Infections in Immunocompromised Host CHRI Class

8/3/2019 Infections in Immunocompromised Host CHRI Class

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Immunocompromised state refers to the inability of an

individual to mount an adequate immune response towards

an infection.

This effectively means problems in innate or adaptive immunity

In practice it also includes non immune conditions like trauma

and severe burns


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Causes of immunocompromised state

1.Neoplastic

- hematological malignancies

2.Organ transplant recipients

3.Autoimmune diseases

4.Immunodeficiency syndromes

congenital

acquired


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Causes of immune compromise in Malignancy

1.Reduction in phagocytic cells specifically neutrophilis henceacute response to infection is lost

2.Functional deficiency without change in number

3.Monocytes and macrophages

These cells collaborate with helper T cells againstintracellular pathogen such as mycobacteria, fungi and

parasites.

4.Quantitative defects in humoral factors

- Circulating IgG and IgM antibodies, secretory IgA

antibodies, and components of the complement cascade


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Host Defect Disease

Impaired phagocytic function Acute leukemia

Phagocyte mobilization Lazy leukocyte syndrome

Neutropenia Aplastic anemia

Acute leukemia

Impaired cell-mediated immunity Hodgkin's disease

Decreased antibody levels Multiple myeloma

Chronic lymphocytic leukemia


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Organ transplant recipients Issues involved

Hematopoietic

stem cell

transplant

Underlying disease

(e.g., hematologic

malignancies)

Defects in primary and secondary

humoral and cellular

immunity. Defects in phagocytic cell

quantity and function

Cytotoxic conditioning

therapy ( total body

irradiation)

Bone marrow suppression. Defects in

primary and secondary

humoral and cellular immunity

Prophylaxis and

treatment of graft-

versus-host disease

(e.g.,corticosteroids,

calcineurin inhibitors,

antimetabolites,

TNF- antagonists)

Defective function in phagocytic cells

and dysfunction of

primary and secondar

humoral and cellular immunity


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Solid organ

transplantation

(SOT)

Underlying disease (e.g., diabetes, end-stage liver

disease)

Organ dysfunction

and miscellaneous

immune

dysfunction

Induction therapies (e.g., corticosteroids,

antilymphocyte

globulin, splenectomy, anti-IL-2 Ab, anti-CD52 Ab,

calcineurin inhibitors

Depletion and

impairment in

primary and

secondary cellular

and humoral

immunity

Surgical intervention and altered anatomy Breach in mucosal

barriers. Defects in

organ function.

Acute and chronic rejection prophylaxis and treatment

(e.g.,corticosteroids, calcineurin inhibitors,

antimetabolites and alkylating agents, plasmapheresis,

antithymocyte

globulin)

Defective function

in phagocytic cells,

primary and

secondary

humoral and

cellular immunity


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Treatment of collagen

vascular and

autoimmune diseases

Anti-inflammatory and

immunosuppressive agents

(corticosteroids,

nonsteroidal anti-

inflammatory drugs,

calcineurin inhibitors,sirolimus, mycophenol ate

mofetil)

Defective function in

phagocytic cells, primary

and secondary

humoral and cellular

immunity

Antimetabolite and

alkylating agents

Bone marrow suppression,

defects in primary and

secondaryhumoral and cellular

immunity

Biologic immune response

modifiers (e.g.,antithymocyte

globulin, monoclonal

antibodies to B and T cells,

anticytokine therapies, T-cell

costimulation blockers)

Defective function in primary

and secondary humoral andcellular immunity


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Approach to the Compromised Patient

Fever in a compromised patient - ominous development,

Fever with neutropenia(


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Approach to fever

Fever should trigger a prompt and thorough bedside evaluation of the

patient

Examination of the head and neck

- Evidence of central nervous system (CNS) infection

Oropharynx and respiratory tract

- Evidence of pharyngitis and gum inflammation and the anterior and

posterior aspects of the lungs for evidence of an abnormality in breathingor an airway abnormality.

Palpation of the abdomen and the costovertebral angles, auscultation of the

abdomen for quality of bowel movements should be undertaken

Perirectal area and pelvic examination in a female patient is mandatory

Intravenous or intra-arterial catheter should be carefully examined


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CNS Infections

Presentation - Brain abscess or meningitis

Pathogen Involved

1.Listeria monocytogenes

2.Encapsulated bacteria such as pneumococci and staphylococci can cause

metastatic CNS disease and meningitis

3.Cryptococcus neoformans4.Candida, Aspergillus

5.Herpes simplex, Cytomegalovirus, and Epstein-Barr virus,

6.Infection of the CSF with HIV-1 can cause CNS reactive pleocytosis.

7.Reactivated or quiescent CNS syphilis

Non Infectious

Drug-related toxicities, e.g., Carbapenem-related seizures

PRES


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SinoPulmonary

Bacterial Infections

PneumoniaCough, shortness of breath, chest pain, and hypoxia.

