Urinary Tract Infection With Sepsis in the Elderly Case File

Urinary Tract Infection With Sepsis in the Elderly Case File

Eugene C. Toy, MD, Gabriel M. Aisenberg, MD

Case 41

An 84-year-old woman is brought to the emergency department by ambulance from her long-term care facility for increased confusion, combativeness, and fever. Her medical history is significant for Alzheimer disease and well-controlled hypertension. The patient is “confused” and combative with the staff, which, per her family, is not her baseline mental status. Her temperature is 100.5 °F, heart rate is 130 beats per minute (bpm), blood pressure is 76/32 mm Hg, respiratory rate is 24 breaths per minute, and oxygen saturation is 95% on room air. On examination, she is lethargic but agitated when disturbed, her neck veins are flat, her lung fields are clear, and her heart rhythm is regular and tachycardic without murmur or gallops. Abdominal examination is unremarkable, and her extremities are warm and pink.

After administration of 2 L of normal saline over 60 minutes, her blood pressure is 95/58 mm Hg. The initial laboratory work returns. Her white blood cell count (WBC) is 14,000/mm3, with 67% neutrophils, 3% bands, and 24% lymphocytes. Serum lactate is 3 mmol/L. No other abnormalities are noted. A chest x-ray obtained in the emergency department is normal. Urinalysis shows 2+ leukocyte esterase, negative nitrites, and trace blood. Microscopy shows 20 to 50 white blood cells per high-power field, 0 to 3 red blood cells, and many bacteria.

▶ What is the most likely diagnosis?

▶ What is your next step?

ANSWERS TO CASE 41:

Urinary Tract Infection With Sepsis in the Elderly

Summary: An 84-year-old woman presents to the emergency department from her nursing home with

• History of Alzheimer disease
• Agitation, confusion, low grade fever, tachycardia, and hypotension
• Flat veins, clear lung fields, no cardiac murmur or gallops, and warm and well-perfused extremities on physical examination
• Improved hemodynamic status with a fluid bolus
• Evidence of urinary tract infection (UTI) on laboratory examination

Most likely diagnosis: Septic shock secondary to a UTI.

Next step: Continued blood pressure support with intravenous (IV) fluids or vasopressors as necessary. Broad-spectrum antibiotics should be started as soon as possible.

ANALYSIS

Objectives

1. Explain how to diagnose a UTI. (EPA 3)
2. List effective treatments for a UTI. (EPA 4)
3. Describe the management of asymptomatic bacteriuria. (EPA 4)
4. Identify and treat septic shock. (EPA 1, 10)
5. Describe goal-oriented therapy of septic shock. (EPA 4, 10)

Considerations

This elderly woman with Alzheimer disease presents with shock, that is, hypotension leading to inadequate tissue perfusion. It is essential to determine the underlying cause and thus initiate appropriate treatment. She has no history or physical examination findings suggestive of hemorrhage or extreme volume losses, so hypovolemic shock is unlikely. She has flat neck veins and clear lung fields, suggesting she does not have right or left heart failure, respectively, so cardiogenic shock (eg, after a myocardial infarction) seems unlikely. Additionally, both hypovolemic and cardiogenic shock typically cause profound peripheral vasoconstriction, resulting in cold, clammy extremities. This patient’s extremities are warm and well perfused (inappropriately so) despite serious hypotension, suggesting a distributive form of shock (early septic shock). Older patients may not be able to mount a high fever; importantly, an afebrile patient does not rule out sepsis. With the elevated WBC count with immature forms as well as the urine findings, septic shock as a consequence of UTI seems most likely.

APPROACH TO:

UTI with Sepsis

DEFINITIONS

ASYMPTOMATIC BACTERIURIA: A condition in which urine Gram stain or culture is positive, but no clinical signs or symptoms of infection are present. This condition is rarely requires treatment unless the patient is a pregnant woman or immunocompromised (eg, transplant recipients).

CARDIOGENIC SHOCK: Shock due to intracardiac conditions leading to decreased cardiac output, such as arrhythmias, myocardial infarction, and valvular insufficiencies.

DISTRIBUTIVE SHOCK: Shock characterized by peripheral vasodilation (ie, decreased systemic vascular resistance). It is divided into the following types: anaphylactic shock (caused by a severe type I hypersensitivity reaction); endocrine shock (caused by an underlying endocrine disease, eg, adrenal failure or myxedema); neurogenic shock (caused by trauma to the central nervous system); and septic shock (caused by a dysregulated immune response to infection).

