What antibiotics are recommended for initial management of sepsis?

Initial Antibiotic Management for Sepsis

Administer broad-spectrum intravenous antibiotics within one hour of recognizing sepsis or septic shock, using empiric therapy that covers all likely bacterial pathogens including gram-positive, gram-negative, and anaerobic organisms. 1

Timing of Antibiotic Administration

• IV antimicrobials must be initiated within the first hour of sepsis or septic shock recognition 1
• Each hour of delay in antibiotic administration increases mortality risk by approximately 8% in patients progressing from severe sepsis to septic shock 2
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, but do not delay antibiotic administration beyond 45 minutes to obtain cultures 1

Empiric Antibiotic Selection

Standard Sepsis (Without Shock)

• Use broad-spectrum monotherapy with an extended-spectrum beta-lactam such as piperacillin-tazobactam 4.5g IV every 6 hours (or 3.375g IV every 6 hours for higher time above MIC) 3, 4
• Alternative agents include carbapenems (imipenem-cilastatin 500mg-1g IV every 6-8 hours) for broader coverage 3
• Coverage must include activity against gram-positive, gram-negative, and anaerobic bacteria 1

Septic Shock

• Combination therapy is recommended using at least two antibiotics from different antimicrobial classes 1, 5
• Beta-lactam component: Piperacillin-tazobactam 4.5g IV every 6 hours OR imipenem-cilastatin 500mg-1g IV every 6-8 hours 3
• PLUS MRSA coverage: Vancomycin (dose adjusted to achieve trough 15-20 mcg/mL) OR linezolid 600mg IV every 12 hours 3
• This combination provides coverage for resistant gram-positive organisms (including MRSA), gram-negative bacteria (including Pseudomonas), and anaerobes 3, 5

Specific Clinical Scenarios

For Pseudomonas aeruginosa with respiratory failure and septic shock:

• Combine an extended-spectrum beta-lactam with either an aminoglycoside OR a fluoroquinolone 1, 5

For Streptococcus pneumoniae bacteremia with septic shock:

• Combine a beta-lactam with a macrolide 1, 5

For neutropenic patients:

• Use broad-spectrum empiric therapy, but do not routinely use combination therapy for ongoing treatment once pathogen is identified 1

Additional Coverage Considerations

• Antifungal therapy (fluconazole or echinocandin) should be considered if the patient has recent antibiotic exposure, central venous catheter, or total parenteral nutrition 3
• Anaerobic coverage is essential for intra-abdominal infections or when anaerobes are likely pathogens 2
• Consider local antibiogram and resistance patterns when selecting agents 2, 6

Dosing Optimization

• Administer loading doses of beta-lactams to rapidly achieve therapeutic levels, especially in critically ill patients with expanded extracellular volume from fluid resuscitation 1
• Extended or continuous infusions of beta-lactams (infused over 3-4 hours rather than 30 minutes) maximize time above MIC and may improve outcomes in critically ill patients 1, 7
• For piperacillin-tazobactam, infuse over at least 30 minutes; extended infusions are preferred for septic shock 4
• Optimize dosing based on pharmacokinetic/pharmacodynamic principles, targeting time above MIC of 100% for severe infections 1, 5

De-escalation Protocol

• Reassess antimicrobial therapy daily for potential narrowing of spectrum 1, 5
• Discontinue combination therapy within 3-5 days once clinical improvement occurs and/or culture results are available 1, 5
• Narrow therapy once pathogen identification and susceptibilities are established 1
• Typical treatment duration is 7-10 days; longer courses may be necessary for slow clinical response, inadequate source control, or S. aureus bacteremia 5, 8, 9

Critical Pitfalls to Avoid

• Do not delay antibiotics to obtain cultures if it will take longer than 45 minutes 1
• Do not use combination therapy routinely for non-shock sepsis or continue it beyond 3-5 days without clear indication 1
• Avoid vancomycin plus piperacillin-tazobactam combination when not necessary, as this increases acute kidney injury risk 6
• Do not mix piperacillin-tazobactam with lactated Ringer's solution or solutions containing only sodium bicarbonate 4
• Separate administration of aminoglycosides from piperacillin-tazobactam due to in vitro inactivation; if Y-site co-administration is necessary, follow specific compatibility guidelines 4