Abstract

The objective of the study was to investigate current species distribution and growing antimicrobial resistance (AMR) of Shigella isolates for proper treatment. Shigellae, isolated from faecal samples in International Centre for Diarrhoeal Disease research, Bangladesh, Dhaka hospital in 2015, were tested for antimicrobial susceptibility by disc diffusion method to ampicillin, co-trimoxazole, ciprofloxacin, azithromycin, mecillinam, ceftriaxone/cefixime and meropenem. Extensively drug-resistant (XDR, resistant to 5 or 6 of 7 useful anti-Shigella drugs tested) Shigella isolates resistant to 6 drugs were analyzed for ESBL and AmpC phenotypes, plasmid profiles, R-plasmids transfer, blaSHV, blaTEM, blaCTX-M, blaOXA; and mphA, mphB, ermA, ermB, ermC, ereA, ereB, mefA and msrA genes by PCR; and clonality of S. sonnei by PFGE. Of 134 isolates cultured from 3722 (3.6%) diarrhoeal faecal samples, 46% were S. sonnei, 37% S. flexneri, 4% S. boydii, 5% S. dysenteriae and 7% non-typeable. Multidrug-resistant (MDR, resistant simultaneously to ≥3 drugs) S. sonnei were 95% compared to 66% (P<0.01) MDR S. flexneri including 18% & 14% XDR types, respectively. All isolates were susceptible to meropenem. Four (6%) S. sonnei, 2 (4%) S. flexneri and 1 (17%) S. boydii (total of 7 isolates) were six-drugs XDR; 5 of them had ESBL phenotypes. Three S. sonnei and 1 S. flexneri had blaTEM and blaCTX-M; 1 S. boydii had blaSHV, blaTEM and blaCTX-M; 1 S. sonnei had blaTEM β-lactamase. All but one S. flexneri had only mphA gene on 62-MDa conjugative-R-plasmid coding azithromycin resistance. PFGE identified MDR-S. sonnei Global III clade. Thus, MDR-S. sonnei replaced S. flexneri as predominant isolate in Dhaka, Bangladesh; many emerged as XDR strains requiring treatment by meropenem. The findings demand judicial use of antibiotics to contain emergence and spread of resistance locally and globally. Physicians should be informed about MDR and XDR Shigella for judicious prescribing of antimicrobial therapy.

Highlights

  • Shigella is one of the significant causes of diarrhoeal diseases globally with ~80 million cases and ~700,000 deaths/year, mostly occurring in developing countries [1]

  • Shigella isolates resistant to multiple first-line antimicrobial agents, such as sulphonamides, tetracycline, ampicillin, trimethoprim-sulphamethoxazole (SXT) and nalidixic acid have been reported from many countries including Bangladesh [2,3,4,5] resulting in difficulties in the selection of empirical therapy

  • Drug-resistant (XDR)-Shigella was defined as isolates resistant to 5 or 6 of 7 anti-Shigella drugs used for the treatment of shigellosis and tested for in-vitro antimicrobial susceptibility of Shigella in our laboratory

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Summary

Introduction

Shigella is one of the significant causes of diarrhoeal diseases globally with ~80 million cases and ~700,000 deaths/year, mostly occurring in developing countries [1]. Shigella isolates resistant to multiple first-line antimicrobial agents, such as sulphonamides, tetracycline, ampicillin, trimethoprim-sulphamethoxazole (SXT) and nalidixic acid have been reported from many countries including Bangladesh [2,3,4,5] resulting in difficulties in the selection of empirical therapy. Ciprofloxacin is recommended as the drug of choice by the World Health Organization for the therapy of first-line drug-resistant Shigella infections in both adults and children [1]. Multidrug-resistant (MDR; resistant to three or more classes of antimicrobial agents) Shigella isolates have been reported worldwide and few reliable treatment options exist, in developing countries. The recent acquisition of ciprofloxacin-resistance and/or extended-spectrum-cephalosporin-resistance and/or azithromycin-nonsusceptibility by the MDR Shigella isolates further narrows the choice of effective antimicrobial agents for treating shigellosis [4,5]

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