Mr. H, 70, presented to the ED with complaints of low back pain, painful urination, fever, and chills that began earlier in the day. He underwent a lithotripsy 1 week earlier and had a medical history significant for diabetes mellitus and liver transplant 5 years earlier. On initial presentation, Mr. H was awake, alert, and ambulatory; his vital signs were: temperature, 102[degrees] F (38.9[degrees] C); heart rate, 120 beats/minute; respiratory rate, 22 breaths/minute; and BP, 110/70 mm Hg.

Forty-five minutes later, Mr. H's vitals were: temperature, 103.2[degrees] F (39.6[degrees] C); heart rate, 132 beats/minute; respiratory rate, 28 breaths/minute; and BP, 80/50 mm Hg. His physical exam was significant for lethargy, dry mucous membranes, costovertebral angle tenderness, and mottling bilaterally up to his knees. His lab tests included a white blood cell count of 1,000/mm3 and lactic acid of 4.3 mmol/L. Mr. H was diagnosed with urosepsis and needed prompt interventions to avoid further hemodynamic compromise.

Introduction

Sepsis is a life-threatening condition that has an associated mortality of up to 41.1%.1 Specifically, sepsis secondary to a urinary tract infection (UTI) accounts for nearly 25% of all sepsis cases.2 The urinary tract is the second most common infection site, accounting for approximately 20% to 40% of all severe cases of sepsis in patients.2 Given the high incidence and severity of sepsis, early recognition and appropriate management of UTIs play a vital role in preventing the disease progression to urosepsis.

Diagnosing sepsis

New definitions for sepsis and septic shock (Sepsis-3) were published in 2016. Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.3 Septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality.3 Patients with septic shock can be identified with the clinical criteria of hypotension, requiring vasopressor therapy to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L in the absence of hypovolemia.3

Risk factors for urosepsis

Urosepsis is an infection arising from the urinary or genital organs that manifests with systemic signs and symptoms. Common causes of urosepsis include obstructive etiologies, such as urethral stones, tumors, urethral strictures, phimosis, ureterocele, polycystic kidney disease, and pregnancy.4 Patients with indwelling urethral catheters, ureteric stents, nephrostomy tubes, neurogenic bladder, cystocele, and vesicoureteral reflux are at a higher risk for developing urosepsis.4 Hospitalized patients and those in long-term-care facilities are at a higher risk to develop infections with drug-resistant organisms.4

Even though microbial pathogens are the primary culprit in any infection, the host defense mechanism also plays a role in urosepsis. Patients with a weakened immune system, such as older adults and patients with chronic metabolic disorders (diabetes mellitus and chronic kidney disease), AIDS, immunosuppression due to transplantation, neutropenia resulting from chemotherapy, or chronic corticosteroid use, are also at a higher risk to develop urosepsis.4 When these high-risk patients develop a UTI, it is considered to be a complicated UTI, which is the most common precursor to urosepsis.4

Clinical signs and symptoms

Clinical signs of UTIs include fever, nausea, vomiting, flank pain, costovertebral angle tenderness, dysuria, hematuria, malodorous urine, urinary retention, urinary frequency, and prostatic/scrotal pain in men.2 In the early stages of urosepsis, the patient will have an increase in cardiac output, systemic vasodilation, and a significant decrease in systemic vascular resistance, resulting in a dramatic intravascular volume loss.4 The patient will also have hyperdynamic circulation with warm skin, bounding pulses, tachycardia, tachypnea, and a febrile flushed appearance.

