What is the appropriate workup for suspected sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

A sepsis workup involves prompt identification and management of suspected sepsis, starting with obtaining blood cultures (at least two sets from different sites) before initiating antibiotics, as recommended by the Surviving Sepsis Campaign guidelines 1. Begin with obtaining blood cultures, along with other relevant cultures like urine, sputum, or wound samples based on suspected infection source. Order laboratory tests including:

• Complete blood count
• Comprehensive metabolic panel
• Lactate level
• Coagulation studies
• Procalcitonin if available Imaging studies should be directed by clinical suspicion, such as:
• Chest X-ray for respiratory symptoms
• CT scans for abdominal sources Begin empiric broad-spectrum antibiotics within one hour of recognition, typically including coverage for both gram-positive and gram-negative organisms. Common regimens include a combination of vancomycin (15-20 mg/kg IV q8-12h) plus either piperacillin-tazobactam (4.5g IV q6h), cefepime (2g IV q8h), or meropenem (1g IV q8h) 1. Administer IV fluids (30 ml/kg crystalloid) for hypotension or elevated lactate, and monitor response closely. Vasopressors (starting with norepinephrine) should be initiated if hypotension persists despite fluid resuscitation. This aggressive approach is necessary because sepsis represents a dysregulated host response to infection that can rapidly progress to organ dysfunction and death, as highlighted in the guidelines 1. Early intervention disrupts this cascade, with each hour of delayed appropriate antibiotics associated with increased mortality. Once culture results return (typically 48-72 hours), narrow antibiotic therapy based on identified pathogens and susceptibilities to reduce resistance development and side effects. The use of FDG-PET/CT may be considered in cases where the source of infection is unknown, as it has been shown to identify the site of infection in a significant proportion of patients and lead to changes in antimicrobial therapy 1. However, it should only be considered for use after source localization with CT has failed. Daily assessment for de-escalation of antimicrobial therapy is recommended, and measurement of procalcitonin levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients 1.

From the Research

Sepsis Workup

• Sepsis is a common consequence of infection, associated with a mortality rate >25% 2
• The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood stream infection, and urinary tract infection 2
• Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens 2

Antibiotic Administration

• Immediate, empiric, broad-spectrum therapy is necessary to reduce mortality in patients with severe sepsis and/or shock 2
• However, this approach can drive antimicrobial overuse and resistance, and should be accompanied by a commitment to de-escalation and antimicrobial stewardship 2
• The use of a premixed bag consisting of 2 g cefepime and 1 g vancomycin in 1000 mL of normal saline can increase the probability of patients receiving Surviving Sepsis Campaign recommendations for the initiation of antimicrobials and fluid challenge 3

Blood Culture Results

• Administering antimicrobial agents before obtaining blood cultures can decrease the sensitivity of blood cultures 4, 5
• Blood culture positivity is significantly lower in patients who have already received antibiotics compared to those who have not 4, 5
• Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection, emphasizing the importance of obtaining blood cultures before antibiotic administration in patients with sepsis 5

Timing of Antibiotic Administration

• There is no clear evidence on the optimal timing of antibiotic administration in patients with severe sepsis, with some studies suggesting that early administration may be beneficial, but others finding no difference between early and late administration 6
• However, it is generally recommended to start antibiotics as soon as possible in patients with severe sepsis, as delaying treatment can be harmful 2, 6