What is the management of urosepsis (urinary tract infection causing sepsis)?

From the Guidelines

Management of urosepsis requires prompt recognition and aggressive treatment with broad-spectrum antibiotics, such as piperacillin-tazobactam 4.5g IV every 6 hours or ceftriaxone 2g IV daily plus an aminoglycoside, within one hour of recognition, as recommended by the Surviving Sepsis Campaign guidelines 1. The initial management should focus on early administration of these antibiotics after obtaining blood and urine cultures.

• Appropriate empiric antibiotic choices also include a carbapenem like meropenem 1g IV every 8 hours.
• Source control is essential, which typically involves relieving urinary tract obstruction through placement of a urinary catheter, percutaneous nephrostomy, or removal of infected stones or devices.
• Fluid resuscitation with crystalloids (30 ml/kg within the first 3 hours) is crucial to maintain adequate tissue perfusion, as suggested by the European Association of Urology guidelines 1.
• Hemodynamic support with vasopressors, particularly norepinephrine starting at 0.05-0.1 mcg/kg/min, may be necessary if hypotension persists despite fluid resuscitation.
• Antibiotic therapy should be tailored based on culture results and continued for 7-14 days depending on clinical response and the specific pathogen, with a recommended duration of 7 to 10 days for most serious infections associated with sepsis and septic shock 1.
• Close monitoring of vital signs, urine output, and laboratory parameters including lactate levels, renal function, and inflammatory markers is essential to guide ongoing management.
• The underlying pathophysiology involves bacterial invasion from the urinary tract triggering a systemic inflammatory response, which can lead to endothelial damage, microcirculatory dysfunction, and ultimately organ failure if not promptly addressed.
• Daily assessment for de-escalation of antimicrobial therapy in patients with sepsis and septic shock is recommended 1.
• Measurement of procalcitonin levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients 1.

From the FDA Drug Label

1.3 Uncomplicated and Complicated Urinary Tract Infections (including pyelonephritis) Cefepime Injection is indicated for uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by Escherichia coli or Klebsiella pneumoniae, when the infection is severe, or caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis, when the infection is mild to moderate, including cases associated with concurrent bacteremia with these microorganisms.

The management of urosepsis may involve the use of cefepime for severe uncomplicated or complicated urinary tract infections, including pyelonephritis, caused by Escherichia coli or Klebsiella pneumoniae. The recommended dose is 2 g IV every 12 hours for 10 days 2.

INDICATIONS AND USAGE: ...Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: ...Escherichia coli, Klebsiella-Enterobacter-Serratia species, ...

Gentamicin may also be considered for the treatment of serious infections, including those caused by Escherichia coli and Klebsiella species 3. However, the use of gentamicin should be based on the results of susceptibility tests and the severity of the infection.

• Key points:
  • Cefepime may be used for severe urinary tract infections, including pyelonephritis.
  • Gentamicin may be considered for serious infections, including those caused by Escherichia coli and Klebsiella species.
  • The choice of antibiotic should be based on susceptibility tests and the severity of the infection.

From the Research

Management of Urosepsis

• Urosepsis is a serious, life-threatening complication of infections originating from the urinary tract, with high morbidity and mortality rates despite optimal treatment 4.
• The management of urosepsis comprises four major aspects:
  • Early diagnosis
  • Early empiric intravenous antimicrobial treatment
  • Identification and control of complicating factors
  • Specific sepsis therapy 4, 5
• Empirical antibiotic therapy should be instigated within the first hour after diagnosis, with urine cultures and blood cultures performed before antibiotic treatment 6.
• The choice of antibiotics should be based on local resistance patterns and the expected pathogen spectrum, with consideration of the risk of resistant organisms 6, 7.

Diagnostic Evaluation

• The diagnostic evaluation of urosepsis includes physical examination, blood cultures, urinalysis, procalcitonin measurement, and ultrasonography 7.
• The quick sequential organ failure assessment is replacing the systemic inflammatory response syndrome scoring for rapid identification of patients with urosepsis 4.

Treatment Challenges

• Treatment challenges arise from the rapid increase of antibiotic resistance in Gram-negative bacteria, especially extended-spectrum β-lactamase (ESBL)-producing bacteria 6, 5.
• The use of broad-spectrum beta-lactam antibiotics, such as piperacillin/tazobactam, carbapenems, and cephalosporin/beta-lactamase inhibitor combinations, may be effective in the treatment of urosepsis 6.
• However, the choice of antibiotic should be guided by local resistance patterns and the expected pathogen spectrum, and combination therapy should be de-escalated to monotherapy after 48-72 hours 6.

Outcomes and Mortality

• Delay in the treatment of urosepsis with antibiotics can lower the survival rate, with each additional hour of delay associated with a 7.6% decrease in survival rate 7.
• Mortality rates for urosepsis are high, ranging from 20-40%, although patients' outcomes have improved recently with the use of minimally invasive treatments to neutralize foci of infection 7.
• The choice of antibiotic may also impact mortality, with some studies suggesting that certain antibiotics may be associated with higher mortality rates 8.