Diarrhea in an infant due to Shigella flexneri 1 carrying multiple cephalosporinase-encoding genes

Abstract

Background: Infections caused by multidrug-resistant shigellae resistant to broad-spectrum cephalosporins are becoming more prevalent in the Middle East. We report a case of severe diarrhea due to a multiresistant Shigella flexneri 1 strain carrying four different ß-lactamase genes.

Case presentation: A one-year-old Syrian infant presented with severe acute diarrhea, vomiting and dehydration. She did not respond to empirical treatment with amoxicillin-clavulanic acid followed by cefotaxime. Later, stool culture revealed S. flexneri 1 resistant to both these drugs. The patient was successfully treated with meropenem to which S. flexneri 1 was susceptible. The isolate was resistant to eight classes of antibiotics, and the whole genome sequence (WGS) identified four ß-lactamase genes (bla_CTX-M-15, bla_EC-8, bla_OXA-1, and bla_TEM-1) along with genes mediating resistance to seven other antibiotic classes. The WGS also identified several virulence genes including senA that encodes ShET-2 which induces watery diarrhea. Phylogenetically, the isolate was closely related to isolates from South Asia.

Conclusions: This report highlights the emergence of extremely resistant Shigella that has acquired multiple resistance genes to cephalosporins rendering these drugs ineffective.

Keywords: Cephalosporinase; Diarrhea; Multidrug-resistance; S. flexneri 1.

Fig. 1

Plasmids present in S. flexneri 1. Plasmids were separated by agarose gel electrophoresis, stained with ethidium bromide and photographed under the UV light. Plasmid sizing in S. flexneri 1 (lanes 2 & 3) was done in comparison to the known plasmids present in E. coli V517 (lane 1)

Fig. 2

A tree showing the relationship between the core genomes of 77 phylogroup 1 S. flexneri isolates from Connor et al. [23] and isolate SF1 (in blue) (metadata can be found in Additional file 1: Table S1). The S. flexneri 2a str. 301 genome sequence (Chr: NC_004,337 and pCP301: NC_004851) was used as a reference for the core genome alignment and is represented in the tree as the unlabeled outgroup. The tree was inferred using IQtree version 1.6.12. Approximately, 80% of the S. flexneri 2a str. 301 genome sequence was used for the core genome and the greatest pairwise SNP distance was 2151 bases. Taxon labels include serotype, isolate name, country (abbreviated using ISO3166 three letter code; note EU = Europe, and UNK = Unknown) and year of isolation. The close relationship of the Kuwaiti isolate with those from Pakistan and Bangladesh is indicated in purple lines. A genotypic antimicrobial resistance profile for 13 resistance genes is shown at the right of the taxon label where an open box or circle (for β-lactamases) indicates gene absence and closed one indicates gene presence. The figure was produced using the interactive tree of life website (https://itol.embl.de)