Computed axial tomography early in course of disease

Pneumococci and Haemophilus influenzae can cause lobar or diffuse

pneumonia.

Gram-negative bacilli can cause pneumonia of a necrotizing type in severelyneutropenic patients.

Ventilatory support - risk of secondary gram-negative bacillary pneumonia

or staphylococcal pneumonia.

Legionella pneumophila

Tuberculosis

M.tuberculosis

Nontuberculous mycobacteria such as Mycobacterium avium


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Fungal Infections of Respiratory tract

Blastomycosis, coccidioidomycosis, and histoplasmosis

Acute pneumonia

Candida - uncommon primary lung pathogens.

Pneumocystis (now referred to as P. jiroveci) has been reclassified as a

fungus on the basis of DNA sequencing

interstitial pattern of lung infiltration

consolidation

pulmonary nodules.

Aspergillus, Zygomycetes,

chest pain

hemoptysis.

Aspergillus infection can spread through the pulmonary vasculature leadingto pulmonary infarction.


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Viral Infections

Difficult to diagnose in immunocompromised patients.

Measles

Varicella-zosterRespiratory Syncytial Virus

Adenoviruses

Reactivated Cytomegalovirus

Non infectious

Drug-related pulmonary toxicities

Pneumonitis (sirolimus)

Diffuse alveolar damage

Bronchiolitis obliterans syndromes


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Gastrointestinal Infections

Diarrheal Syndromes

Salmonella

Shigella

Campylobacter

Clostridium difficile

Should be suspected in patients who had received a course of

antibiotics as long as a month previously.

Isospora belli and Cryptosporidium- Impairments in cell-mediated immunity.

Microsporidians.

Giardia lamblia - hypogammaglobulinemia.


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Esophagitis

Candida mucosal overgrowth in the mouth and esophagus.

Herpes simplex virus and cytomegalovirus - esophagitis.In severely neutropenic patients

Pseudomonas aeruginosa - mucositis/pharyngitis.

Non Infectious

Drug-related toxicities, e.g., MMF


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Cutaneous Syndromes

Infectious

Ascending streptococcal or staphylococcal cellulitis

Metastatic abscesses - Staphylococcus aureus

Necrotizing vasculitis - P. aeruginosa infections

Aspergillus and Candida - metastatic cutaneous lesions.

Non infectious

Drug eruptions

GVHD

Sweets syndrome


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APPROACH TO FEVER DURING

CHEMOTHERAPY-INDUCED NEUTROPENIA

PAST AND CURRENT CLINICAL CONSIDERATIONS

What is the type and duration of immunologic deficiency?

Does the patient have any organ dysfunction that would predispose to

particular infection?

Does the patient have any unique environmental or epidemiologicexposures?

What are the patients prior infections and colonizing organisms?

What are the current and recently administered antimicrobial agents?

Are there any specific presenting signs or symptoms that suggest a

particular type of infection or syndrome


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MULTINATIONAL ASSOCIATION OF SUPPORTIVE CARE IN CANCER (MASCC)

RISK SCORING INDEX FOR IDENTIFICATION OF LOW-RISK PATIENTS WITH

FEBRILE NEUTROPENIA

CHARACTERISTIC SCORE

Extent of illness

No symptoms 5

Mild symptoms 5

Moderate symptoms 3No hypotension 5

No chronic obstructive lung disease 4

Solid tumor or no fungal infection 4

No dehydration 3

Outpatient at onset of fever 3

Age < 60 yr 2

POINTS > 21 low risk

less than 5 % risk of complications


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Investigations

Gram stain of body fluids, exudates,or aspirates.

Complete blood count with differential, serum creatinine, and screening liver

function.

Chest radiograph

Routine urinalysis.

Computed Tomography (CT) - persistent fever

especially in the presence of airway symptoms.


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Noninfectious cause of fever

Hematoma

Drug reactionsTransfusion reactions

Pulmonary emboli

Splenic infarcts

Underlying malignancy.


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Persistent fever

The possibility of infection caused by nonbacterial pathogens

Fungi (especially Candida and Aspergillus species)

Widespread adoption of routine antifungal

empirical therapies in the setting

of fever that persists more than 4 to 7 days.

Azole drugs, echinocandins and polyenes.


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Fever (temperature 38.3 C) + Neutropenia

(


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Susceptible to capsulated bacteria

Risk of systemic pneumococcal disease 75 %

Functional splenectomy in sickle cell disease

Prevention of infection

Vaccination (preferably before splenectomy)

Prophylactic antibiotics

Pen V or amoxycillin


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Conclusion

Infections are a major cause of mortality in

immunocompromised hosts.

The approach to fever and suspected infection requires

knowledge of specific risks inherent to the type and durationof immunodeficiency

Diagnostic diligence

Tailored therapeutics

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Infections in Immunocompromised Host CHRI Class

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