Enterohemorrhagic Escherichia coli Hybrid Pathotype O80:H2 as a New Therapeutic Challenge

Abstract

We describe the epidemiology, clinical features, and molecular characterization of enterohemorrhagic Escherichia coli (EHEC) infections caused by the singular hybrid pathotype O80:H2, and we examine the influence of antibiotics on Shiga toxin production. In France, during 2005-2014, a total of 54 patients were infected with EHEC O80:H2; 91% had hemolytic uremic syndrome. Two patients had invasive infections, and 2 died. All strains carried stx2 (variants stx2a, 2c, or 2d); the rare intimin gene (eae-ξ); and at least 4 genes characteristic of pS88, a plasmid associated with extraintestinal virulence. Similar strains were found in Spain. All isolates belonged to the same clonal group. At subinhibitory concentrations, azithromycin decreased Shiga toxin production significantly, ciprofloxacin increased it substantially, and ceftriaxone had no major effect. Antibiotic combinations that included azithromycin also were tested. EHEC O80:H2, which can induce hemolytic uremic syndrome complicated by bacteremia, is emerging in France. However, azithromycin might effectively combat these infections.

Keywords: E. coli; HUS; O80:42; Shiga toxin; antibiotic resistance; antibiotic treatment; antimicrobial; antimicrobial resistance; bacteremia; bacteria; emergence; enteric infections; enterohemorrhagic Escherichia coli; extraintestinal virulence factors; hemolytic uremic syndrome; pS88 plasmid.

Figure 1

Number of enterohemorrhagic Escherichia coli O80:H2 strains detected annually, France, January 2005–October 2014.

Figure 2

Regional 10-year cumulative incidence rates of hemolytic uremic syndrome cases caused by enterohemorrhagic Escherichia coli serotypes O157:H7 and O80:H2, France, January 2005–October 2014. A) Serotype O157:H7. B) Serotype O80:H2. White, <0.5 cases/100,000 children; light gray shading, 0.5–0.7 cases/100,000 children; medium gray shading, 0.8–0.9 cases/100,000 children; dark gray shading, 1–2 cases/100,000 children; black, >2 cases/100,000 children.

Figure 3

Dendrogram obtained after DiversiLab genotyping analysis (based on PCR amplification of repeat sequences of DNA) of 56 enterohemorrhagic Escherichia coli (EHEC) O80 strains from humans in France compared with other isolates detected in France, Germany, and Spain, January 2005–October 2014. Other isolates include 1 animal-origin strain from France (LNR511-4, bovine, 2012); 5 animal- and human-origin isolates from Spain (FV4476, porcine; VTB-262, bovine; IH43632/03a, IH33264/07a, and IH 102878/12a, human); and 6 comparison strains from other serogroups (EDL933 and 32031, O157; 32527 and 32573, O104, isolated during a 2011 outbreak in Germany; 36061, O121; and 34593, O111). ID, identification.

Figure 4

Mean concentrations (logarithmic scale) of Shiga toxin produced in the absence of antibiotics by selected strains of enterohemorrhagic Escherichia coli serotypes O80, France, January 2005–October 2014. O157 reference strain (EDL933) was used as control. Error bars indicate SDs.

Figure 5

Relative production rate of Shiga toxin produced in 5 strains of enterohemorrhagic Escherichia coli (4 O80 strains and 1 O157 strain) at subinhibitory concentrations of azithromycin, ciprofloxacin, and ceftriaxone, compared with basal production rate (no antibiotics), France, January 2005–October 2014. A) Isolate 35344. B) Isolate 33115. C) Isolate 35431. D) Isolate 36047. E) Isolate EDL933. Error bars indicate SDs.

Figure 6

Relative production rate of Shiga toxin produced in 2 strains of enterohemorrhagic Escherichia coli O80 (isolates 35344 and 33115) at subinhibitory concentrations of azithromycin, ciprofloxacin, ceftriaxone (alone and in combination), compared to basal production rate (no antibiotics), France, January 2005–October 2014. AZM, azithromycin; AZM/CIF, azithromycin/ciprofloxacin; AZM/CRO, azithromycin/ceftriaxone; CIF, ciprofloxacin; CRO, ceftriaxone. Error bars indicate SDs.