Guidelines for Antibiotic Therapy in Sepsis Treatment

Intravenous antimicrobials must be initiated within one hour of sepsis recognition to reduce mortality and improve outcomes. 1, 2

Initial Antimicrobial Selection

Obtain appropriate microbiological cultures, including at least two sets of blood cultures, before starting antimicrobial therapy, as long as this does not significantly delay treatment 2, 3
Use empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens (bacterial, fungal, or viral) 1, 3
For septic shock, use combination therapy with at least two antibiotics from different antimicrobial classes targeting the most likely pathogens 1, 2, 3
For infections associated with respiratory failure and septic shock, use a combination of a broad-spectrum beta-lactam and an aminoglycoside or fluoroquinolone when Pseudomonas aeruginosa is suspected 1, 2
For septic shock caused by Streptococcus pneumoniae bacteremia, use a combination of a beta-lactam and a macrolide 1, 2
Against combination therapy for routine treatment of neutropenic sepsis/bacteremia 1

Empiric combination therapy should not be administered for more than 3-5 days 1, 2, 4
De-escalate antimicrobial therapy within the first few days in response to clinical improvement and/or evidence of infection resolution 1, 2
Narrow antimicrobial therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted 1, 2
Standard duration of therapy is 7-10 days for most serious infections associated with sepsis and septic shock 1, 5
Consider longer courses for patients with slow clinical response, undrainable infection foci, Staphylococcus aureus bacteremia, certain fungal/viral infections, or immunologic deficiencies including neutropenia 1, 6
Consider shorter courses for patients with rapid clinical resolution following effective source control of intra-abdominal or urinary sepsis and anatomically uncomplicated pyelonephritis 1
Perform daily assessment for de-escalation of antimicrobial therapy 1, 7

Optimize dosing strategies based on pharmacokinetic/pharmacodynamic principles and specific drug properties 1, 2, 8
Consider loading doses of antimicrobials regardless of organ dysfunction to rapidly achieve therapeutic concentrations 7, 8
Consider extended or continuous infusion of beta-lactams to achieve and maintain therapeutic levels 7, 8
Adjust doses according to the presence of renal or liver dysfunction 9, 7
Procalcitonin levels can be used to support shortening antimicrobial therapy duration or discontinuing empiric antibiotics when limited clinical evidence of infection exists 1, 2

Do not use antimicrobial agents in patients with severe inflammatory states determined to be of non-infectious origin 1, 4
Initiate antiviral therapy as early as possible in patients with sepsis or septic shock of viral origin 1
Source control should be achieved within 12 hours of diagnosis when possible 1, 5
For infected peripancreatic necrosis, delay definitive intervention until adequate demarcation of viable and nonviable tissues has occurred 1

Delaying antimicrobial administration beyond one hour of sepsis recognition significantly increases mortality (8% increase in mortality for each hour of delay) 3, 5
Failing to obtain appropriate cultures before starting antimicrobials can hinder pathogen identification 2, 3
Continuing broad-spectrum or combination therapy beyond 3-5 days when de-escalation is possible increases risk of resistance, toxicity, and costs 1, 2, 6
Using antimicrobials in non-infectious inflammatory conditions 1
Inadequate dosing that fails to achieve therapeutic concentrations at infection sites 7, 8
Not adjusting antimicrobial regimens based on organ dysfunction, particularly renal impairment 9, 7