What is the initial treatment approach for a patient presenting with sepsis?

Sepsis Workup and Treatment: A Practical Approach

Administer IV broad-spectrum antibiotics within one hour of recognizing sepsis or septic shock—this is the single most critical intervention, as each hour of delay increases mortality by approximately 7.6-8%. 1, 2

Immediate Recognition and Initial Assessment (Minutes 0-15)

Screen all acutely ill, high-risk patients for sepsis using clinical criteria. 3 Look for:

• Altered mental status
• Systolic blood pressure ≤100 mmHg
• Respiratory rate ≥22/min
• Signs of tissue hypoperfusion (mottled skin, delayed capillary refill, decreased urine output) 1

Do not wait for qSOFA scores or laboratory confirmation—qSOFA has poor sensitivity (31-50%) and should never delay treatment. 1

The Hour-1 Bundle: Five Critical Actions (Minutes 0-60)

1. Obtain Blood Cultures Immediately

Draw at least two sets of blood cultures (aerobic and anaerobic bottles) before antibiotics, but never delay antibiotics beyond 45 minutes if cultures cannot be obtained quickly. 3, 1 One set should be drawn percutaneously and one through each vascular access device (if present >48 hours). 3

2. Measure Lactate Level

Obtain lactate immediately and remeasure within 2-4 hours if elevated (≥2 mmol/L). 1 Target lactate normalization as a marker of adequate resuscitation. 3

3. Administer Broad-Spectrum Antibiotics Within One Hour

Start IV broad-spectrum antibiotics covering all likely pathogens (bacterial, and potentially fungal or viral) within 60 minutes of sepsis recognition. 3

Antibiotic Selection Strategy:

• For septic shock: Use combination therapy with at least two antibiotics from different classes targeting the most likely bacterial pathogens 3, 4
• For Pseudomonas aeruginosa risk (respiratory failure + septic shock): Extended-spectrum β-lactam PLUS aminoglycoside or fluoroquinolone 3
• For Streptococcus pneumoniae bacteremia with septic shock: β-lactam PLUS macrolide 3
• For sepsis without shock: Broad-spectrum monotherapy is usually sufficient 3

Administer β-lactam antibiotics as a prolonged or continuous infusion after an initial loading dose to optimize pharmacokinetics. 5

4. Rapid Fluid Resuscitation

Administer 30 mL/kg IV crystalloid bolus rapidly (over 5-10 minutes) for hypotension or lactate ≥4 mmol/L. 1, 4 Use either balanced crystalloids or normal saline. 1

Continue fluid administration as long as hemodynamic parameters improve (capillary refill, skin temperature, mental status, urine output >0.5 mL/kg/hour). 3, 4 After the initial 2L (~30 mL/kg), be cautious—less is more. 5

Consider albumin when patients require substantial crystalloids. 1, 4 Never use hydroxyethyl starches—they are contraindicated in sepsis due to renal and coagulation toxicity. 1, 4

5. Initiate Vasopressors for Persistent Hypotension

Start vasopressors if hypotension persists despite adequate fluid resuscitation, targeting mean arterial pressure (MAP) ≥65 mmHg. 3, 1, 4 Norepinephrine is the first-line vasopressor agent. 1

Consider hydrocortisone or prednisolone for patients requiring escalating vasopressor doses, particularly those with refractory septic shock. 1, 4

Source Control (Within 12 Hours)

Identify and control the infection source within 12 hours when feasible—do not delay surgical intervention or drainage procedures. 1, 4 Use the least invasive effective intervention (percutaneous drainage over open surgery when possible). 1, 4

Remove intravascular access devices promptly after establishing alternative access if they are a possible infection source. 1, 4

Antimicrobial De-escalation and Duration (Days 1-10)

Reassess antimicrobial therapy daily for potential de-escalation once culture results and clinical response are available. 3, 1

Narrow therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted. 3

If combination therapy was used for septic shock, discontinue it within 3-5 days in response to clinical improvement and/or evidence of infection resolution. 3, 4

Duration Guidelines:

• Standard duration: 7-10 days for most serious infections 3, 4
• Longer courses (>10 days): Slow clinical response, undrainable foci, Staphylococcus aureus bacteremia, fungal/viral infections, immunodeficiency including neutropenia 3, 4
• Shorter courses (<7 days): Rapid clinical resolution with effective source control (uncomplicated pyelonephritis, intra-abdominal/urinary sepsis with source control) 3

Use procalcitonin levels to support discontinuing empiric antibiotics in patients initially suspected of sepsis but with no subsequent evidence of infection. 1

Ongoing Monitoring and Supportive Care

Reassess hemodynamic status frequently after initial interventions: 1

• Capillary refill time and skin temperature
• Mental status
• Urine output (target >0.5 mL/kg/hour)
• Lactate clearance

For mechanically ventilated patients with sepsis-induced ARDS, use lower tidal volumes (6 mL/kg ideal body weight) and limit plateau pressures to ≤30 cmH₂O. 1

Target hemoglobin between 8-9 g/dL for acute anemia, adjusting based on clinical tolerance. 1

Provide pharmacological or mechanical deep vein thrombosis prophylaxis. 1

Critical Pitfalls to Avoid

• Delaying antibiotics beyond one hour—mortality increases 8% per hour of delay 1, 2
• Inadequate initial fluid resuscitation or failure to reassess after the first bolus 4
• Continuing broad-spectrum antibiotics without de-escalation once cultures return 4
• Using hydroxyethyl starches for resuscitation 1, 4
• Failure to identify and control infection source within 12 hours 4
• Relying on qSOFA scores to initiate treatment—start the Hour-1 Bundle immediately when sepsis is suspected 1