Shigella dysenteriae serotype 1 was isolated on 23 March 2004. Antimicrobial susceptibility testing was done by the Kirby-Bauer method (Bauer et al., 1995) and MIC testing was performed by the National Committee for Clinical Laboratory Standards agar dilution method (NCCLS, 2000). The isolate was found to be resistant to ciprofloxacin with a MIC of 8 µg ml–1. The other antibiotics to which resistance was observed were amoxycillin, nalidixic acid and co-trimoxazole, and the isolate was sensitive to cefotaxime, gentamicin, amikacin and furoxone. Ciprofloxacin was replaced with cefotaxime (50 mg kg–1 day–1) on 24 March 2004. The child responded to the treatment with cefotaxime and peritoneal dialysis. Subsequent stool samples for culture sent on 28 March 2004 were negative for S. dysenteriae.
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Discussion
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The triad of micro-angiopathic haemolytic anaemia, thrombocytopenia and acute renal failure characterizes HUS (Safdar et al., 2002). Although a variety of organisms have been implicated in the pathogenesis of post-diarrhoeal HUS (Siegler, 1995), most cases are due to Shiga-toxin-producing Escherichia coli (STEC) or, in regions such as South Asia and Africa, S. dysenteriae serotype 1 (Tarr et al., 2005; Koster et al., 1978).
HUS following diarrhoea caused by E. coli O157 : H7 is one of the most important causes of renal failure in childhood and has been well described. Studies from Europe and Americas have documented evidence of STEC infections in 33–60 % of patients with HUS (Karmali et al., 1983; Scotland et al., 1988; Lopez et al., 1989). However, in South-East Asia and Africa, HUS has been related to epidemics of S. dysenteriae type 1 (Raghupathy et al., 1978; Nathoo et al., 1995; Bhimma et al., 1997; Oneko et al., 2001; Nathoo et al., 1998). A 15-fold increase in incidence of HUS has been reported that coincided with an epidemic of S. dysenteriae 1 (Rollins et al., 1995). HUS has been reported to be a frequent complication during such outbreaks, with an incidence ranging from 14 out of 91 cases to almost one-third of cases (Oneko et al., 2001; Nathoo et al., 1998). HUS following shigellosis appears to be a much more aggressive and severe disease than HUS due to enterohaemorrhagic E. coli because of severe renal involvement with prolonged oliguria (Bhimma et al., 1997; Raghupathy et al., 1978; Koster et al., 1984; Bhuyan et al., 1985). The reported mortality (range 17.3–50 %) is also higher compared to the STEC infections, in which it is around 6 % (Bhimma et al., 1997; Remuzzi & Ruggenenti, 1995; Oneko et al., 2001).
There is agreement in the international literature that dysentery due to S. dysenteriae type 1 should be treated with antibiotics especially in tropical climates and/or when the course of disease is so severe that hospitalization is needed (Legros et al., 1999). A case control study conducted at the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh, showed that prior treatment with inappropriate antimicrobial drugs and elevated leukocyte count were factors associated with the development of HUS (Butler et al., 1987). In the same study, early initiation of appropriate antibiotic therapy in those with dysentery was shown to reduce the incidence of HUS. Most of the patients who had received treatment before admission, had received drugs that were ineffective against the infections because of bacterial resistance. In our case, the child was treated with ciprofloxacin prior to culture and antibiotic susceptibility testing. The use of inappropriate drugs in shigellosis may simply allow untreated disease to progress and may enhance the severity of disease. The increasing resistance to many of the more commonly available antimicrobial agents, including ciprofloxacin, in this geographical area presents a major dilemma in the management of dysentery due to S. dysenteriae 1. The choice of antimicrobial treatment for infections with S. dysenteriae serotype 1 should therefore take into account widespread drug resistance and the risk of HUS.
In conclusion, we reported a case of HUS due to ciprofloxacin-resistant S. dysenteriae serotype 1. To the best of our knowledge this is the first such report to be published. The risk of developing HUS may be further enhanced by widespread multi-drug resistant S. dysenteriae, leading to severe morbidity and mortality.
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References
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Introduction
Case report
