Buenos Aires 01 de Agosto del 2020

Focus on infection and sepsis 2017



Focus on infection and sepsis 2017


                                           Ignacio Martin‑Loeches, Jose Garnacho‑Montero and Saad Nsei

                                                               Intensive Care Med (2017) 43:867-869



Management of severe infections and sepsis in intensive care units (ICU) represents one of the most common and complex problems in daily clinical practice. Year by year, new studies are helping to improve physicians'

management and this manuscript aims to summarize the most relevant works published during 2015-2016 on these difficult areas of knowledge (Table 1).


Table 1 Selected recent findings on infection and sepsis in the critically ill patient

2017 Surviving Sepsis Campaign


  • Critically ill patients frequently not receiving the recommended quantity of fluids during the first 24 h of sepsis or septic shock, mortality increased in patients with severe sepsis receiving <5 L of fluids
  • Lower hemoglobin levels not associated with higher mortality or worse quality of life at 1 year after randomization

"Area of need" population studies in sepsis

  • Refractory septic shock in pediatric population
  • Sepsis in resource‑limited settings


  • qSOFA accurate in patients with community acquired pneumonia
  • Older patients with influenza prone to higher rates of bacterial co‑infection, and higher mortality rates

ICU‘acquired infections

  • Duration of mechanical ventilation, but not antibiotics, associated with changes in lung microbiome
  • Highly heterogeneous patterns of intestinal microbiota in both septic and non‑septic ICU patients
  • Treatment with probiotics effective and safe to prevent VAP
  • De‑escalation in ICU patients feasible and associated with better outcomes


2017 Surviving Sepsis Campaign controversies

Probably, one of the most important landmarks in 2016 was the publication of the new edition of theSurviving Sepsis Campaign guidelines [1]. Not all is done andnew data will be incorporated in further editions. Forinstance, in this edition, it is recommended to give a minimum of 30 mL/kg of crystalloid solutions within the first 3  h. Interestingly, a recent study found [2] that less fluids were administered to patients with severe sepsis and septic shock in the USA during the first ICU day than recommended by the Surviving Sepsis Campaign guidelines, and this was associated with an increased mortality of 2.3% per liter of fluid administered above 5 L.Hjortrup [3] randomized 151 adult patients with septic shock in Scandinavia and found that in patients assigned to fluid restriction (fluid boluses only if severe hypoperfusion was detected), fluid volumes at day  5 and during ICU stay were lower than in the standard care group by more than 1 L with no differences in outcome. The trial was a feasibility trial that actually suggested benefit with fluid restriction but was not powered to address patient centered outcomes. Following the same idea of "less is more", Rygard [4] reported that a lower hemoglobin threshold for transfusion was associated with neither higher long-term mortality (1  year after randomization) rates in patients with sepsis nor a worse health-related quality of life (HRQoL).

"Area of need" population studies in sepsis

Intensive Care Medicine published several special papers in 2016 focused on sepsis management in two types of populations that are commonly not addressed widely: resource-limited settings and the pediatric population.

Pediatric populations will benefit from the recently published consensus documents for refractory septic shock in children that included a clinical case-based Delphi survey involving 114 pediatric intensivists [5]. Regarding resource-limited settings, recommendations were published by a multidisciplinary group of experts from different geographic areas who agreed that there is scarce evidence for the management of pediatric and adult sepsis in resource-limited settings [6]. Further efforts should be made from scientific societies to adequately provide resources for this population. A worldwide study demonstrated that gross national income (GNI) was a major determinant of time to death in hospital in ICU patients[7]. Not only GNI but also age (older patients), type of population (surgical), and infection increased the duration of hospital stay prior to death in critically ill patients.

Quick sequential organ failure assessment (qSOFA)65?

Studies of sepsis have shown an exponential increase in the population-based incidence of sepsis with age, followed closely by an increased mortality [8]. New sepsis definitions (Sepsis  3.0) were launched in 2016 [9] and have generated some controversy [10]. As Community Acquired Pneumonia (CAP) is the most common cause of sepsis, Kolditz [11] performed a multicenter validation of the qSOFA score (also known as quickSOFA) in patients with CAP. qSOFA uses three criteria, assigning one point for low blood pressure (SBP ≤ 100  mmHg), high respiratory rate (≥22  breaths per min), or altered mentation (Glasgow coma scale  <15). The authors compared its accuracy to predict disease course to the CRB-65 (confusion, respiratory rate ≥ 30/min, systolic blood pressure  < 90  mmHg or diastolic blood pressure ≤ 60mmHg, age ≥65 years) score. qSOFA and CRB(-65) score do share the same items except age, and the authors found that qSOFA was similar to CRB(-65), with a slightly higher sensitivity and lower specificity.
On the basis of their findings, age (>65  years) might be applied as an additional criterion in both scores for optimal low-risk prediction. In a recent observational multicenter study with almost 3000 patients with severe CAP, older patients more often had co-infection when infected by influenza, and co-infection was independently associated with higher mortality [12]. More appropriate triage (resource limitation enforced decisions), admission decisions based on shared decision-making, and improved prediction models should be incorporated in aging populations [13].

