Rosen & Barkin's 5-Minute Emergency Medicine Consult (390 page)

DIAGNOSIS

• Fever may be the only symptom of a life-threatening infection in an immunocompromised host
  
• Perform a careful review of systems to identify any localizing symptoms
  
• Identify risk factors for nosocomial infections, such as recent hospitalization or nursing home residence
  
• Ask about close contacts with transmissible illnesses, such as influenza
  
• Review medications for the presence of immunosuppressive agents, such as steroids
  
• Recognize that prophylactic medicines, such as trimethoprim/sulfamethoxazole or fluconazole, may alter both the spectrum of likely pathogens and their resistance patterns
  

• Examine the patient from head to toe
  
• Some clinicians advise avoiding digital rectal exams in patients with febrile neutropenia
  
• Inflammation may be subtle or absent:
  
  • Surgical abdomen without peritoneal signs
    
  • Meningitis without nuchal rigidity
    
  • Infected wounds or indwelling lines without induration, erythema, or purulent discharge
    

• Choice of studies must be tailored to the patient and the presenting complaint
  
• Test interpretation may be difficult since inflammatory responses are often blunted in immunosuppressed patients:
  
  • Pneumonia without radiographic infiltrates
    
  • UTIs without pyuria
    
  • Meningitis without CSF pleocytosis
    

• CBC with differential:
  
  • Identify leukocytosis, left shift, bandemia, or neutropenia
    
  • Risk of infection begins to increase once ANC <1,000/mm
    ³
    
• Blood cultures:
  
  • 2 sets of bacterial cultures
    
  • Draw 1 culture from an indwelling line, if present
    
  • Obtain fungal cultures if indicated
    
• Urinalysis/urine culture:
  
  • Obtain by clean catch, if possible, as catheterization may introduce infection
    
• Serum lactate:
  
  • Useful for identifying occult hypoperfusion in sepsis
    
• Arterial blood gas:
  
  • Useful in determining the need for steroids in suspected cases of
    Pneumocystis jirovecii
    pneumonia (PCP)
    
• Pregnancy testing in women of childbearing age
  

• Chest x-ray recommended if patient is neutropenic, hypoxic, or has abnormal pulmonary signs
  
• Further imaging, such as CT or MRI, can be tailored to the patient’s presentation and risk factors
  

• Lumbar puncture should be performed if there is a clinical suspicion for meningitis:
  
  • Check platelet counts and coagulation studies prior to procedure if thrombocytopenia or coagulopathy is suspected
    
  • Consider cryptococcal antigen testing even in the absence of CSF pleocytosis
    

• Infection:
  
  • Oropharynx
    
  • Sinuses
    
  • Lung
    
  • GI tract
    
  • Perineum/anus
    
  • Urinary tract
    
  • Skin/soft tissue
    
  • Bone
    
  • Indwelling catheters/devices
    
• Noninfectious etiology of fever:
  
  • Drug fever
    
  • Allograft rejection
    
  • Malignancy
    
  • Vasculitis
    
  • Rheumatologic disease
    
  • Pulmonary embolism
    
  • Thyroid dysfunction
    
  • Blood product transfusion
    

TREATMENT

• Establish IV access
  
• IV fluid bolus
  

• Aggressive fluid resuscitation for patients with hypovolemia
  
• Goal-directed therapy for patients with sepsis
  
• Ultrasound can be used to evaluate the IVC (caval index) to estimate volume status as well as screen for malignant pericardial tamponade
  
• Administer pressors for hypotension that fails to respond to IV fluids:
  
  • Dopamine 5–20 μg/kg/min IV
    
  • Norepinephrine 2–12 μg/min IV
    

• Institute appropriate infection control precautions, such as neutropenic or contact precautions
  
• Rapidly collect appropriate cultures and administer broad-spectrum antibiotics
  
• Most patients with febrile neutropenia are admitted, but low-risk patients with fever may be candidates for outpatient treatment
  