HYPOVOLEMIC SHOCK: Shock due to volume depletion causing decreased intravascular volume, which leads to a compensatory increase in systemic vascular resistance in an attempt to maintain adequate tissue perfusion. Caused by hemorrhagic (eg, gastrointestinal bleeding) and nonhemorrhagic (eg, dehydration, third-spacing) etiologies.

OBSTRUCTIVE SHOCK: Shock due to extracardiac conditions leading to decreased cardiac output, such as pulmonary embolism, tension pneumothorax, and pericardial tamponade.

SEPSIS: A life-threatening multiorgan dysfunction due to dysregulated host response to an infection.

SEPSIS SCORING SYSTEMS: There are various sepsis scoring systems such as SOFA (sequential organ failure assessment) score or simplified qSOFA (quick SOFA) that attempts to estimate morbidity or mortality risk due to sepsis.

SEPTIC SHOCK: Subset of sepsis with circulatory and metabolic/cellular dysfunction that is associated with a higher mortality risk.

SHOCK: A life-threatening condition due to circulatory failure leading to hypotension and thus inadequate oxygen delivery to and utilization by tissues. There are four main categories: cardiogenic, distributive, hypovolemic, and obstructive shock.

SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS): Criteria that illustrate systemic inflammation that may or may not indicate underlying infection. The criteria include temperature deviation (> 38 °C or < 36 °C), tachypnea (respiratory rate > 20 breaths per minute or Paco2 < 32 mm Hg), tachycardia (heart rate > 90 bpm), and leukocyte shifts with WBC > 12,000/mm3 or < 4000/mm3 or > 10% immature forms (bands).

CLINICAL APPROACH

Epidemiology

UTIs are a common affliction of the elderly, affecting both debilitated and healthy adults. UTIs are second only to respiratory infections as the most common infections in patients older than 65 years. Risk factors that contribute to the high incidence of UTIs in the elderly, as well as in institutionalized patients, include incontinence, a history of prior UTIs, neurologic impairment, immunosuppression, poor nutrition, and comorbid disease states. These conditions may confer functional abnormalities within the urinary tract or altered defenses against infection. Furthermore, frequent hospitalizations expose these patients to nosocomial pathogens and invasive instrumentation, such as indwelling catheters.

Pathophysiology

Most UTIs occur as one of three clinical syndromes: acute uncomplicated cystitis (lower tract infection), acute pyelonephritis (upper tract infection), or catheter-associated UTI (in hospitalized, institutionalized, or neurogenic bladder patients). Symptoms of cystitis reflect bladder irritation and generally include dysuria, increased frequency, urgency, or hematuria. Pyelonephritis typically presents with systemic symptoms such as fever, chills, or nausea; flank pain; and findings of WBC casts on urinalysis. Catheter-associated UTI can be diagnosed by fever, suprapubic pain, or other symptoms attributable to infection, along with a positive urine culture in patients with permanent or intermittent catheterization of the urinary tract.

Another common situation that deserves mention is asymptomatic bacteriuria. Asymptomatic bacteriuria is characterized by positive urine culture without clinical symptoms. Outside of pregnancy or immunocompromised patients such as transplant recipients, no adverse clinical outcomes have been reported as a result of asymptomatic bacteriuria, and no benefits of treatment have been demonstrated.

Diagnostic Criteria. UTIs typically are diagnosed based on a combination of symptoms and urinary findings. In symptomatic patients, bacteria typically are found in high concentrations in the urine, and 105 colony-forming units (CFUs)/mL typically are recovered from a clean-catch specimen. If the specimen is obtained by catheterization, finding more than 102 CFU/mL is considered significant. In women with symptoms of acute cystitis (such as dysuria, frequency, and urinary tenesmus), urine cultures are often not obtained, but empiric treatment can be initiated based on the dipstick findings of leukocyte esterase (used as a marker for pyuria) or nitrites (produced by some bacteria that cause UTIs).

