Shigellosis remains a significant public health concern, particularly in children under 5 years of age in developing countries like Bangladesh. Azithromycin (AZM) has been the first-line treatment for shigellosis in Bangladesh, with ciprofloxacin (CIP) and ceftriaxone (CRO) also commonly used. This study aims to assess the current epidemiology of antimicrobial resistance (AMR) and investigate the mechanisms driving the increase in macrolide resistance in Shigella spp. in Bangladesh.
Key Scientific Findings
Epidemiology of Antimicrobial Resistance:
- A total of 2407 clinical isolates of Shigella from 2009 to 2016 were analyzed.
- Shigella sonnei gradually became predominant, accounting for 55% of isolates by 2016, surpassing Shigella flexneri (36%).
- AZM resistance increased from 22% in 2009 to approximately 60% by 2016.
- CIP resistance increased by 40%, while CRO resistance increased from zero to 15% over the study period.
- The mphA gene was identified as the key macrolide resistance factor in Shigella.
- Horizontal gene transfer (HGT) via a 63MDa conjugative middle-range plasmid was implicated in the spread of AZM and CRO resistance factors.
Mechanisms of Macrolide Resistance:
- The mphA gene was identified as the primary mechanism of macrolide resistance.
- Horizontal gene transfer (HGT) through plasmids was found to be the main driver of resistance spread, rather than direct lineage.
- The involvement of a 63MDa plasmid carrying resistance genes for AZM and CRO indicates the potential for rapid dissemination of resistance factors.
Evolution of Shigella Resistance:
- Shigella sonnei showed a dramatic increase in prevalence over 15 years, indicating a temporal alteration in dominance.
- Changes in environmental factors such as improved sanitation and industrialization may contribute to the shift in Shigella species prevalence.
- Resistance to previously effective antibiotics like CIP has rendered them unsuitable for shigellosis treatment in Bangladesh.
- Empirical administration of AZM has been hindered by the lack of clear breakpoints, leading to uncertainty in its effectiveness.
Implications for Shigellosis Treatment:
- The rapid increase in resistance to first-line antibiotics underscores the urgency of robust AMR surveillance and transmission dynamics studies.
- The emergence of AZM resistance in Shigella spp. following the publication of CLSI-defined epidemiological cutoff values highlights the need for ongoing monitoring and adaptation of treatment guidelines.
- AZM offers an attractive treatment option due to its low dosage frequency and high intracellular concentration, but its efficacy is compromised by rising resistance rates.
This study provides insight into the evolving landscape of antimicrobial resistance in Shigella spp. in Bangladesh. The findings underscore the urgent need for enhanced surveillance and the development of alternative treatment strategies to combat the growing threat of AMR in shigellosis.
Link to the article : https://tinyurl.com/mr3264vz