• Low risk:
  
  • Age <60 yr
    
  • Outpatient status at time of fever
    
  • ANC >100 cells/mm
    ³
    
  • Duration of neutropenia <7 days
    
  • Expected resolution of neutropenia <10 days
    
  • Well appearing
    
  • Stable vital signs
    
  • No change in mental status
    
  • No dehydration
    
  • Lack of significant comorbid conditions:
    
    • Chronic pulmonary disease
      
    • Diabetes
      
    • Organ failure
      
  • Disease in remission
    
  • No history of fungal infections
    
  • Normal chest x-ray
    

• Treatment regimens should, if possible, be tailored to the patient
  
• Empiric therapy with broad-spectrum agents must be rapidly administered in febrile neutropenia or sepsis
  
• Oral antibiotic therapy:
  
  • Produces comparable results in low-risk adults with febrile neutropenia
    
  • Ciprofloxacin 750 mg PO BID + amoxicillin–clavulanate 875 mg PO BID
    
• Parenteral monotherapy options:
  
  • Ceftazidime: 2 g IV q8h (peds: 50 mg/kg IV q8h)
    
  • Cefepime: 2 g IV q8h (peds: 50 mg/kg IV q8h)
    
  • Imipenem–cilastatin: 500 mg IV q6h (peds: Dose based on age/weight)
    
  • Meropenem: 1 g IV q8h (peds: Dose based on age/weight)
    
  • Piperacillin–tazobactam: (Less well studied in neutropenia) 4.5 g IV q6h (peds: Dose based on age)
    
• For high-risk patients, consider adding an aminoglycoside (AG) for synergism:
  
  • Gentamicin: Dose based on Cr clearance (peds: Dose based on age)
    
  • AG use increases risk of adverse events, such as acute renal failure and ototoxicity
    
• Empiric vancomycin is usually not indicated:
  
  • Consider adding if suspected line sepsis or history of methicillin-resistant
    Staphylococcus aureus
    
  • Vancomycin: 1 g IV q12h (peds: Dose based on age/weight)
    
• Anaerobic coverage may be added if there is concern for oral or abdominal/perianal infections:
  
  • Clindamycin: 600–900 mg IV q8h (peds: Dose based on age)
    

FOLLOW-UP

• ANC <100 cells/mm
  ³
  
• Immunocompromised patients with infection who do not meet low-risk criteria
  
• Patients with inadequate access to outpatient medical care
  
• Maintain lower admission criteria for:
  
  • Elderly
    
  • Diabetics
    
  • Children
    

• Low-risk patients that are well appearing and can tolerate oral antibiotics and fluids may be considered for outpatient management
  
• Discuss the disposition with the responsible hematology/oncology, infectious disease, or transplant physician prior to discharge
  

24-hr follow-up must be available in order to reassess the patient and monitor culture results

• Failure to learn institutional/regional infection and antibiotic resistance patterns
  
• Failure to recognize that a vague symptom or isolated fever may be the sole warning sign of serious infection in an immunocompromised host
  
• Failure to administer broad-spectrum antibiotics rapidly in febrile neutropenia or sepsis
  
• Failure to review the patient’s previous microbiology results
  
• Failure to involve the appropriate primary care and specialty physicians who are familiar with the patient and can help tailor therapy and ensure follow-up
  

• Fishman JA. Infection in solid-organ transplant recipients.
  N Engl J Med
  . 2007;357(25):2601–2614.
  
• Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america.
  Clin Infect Dis
  . 2011;52(4):e56–e93.
  
• Kamana M, Escalante C, Mullen CA, et al. Bacterial infections in low-risk, febrile neutropenic patients.
  Cancer
  . 2005;104(2):422–426.
  
• Sipsas NV, Bodey GP, Kontoyiannis DP. Perspectives for the management of febrile neutropenic patients with cancer in the 21st century.
  Cancer
  . 2005;103(6):1103–1113.
  

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