Emergence of Extensively Drug-resistant Shigella sonnei in Bangladesh

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, bla SHV , bla TEM , bla CTX-M , bla OXA; 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 bla TEM and bla CTX-M ; 1 S. boydii had bla SHV, bla TEM and bla CTX-M ; 1 S. sonnei had bla TEM 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.

Genotypic and phenotypic profiles of antibiotic‐resistant bacteria isolated from hospitalised patients in Bangladesh

“…In Bangladesh, many infectious diseases such as pneumonia, diarrhoea and typhoid are treated with azithromycin, an antimicrobial readily available over the counter. The observed frequent detection of ermB appeared concordant with results from studies reporting ermB detected from S. Typhi [14], S. pneumoniae [15] and Shigella sonnei [45]. Notably, we also detected other macrolide resistance genes such as ermC and ermF.…”

Antibodies Elicited by the Shigella sonnei GMMA Vaccine in Adults Trigger Complement-Mediated Serum Bactericidal Activity: Results From a Phase 1 Dose Escalation Trial Followed by a Booster Extension

“…Several vaccine candidates, developed using different techniques, are under investigation (21)(22)(23)(24)(25), but no vaccine is widely available. However, the morbidity of the disease coupled with the rise of antimicrobial resistance (26,27) urges for the introduction of an effective vaccine.…”

Multiple Mechanisms Confer Resistance to Azithromycin in Shigella in Bangladesh: a Comprehensive Whole Genome-Based Approach

“…The emergence of the invasive mph (A) gene in Shigella has long been postulated by several studies from Europe, the United States, and Asia ( 12 , 14 , 15 ). One study in Bangladesh reported the presence of the mph (A) gene as one mechanism of AZM resistance in Shigella ( 15 ).…”

“…The emergence of the invasive mph (A) gene in Shigella has long been postulated by several studies from Europe, the United States, and Asia ( 12 , 14 , 15 ). One study in Bangladesh reported the presence of the mph (A) gene as one mechanism of AZM resistance in Shigella ( 15 ). Our investigation conveys a clear message that the mph (A) gene appears to play a key role in the rising AZM resistance among Shigella in Bangladesh.…”

“…However, recent global reports show a worsening scenario of decreased susceptibility to AZM in Shigell a spp. ( 12 – 15 ). About 67% of Shigella sonnei isolates were reported to be AZM resistant in a recent observational study conducted in Bangladesh ( 11 ).…”