Infections in Immunocompromised Host CHRI Class
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Transcript of 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