Management of Gram-Negative Sepsis

Initial Assessment and Diagnosis

Obtain at least 2 sets of blood cultures before starting antimicrobial therapy if no significant delay will occur, to identify the source of infection in patients with suspected Gram-negative sepsis 3
Perform appropriate imaging studies promptly to identify the source of infection in patients with suspected Gram-negative sepsis 3
Consider using procalcitonin levels to guide antibiotic therapy decisions, particularly when evaluating the need to discontinue empiric antibiotics in patients with suspected Gram-negative sepsis 3

Administer effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis, as recommended by the American College of Critical Care Medicine 1, 2, 3
Select empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens, including bacterial and potentially fungal or viral coverage, in patients with suspected Gram-negative sepsis 2
Consider patient risk factors for multidrug-resistant organisms, such as prior infection or colonization with Gram-negative MDROs, when selecting initial therapy for patients with suspected Gram-negative sepsis 4

Rapidly identify and address the anatomical source of infection within 12 hours of diagnosis when feasible, to reduce mortality in patients with Gram-negative sepsis 3
Remove potentially infected intravascular access devices promptly after establishing alternative access, to prevent further infection in patients with Gram-negative sepsis 3

Reassess antimicrobial therapy daily for potential de-escalation based on culture results, to minimize the risk of antibiotic resistance in patients with Gram-negative sepsis 2, 3
Narrow empiric antimicrobial therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted, to reduce the risk of antibiotic resistance in patients with Gram-negative sepsis 1, 2
Typical duration of therapy is 7-10 days; longer courses may be needed for patients with slow clinical response or undrainable foci of infection, as recommended by the American College of Critical Care Medicine 3

The prevalence of MDR Gram-negative bacteria is increasing, particularly in healthcare settings, highlighting the need for careful selection of empiric antibiotic therapy in patients with suspected Gram-negative sepsis 4
Local antimicrobial resistance patterns should guide empiric therapy choices, to minimize the risk of antibiotic resistance in patients with Gram-negative sepsis 2
Consider region-specific empirical antibiotic regimens based on local epidemiology, to minimize the risk of antibiotic resistance in patients with Gram-negative sepsis 7

Delaying antimicrobial therapy beyond one hour of recognition of sepsis or septic shock significantly increases mortality, emphasizing the need for prompt treatment in patients with suspected Gram-negative sepsis 1, 2
Using inadequate antimicrobial coverage for likely pathogens based on patient risk factors and local resistance patterns, can lead to treatment failure in patients with Gram-negative sepsis 4
Failing to reassess and de-escalate antimicrobial therapy once culture results are available, can lead to unnecessary antibiotic use and resistance in patients with Gram-negative sepsis 2, 3
Neglecting source control, which is essential for successful treatment of Gram-negative sepsis, can lead to poor outcomes in patients with Gram-negative sepsis 3
Overuse of broad-spectrum antibiotics when narrower spectrum options would be effective based on culture results, can lead to antibiotic resistance in patients with Gram-negative sepsis 4