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

Immediate Actions (Hour-1 Bundle)

Blood Cultures and Antimicrobial Therapy

• Collect at least 2 sets of blood cultures before starting antimicrobials—one drawn percutaneously and one through each vascular access device (unless inserted <48 hours prior)—but do not delay antibiotic administration beyond 1 hour waiting for cultures, as each hour of delay decreases survival by approximately 7.6% 1, 2
• Administer broad-spectrum intravenous antibiotics within the first hour, with initial empiric therapy active against all likely pathogens (predominantly Gram-negative organisms including Pseudomonas aeruginosa, E. coli, Klebsiella pneumoniae, and Enterobacter species) 1, 3, 4
• For empiric therapy, use piperacillin/tazobactam, carbapenems, or cephalosporin/beta-lactamase inhibitor combinations as monotherapy; alternatively, combine cephalosporins (such as cefepime 2g IV every 8-12 hours) with aminoglycosides (preferred) or fluoroquinolones 5, 4
• Consider ESBL-producing organisms in nosocomial cases and adjust empiric coverage accordingly 4

Lactate Measurement and Resuscitation Goals

• Obtain initial lactate level to assess tissue hypoperfusion, and remeasure within 2-4 hours if elevated (≥2 mmol/L), targeting lactate normalization as a marker of adequate resuscitation 1, 2
• Target the following resuscitation goals: central venous pressure (CVP) 8-12 mmHg, mean arterial pressure (MAP) ≥65 mmHg, urine output ≥0.5 mL/kg/hr, and central venous oxygen saturation (ScvO2) ≥70% or mixed venous oxygen saturation (SvO2) ≥65% 3

Fluid Resuscitation

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

Vasopressor Support

• Start vasopressors if hypotension persists despite adequate fluid resuscitation, with norepinephrine as the first-choice vasopressor, targeting MAP ≥65 mmHg 1, 2, 3
• Add vasopressin or epinephrine to norepinephrine when an additional agent is needed 3

Source Control (Critical for Urosepsis)

Implement source control within 12 hours when feasible, as urosepsis is most commonly caused by obstructive uropathy of the upper urinary tract, with ureterolithiasis being the most common cause. 1, 6

• Obtain urgent imaging (ultrasound, CT) to identify urological obstruction, abscess, or other complicating factors 1, 7, 6
• Use the least invasive effective approach, such as percutaneous drainage or ureteral stent placement, to manage urological obstruction or abscess 1, 2, 3
• Remove potentially infected intravascular access devices promptly after establishing alternative vascular access 2, 3
• Early control of the infectious focus is as important as early antibiotic therapy and is uniquely achievable in most urosepsis cases 8, 6

Additional Hemodynamic Support

Inotropic Therapy

• Use dobutamine when cardiac output remains low with ScvO2 <70% despite adequate fluid resuscitation and vasopressor use (occurs in 10-20% of adult sepsis cases) 1, 2, 3

Corticosteroid Therapy

• Use hydrocortisone 200-300 mg/day only for septic shock refractory to adequate fluid resuscitation and vasopressor therapy 1, 2, 3

Antimicrobial De-escalation and Duration

• Reassess antimicrobial regimen daily for potential de-escalation once culture results and clinical response are available 1, 2, 3
• If combination therapy is given initially, 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, 3

Supportive Measures

Transfusion Therapy

• Transfuse red blood cells when hemoglobin <7.0 g/dL once tissue hypoperfusion has resolved, targeting hemoglobin 8-9 g/dL during acute resuscitation if ScvO2 <70% 1, 2, 3
• Administer platelets prophylactically when counts <10,000/mm³ without bleeding or <20,000/mm³ with significant bleeding risk 3

Nutrition and Prophylaxis

• Provide early enteral nutrition rather than complete fasting or IV glucose alone, avoiding mandatory full caloric feeding in the first week 1, 3
• Administer daily pharmacologic VTE prophylaxis with low-molecular weight heparin or unfractionated heparin 1, 2

Respiratory Support

• Administer oxygen to achieve saturation ≥90% and position patients semi-recumbent or laterally 2
• 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 2

Key Urosepsis-Specific Considerations

Optimal antibacterial exposure requires achieving therapeutic concentrations both in plasma and in the urinary tract, making drugs with low renal excretion rates less suitable for urosepsis. 8

• Renal pharmacokinetics differ in unilateral versus bilateral renal impairment and obstruction, requiring dose adjustments 8
• Biofilm infections frequently found in catheter-associated UTI may increase MICs by several hundred-fold, necessitating higher doses 8
• Optimal catheter care and strategies to prevent nosocomial UTI can reduce the frequency of urosepsis 8, 9