Sepsis associated with susceptibility to further infections and immunosuppression

1. Patients with sepsis were predisposed to ICU-acquisition of further infections.

2. Sepsis is associated with a degree of immunosuppression.

Evidence Rating Level: 2 (Good)       

Study Rundown: Sepsis is one of the leading causes of death in hospitalized patients, and has been associated with an increased risk of secondary infections and late mortality. This study assessed the incidence, risk factors, and attributable mortality of secondary infections in septic patients in the ICU.

The study found that 13.5% of patients admitted to the ICU with sepsis acquired a secondary infection, a rate similar to ICU patients without sepsis. Septic patients who did become secondarily infected tended to have more severe disease than those who did not acquire a new infection, although the genetic expression, as assessed by leukocyte whole-genome sequencing, was largely similar. The population attributable mortality of ICU-acquired infections among septic patients was 10.9% by 60 days.

This study thus confirmed that patients with more severe sepsis in the ICU are at an increased risk of developing secondary infections, but that these infections contribute only modestly to the overall mortality in these patients. Though genetic differences between patients who developed a new infection and those who did not were small, the findings suggest that immune suppression plays a role in the pathogenesis of infection. Further research should be aimed at quantifying the risk factors for secondary infection and determining the appropriate intervention.

Click to read the study in JAMA

Relevant Reading: Immunosuppression in patients who die of sepsis and multiple organ failure

In-Depth [prospective cohort]: This study is a prospective observational study conducted in two ICUs in the Netherlands. Groups consisted of patients who were in the ICU for >48 hours. ICU-acquired infection was defined as a new-onset infection that was diagnosed >48 hours after the admission. Primary outcome was a first occurrence of an ICU-acquired infection. Out of 1504 patients, 199 developed an ICU-acquired infection. These patients tended to be more ill, as demonstrated by APACHE II and SOFA scores. These patients were also found to have comorbid conditions (CI 1.05-4.35), central line catheters (CI 1.26-3.34), and mechanical ventilation (CI 1.54-25.17). Patients with secondary infections tended to have a longer ICU stays (22 days vs. 5 days, p < 0.001), and higher mortality (44.2% vs. 29.1%, p < 0.001). In a subgroup analysis, type of infection did not appear to change outcomes. Most importantly, patients with ICU-acquired infections were more likely to obtain multiple infections and acquire infections with opportunistic pathogens, demonstrating a likely association between sepsis and immunosuppression.

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