Fever in the Hospitalized Patient (Case 51)

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Chapter 59
Fever in the Hospitalized Patient (Case 51)

Patricia D. Brown MD

Case: A 56-year-old man was admitted to the hospital with 3 days of productive cough, fever, and chills. A chest radiograph revealed an extensive area of consolidation in the left lower lobe; because of hypoxia on presentation, he was admitted to the hospital for management of community-acquired pneumonia. The patient has no history of chronic medical illness but does have a 40-pack-year smoking history and a long-standing history of heavy alcohol use, drinking one pint of whiskey every few days for over 20 years. The patient was initially started on ceftriaxone and azithromycin; two sets of blood cultures obtained on admission grew Streptococcus pneumoniae, sensitive to penicillin. His antibiotics were changed to IV penicillin, and over the next 72 hours he slowly improved with resolution of fever and hypoxia, decreased cough, and good oral intake. The plan was to discharge him to home on hospital day 4 to complete a course of oral antibiotics; however, the patient developed a fever of 39.7°C.

Differential Diagnosis

Hospital-Acquired Infections

Complications/Inadequate Treatment of Community-Acquired Pneumonia

Noninfectious Causes of Fever

Urinary tract infection (UTI)

Drug-resistant pathogen

(Sterile) IV-site phlebitis

Catheter-related bloodstream infection (BSI)

Parapneumonic effusion

Drug fever

Hospital-acquired pneumonia (HAP)


DVT/pulmonary embolism

Clostridium difficile infection (CDI)

Alcohol withdrawal


Speaking Intelligently

Often the approach in a febrile hospitalized patient will be a directive to “pan-culture” the patient and obtain a chest radiograph. A much better and certainly more cost-effective approach to the problem is to return to the bedside to perform a problem-focused history and physical examination in order to narrow down the potential sources of fever. Additional testing can then be selectively utilized to confirm the clinical diagnosis. The evaluation should begin with an assessment of the patient at the bedside, not with telephone orders for multiple cultures and other diagnostic testing that may be unnecessary.


Clinical Thinking

• The evaluation of a new fever in a hospitalized patient will focus on three broad categories of conditions: (1) a hospital-acquired infection, (2) a complication of the current infection (when present), and (3) noninfectious causes of fever.

• This broad differential diagnosis can be rapidly narrowed by a focused history and careful physical examination; selected diagnostic testing can then be utilized to confirm the diagnosis.

• The differential diagnosis and approach to the evaluation and management of fever in patients with cancer chemotherapy-induced neutropenia are distinct from what is discussed below. Because these patients are at extraordinarily high risk for bacterial infections and poor outcome if appropriate treatment is delayed, broad-spectrum empirical antibiotic therapy is always started after appropriate cultures have been obtained.


• A focused history should start with specific questioning regarding new symptoms that may be suggestive of a hospital-acquired infection, including dysuria, urgency, frequency, cough, sputum production, dyspnea, pain at the IV catheter site, and diarrhea.

• A complication of that infection may be heralded by worsening of symptoms that had originally improved in response to therapy.

• Unilateral lower extremity pain and swelling suggests the possibility of DVT.

• Careful review of the medication list will help to determine if any current medications are likely to be associated with drug fever. Drug fever can be a difficult diagnosis to make and is often entertained as a “diagnosis of exclusion” only after other etiologies of fever have been ruled out.

• The presence of rash or peripheral eosinophilia is helpful in implicating a drug reaction as the potential etiology of fever; however, in the majority of cases fever alone is the sole manifestation of an adverse reaction to a medication.

Physical Examination

• Perform a meticulous general physical examination with very careful attention to the skin to look for the presence of rash that may be present with drug fever and careful examination of the IV catheter insertion site to look for erythema, induration, or tenderness.

• Inspect sites of earlier IV catheter insertion, and palpate the proximal extent of the veins to look for evidence of superficial phlebitis.

• Upper extremity DVT can occur in patients with central venous catheters (CVCs) and should be considered in patients who develop ipsilateral swelling of the extremity in the presence of a CVC.

• Carefully examine the lungs to look for evidence of the development of pleural effusion that suggests parapneumonic effusion or empyema.

• Alcohol withdrawal can occur 3 to 4 days after admission. In addition to fever, there should be other signs of autonomic hyperactivity, including hypertension and clinical findings of diaphoresis, restlessness, and tremors.

Tests for Consideration

• For almost all patients with a new fever that develops during hospitalization, one should obtain two sets of blood cultures to exclude the possibility of BSI.


• The history and physical examination should guide other diagnostic testing. Patients with diarrhea should have a stool sample submitted for C. difficile toxin assay; clinicians should follow the “3-day rule,” which reminds us that when diarrhea develops more than 3 days after hospital admission, the potential etiologies are relatively few and testing for community-associated pathogens with routine stool culture and examination for ova and parasites is of very low diagnostic yield.


• Patients with symptoms suggestive of UTI or those who are or were catheterized or underwent some other form of urinary tract instrumentation during the admission should have a urinalysis with microscopic examination followed by urine culture if pyuria is detected. Clinicians should be very cautious regarding the interpretation of findings from a urine sample obtained from patients with indwelling bladder catheters.
Even with short-term catheter use, 10% to 30% of patients will develop colonization of the urinary tract with bacteria.

It can be very difficult to distinguish symptomatic infection from asymptomatic bacteriuria in this setting; therefore, even in the presence of a positive urine culture, the diagnosis of symptomatic UTI as the etiology of fever should be considered only when other sources of infection have been excluded by careful clinical assessment.



HAP should be considered if new or worsening cough, dyspnea, or hypoxia occurs in association with fever; hypoxia would also raise the possibility of venous thromboembolic disease. A chest radiograph will document the presence of new or worsening infiltrates; thoracentesis should be performed if there is a pleural effusion to exclude the possibility of empyema.


If pulmonary embolism is a diagnostic consideration, spiral CT or ventilation–perfusion scanning can be utilized.

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Clinical suspicion for DVT can be evaluated by duplex ultrasonography.



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Hospital-Acquired Urinary Tract Infection

Like the vast majority of all UTIs, hospital-acquired infections are ascending infections due to pathogens that colonize the periurethral area and distal urethral meatus, and then gain entry to the urinary tract via the ascending route. Instrumentation of the urinary tract facilitates ascending infection. Infection may be confined to the bladder (cystitis) or ascend to involve the kidney (pyelonephritis).


Like all UTIs, the most common cause of health care–associated UTI is Escherichia coli. Depending on the length of hospitalization and prior antibiotic exposure, other pathogens that should be considered include other Enterobacteriaceae (Klebsiella, Enterobacter) and nosocomial gram-negative organisms such as Serratia, Providencia, Citrobacter, and Pseudomonas. Enterococcus species, including vancomycin-resistant enterococci (VRE), may also cause UTI in the hospital.