What are the recommended antibiotics for treating sepsis?

Recommended Antibiotics for Sepsis

Administer broad-spectrum IV antimicrobials within 60 minutes of recognizing sepsis or septic shock, using agents that cover all likely pathogens including gram-positive, gram-negative, and potentially anaerobic bacteria, with piperacillin/tazobactam being a preferred first-line option due to its comprehensive coverage. 1, 2, 3

Timing: The Most Critical Factor

• Start IV antibiotics within 1 hour of recognition—this is the single most important intervention for reducing mortality in sepsis 1, 3, 4
• Each hour of delay increases mortality by approximately 7.6% over the first 6 hours 1
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but never delay antimicrobials beyond 45 minutes waiting for cultures 1, 3, 4

Initial Empiric Antibiotic Selection

First-Line Broad-Spectrum Options

For most sepsis/septic shock patients, use one of the following antipseudomonal beta-lactams: 1, 2

• Piperacillin/tazobactam 4.5 g (preferred due to broad gram-positive, gram-negative, and anaerobic coverage) 1, 2
• Meropenem or imipenem/cilastatin (alternative options with similar spectrum) 1
• Ceftazidime (alternative, though narrower gram-positive coverage) 1

Dosing Strategy for Beta-Lactams

Administer piperacillin/tazobactam via extended (4-hour) or continuous infusion rather than standard 30-minute bolus to improve mortality and clinical cure rates in critically ill patients 2

• For patients with APACHE II scores ≥17, extended infusion reduces mortality from 31.6% to 12.2% 2
• Standard dosing: 4.5 g every 6-8 hours as a 4-hour extended infusion or continuous infusion after loading dose 2

Combination Therapy Considerations

When to Add a Second Agent

Consider combination therapy (two antibiotics from different classes) for septic shock, particularly in these scenarios: 1

• Septic shock with respiratory failure and suspected Pseudomonas aeruginosa—add aminoglycoside or fluoroquinolone to beta-lactam 1, 4
• Bacteremic Streptococcus pneumoniae with septic shock—add macrolide to beta-lactam 1
• Suspected catheter-related infection—add vancomycin for MRSA coverage 1
• High local resistance rates to first-line agents 2

Important Caveat on Combination Therapy

• Do NOT routinely use combination therapy for sepsis without shock or for neutropenic sepsis/bacteremia 1
• Combination therapy has not improved efficacy but has increased renal toxicity in many studies 1
• Limit combination therapy to 3-5 days maximum, then de-escalate to single-agent therapy once susceptibilities are known 1, 2

Pathogen-Specific Coverage

Common Organisms to Cover

Your empiric regimen must cover these most common sepsis pathogens: 5

• Enterobacteriaceae (E. coli, Klebsiella)
• Pseudomonas aeruginosa
• Staphylococcus aureus (including MRSA if risk factors present)
• Streptococcus pneumoniae
• Anaerobes (if intra-abdominal or aspiration source)

When to Add Specific Agents

• Add vancomycin if suspected MRSA (catheter-related, skin/soft tissue source, known colonization, high local MRSA rates) 1
• Add antifungal coverage if risk factors present (prolonged broad-spectrum antibiotics, TPN, immunosuppression) 1
• Add antiviral therapy if viral sepsis suspected (influenza season, known viral exposure) 1

De-escalation Strategy

Reassess antimicrobial therapy daily for potential narrowing once pathogen identification and sensitivities are available 1

• Narrow to the most appropriate single agent as soon as susceptibility profiles are known 1, 2
• This optimizes efficacy, prevents resistance, reduces toxicity, and minimizes costs 6, 7

Duration of Therapy

Treat for 7-10 days for most serious infections associated with sepsis 1, 6, 7

Longer Courses (>10 days) Warranted For:

• Slow clinical response 1
• Undrainable foci of infection 1
• Staphylococcus aureus bacteremia 1
• Fungal or viral infections 1
• Immunologic deficiencies including neutropenia 1

Shorter Courses Appropriate For:

• Rapid clinical resolution with effective source control 1
• Uncomplicated pyelonephritis 1
• Intra-abdominal or urinary sepsis with successful source control 1

Critical Pitfalls to Avoid

• Never delay antibiotics beyond 1 hour while awaiting additional diagnostic tests—the mortality penalty is severe 1, 3
• Avoid routine vancomycin use without specific MRSA risk factors—this contributes to resistance 5
• Do not continue combination therapy beyond 3-5 days—toxicity increases without added benefit 1
• Do not use antibiotics if severe inflammatory state is determined to be of noninfectious cause (severe pancreatitis, burns) 1
• Recent data shows 1 in 3 patients treated for suspected sepsis may not have bacterial infection, and 1 in 6 develop antibiotic-associated complications—emphasizing the importance of daily reassessment and de-escalation 8

Optimizing Pharmacokinetics

Dose antimicrobials based on pharmacokinetic/pharmacodynamic principles specific to sepsis patients 1

• Septic patients have altered volumes of distribution and clearance
• Extended or continuous infusion of beta-lactams improves outcomes in critically ill patients 2
• Consider therapeutic drug monitoring for aminoglycosides and vancomycin