1 Department of Paediatrics A and 2 Unit of Infectious Diseases, Schneider Childrens 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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Keywords: diarrhoea, shigellosis, antibiotic therapy
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Introduction |
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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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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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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 trimethoprimsulfamethoxazole (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 (0.21%) and aminoglycosides (1%). Resistance to quinolones was noted (0.52%).
Of the 40 representative strains examined further, a single strain (2.5%) was ESBL-positive.
S. sonnei was more resistant than S. flexneri to trimethoprimsulfamethoxazole (97% versus 69%, P < 0.0001), ampicillin (87% versus 71%, P = 0.0164), both ampicillin and trimethoprimsulfamethoxazole (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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We compared the current (19982000) resistance rates of Shigella isolates with those over the years 19911992, 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 trimethoprimsulfamethoxazole and ampicillin increased to 94% and 85%, respectively, but it was already high (>80%) in 19911992, 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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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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Footnotes |
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References |
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