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Immunosuppression, Emergency Medicine

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Immunosuppression, Emergency Medicine

Basics

Description

Congenital or acquired deficiency in the ability to fight infection:

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

  • Antibody production (B cell)
  • Cellular immunity (T cell)
  • Phagocytic dysfunction
  • Complement deficiency
  • Breach of skin/mucosal barriers

Etiology

  • Congenital disorders
  • Immunosuppressive medications
  • Aging:ImmunosenescencePoor circulation and wound healing
  • Chronic (lung, kidney, or heart) disease
  • HIV infection:CD4 count determines susceptibility to pathogens
  • Diabetes:Hyperglycemia impairs immune responseVascular insufficiency
  • Malnutrition:PovertyAlcoholism and drug abuseEating disorders
  • Asplenia:Functional asplenia (sickle cell disease) or surgical splenectomy increases risk of infection with encapsulated organisms
  • Organ transplantation:Antirejection medications suppress immune responseInfections may be donor derived, recipient derived, or nosocomialIncreased risk of viral pathogens, such as cytomegalovirus, Epstein-Barr virus, and human herpes virusesTime elapsed since transplantation is crucial, as different patterns of infection arise in early, intermediate, and late posttransplantation periods
  • Malignancy
  • Chemotherapy:Increased risk of infection with pyogenic bacteria and fungiInfection risk related to length and severity of neutropenia
  • Neutropenia:Defined as absolute neutrophil count (ANC) <500/mm3 or <1,000/mm3 with an anticipated nadir of <500/mm3In US, gram-positive organisms are the leading etiology of infectionGram-negative organisms are somewhat less common but often virulentPolymicrobial infections are increasingly frequentAnaerobic isolates remain relatively rareThe risk of fungal pathogens increases with prolonged neutropenia (>1 wk), prior use of broad-spectrum antibiotics, or intense chemotherapy
  • Immunosenescence
  • Poor circulation and wound healing
  • CD4 count determines susceptibility to pathogens
  • Hyperglycemia impairs immune response
  • Vascular insufficiency
  • Poverty
  • Alcoholism and drug abuse
  • Eating disorders
  • Functional asplenia (sickle cell disease) or surgical splenectomy increases risk of infection with encapsulated organisms
  • Antirejection medications suppress immune response
  • Infections may be donor derived, recipient derived, or nosocomial
  • Increased risk of viral pathogens, such as cytomegalovirus, Epstein-Barr virus, and human herpes viruses
  • Time elapsed since transplantation is crucial, as different patterns of infection arise in early, intermediate, and late posttransplantation periods
  • Increased risk of infection with pyogenic bacteria and fungi
  • Infection risk related to length and severity of neutropenia
  • Defined as absolute neutrophil count (ANC) <500/mm3 or <1,000/mm3 with an anticipated nadir of <500/mm3
  • In US, gram-positive organisms are the leading etiology of infection
  • Gram-negative organisms are somewhat less common but often virulent
  • Polymicrobial infections are increasingly frequent
  • Anaerobic isolates remain relatively rare
  • The risk of fungal pathogens increases with prolonged neutropenia (>1 wk), prior use of broad-spectrum antibiotics, or intense chemotherapy

Diagnosis

Signs and Symptoms

  • 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 signsMeningitis without nuchal rigidityInfected wounds or indwelling lines without induration, erythema, or purulent discharge
  • Surgical abdomen without peritoneal signs
  • Meningitis without nuchal rigidity
  • Infected wounds or indwelling lines without induration, erythema, or purulent discharge

Essential Workup

  • 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 infiltratesUTIs without pyuriaMeningitis without CSF pleocytosis
  • Pneumonia without radiographic infiltrates
  • UTIs without pyuria
  • Meningitis without CSF pleocytosis