Clinical Presentation

Fever, dysuria, urgency, or flank pain may be presenting symptoms for a UTI in younger patients. However, elderly and institutionalized patients often present with less obvious symptoms. These patients may be febrile or hypothermic. Common manifestations include confusion or combativeness. Mental status or behavioral changes in the elderly should be considered strong indicators for serious illness, and a thorough workup should consider etiologies beyond infections. Even with localizing symptoms suggestive of a UTI, other sources of infection should still be investigated. Both urine and blood cultures should be obtained in addition to a urinalysis and complete blood count (CBC). The results of the urine and blood cultures may take 2 to 3 days to yield an organism. If the clinical picture suggests a UTI and sepsis, antibiotic treatment should be initiated immediately. Empiric antimicrobial therapy can be directed at the most common pathogens (Table 41–1).

Treatment

For uncomplicated cystitis, oral trimethoprim-sulfamethoxazole, fluoroquinolones such as ciprofloxacin, and nitrofurantoin are acceptable first-line therapies and are typically given for 3 days. Empiric therapy should be guided by knowledge of local antibiotic resistance patterns. Similar empiric treatment may be initiated for pyelonephritis, but urine and blood cultures should be obtained. Treatment is then guided by culture results and should be continued for 10 to 14 days. Catheter-associated UTI can only be diagnosed with a positive culture (the sample should be obtained from a new catheter, or the catheter port, but not the drainage bag), and antibiotic therapy is tailored to the identified pathogen. If possible, the catheter should be removed or replaced. Bacteria commonly secrete a biofilm in which they embed, making the full sterilization of the urine less likely.

Elderly and institutionalized patients commonly acquire gram-positive and mixed infections, so broad-spectrum antibiotics pending culture results are recommended. In patients presenting with a clinical picture of sepsis, broad-spectrum antibiotic coverage against gram-positive and gram-negative organisms, including antipseudomonal activity, is recommended until cultures are available to guide therapy. The duration of therapy should be dictated by the patient’s clinical status. In cases where UTIs have progressed to bacteremia, aggressive and prompt treatment is necessary to prevent the onset of septic shock. This life-threatening state may develop with little warning in elderly and institutionalized patients with multiple comorbidities, as it did in the patient in the case, who presented with hypotension and altered mental status because of infection, that is in septic shock.

CLINICAL APPROACH TO SHOCK

Pathophysiology

Shock is the clinical syndrome that results from inadequate tissue perfusion. It can be classified in a variety of ways, but one useful schema divides the causes into hypovolemic shock, cardiogenic shock, or distributive shock, usually caused by sepsis. Hypovolemic shock is the most common form. It results from either hemorrhage or profound vomiting or diarrhea, resulting in loss of 20% to 40% of blood volume. Cardiogenic shock results from a primary cardiac insult, such as a myocardial infarction, arrhythmia, or end-stage systolic heart failure. Both hypovolemic and cardiogenic shock cause a marked fall in cardiac output and may appear clinically similar with tachycardia, hypotension, and cold, clammy extremities. It is essential to differentiate between the two, however, because the treatments are markedly different. Patients with hypovolemic shock should have flat neck veins and clear lung fields; those with cardiogenic shock are more likely to have markedly elevated jugular venous pressure and pulmonary edema.

Distributive shock, in contrast, is characterized by an increase in cardiac output but an inability to maintain systemic vascular resistance, that is, there is inappropriate vasodilation. Clinically, it appears different from the other forms of shock in that, despite the hypotension, the extremities are warm and well perfused, at least initially. If septic shock continues, cardiac output falls as a consequence of myocardial depression, multiorgan dysfunction ensues, and intense vasoconstriction occurs in an attempt to maintain blood pressure, the so-called cold phase. These findings portend a poor prognosis; hence, prompt recognition of septic shock in the early (warm) phase is paramount.

Although distributive shock may occur in neurogenic shock as a consequence of spinal cord injury or adrenal crisis, the most common cause is septic shock, with the most common infectious etiologies of sepsis being UTIs and pneumonia. Septic shock is associated with high 30-day mortality rates, exceeding 50%. Early diagnosis and prompt treatment are imperative because untreated shock progresses to an irreversible point that is refractory to volume expansion and other medical therapies. The qSOFA score is a rapid, bedside assessment of three variables: Glasgow Coma Score (≤ 14), systolic blood pressure (≤ 100 mm Hg), and respiratory rate (> 22 breaths per minute). The presence of two of those three is associated with high mortality.

