JAC Advance Access originally published online on January 6, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 427-429
© 2003 The British Society for Antimicrobial Chemotherapy
Growing antimicrobial resistance of Shigella isolates
1 Department of Paediatrics A and 2 Unit of Infectious Diseases, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, Petah Tiqva 49202; 3 Felsenstein Medical Research Centre, Petah Tiqva; 4 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; 5 Department of Clinical Microbiology, Rabin Medical Center, Petah Tiqva, Israel
Received 19 July 2002; returned 26 September 2002; revised 6 November 2002; accepted 7 November 2002
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Abstract |
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Appropriate antibiotic treatment of shigellosis depends on identifying resistance patterns. By studying Shigella isolates in central Israel from 1998 to 2000, and comparing with the period 1991–1992, we identified a significantly increased resistance to tetracycline (from 23% to 87%, P < 0.00001), high resistance to trimethoprim–sulfamethoxazole (94%) and ampicillin (85%) and emerging resistance to quinolones (0.5–2%). These data mandate local monitoring of resistance and its consideration in empirical therapy.
Keywords: diarrhoea, shigellosis, antibiotic therapy
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Treatment of shigellosis by appropriate antimicrobial agents has proven efficacious in shortening the duration of fever, diarrhoea and toxaemia,1,2 and apparently in reducing the risk of lethal complications as well.1 Concomitantly, the excretion of the pathogen in stools is shortened significantly, reducing spread of the infection.1,2 A major problem, however, is the increasing antibiotic resistance of Shigella spp.1 Although initially susceptible to many antimicrobial agents, Shigella isolates resistant to multiple agents have been reported.3–6 The changing resistance indicates the need for continuous monitoring of antibiotic resistance in order to update the recommendations for empirical antibiotic therapy of suspected shigellosis.1,7
The aims of the present study were to analyse current trends in antimicrobial resistance of Shigella isolates, to compare them with previous data and to suggest timely recommendations for empirical antibiotic therapy.
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Source of specimens
We evaluated 25 015 stool specimens submitted from 1998 to 2000 to the Laboratory of Clinical Microbiology at Rabin Medical Centre, which serves a paediatric and adult population of 
350 000. Only one Shigella isolate per patient per diarrhoeal episode was included in the analysis; there were no outbreaks during the study period.
Microbiological examination
The stool specimens were cultured on Salmonella-Shigella agar, Campylobacter agar and selenite broth. Shigella species were identified biochemically by standard methods8 and grouped serologically by slide agglutination with specific antisera (Wellcome Research Laboratories, Beckenham, UK). Antibiotic susceptibility was determined by the disc diffusion method according to the NCCLS,8 and MIC was determined by Etest (AB Biodisk, Solna, Sweden). Extended spectrum ß-lactamase (ESBL) production was tested according to NCCLS, using ceftazidime (30 µg) and combination ceftazidime/clavulanate (30/10 µg) discs, with a 
5 mm difference indicating positivity.8
Statistical analysis
The significance of differences in the proportions of antimicrobial resistance and of the relative prevalences of each Shigella species was determined by the 
2 test or the Fisher exact test (when the expected value in >20% of the cells was <5). Two-tailed tests were applied.
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Results |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Of the stool specimens examined, 617 (2.5%) isolates of Shigella spp. were identified.
Relative prevalence of the various Shigella species
Shigella sonnei was the predominant Shigella species: 560 isolates (90.8%), followed by Shigella flexneri (7.3%). Shigella boydii (1.6%) and Shigella dysenteriae (0.3%) were relatively rare.
Antimicrobial resistance during the study period (Table 1)
The Shigella isolates had high rates of resistance to trimethoprim–sulfamethoxazole (94%, MIC50 32 mg/L), tetracycline (87%, MIC50 16 mg/L, MIC90 128 mg/L) and ampicillin (85%, MIC50 256 mg/L). Resistance was low to chloramphenicol (4%), third-generation cephalosporins (0.2–1%) and aminoglycosides (1%). Resistance to quinolones was noted (0.5–2%).
Of the 40 representative strains examined further, a single strain (2.5%) was ESBL-positive.
S. sonnei was more resistant than S. flexneri to trimethoprim–sulfamethoxazole (97% versus 69%, P < 0.0001), ampicillin (87% versus 71%, P = 0.0164), both ampicillin and trimethoprim–sulfamethoxazole (84% versus 51%, P < 0.0001) and tetracycline (89% versus 73%, P < 0.001) (Table 1). Resistance was similarly low to the other antimicrobial agents.
