Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly virulent Escherichia coli

Abstract

Neonatal meningitis is a rare but devastating condition. Multi-drug resistant (MDR) bacteria represent a substantial global health risk. This study reports on an aggressive case of lethal neonatal meningitis due to a MDR Escherichia coli (serotype O75:H5:K1). Serotyping, MDR pattern and phylogenetic typing revealed that this strain is an emergent and highly virulent neonatal meningitis E. coli isolate. The isolate was resistant to both ampicillin and gentamicin; antibiotics currently used for empiric neonatal sepsis treatment. The strain was also positive for multiple virulence genes including K1 capsule, fimbrial adhesion fimH, siderophore receptors iroN, fyuA and iutA, secreted autotransporter toxin sat, membrane associated proteases ompA and ompT, type II polysaccharide synthesis genes (kpsMTII) and pathogenicity-associated island (PAI)-associated malX gene. The presence of highly-virulent MDR organisms isolated in neonates underscores the need to implement rapid drug resistance diagnostic methods and should prompt consideration of alternate empiric therapy in neonates with Gram negative meningitis.

Keywords: Escherichia coli; hypervirulence; meningitis; meningoencephalitis; multi-drug resistance; neonate.

Figure 1. Virulence of NMEC strain evidenced by clinical laboratory results, gross pathology, and histopathology

(A) Laboratory characteristics of the patient; (B) Antibiotic sensitivity report for NMEC-MCJCHV1; (C) Gross image of the dorsal brain surface at the vertex of the neocortical hemispheres including attached portions of dura at the lateral edges of the image. The frontal drainage catheter is on the left side and there is extensive fibrinopurulent exudates involving the dura and skull; (D) Gross image of the dorsal brain surface at the vertex of the neocortical hemispheres with the dura removed. There is right frontal and parietal leptomeningitis with diffuse parenchymal involvement (right side of image) and leptomeningitis with cloudy exudate (left side of image); (E) Coronal section of the neocortex at the level of the posterior parietal lobe showing bilateral brain edema and right parietal thickening of the leptomeninges with purulent exudates and friable underlying parenchyma, consistent with encephalitis (right side of image). There is asymmetry of the lobes with compression of the left side, consistent with right to left midline shift; (F) Microscopic image of the right parietal neocortex (H&E, 100×) showing hypercellular leptomeninges (top of image) with abundant acute inflammation (inset, H&E, 400×) including neutrophils and macrophages.

Figure 2. Phenotypic and genotypic characteristics of NMEC-MCJCHV1

(A) Summary of virulence genes, disrupted tRNA genes (tDNA), serotype and other phenotypic features of NMEC-MCJCHV1; (B) Transmission electron micrograph of negatively stained NMEC-MCJCHV1. Note bacterial cells are surrounded by capsular structure (white arrow); (C) Phylogenetic tree of NMEC-MCJCHV1 (arrow), ECOR control strain and different NMEC representing all the known sequence types (STs) from MLST data base.