New Terminology. In 2016, the International Sepsis Consensus Conference (Sepsis-3) recommended deemphasizing the use of SIRS (nonspecific) and instead adopting SOFA as a more accurate prognostic indicator of the effects of sepsis. Their recommendation is that a total SOFA score of two or more points from baseline represents organ dysfunction; however, the SOFA scores are research tools and have not yet been validated widely in clinical practice.

Treatment

Treatment of hypovolemic shock is aggressive volume resuscitation, either with crystalloid solution or with blood products, as necessary. Treatment of cardiogenic shock focuses on maintaining blood pressure with dopamine or norepinephrine infusions, relief of pulmonary edema with diuretics, and reducing cardiac afterload, for example, with an intra-aortic balloon pump.

The initial treatment for distributive shock is isotonic fluid resuscitation to maintain adequate intravascular volume. Other cornerstones of therapy include broad-spectrum antibiotics targeted to the underlying infection and removing the source of the infection. Patients often require vasopressor support (norepinephrine is the agent of choice) and mechanical ventilation to optimize tissue oxygenation. Vasopressors increase systemic vascular resistance via vasoconstriction to increase organ perfusion. The three main subtypes are catecholamine–, smooth muscle–, and dopaminergic receptor–targeting vasopressors. Catecholamine vasopressors target the alpha and/or beta receptors and include phenylephrine, norepinephrine, and epinephrine. Vasopressin acts on smooth muscle V-1 receptors and renal V-2 receptors for vasoconstrictive and antidiuretic uses, respectively; it has no ionotropic or chronotropic effects. Dopamine acts on dopaminergic, alpha, and beta receptors in a dose-dependent manner. IV hydrocortisone may be administered to patients with hypotension that is refractory to fluid resuscitation and vasopressors.

Surviving Sepsis Campaign. The Surviving Sepsis Campaign is an international collaborative that develops evidence-based guidelines on reducing morbidity and mortality. Some of the key recommendations include

• Hour-1 bundle for expected interventions, therapy, and goals
• Early administration of antibiotics
• Early use of serum lactate and if elevated, measure again
• Vasopressors if hypotension continues despite IV fluids

CASE CORRELATION

• See also Case 40 (Anaphylaxis/Drug Reactions) and Case 42 (Vascular Catheter Infection in a Patient With Neutropenic Fever).

COMPREHENSION QUESTIONS

41.1 Which of the following asymptomatic patients would most benefit from treatment of the finding of more than 105 CFU/mL of Escherichia coli on urine culture?

A. A 23-year-old sexually active woman

B. A 33-year-old pregnant woman

C. A 53-year-old diabetic woman

D. A 73-year-old woman in a nursing home

41.2 Which of the following is the best treatment for a 39-year-old woman with fever of 103 °F, nausea, flank pain, and more than 105 CFU/mL of E. coli in a urine culture?

A. Oral trimethoprim-sulfamethoxazole for 3 days

B. Single-dose ciprofloxacin

C. Intravenous and then oral levofloxacin for 14 days

D. Oral ampicillin for 21 to 28 days

41.3 A 57-year-old man is brought into the emergency center for shortness of breath and light-headedness. He is found to have a blood pressure of 68/50 mm Hg and heart rate of 140 bpm. His jugular venous pulses are elevated. The lungs have inspiratory crackles on examination. All four extremities are cold and clammy. Which of the following is the most likely etiology for this patient’s condition?

A. Septic shock

B. Adrenal crisis

C. Cardiogenic shock

D. Hypovolemic shock

41.4 A 45-year-old man is brought into the emergency center for severe abdominal pain and light-headedness. His wife states that the patient has had lower abdominal pain for 2 days but did not want to see a doctor. He is noted to have a blood pressure of 80/40 mm Hg, heart rate of 142 bpm, and temperature of 102 °F. His abdomen is tender with guarding and rebound, particularly in the right lower quadrant. Acute appendicitis is diagnosed. Three liters of 0.9% saline are infused, and IV antibiotics are administered as he is prepared for surgery. After the saline, his blood pressure is 70/42 mm Hg. Which of the following is the most appropriate next step?

