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The post diarrheal hemolytic uremic syndrome (HUS) is a major complication of enteric infections with Shiga toxin producing (STEC). According to the present recommendations, antibiotic therapy of acute bloody diarrhea caused by STEC is generally discouraged. These recommendations are based on historically conflicting results describing the potential induction of HUS by antibiotic treatment during the early phase of infection with enterohemorrhagic O157 whereas no guidelines are available for the use of antibiotics in cases of already fully established HUS or in asymptomatic long term STEC carriers. In 2011, a large outbreak of hemorrhagic colitis complicated by HUS occurred in northern Germany caused by a STEC strain of serotype O104:H4 harbouring both a phage encoding Stx 2 as well as a plasmid mediated enteroaggregative phenotype. The majority of infections were observed in adults, complicated by the highest number of HUS cases ever encountered. Due to different newly introduced therapeutic strategies (e.g. complement blockade) antibiotic therapy was used in many patients once HUS was established. The outbreak therefore provided important new insights for the understanding of antibiotic therapy of STEC associated HUS in adults and for decolonization of long term STEC carriers. This review highlights new aspects concerning use of antibiotics in STEC infection and colonization.

Am J Physiol Regul Integr Comp Physiol 298: R191-R197, 2010. First published November 11, 2009; doi: 10.1152/ajpregu.00368.2009.--Nocturnal blood pressure (BP) decline or 'dipping' is an active, central, nervously governed process, which is important for BP regulation during daytime. It is, however, not known whether the sleep process itself or, more specifically, slow-wave sleep (SWS) is important for normal dipping. Therefore, in the present study, healthy subjects (6 females, 5 males) were selectively deprived of SWS by EEG-guided acoustic arousals. BP and heart rate (HR) were monitored during experimental nights and the following day. Additionally, nocturnal catecholamine excretion was determined, and morning baroreflex function was assessed by microneurographic measurements of muscle sympathetic nerve activity (MSNA) and heart rate variability (HRV). Data were compared with a crossover condition of undisturbed sleep. SWS was successfully deprived leading to significantly attenuated mean arterial BP dipping during the first half (P < 0.05), but not during the rapid-eye-movement-dominated second half of total sleep; however, dipping still evolved even in the absence of SWS. No differences were found for nighttime catecholamine excretion. Moreover, daytime resting and ambulatory BP and HR were not altered, and morning MSNA and HRV did not differ significantly, indicating that baroreflex-mediated sympathoneural BP regulation was not affected by the preceding SWS deprivation. We conclude that in healthy humans the magnitude of nocturnal BP dipping is significantly affected by sleep depth. Deprivation of SWS during one night does not modulate the morning threshold and sensitivity of the vascular and cardiac baroreflex and does not alter ambulatory BP during daytime. nondipping; baroreflex; muscle sympathetic nerve activity

Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-[alpha] and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean [+ or -] SE: 12.1 [+ or -] 2.9 vs. 27.5 [+ or -] 3.3 burst/min (post-vs. pre-LPS); P < 0.005] but increased heart rate [78.4 [+ or -] 3.1 vs. 60.6 [+ or -] 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis. baroreceptors; nervous system; sympathetic; MSNA; endotoxin; systemic inflammation

Abstract Pattern recognition receptors are a key component of the first line host defense against infection, recognizing specific microbial products. We hypothesize that monocyte hyporesponsiveness in human sepsis is associated with a downregulation of the pattern recognition receptors Toll-like receptor (TLR)-2 and TLR4. Protein expression of CD14, TLR2 and TLR4 on blood monocytes was examined using flow cytometry from 29 patients with sepsis and 14 healthy controls. In addition LPS stimulated TNF-α and IL-10 production was studied in a 24 hour whole blood assay. We found an increased expression of CD14, TLR2 and TLR4 in patients with sepsis compared to controls (p < 0.01). In patients with sepsis, death was associated with significant lower CD14 and TLR2 expression at admission (CD14: 25.7 +- 19.1 vs 39.1 +- 17.3 mean fluorescence intensity [MFI], p = 0.02; TLR2: 21.8 +- 9.4 vs. 30.9 +- 9.6, p = 0.01). At 72 hours the TLR2 expression on monocytes was associated with the IL-10 inducibility after LPS stimulation (r = 0.52, p = 0.02) and the CD14 expression with the IL-6, IL-10 and TNF inducibility. We conclude that septic patients are characterized by an increased expression of CD14, TLR2 and TLR4 on monocytes compared to controls. Death is associated with downregulation of TLR2 and CD14 expression on monocytes correlating with reduced cytokine inducibility. We suggest that CD14 and TLR2 are a key factor in monocyte hyporesponsibility during severe sepsis.