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40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)

17-20 September, 2000, Toronto, Ontario, Canada
Poster # 1214

High prevalence of resistance in shigellae in European part of Russia

L.S. STRATCHOUNSKI1, O.I. KRETCHIKOVA2, M.V. SUKHORUKOVA2, A.S. IVANOV1, A.V. DEKHNITCH1
1 Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Smolensk, Russia
2 Smolensk Regional Centre for Sanitar and Epidemiological Surveillance, Smolensk, Russia

The PDF format poster (61 kb)




ABSTRACT

Background: Shigellosis is an increasing cause of bacterial diarrhoea and hospitalisation in the European part of Russia. Effective antimicrobial therapy can reduce the severity and duration of illness and prevent potential complications. However data on susceptibility of Shigella spp. to antimicrobials in Russia are very limited. The objective of this study was the determination of the antimicrobial resistance of Shigella spp. isolated in the European part of Russia.

Methods: The total of 132 strains of S. flexneri and 69 strains of S. sonnei isolated in Smolensk Region and in Moscow during 1998-1999 were tested to 9 antimicrobials: ampicillin (AM), ampicillin/sulbactam (AMS), cefotaxime (CTX), tetracycline (TE), chloramphenicol (CL), nalidixic acid (NLA), norfloxacin (NOR), ciprofloxacin (CIP), trimethoprim/sulfamethoxazole (SXT) by agar dilution method. All procedures and interpretation of the results were performed according to the NCCLS guidelines.

Results: High rates of antimicrobial resistance were found in both S. flexneri and S. sonnei, respectively: SXT (97.7% and 94.2%), TE (98.5% and 92.8%), CL (93.9% and 50.7%), AM (95.5% and 26.1%) and AMS (94.7% and 23.2%). No resistance to NLA, NOR, CIP and CTX was determined. High rates of multiresistance (to 3 and more antimicrobials) were showed: 95.5% and 63.8% in S. flexneri and in S. sonnei, respectively. Among S. flexneri 88.6% of strains were characterized by the AM, AMS, CL, TE, SXT phenotype of resistance and 37.7% of S. sonnei strains had SXT, CL, TE resistance phenotype.

Conclusions: Commonly prescribing in Russia for treatment of shigellosis antimicrobials such as AM, CL, TE and SXT have lost their efficacy against Shigella spp. and can not be recommended for the empirical therapy of shigellosis. Quinolones and III generation cephalosporins can be considered as drugs of choice for the treatment of shigellosis.


INTRODUCTION

Bacillary dysentery is a severe inflamation of the large intestinum caused by enteroinvasive bacteria belonging to the genus Shigella. The disease is endemic throughout the world, and one of the leading causes of the hospitalisation of patients with diarrhoea in Russia. Current epidemiological and socio-economical situation in Russia is promoting the morbidity associated with Shigella spp. Moreover, the incidence of severe forms and complications is also increased. Official data show the prevalence of bacterial dysentery in Russia in 1999 constituted 148.2 cases per 100,000, compared to 78.0 cases in 1998, reached 138.822 for 1999 and 99.27 versus 70.12 and 187.83 in Smolensk region in 1998 and 1999, respectively.

Effective antimicrobial therapy can reduce both the severity and duration of illness and can prevent potential complications. Over the years, in many parts of the world Shigella spp. have acquired resistance to the commonly used antimicrobials, resulting in treatment failure and increased mortality. But for the time beeng there are limited data on antimicrobial resistance of shigellae in Russia.


METHODS

The total of 132 strains of Shigella flexneri and 69 strains of Shigella sonnei isolated in Smolensk Region and Moscow during 1998-1999 from hospitalised patients were included in the study. Activity of of 9 antimicrobials: ampicillin (AM), ampicillin/sulbactam (AMS), cefotaxime (CTX), tetracycline (TE), chloramphenicol (CL), nalidixic acid (NLA), norfloxacin (NOR), ciprofloxacin (CIP) and sulfamethoxazole/trimethoprim (SXT) against above strains has been determined by agar dillution. All procedures and interpretation of results were provided according to NCCLS guidelines (January 2000). Reference strains E.scherichia coli ATCC 25922 and ATCC 35218 were used as a control strains for susceptibility testing procedures.


