Infections are often caused by pathobionts, endogenous bacteria that belong to the microbiota.Trauma and surgical intervention can allow bacteria to overcome host defences, ultimately leading to sepsis if left untreated.One of the main defence strategies of the immune system is the production of highly specific antibodies.In the present proof-of-concept study, plasma antibodies against 9 major pathogens were measured in sepsis patients, as an example of severe systemic infections.The binding of plasma antibodies to bacterial extracellular proteins was quantified using a semi-automated immunoblot assay.Comparison of the pathogen-specific antibody levels before and after infection showed an increase in plasma IgG in 20 out of 37 tested patients.This host-directed approach extended the results of pathogen-oriented microbiological and PCR diagnostics: a specific antibody response to additional bacteria was frequently observed, indicating unrecognised polymicrobial invasion.This might explain some cases of failed, seemingly targeted antibiotic treatment.

Objectives: Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy. Methods: Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity. Results: In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p < 0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3e0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p < 0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p < 0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy. Conclusions: Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis. (c) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Editor—We thank Dr Natesan for his comment1Natesan V. Adrenergic blockade inhibits bacterial quorum sensing and reverses Warburg effect in septic shock.Br J Anaesth. 2018; 120: 412-413Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar on our paper2Fuchs C. Wauschkuhn S. Scheer C. et al.Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality ratesup to 90 days.Br J Anaesth. 2017; 119: 616-625Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar and the interesting facts he pointed out. The sympathetic system and subsequent adrenergic storm affect various organ systems, such as the cardiovascular, metabolic, coagulation, and immune systems. Therefore, the sepsis induced catecholamine storm might be beneficially influenced by β-blockers.3de Montmollin E. Aboab J. Mansart A. Annane D. Bench-to-bedside review: beta-adrenergic modulation in sepsis.Crit Care. 2009; 13: 230Crossref PubMed Scopus (115) Google Scholar α1-Blockers are mainly used in the long-term treatment of chronic heart failure and hypertension. However, because of their relevant side-effects, such as severe and unpredictable hypotension4Stein L. Foster P.R. Friedman A.W. Statza J. McHenry P.L. Acute and chronic haemodynamic effects of prazosin in left ventricular failure.Br Heart J. 1981; 45: 186-192Crossref PubMed Scopus (10) Google Scholar, 5Taylor S.H. Silke B. The pharmacokinetic, pharmacodynamic and haemodynamic effects of acute and chronic alpha-adrenoceptor blockade in chronic heart failure.Ann Acad Med Singapore. 1981; 10: 45-51PubMed Google Scholar and fluid retention,4Stein L. Foster P.R. Friedman A.W. Statza J. McHenry P.L. Acute and chronic haemodynamic effects of prazosin in left ventricular failure.Br Heart J. 1981; 45: 186-192Crossref PubMed Scopus (10) Google Scholar they are restricted to very specific indications. These side-effects can be related to the level of sympathetic tone.6Colucci W.S. Williams G.H. Braunwald E. Clinical, hemodynamic, and neuroendocrine effects of chronic prazosin therapy for congestive heart failure.Am Heart J. 1981; 102: 615-621Abstract Full Text PDF PubMed Scopus (20) Google Scholar Against this background, classic α1-blockers seem not to be favourable in the treatment of septic patients with haemodynamic instability and capillary leakage. In hypertensive heart failure in particular, metoprolol combined with prazosin caused significant depression of cardiac function.7Nelson G.I. Donnelly G.L. Hunyor S.N. Haemodynamic effects of sustained treatment with prazosin and metoprolol, alone and in combination, in borderline hypertensive heart failure.J Cardiovasc Pharmacol. 1982; 4: 240-245Crossref PubMed Scopus (11) Google Scholar Within the observed study population, patients that received α1-blockers were very rare. Therefore, based on our data, we cannot make any conclusion about the effects of α1-blocker in patients with sepsis. Dr Natesan emphasized the Warburg effect – the anaerobic metabolic state of cancer cells. Similarly, mitochondrial dysfunction in sepsis can contribute to multiple organ failure. But the complex regulation is far from being understood and thus there is no specific therapeutic target so far.8Harrois A. Huet O. Duranteau J. Alterations of mitochondrial function in sepsis and critical illness.Curr Opin Anaesthesiol. 2009; 22: 143-149Crossref PubMed Scopus (90) Google Scholar Interestingly, catecholamines affect not only the human body, but also bacteria growth.9Belay T. Sonnenfeld G. Differential effects of catecholamines on in vitro growth of pathogenic bacteria.Life Sci. 2002; 71: 447-456Crossref PubMed Scopus (59) Google Scholar In our view, this supports the malignant effects of catecholamine storm and excessive catecholamine concentrations, respectively, that can be reduced by β-blockers. In conclusion, sepsis is a complex syndrome. What we have learned over the past decades in clinical sepsis management is that no one single therapeutic step, such as β-blockers, nor one single target, for example protein C pathway, is important to counteract the septic multifactorial disorder. Instead, a time-sensitive sepsis bundle is the crucial way to reduce mortality in critically ill patients with sepsis. None declared.

Background There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. Methods The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. Results A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). Conclusions Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

Actual guidelines for the management of severe sepsis and septic shock recommend to draw blood cultures before anti-infective therapy. The grade of recommendation for this approach is high, the evidence, however, is low (1C) [1]. Thus, data on the influence of anti-infective therapy on microbiology results in seriously ill patients are urgently warranted.

A continuous infusion of the beta-blocker esmolol has recently been demonstrated to increase stroke volume without increasing norepinephrine dosage or impairing microcirculation in patients with septic shock [1]. In addition, a pre-existing oral therapy with beta-blockers was associated with a potential 28-day mortality survival benefit in septic patients [2]. The influence of a new initiated or discontinued oral beta-blocker therapy upon 90-day mortality, however, remains unclear.

The overwhelming postsplenectomy infection syndrome (OPSI) is a fulminant sepsis that is mainly caused by Streptococcus pneumoniae and is characterized by a particular high mortality. Patients whose spleen was removed due to a hematological disease are at special risk. Even after the recommended immunization against Streptococcus pneumoniae 20-30 % of these patients do not develop an adequate level of antibody response. Therefore, this particular group of patients must be trained how to behave in case of fever and need to obtain immediate specific sepsis therapy with antibiotic prophylaxis.

Die fulminante Pneumokokkensepsis nach Splenektomie („overwhelming post-splenectomy infection syndrome“, OPSI) ist eine fulminant verlaufende Sepsis, die hauptsächlich durch Streptococcus pneumoniae verursacht wird und eine hohe Letalität besitzt. Patienten, die aufgrund einer hämatologischen Grunderkrankung splenektomiert wurden, tragen ein besonders hohes Risiko. Auch nach Durchführung der geforderten Impfung gegen Streptococcus pneumoniae entwickeln 20–30 % dieser Patienten keine ausreichende Antikörperantwort. Deshalb muss diese Patientengruppe hinsichtlich des Verhaltens bei Fieber besonders geschult werden und bedarf der sofortigen spezifischen Sepsistherapie und Antibiotikagabe.