To compensate for the low intravascular volume, catecholamines are released to increase cardiac output and myocardial contractility. However, given the low intravascular volume, these compensatory mechanisms are not adequate enough to maintain BP. This progresses to hypotension and hypoperfusion to the tissues, resulting in cellular energy loss and lactic acid production.4 This is seen as severe lactic acidosis and septic shock. This state of septic shock is usually irreversible with severe tissue hypoperfusion and systemic vasoconstriction. The two ominous signs of septic shock include hypothermia and leukopenia.5

Other signs and symptoms of tissue hypoperfusion include cold extremities, mottled skin far above the knees, flank pain, renal angle tenderness, ureteric or renal colic, and dysuria. This toxic sequela further leads to hypoperfusion in other organs clinically seen with multiple organ failure, such as respiratory failure with acute respiratory distress syndrome, acute kidney failure, hepatic failure, and disseminated intravascular coagulation.3

Antimicrobial management

Appropriate antimicrobial management is essential in preventing UTIs from progressing to urosepsis. Previous antimicrobial regimens that have failed patients presenting with urosepsis should be avoided. Urosepsis is most frequently caused by Gram-negative bacilli organisms, with Escherichia coli (50%) being the most common organism in urosepsis.4Proteus spp. (15%), Enterobacter and Klebsiella (15%), and Pseudomonas aeruginosa (5%) are the other common organisms isolated in urosepsis.4

Gram-positive organisms are less frequently seen in urosepsis.4 Antibiotic therapy should be individualized for each patient based on local pathogen susceptibility and resistant pathogens.6 According to local susceptibility patterns, a third-generation cephalosporin, piperacillin in combination with beta-lactamase inhibitor (BLI), or a fluoroquinolone (without history of fluoroquinolone therapy in the past 6 months) may be appropriate antibiotic choices.2

Candida and Pseudomonas are more frequently seen in patients with an impaired host defense; therefore, an antifungal and antipseudomonal drug, such as third-generation cephalosporin, piperacillin in combination with BLI, or a carbapenem, should be considered in this high-risk patient population.2 Institutions with a high incidence of enterobacteriaceae with extended-spectrum beta-lactamase or fluoroquinolone-resistant E. coli should initiate empirical therapy with a carbapenem.2

Surviving Sepsis Campaign

The Surviving Sepsis Campaign (SSC) aims to reduce sepsis mortality, and along with new definitions, the guidelines for management of sepsis and septic shock were updated in 2016. Upon initial clinical suspicion of sepsis, SSC guidelines recommend initial fluid resuscitation with at least 30 mL/kg of I.V. crystalloid fluid given within the first 3 hours.1 Ongoing reevaluation including clinical exam of physiologic variables (such as temperature, heart rate, respiratory rate, BP, arterial oxygen saturation, and urine output) remains key in assessing response to therapy.1

Aggressive fluid resuscitation can help restore hemodynamics and increase oxygen delivery to tissues in patients with sepsis. Empiric broad-spectrum antimicrobials should be initiated as soon as possible and within 1 hour of diagnosis.1 Microbiologic cultures including blood and urine should be collected prior to antimicrobial administration; however, antimicrobial administration should not be delayed.1 Delay in antimicrobial administration is associated with an increase in mortality.1 De-escalation of antimicrobials should be done once culture data results in pathogen identification and sensitivities are obtained.1

Norepinephrine, the first vasopressor of choice, should be given to patients with septic shock to maintain a mean arterial pressure greater than 65 mm Hg.1 SSC guidelines recommend additional intensive care strategies to manage sepsis and septic shock, with the emphasis on early antimicrobial therapy, and initial aggressive fluid resuscitation.1

Case study revisited

Mr. H received antimicrobials within the hour, was adequately fluid resuscitated, and was transferred to ICU where he recovered from urosepsis.

Achieving optimal outcomes

Urosepsis has a high mortality, and the main focus still remains on prevention with a proactive approach. High-risk patients should always be carefully monitored and assessed for any signs and symptoms of developing UTIs. Patients with diagnosed UTIs should be closely monitored for worsening infection and developing sepsis or septic shock. Screening tools can aid in identifying sepsis early in acutely ill hospitalized patients, leading to lower mortality.1 Early detection of urosepsis allows for early intervention, which can hinder the progression of the disease process and optimize outcomes.

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