ICU acquired infections

Nosocomial infections play a major role in the development of sepsis, and ventilator-associated pneumonia (VAP) remains the most common infection in ICU [14]. controlled trial involving 235 critically ill adult patients, therapy with the probiotic bacteria Bacillus  subtilis and Enterococcus faecalis were found to be effective and safe for preventing VAP and the acquisition ofmultidrugresistant pathogen (MDR) colonization [17].
Antibiotic stewardship programs have been found to be effective in ICU settings to face the ongoing problem of bacterial resistance and acquisition of MDR [18].
Recently, the World Health Organization, US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control, European Medicines Agency, Institute of Medicine, World Economic Forum, and the US Presidential Advisory Council on Science and Technology asked for action to take in this mater [19]. A recent pooled individual data analysis of prospective studies of de-escalation in critically ill patients with sepsis found that while SOFA score and aging were both factors independently associated with mortality, de-escalation was independently associated with a better outcome in the adjusted multivariate analysis [20]. Formal antibiotic stewardship programs are essential to help in reducing either unnecessary or inappropriate antibiotic prescription and subsequently to avoid a rise in antimicrobial resistance.

Concluding remarks

Mortality and morbidity associated with sepsis remain unacceptably high. Detection of patients in their early stages of the infection is crucial to diminish the high mortality rate associated with sepsis. Further studies are warranted to determine the optimal targets for resuscitation and the best antimicrobial management especially when MDR pathogens are involved.
A recent manuscript by Zakharkina et  al. found that duration of mechanical ventilation, but not antibiotic administration, was associated with changes in the respiratory microbiome [15]. Recent studies reported that despite previous evidence [16], highly heterogeneous patterns of intestinal microbiota existed in both septic and non-septic critically ill patients. This might shed light on our understanding of the conflicting results with the effect of probiotics on the incidence of VAP in critically ill patients. In an open-label, multicenter randomized.



1. Rhodes A, Evans LE, Alhazzani W et al (2017) Surviving Sepsis Campaign:international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43:304-377. doi:10.1007/s00134‑017‑4683‑6

2. Marik PE, Linde‑Zwirble WT, Bittner EA et al (2017) Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med. doi:10.1007/ s00134‑016‑4675‑y

3. Hjortrup PB, Haase N, Bundgaard H et al (2016) Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel‑group, multicentre feasibility trial. Intensive Care Med 42:1695-1705. doi:10.1007/s00134‑016‑4500‑7

4. Rygard SL, Holst LB, Wetterslev J et al (2016) Long‑term outcomes in patients with septic shock transfused at a lower versus a higher haemoglobin threshold: the TRISS randomised, multicentre clinical trial. Intensive Care Med 42:1685-1694. doi:10.1007/s00134‑016‑4437‑x

5. Morin L, Ray S, Wilson C et al (2016) Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition. Intensive Care Med 42:1948-1957. doi:10.1007/s00134‑016‑4574‑2

6. Thwaites CL, Lundeg G, Dondorp AM (2016) Infection management in patients with sepsis and septic shock in resource‑limited settings. Intensive Care Med 42:2117-2118. doi:10.1007/s00134‑016‑4547‑5

7. Martin‑Loeches I, Wunderink RG, Nanchal R et al (2016) Determinants of time to death in hospital in critically ill patients around the world. Intensive Care Med 42:1454-1460. doi:10.1007/s00134‑016‑4479‑0

8. Yebenes JC, Ruiz‑Rodriguez JC, Ferrer R et al (2017) Epidemiology of sepsis in Catalonia: analysis of incidence and outcomes in a European setting. Ann Intensive Care 7:19. doi:10.1186/s13613‑017‑0241‑1
9. Singer M, Deutschman CS, Seymour CW et al (2016) The third international consensus definitions for sepsis and septic shock (Sepsis‑3). JAMA 315:801-810. doi:10.1001/jama.2016.0287