Biology Reference
In-Depth Information
Treatment
Treatment of STEC disease does not typically involve specific regimens, but
rather involves supportive therapy for management of symptoms and mitigation
of sequelae. The main goal of therapy is to restrain the severity and duration of
gastrointestinal symptoms and hinder the development of systemic complications
such as HUS. Currently, antibiotics are not recommended for treatment of STEC
disease because as mentioned above, several epidemiological studies have con-
cluded that antibiotic administration either does not provide significant benefit to
EHEC-infected individuals or results in increased risk of HUS (
Bell et al., 1997
;
Wong et al., 2000
). Anti-motility agents and narcotics are also contraindicated
during the diarrheal phase of STEC disease as these agents have been shown to
be associated with increased risk of HUS development (
Cimolai et al., 1992
;
Bell
et al., 1997
). Similarly, non-steroidal anti-inflammatory drugs can diminish renal
blood flow and are therefore avoided (
Murray and Brater, 1993
).
One of the most serious consequences of STEC infection is renal failure,
and standard rehydration protocols are considered insufficient for STEC dis-
ease management. Instead, optimal nephroprotection during the diarrhea phase
of the disease is achieved by aggressive intravenous rehydration and mainte-
nance, and patients are often admitted to the hospital for careful monitoring
during administration of high sodium infusions (
Ake et al., 2005
;
Tarr et al.,
2005
). After development of HUS, more intense monitoring and management
strategies are required. The therapeutic focus at this stage is to maintain renal
perfusion while avoiding fluid overload. HUS patients are highly prone to rapid
development of anemia, which is treated with erythrocyte transfusion. In cases
of clinically significant central volume overload, dialysis is preferred to diuret-
ics. Other indications for dialysis in HUS include hyperkalemia, high serum
urea concentration, persistent acidosis, oliguria or anuria, and hypertension irre-
sponsive to treatments (
Tarr et al., 2005
;
Pennington, 2010
).
Development of therapeutic strategies that focus on hindering the progress of
STEC disease has recently gained momentum. Stx is a potent activator of comple-
ment, resulting in complement hyperactivation observed in STEC-HUS in children
(
Noris et al., 2012
). During the 2011 German STEC O104:H4 outbreak, eculi-
zumab, a monoclonal antibody that modulates the hemolytic cascade by inhib-
iting cleavage of complement component C5, was widely used in patients with
severe symptoms (
Loos et al., 2012
). The FDA has approved eculizumab for treat-
ing atypical HUS, and its utility for treating STEC-HUS deserves further careful
investigation (
Gruppo and Rother, 2009
;
Schrezenmeier and Hochsmann, 2012
).
Immune response
An innate immune response may exacerbate STEC disease by inducing an
inflammatory response that results in increased Stx toxicity. For example, pre-
treatment of human vascular endothelial cells with TNF-α or IL-1β induced
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