RESULTS

According to the study results, majority of the cases of shigellosis in Smolensk Region and Moscow are caused by S. flexneri 2a and S. sonnei. High rates of resistance to SXT (97.7% and 94.2%), TE (98.5% and 92.8%) and CL (93.9% and 50.7%) were found in both S. flexneri and S. sonnei, respectively (see Table). S. flexneri were significantly more resistant to AM than S. sonnei (95.5% vs. 26.1%). Addition of a b-lactamase inhibitior sulbactam did not improve activity of AM - 94.7% and 23.2% of strains of S. flexneri and S. sonnei were resistant to AMS, respectively. At the same time no resistance to quinolones (NAL, NOR and CIP) and III generation cefalosporins (CTX) have been determined. Distribution of resistanse of tested strains did not differ significantly in Smolensk and Moscow.

The MIC for 50% and 90% of tested strains as well as MIC ranges are given in the Table presented below.


Table. Susceptibility of Shigella flexneri and Shigella sonnei to tested antimicrobials

Antibiotic S. flexneri (n=132) S. sonnei (n=69)
MIC50 mg/L MIC90 mg/L MIC ranges mg/L R % MIC50 mg/L MIC90 mg/L MIC ranges mg/L R %
Ampicillin 256 >256 2->256 95.5 4 256 2->256 26.1
Ampicillin / sulbactam 16 128 1-256 94.7 2 32 1-64 23.2
Cefotaxim 0.12 0.12 0.015-8 0 0.03 0.06 0.015-0.12 0
Nalidixic acid 2 4 1-4 0 2 4 0.5-4 0
Norfloxacin 0.12 0.12 0.015-1 0 0.03 0.12 0.008-1 0
Ciprofloxacin 0.015 0.03 0.004-0.25 0 0.008 0.03 0.002-0.12 0
Chloramphenicol 64 256 1->256 93.9 16 256 4->256 50.7
Tetracycline 128 256 1->256 98.5 128 256 1->256 92.8
Sulfamethoxazole / trimethoprim 128 128 0.25->128 97.7 128 128 0.5->128 94.2

High rates of multiresistance (to 3 and more antimicrobials) have been observed: 95.5% and 63.8% in S. flexneri and S. sonnei, respectively. Among S. flexneri 88.6% of strains were characterized by AM, AMS, CL, TE, SXT phenotype of resistance and 37.7% of S. sonnei strains had SXT, CL, TE resistance phenotype.


DISCUSSION

The main problem in the antibacterial therapy of this disease seems to be the high level of resistance of shigellae to antimicrobials that are commonly used for treatment of bacterial diarrhoea in Russia. For instance nearly all strains now are resistant to AM, SXT, TE and CL. Surprisingly low activity of anpicillin/sulbactam can be explaned by production of inhibitor-resistant b-lactamases such as OXA and PSE, but this hypothesis is needed to be proved by molecular methods. Another problem is a high prevalence of multiresistance (to 3 and more antimicrobials): majority of strais were highly resistante at the same time to SXT, TE and CL and in additition - to AM in the case of S. flexneri. However, quinolones, fluoroquinolones and III generation cephalosporines remain highly active against all tested strains.


CONCLUSIONS

  • Commonly prescribed in Russia for treatment of shigellosis antimicrobials such as ampicillin, chloramphenicol, tetracycline and trimethoprim/sulfamethoxazole lost its efficacy against Shigella spp. and can not be recomended for the empirical therapy of shigellosis.
  • Quinolones and III generation of cephalosporins should be considered as drugs of choice for the treatment of shigellosis.


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