Abstract
ObjectiveThe aims of this study were to describe azithromycin (AZM) susceptibility patterns among Shigella isolates in Anhui, China and identify predictors of resistance with mobile element-mediated genes.MethodsA total of 517 non-duplicate Shigella isolates (449 S. flexneri and 68 S. sonnei) were collected in the Anhui Province of China from September 2011–September 2015, and screened for the plasmid-mediated genes of decreased susceptibility to AZM (DSA), using polymerase chain reaction amplification and sequencing. Conjugation experiments and pulsed-field gel electrophoresis were conducted for all mphA-positive DSA isolates.ResultsThe DSA rate for 449 S. flexneri isolates was 33.6%, compared with 39.7% for 68 S. sonnei isolates. Among 161 DSA S. flexneri isolates, 93 (57.8%) carried the mphA gene. Among 27 DSA S. sonnei isolates, 11 (40.7%) carried the mphA gene. However, other plasmid-mediated DSA genes were not found in these isolates. A total of 89 transconjugants (95.7%) were obtained from 93 mphA-positive S. flexneri isolates through conjugation, and 10 transconjugants (90.9%) were obtained from 11 mphA-positive S. sonnei isolates. Furthermore, the minimum inhibitory concentrations (MICs) of AZM among 89 S. flexneri transconjugants ranged from 4 to 128 μg/mL, with an MIC50 of 8 μg/mL and MIC90 of 32 μg/mL. The MICs of AZM among 10 S. sonnei transconjugants ranged from 4 to 256 μg/mL, with an MIC50 of 8 μg/mL and MIC90 of 64 μg/mL. Thirteen clusters were found for mphA-positive S. flexneri, and five clusters were found for mphA-positive S. sonnei. Furthermore, 10 homologous isolates among 13 mphA-positive S. flexneri isolates with high-level DSA were from Sixian county and were multidrug-resistant strains. Of the 10 homologous S. flexneri isolates, eight were from children (≤5 years old), and two from the elderly (>60 years old).ConclusionOur study demonstrates that the DSA for Shigella isolates was severe, and the plasmid-mediated mphA gene was the most common macrolide resistance gene detected in Shigella isolates collected in Anhui, China. The mphA-positive S. flexneri isolates with high-level DSA facilitated clonal spread in children and the elderly. This finding is noteworthy and warrants further study.
Highlights
Shigellosis is an acute invasive enteric infection caused by bacteria of the genus Shigella, including S. dysenteriae, S. flexneri, S. boydii, and S. sonnei
No significant differences were noted in gender or age between S. flexneri and S. sonnei isolates with decreased susceptibility to AZM (DSA)
Regarding CIP resistance, no significant differences were noted between S. flexneri and S. sonnei among male participants and all age groups, and no significant differences were noted among female participants
Summary
Shigellosis is an acute invasive enteric infection caused by bacteria of the genus Shigella, including S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. In guidelines published by the WHO in 2005, ciprofloxacin (CIP) was considered the first-line treatment for shigellosis, with ceftriaxone (CRO) and azithromycin (AZM) listed as alternative options. Widespread use of CIP and third-generation cephalosporins have led to increasing resistance to these antimicrobials among Shigella isolates, especially in Asia (Liu et al, 2012, 2017; Zhang et al, 2014; Kotloff et al, 2018). The American Academy of Pediatrics and the Infectious Diseases Society of America have recommended the use of AZM to treat multidrug-resistant shigellosis (Erdman et al, 2008; Pickering et al, 2009; Shane et al, 2017). In China, AZM is infrequently used to treat shigellosis. There is a relative lack of published research on decreased susceptibility to AZM (DSA) for Shigella in China
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