Diagnosis Tests & Interpretation

  • CBC with differential:Identify leukocytosis, left shift, bandemia, or neutropeniaRisk of infection begins to increase once ANC <1,000/mm3
  • Blood cultures:2 sets of bacterial culturesDraw 1 culture from an indwelling line, if presentObtain 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
  • Identify leukocytosis, left shift, bandemia, or neutropenia
  • Risk of infection begins to increase once ANC <1,000/mm3
  • 2 sets of bacterial cultures
  • Draw 1 culture from an indwelling line, if present
  • Obtain fungal cultures if indicated
  • Obtain by clean catch, if possible, as catheterization may introduce infection
  • Useful for identifying occult hypoperfusion in sepsis
  • Useful in determining the need for steroids in suspected cases of Pneumocystis jirovecii pneumonia (PCP)
  • 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 patients 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 suspectedConsider cryptococcal antigen testing even in the absence of CSF pleocytosis
  • 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

Differential Diagnosis

  • Infection:OropharynxSinusesLungGI tractPerineum/anusUrinary tractSkin/soft tissueBoneIndwelling catheters/devices
  • Noninfectious etiology of fever:Drug feverAllograft rejectionMalignancyVasculitisRheumatologic diseasePulmonary embolismThyroid dysfunctionBlood product transfusion
  • Oropharynx
  • Sinuses
  • Lung
  • GI tract
  • Perineum/anus
  • Urinary tract
  • Skin/soft tissue
  • Bone
  • Indwelling catheters/devices
  • Drug fever
  • Allograft rejection
  • Malignancy
  • Vasculitis
  • Rheumatologic disease
  • Pulmonary embolism
  • Thyroid dysfunction
  • Blood product transfusion

Treatment

Pre-Hospital

  • Establish IV access
  • IV fluid bolus

Initial Stabilization/Therapy

  • 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 IVNorepinephrine 2-12 μg/min IV
  • Dopamine 5-20 μg/kg/min IV
  • Norepinephrine 2-12 μg/min IV

Ed Treatment/Procedures

  • 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 yrOutpatient status at time of feverANC >100 cells/mm3Duration of neutropenia <7 daysExpected resolution of neutropenia <10 daysWell appearingStable vital signsNo change in mental statusNo dehydrationLack of significant comorbid conditions:Chronic pulmonary diseaseDiabetesOrgan failureDisease in remissionNo history of fungal infectionsNormal chest x-ray
  • Age <60 yr
  • Outpatient status at time of fever
  • ANC >100 cells/mm3
  • 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 diseaseDiabetesOrgan failure
  • Disease in remission
  • No history of fungal infections
  • Normal chest x-ray
  • Chronic pulmonary disease
  • Diabetes
  • Organ failure

Medication

  • 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 neutropeniaCiprofloxacin 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 aureusVancomycin: 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)
  • Produces comparable results in low-risk adults with febrile neutropenia
  • Ciprofloxacin 750 mg PO BID + amoxicillin-clavulanate 875 mg PO BID
  • 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)
  • 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
  • Consider adding if suspected line sepsis or history of methicillin-resistant Staphylococcus aureus
  • Vancomycin: 1 g IV q12h (peds: Dose based on age/weight)
  • Clindamycin: 600-900 mg IV q8h (peds: Dose based on age)

Follow-Up

Disposition

  • ANC <100 cells/mm3
  • Immunocompromised patients with infection who do not meet low-risk criteria
  • Patients with inadequate access to outpatient medical care
  • Maintain lower admission criteria for:ElderlyDiabeticsChildren
  • 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

Followup Recommendations

Pearls and Pitfalls

  • 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 patients 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

Additional Reading

  • 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.

See Also (Topic, Algorithm, Electronic Media Element)

Codes

ICD9

  • 279.2 Combined immunity deficiency
  • 279.3 Unspecified immunity deficiency
  • 279.8 Other specified disorders involving the immune mechanism

ICD10

  • D83.8 Other common variable immunodeficiencies
  • D84.1 Defects in the complement system
  • D84.9 Immunodeficiency, unspecified
  • D84.8 Other specified immunodeficiencies

SNOMED

  • 38013005 immunosuppression (finding)
  • 24743004 complement deficiency disease (disorder)
  • 398293003 Cellular immune defect (finding)
  • 58606001 Primary immune deficiency disorder (disorder)