What is the treatment for severe urosepsis?

Treatment of Severe Urosepsis

Administer broad-spectrum intravenous antibiotics within the first hour of recognition, initiate aggressive fluid resuscitation with 30 mL/kg crystalloid bolus, and obtain urgent imaging to identify and control any urological obstruction or abscess within 12 hours. 1, 2, 3

Immediate Actions (Hour-1 Bundle)

1. Obtain Cultures Before Antibiotics

• Collect at least 2 sets of blood cultures (one percutaneous, one through vascular access if present) before starting antimicrobials 1, 2
• Obtain urine cultures simultaneously 4, 5
• Do not delay antibiotic administration beyond 1 hour waiting for cultures - each hour of delay decreases survival by approximately 7.6% 2

2. Measure Lactate Immediately

• Obtain initial lactate level to assess tissue hypoperfusion 1, 2
• Remeasure within 2-4 hours if elevated (≥2 mmol/L) to guide resuscitation 2
• Target lactate normalization as a marker of adequate resuscitation 6, 1

3. Administer Broad-Spectrum Antibiotics Within 1 Hour

Empiric antibiotic selection for urosepsis:

• First-line monotherapy options: 4

  • Piperacillin-tazobactam
  • Carbapenems (meropenem or imipenem)
  • New cephalosporin/beta-lactamase inhibitor combinations

• Alternative combination therapy: 4

  • Cephalosporin (e.g., cefepime 2g IV every 8-12 hours) 7 PLUS aminoglycoside (preferred) or fluoroquinolone
  • De-escalate combination to monotherapy after 48-72 hours based on culture results 4

• Key consideration: Gram-negative pathogens predominate in urosepsis, with increasing prevalence of ESBL-producing bacteria; carbapenemase-producing Enterobacteriaceae remain rare 4, 8

4. Aggressive Fluid Resuscitation

• Administer 30 mL/kg crystalloid bolus rapidly (over 5-10 minutes) for hypotension or lactate ≥4 mmol/L 1, 2
• Use crystalloids (normal saline or balanced crystalloids) as initial fluid of choice 1, 2
• Continue fluid administration as long as hemodynamic parameters improve based on dynamic assessment (pulse pressure variation, stroke volume variation) or static variables (MAP, heart rate, capillary refill, skin mottling) 2
• Consider albumin when substantial crystalloids are required 2
• Never use hydroxyethyl starches - they are contraindicated in sepsis 2

5. Initiate Vasopressors for Persistent Hypotension

• Start vasopressors if hypotension persists despite adequate fluid resuscitation 1, 2
• Norepinephrine is the first-choice vasopressor 6, 1
• Target mean arterial pressure (MAP) ≥65 mmHg 6, 1
• Add vasopressin (0.01-0.04 units/min) or epinephrine as second-line agents for refractory shock 6, 1

Early Goal-Directed Therapy (First 6 Hours)

Target the following physiologic endpoints during initial resuscitation: 6, 1

• Central venous pressure (CVP): 8-12 mmHg
• Mean arterial pressure (MAP): ≥65 mmHg
• Urine output: ≥0.5 mL/kg/hour
• Central venous oxygen saturation (ScvO2): ≥70% OR mixed venous oxygen saturation (SvO2) ≥65%
• Lactate normalization: Target resolution of elevated lactate

Source Control - Critical for Urosepsis

This is the defining feature that distinguishes urosepsis management from general sepsis:

• Obtain urgent imaging (CT or ultrasound) to identify urological obstruction or abscess 3, 5

• Implement source control within 12 hours when feasible - do not delay 1, 2, 5

• Common causes requiring intervention: 5

  • Obstructed uropathy (most common - ureterolithiasis)
  • Renal or perinephric abscess
  • Prostatic abscess
  • Infected hydronephrosis

• Use the least invasive effective approach: 1, 2

  • Percutaneous drainage preferred over surgical drainage when possible
  • Ureteral stent or nephrostomy tube for obstruction
  • Remove infected urinary catheters and replace after establishing alternative access 1

Inotropic Support (If Needed)

• Use dobutamine when cardiac output remains low with ScvO2 <70% despite adequate fluid resuscitation and vasopressor use 6, 1
• Indication: 10-20% of adults with sepsis develop persistent cardiac failure (low cardiac index and mixed venous oxygen saturation) despite adequate volume expansion 6, 2
• Combination of dobutamine plus norepinephrine is first-line inotropic strategy 6

Corticosteroid Therapy

• Use hydrocortisone 200-300 mg/day (or 50 mg IV every 6 hours) only for septic shock refractory to adequate fluid resuscitation and vasopressor therapy 6, 1
• Continue for at least 5 days, then taper 6
• Consider in patients with suspected absolute adrenal insufficiency 6

Antimicrobial De-escalation and Duration

• Reassess antimicrobial regimen daily for potential de-escalation once culture results and clinical response are available 1, 2, 4
• If combination therapy was initiated, de-escalate to monotherapy after 48-72 hours 4
• Use procalcitonin or similar biomarkers to assist in discontinuing empiric antibiotics when no subsequent evidence of infection 1, 2
• Typical duration: 7-10 days for uncomplicated urosepsis, longer if source control incomplete 5

Additional Supportive Measures

Blood Product Management

• Transfuse red blood cells when hemoglobin <7.0 g/dL once tissue hypoperfusion has resolved 1
• Target hemoglobin 8-9 g/dL during acute resuscitation if ScvO2 <70% 6
• Administer platelets prophylactically when counts <10,000/mm³ without bleeding or <20,000/mm³ with significant bleeding risk 1

Glucose Control

• Target blood glucose <180 mg/dL using protocolized insulin therapy 6, 1
• Monitor glucose every 1-2 hours until stable, then every 4 hours 6

Nutrition

• Provide early enteral nutrition rather than complete fasting or IV glucose alone 6, 1, 2
• Avoid mandatory full caloric feeding in first week; use low-dose feeding (up to 500 calories/day) advancing as tolerated 6

Thromboprophylaxis

• Administer daily pharmacologic VTE prophylaxis with low-molecular weight heparin or unfractionated heparin 6, 1, 2
• Use mechanical prophylaxis (compression devices) if anticoagulation contraindicated 6

Stress Ulcer Prophylaxis

• Provide H2 blocker or proton pump inhibitor (PPI preferred) for patients with bleeding risk factors 6

Common Pitfalls to Avoid

• Delaying antibiotics to obtain cultures - cultures are important but should never delay antibiotics beyond 1 hour 2, 3
• Inadequate initial fluid resuscitation - the 30 mL/kg bolus is a minimum starting point, not a maximum 1, 2
• Failure to obtain early imaging - urological obstruction is the most common cause and requires urgent intervention 3, 5
• Using static CVP measurements alone to guide fluid therapy - dynamic assessments are superior 2
• Continuing combination antibiotic therapy beyond 48-72 hours without reassessment 4
• Inadequate dosing of antibiotics - use high-dose regimens appropriate for severe infection (e.g., cefepime 2g every 8 hours for Pseudomonas coverage) 7, 4

Goals of Care Discussion

• Discuss goals of care and prognosis with patients and families early, ideally within 72 hours of ICU admission 6, 1
• Incorporate palliative care principles where appropriate given the 30-40% mortality rate of severe sepsis/septic shock 5