What antibiotic should be started in a patient with suspected sepsis?

Empiric Antibiotic Selection for Suspected Sepsis

Initiate broad-spectrum intravenous antibiotics within one hour of sepsis recognition, selecting agents that cover all likely bacterial pathogens based on the suspected source of infection and local resistance patterns. 1

Immediate Antibiotic Administration

• Administer IV antimicrobials within the first hour of recognizing sepsis or septic shock—this is a strong recommendation that directly impacts mortality. 1, 2
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, but do not delay antibiotic administration beyond 45 minutes if cultures cannot be obtained quickly. 1

Empiric Antibiotic Selection Strategy

For Septic Shock (Most Critical)

Use combination therapy with at least two antibiotics from different antimicrobial classes targeting the most likely bacterial pathogens. 1, 2

Specific regimens based on suspected source:

• Respiratory source with shock and suspected Pseudomonas: Combine an extended-spectrum β-lactam (such as piperacillin-tazobactam or ceftazidime) with either an aminoglycoside or fluoroquinolone. 1, 2
• Suspected Streptococcus pneumoniae bacteremia with shock: Combine a β-lactam with a macrolide. 1, 2
• Neutropenic patients or suspected multidrug-resistant organisms (Acinetobacter, Pseudomonas): Use combination therapy with broad-spectrum coverage. 1

For Sepsis Without Shock

• Broad-spectrum monotherapy is generally sufficient unless specific risk factors for resistant organisms exist. 1
• An antipseudomonal β-lactam (such as ceftazidime, cefepime, or piperacillin-tazobactam) provides appropriate initial coverage for most community-acquired and healthcare-associated infections. 3, 4, 5

Critical Selection Factors

Base antibiotic choice on:

• Suspected infection source (pneumonia, urinary tract, intra-abdominal, skin/soft tissue, catheter-related). 1
• Local antibiotic resistance patterns in your institution and community. 1, 4
• Recent antibiotic exposure within 90 days (increases MDR risk). 6
• Healthcare exposure (hospitalization, nursing home residence, dialysis, immunosuppression). 6
• Adequate tissue penetration to the presumed infection site. 1

Common Empiric Regimens

For most sepsis presentations without specific risk factors:

• Cefepime 2g IV every 8-12 hours OR piperacillin-tazobactam 4.5g IV every 6 hours. 5, 7

Add vancomycin (15-20 mg/kg loading dose) if:

• MRSA risk factors present (prior MRSA, IV drug use, hemodialysis, recent hospitalization). 4, 7
• Severe skin/soft tissue infection. 4
• Pneumonia with necrotizing features or post-influenza. 4

Avoid routine vancomycin use without specific indications to reduce nephrotoxicity risk. 7

De-escalation Protocol (Critical for Outcomes)

• Reassess antimicrobial regimen daily for potential narrowing based on culture results and clinical response. 1
• Discontinue combination therapy within 3-5 days and switch to targeted single-agent therapy once susceptibilities are known. 1, 2
• Stop antibiotics entirely if infection is ruled out as the cause of the inflammatory state. 1
• Use procalcitonin levels to guide discontinuation in patients without confirmed infection. 1

Duration of Therapy

• Typical duration is 7-10 days for most sepsis cases. 1, 2
• Extend therapy beyond 10 days only for slow clinical response, undrainable infection foci, S. aureus bacteremia, or immunocompromised states. 1, 2

Dosing Optimization

• Use loading doses for all patients regardless of renal function to achieve rapid therapeutic levels. 6
• Optimize subsequent dosing based on pharmacokinetic/pharmacodynamic principles, considering renal/hepatic function. 1, 2
• Consider extended or continuous infusion of β-lactams in critically ill patients to maximize time above MIC. 6
• Implement therapeutic drug monitoring when available. 6

Common Pitfalls to Avoid

• Delaying antibiotics to obtain cultures—cultures are important but never worth delaying treatment beyond one hour. 1, 8
• Using narrow-spectrum agents initially—inadequate initial coverage increases mortality; you can always de-escalate later. 1
• Continuing combination therapy beyond 3-5 days—this increases toxicity without improving outcomes. 1, 2
• Failing to reassess daily—prolonged unnecessary antibiotics drive resistance and cause harm. 1, 6