A. Administer a beta-blocker to control his heart rate.

B. Check a cortisol level and administer corticosteroids.

C. Infuse fresh frozen plasma (FFP).

D. Initiate norepinephrine IV infusion.

E. Initiate IV morphine for pain control.

ANSWERS

41.1 B. All these patients are asymptomatic, and no benefit from treatment in terms of reduction in hospitalization has been shown for any of the cases mentioned, except for pregnancy. Treatment is undertaken to prevent upper UTI, preterm delivery, and possible fetal loss.

41.2 C. The patient in this scenario has symptoms of an upper UTI (eg, pyelonephritis) and is moderately ill with nausea. She will need a 14-day course of treatment and may not be able to take oral antibiotics initially, so hospitalization and treatment with IV antibiotics likely will be necessary. Single-dose (answer B) and 3-day (answer A) regimens are useful only for acute uncomplicated cystitis in women. E. coli is frequently resistant to ampicillin (answer D).

41.3 C. The patient is a middle-aged man who presents with shortness of breath and light-headedness. He is hypotensive with signs of left and right heart failure, that is, probably cardiogenic shock. The findings of pulmonary crackles and jugular venous distension are consistent with right heart failure; the presence of arterial hypotension and cold and clammy extremities is consistent with left heart failure. The most common cause of acute heart failure would be myocardial infarction, even in the absence of chest pain. Septic shock (answer A) and adrenal crisis (answer B) both are forms of distributive shock that would produce warm extremities. Hypovolemic shock (answer D) would present with flat neck veins, no pulmonary edema, and often a history of trauma, diarrhea, or blood loss.

41.4 D. When septic shock is refractory to volume resuscitation with isotonic fluid of at least 30 mL/kg of ideal body weight administration, the next step is adding a vasopressive agent (currently the favored medication is IV norepinephrine). Corticosteroids (answer B) can be administered, empirically if hypotension is refractory to vasopressors; steroids have fallen in and out of favor, but the most current evidence seems to indicate its positive effects. However, steroids are an adjunct and not primary therapy. IV morphine (answer E) might lower his blood pressure further. FFP (answer C) is used when the patient shows evidence of coagulopathy such as disseminated intravascular coagulation. Answer A (beta-blocking agent) is not indicated since this patient’s tachycardia is in response to the hypotension and not a primary cardiac arrhythmia.

CLINICAL PEARLS

▶ UTIs and pneumonia are the most common causes of sepsis in older patients.

▶ UTIs can be diagnosed by the presence of urinary symptoms and by more than 105 CFU/mL of bacteria in a clean-catch specimen or more than 102 CFU/mL in a catheterized specimen.

▶ In healthy women with symptoms of acute uncomplicated cystitis, cultures are not routinely sent, and treatment can be initiated based on symptoms and a urine dipstick finding of leukocyte esterase or nitrites.

▶ Asymptomatic bacteriuria is a common finding among elderly patients and requires no treatment; it is only routinely treated in pregnancy and in immunocompromised patients.

▶ Sepsis is a syndrome characterized by fever, tachycardia, tachypnea, leukocytosis, and presence of a known or suspected infection. It requires early and aggressive intervention to prevent clinical deterioration.

▶ The qSOFA score is a way of assessing organ dysfunction due to septic shock and attempts to estimate morbidity and mortality risks.

▶ The best treatment for septic shock is IV isotonic fluids, and if the blood pressure is unresponsive, then a vasopressor agent such as norepinephrine.

▶ Goal-oriented therapy for septic shock, including the early administration of antibiotics and assessment of serum lactate, has been shown to improve outcome.

REFERENCES

Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369:840-851. 

Fihn SD. Acute uncomplicated urinary tract infection in women. N Engl J Med. 2003;349:259-266. 

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348:138-150. 

Koya HH, Paul M. Shock. In: StatPearls. Treasure Island, FL: StatPearls; 2019. https://www.ncbi.nlm .nih.gov/books/NBK531492/. Accessed April 23, 2020. 

Maier RV. Approach to the patient with shock. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw Hill; 2012:2215-2222 

Munford RS. Severe sepsis and septic shock. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw Hill; 2012:2223-2232. 

Shortliffe LMD, McCue JD. Urinary tract infection at the age extremes: pediatrics and geriatrics. Am J Med. 2002;113:S55-S66. 

VanValkinburgh D, McGuigan JJ. Inotropes and vasopressors. In: StatPearls. Treasure Island, FL: StatPearls, 2019. https://www.ncbi.nlm.nih.gov/books/NBK482411/. Accessed April 23, 2020.

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