Immunosuppression, Emergency Medicine

Basics

Description

Congenital or acquired deficiency in the ability to fight infection:

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

Etiology

Congenital disorders
Immunosuppressive medications
Aging:
- Immunosenescence
- Poor circulation and wound healing
Chronic (lung, kidney, or heart) disease
HIV infection:
- CD4 count determines susceptibility to pathogens
Diabetes:
- Hyperglycemia impairs immune response
- Vascular insufficiency
Malnutrition:
- Poverty
- Alcoholism and drug abuse
- Eating disorders
Asplenia:
- Functional asplenia (sickle cell disease) or surgical splenectomy increases risk of infection with encapsulated organisms
Organ transplantation:
- 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
Malignancy
Chemotherapy:
- Increased risk of infection with pyogenic bacteria and fungi
- Infection 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/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

History

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

Physical Exam

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

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 infiltrates
- UTIs without pyuria
- Meningitis without CSF pleocytosis

Diagnosis Tests & Interpretation

Lab

CBC with differential:
- Identify leukocytosis, left shift, bandemia, or neutropenia
- Risk of infection begins to increase once ANC <1,000/mm3
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

Imaging

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

Diagnostic Procedures/Surgery

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

Differential Diagnosis

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

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 Î¼g/kg/min IV
- Norepinephrine 2-12 Î¼g/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 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 disease
  - Diabetes
  - Organ failure
- Disease in remission
- No history of fungal infections
- Normal chest x-ray

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 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

Disposition

Admission Criteria

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:
- Elderly
- Diabetics
- Children

Discharge Criteria

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

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

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.

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)

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