Lessons Learned From Outbreaks of Shiga Toxin Producing Escherichia coli

Abstract

In 2011, a large outbreak caused by a Shiga toxin producing E. coli (STEC) occurred in Northern Germany, with a satellite outbreak in Western France, including the highest number of hemolytic uremic syndrome (HUS) cases ever encountered during a STEC outbreak. The outbreak strain was characterized as an enteroaggregative E. coli of serotype O104:H4 expressing a phage-encoded Shiga toxin 2. The majority of STEC infections and HUS cases were observed in adults, with a preponderance of the female gender. The outbreak imposed huge challenges on clinicians, microbiologists, and epidemiologists but also provided important new insight for the understanding of STEC infection. Thus, novel therapeutic strategies in the treatment of HUS in adults and for decolonization of long-term STEC carriers were evaluated. This review highlights the unusual features of the recent O104:H4 outbreak and focuses on emerging new strategies in diagnostics and treatment of acute STEC-related disease, as well as STEC long-term carriage.

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

“…During the 2011 German outbreak, 3 children with Stx-associated HUS showed rapid clinical improvement with eculizumab, but results from a subsequent nonrandomized trial with 298 patients were unclear (677)(678)(679). Patients who had no clinical improvement during plasmapheresis and/or were suffering from severe neurological complications were preferentially selected for the trial, leading to a selection bias that complicates the results (677,679). As eculizumab disrupts the complement cascade, clinicians at the time were required to treat with a prophylactic antibiotic to prevent meningitis.…”

“…In general, antibiotics are normally not recommended for STEC, as they increases the risk for development of HUS by stimulating Stx production. Because of this risk, clinicians treating stx-expressing EAEC strain O104:H4 selected azithromycin, which in vitro represses stx expression (677,679,680). Monitoring of STEC shedding in patients receiving azithromycin showed that these patients were rapidly decolonized (677,681).…”

“…Because of this risk, clinicians treating stx-expressing EAEC strain O104:H4 selected azithromycin, which in vitro represses stx expression (677,679,680). Monitoring of STEC shedding in patients receiving azithromycin showed that these patients were rapidly decolonized (677,681). Because of this, long-term (Ͼ28 days) carriers of STEC O104:H4 were treated with azithromycin, and after a 3-day course of treatment, all 15 were negative for shedding as well as HUS-related symptoms (677,681).…”

“…Monitoring of STEC shedding in patients receiving azithromycin showed that these patients were rapidly decolonized (677,681). Because of this, long-term (Ͼ28 days) carriers of STEC O104:H4 were treated with azithromycin, and after a 3-day course of treatment, all 15 were negative for shedding as well as HUS-related symptoms (677,681). Further studies have since shown that subinhibitory concentrations of ciprofloxacin increase Stx production in STEC O104:H4 but that meropenem, rifaximin, tigecycline, and azithromycin do not (677,680).…”

“…Because of this, long-term (Ͼ28 days) carriers of STEC O104:H4 were treated with azithromycin, and after a 3-day course of treatment, all 15 were negative for shedding as well as HUS-related symptoms (677,681). Further studies have since shown that subinhibitory concentrations of ciprofloxacin increase Stx production in STEC O104:H4 but that meropenem, rifaximin, tigecycline, and azithromycin do not (677,680). Stx production by STEC O157:H7 responds differently to these same antibiotics (677,680).…”