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Comparison to previous years (Table 2)
We compared the current (1998–2000) resistance rates of Shigella isolates with those over the years 1991–1992, which constitute part of our previous report.4 Resistance increased during the 1990s. In particular, the resistance to tetracycline increased gradually from 23% to 87% (P < 0.00001), and resistance to trimethoprim–sulfamethoxazole and ampicillin increased to 94% and 85%, respectively, but it was already high (>80%) in 1991–1992, and the change did not reach statistical significance. Resistance to ciprofloxacin was noted only during the current period.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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The present study, covering the years 1998–2000, demonstrates the increasing antimicrobial resistance of Shigella isolates in central Israel. During the 1990s, resistance rates rose continuously. The resistance to antimicrobial agents used to treat shigellosis in young children, namely trimethoprim–sulfamethoxazole and ampicillin, reached 94% and 85%, respectively. The resistance to tetracycline, which is used in children older than 7 years, increased from 23% to 87%.
We have previously shown that the resistance rate observed in a hospital-based microbiology laboratory was similar to that in a large community-based microbiology laboratory.4 This was expected, since nearly all cases were community acquired, and the cultures were obtained on admission. This suggests that the resistance rates found in the present study are representative of the situation in the community.
By analysing trends in the resistance patterns of the various Shigella species, we found that S. sonnei is currently significantly more resistant than the other Shigella species in Israel, especially to the commonly used antimicrobial agents. This finding is of special importance because S. sonnei is at present the predominant species in Israel, the USA and other developed countries1,9,10 and is more common in children than in adults.10 In developing countries and low socio-economic conditions, S. flexneri is still the predominant serotype.1,2
Although resistance to fluoroquinolones has been rarely reported, nearly all Shigella isolates are susceptible to these agents.1 Indeed, quinolones, which are efficacious also against other causes of bacterial gastroenteritis, are often recommended as empirical therapy in areas with high resistance to Shigella. They are, however, not approved for children because of the potential risk of damage to growing cartilage.7 In children with severe shigellosis, especially in those who are hospitalized, parenteral ceftriaxone is effective and usually recommended. In milder cases in children, choosing the optimal oral therapy is more problematic and should be based on local epidemiological data. Nalidixic acid or extended-spectrum cephalosporins are usually adequate.
In conclusion, physicians should be aware of the high antimicrobial resistance rates of Shigella species, especially S. sonnei. Because resistance varies according to the specific location, continuous local monitoring of resistance patterns is necessary for the appropriate selection of empirical antimicrobial therapy. Additionally, susceptibility testing should be carried out on all clinical isolates, and the empirical antibiotic treatment changed accordingly.
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Acknowledgements |
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Presented in part at the Twentieth Annual Meeting of the European Society for Paediatric Infectious Diseases, May 2002, Vilnius, Lithuania.
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Footnotes |
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* Corresponding author. Tel: +972-3-9253680; Fax: +972-3-9253056; E-mail: ashai{at}post.tau.ac.il
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References |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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1 . Ashkenazi, S. (1999). Shigella spp. In Antimicrobial Therapy and Vaccines (Yu, V. L., Merigan, T. C. & Borriere, S. L., Eds), pp. 382–7. Williams & Wilkins, Baltimore, MD, USA.
2 . DuPont, H. L. (1988). Shigellosis. Infectious Disease Clinics of North America 2, 599–605.[Medline]
3 . Voogd, C. E., Schot, C. S., van Leeuwen, W. J. & van Klingeren, B. (1992). Monitoring of antibiotic resistance in shigellosis isolated in The Netherlands 1984–1989. European Journal of Clinical Microbiology and Infectious Diseases 11, 164–7.[CrossRef][Web of Science][Medline]
4 . Ashkenazi, S., May-Zahav, M., Sulkes, J., Zilberberg, R. & Samra, Z. (1995). Increasing antimicrobial resistance to Shigella isolates in Israel during the period 1984 to 1992. Antimicrobial Agents and Chemotherapy 39, 819–23.[Abstract]
5 . Replogle, M. L., Fleming, D. W. & Cieslak, P. R. (2000). Emergence of antimicrobial-resistant shigellosis in Oregon. Clinical Infectious Diseases 30, 515–9.[CrossRef][Web of Science][Medline]
6 . Mates, A., Eyny, D. & Philo, S. (2000). Antimicrobial resistance trends in Shigella serogroups isolated in Israel, 1990–1995. European Journal of Clinical Microbiology and Infectious Diseases 19, 108–11.[CrossRef][Web of Science][Medline]
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Bennish, M. L. & Salam, M. A. (1992). Rethinking options for the treatment of shigellosis. Journal of Antimicrobial Chemotherapy 30, 243–7.
8 . National Committee for Clinical Laboratory Standards. (2000). Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard M2-A7. NCCLS, Villanova, PA, USA.
9 . Green, M. S., Block, C., Cohen, D. & Slater, P. (1991). Four decades of shigellosis in Israel—the epidemiology of a growing public health problem. Review of Infectious Diseases 13, 248–53.[Web of Science][Medline]
10 . Ashkenazi, S., May-Zahav, M., Dinari, G., Gabbay, U., Zilberberg, R. & Samra, Z. (1993). Recent trends in the epidemiology of Shigella species in Israel. Clinical Infectious Diseases 17, 897–9.[Web of Science][Medline]
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