Broad-Spectrum Antibiotics for Sepsis
For sepsis, the recommended first-line empiric broad-spectrum antibiotics include third-generation cephalosporins (ceftriaxone), piperacillin/tazobactam, or a combination of a beta-lactam with an aminoglycoside (such as gentamicin). 1
Initial Antibiotic Selection
First-line options:
Third-generation cephalosporins:
- Ceftriaxone: 1-2 g IV every 24 hours
- Cefotaxime: 2 g IV every 8 hours
Beta-lactam/beta-lactamase inhibitor combinations:
Carbapenems (for suspected resistant organisms):
- Meropenem or imipenem 3
For severe sepsis/septic shock:
- Combination therapy is recommended:
- Third-generation cephalosporin + aminoglycoside (gentamicin 5 mg/kg IV every 24 hours or amikacin 15 mg/kg IV every 24 hours)
- OR Piperacillin/tazobactam + aminoglycoside 1
Special Populations
Neonatal Sepsis:
Early-onset (first 72 hours of life):
- Benzylpenicillin plus gentamicin OR
- Ampicillin plus gentamicin 4
Late-onset (>72 hours to 1 month):
- For coagulase-negative staphylococci: vancomycin
- For GBS, E. coli, enterococci: cefotaxime or piperacillin/tazobactam 4
Pediatric Sepsis:
- Suspected sepsis:
- Ceftriaxone (plus ampicillin or amoxicillin in neonates up to 3 months)
- Benzylpenicillin and gentamicin in neonates with early-onset sepsis 4
Antibiotic Resistance Considerations
Antibiotic resistance patterns should guide therapy, particularly for:
- MRSA (11.7% prevalence in community-onset sepsis)
- Ceftriaxone-resistant organisms (13.1%)
- Extended-spectrum β-lactamase producers (0.8%) 5
Despite relatively low prevalence of resistant organisms in community-onset sepsis (13.6% for resistant gram-positive and 13.2% for resistant gram-negative organisms), broad-spectrum antibiotics are frequently administered 5
Important Caveats
Obtain blood cultures before initiating antibiotics but do not delay antibiotic administration while waiting for cultures 1
Reassess antibiotic regimen daily for de-escalation opportunities once culture and susceptibility results are available (typically within 48-72 hours) 1
Both inadequate and unnecessarily broad empiric antibiotic therapy are associated with increased mortality (OR 1.19 and 1.22 respectively) 5
The timing of antibiotic administration is critical - initiate within 1 hour of recognition of sepsis 1
Source control (identifying and addressing the source of infection within 12 hours) is essential for optimal outcomes 1
Duration of Treatment
- Standard duration: 7-10 days
- Consider shorter treatment (5-7 days) in patients with rapid clinical resolution
- Longer treatment may be necessary for slow clinical response, undrainable infectious foci, or immunocompromised patients 1
Empiric antibiotic therapy should be tailored based on local resistance patterns, patient risk factors, and suspected source of infection, with prompt de-escalation once culture results become available to minimize the risk of developing antibiotic resistance.