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Assessment of Life-
Threatening Infections in
the Immuno-suppressed
Section of Critical Care Medicine
Section of Infectious Diseases University of Manitoba, Winnipeg Manitoba
Anand Kumar, MD
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Increased Incidence of Infections in the
Immunosuppressed: Causes
• use of immunosuppressive chemotherapy of
malignancies and various autoimmune conditions
• organ transplantation with improved survival and
concomitant long-term immunosuppression
• supportive therapies (dialysis, TPN) allowing
longer life spans for chronically ill with immune
dysfunction
• numbers and longevity of HIV infected patients
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Pathogens
1) Newly acquired opportunistic
2) Latent organisms
3) Typical community or nosocomial pathogens
Exceptionally broad range
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Importance
atypical organisms
atypical therapies
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Definitions
immune (specific) vs. non-immune (non-
specific) host defenses
immunosuppressed vs. immunocompromised
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Non-Specific (Non-Immune)
Defenses • integrity of skin and mucous membranes (deficient
in burns, wounds, invasive lines and chemotherapy
with agents such as cis-platinum)
• integrity of valvular barriers (e.g. ureteral reflux)
• chemical barriers (e.g. stomach acidity)
• normal indigenous microbial flora
• normal flow of secretions and excretion
• appropriate nutrition and hormonal function
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Specific (Immune) Defenses
• polymorphonuclear leukocytes (i.e. neutrophils) – phagocytosis of extracellular microbes
• cell mediated immunity (monocytes, natural killer
cells, T-lymphocytes) – elimination of intracellular pathogens
• humoral immunity (B-lymphocytes) and spleen – contributes to effective phagocytosis by PMNs
• complement cascade – amplifies killing of extracellular pathogens
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Clinical Approach
• early assessment
• careful evaluation (subtle physical findings)
• aggressive diagnostic tests
• empiric broad spectrum antimicrobial therapy
• anticipate potential complications and co-
infections
• close monitoring of response and side effects
• where possible, reduction of immunosuppression
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History • nature, severity and duration of immune defect
• stage of the underlying disease
• nature of prior treatment (e.g. bleomycin pulmonary
fibrosis vs interstitial pneumonia)
• prior infections (esp. with cell mediated defects) and
results of surveillance cultures
• prior, recent antibiotic use
• recent medication adjustments
• localizing symptoms esp pain/tenderness or erythema
• travel and exposure history
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Principles in Assessment
1) nature of the immune defect
2) severity of the immune defect
3) duration of the immune defect
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Physical Exam • many signs of infection (induration, fluctuance,
warmth, regional lymphadenopathy, exudation of pus) may be absent
• pain/erythema most reliable irrespective of WBC
• specific overlooked sites/findings – funduscopic evaluation
– skin
– oropharyngeal mucositis
– intertriginous areas
– perirectal exam
– neurologic (confusion, headache)
– line and invasive procedure sites
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CMV retinitis
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Ocular toxoplasmosis
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Integumentary Defects
• Damage to mucosal surfaces – endotracheal tube
– nasogastric tube
– cytotoxic agent-induced damage to GI and respiratory epithelium
– endoscopic diagnostic procedures
• Damage to skin and soft tissue – peripheral IV catheters
– central venous catheters
– implanted venous catheters
– arterial lines
– injection sites
– biopsy sites (marrow, nodes, skin)
– surgical wounds
• Disruption of normal excretions – indwelling urinary catheters
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Skin Lesions in the Immunosuppressed
• Abscess: Aspergillus, Crytococcus, Mucor, MAI and other atypical mycobacteria,
Nocardia, Ps. aeruginosa
• Cellulitis: A. hydrophila, Aspergillus, C. neoformans, halophilic marine vibrios, H.
capsulatum, Mucor, Nocardia, M. kansasii, Ps. aeruginosa
• Ecthyma gangrenosum: Candida spp, Mucor, Pseudomonas and other gram
negs
• Erythematous macules: Alternaria, Mucor, H. capsulatum, HIV (acute)
• Hemorrhagic lesions: Aspergillus, Candida, C. neoformans, Trichosporon
beigleii, Pseudomonas
• Papules/nodules: Aspergillus, Candida, C. neoformans, M. tuberculosis, atypical
mycobacteria, Trichosporon, P. carinii
• Pustules: Aspergillus, C. neoformans, H. capsulatum, Mucor, M. kansasii
• Vesicles/bullae: Aspergillus, Alternaria, Candida, C. neoformans, HSV, VZV,
Mucor, Ps. aeruginosa
• Ulcers: Candida, Rhizopus, H. capsulatum, CMV, HPV
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Ecthyma Gangrenosum
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Ecthyma Gangrenosum
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Other Skin Lesions in Neutropenia
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Disseminated Cryptococcus
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Disseminated
Candida in
AML
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Diseminated Varicella
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Thrush
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HSV Esophagitis
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Laboratory Evaluation
• CBC including WBC with manual differential
• electrolytes, BUN, creatinine, liver function
• blood cultures (bacterial, fungal, ?viral), MAI in HIV infected
• line cultures?
• sputum gram stain/culture (if symptomatic), legionella culture and DFA,
special stains if cell mediated immune defect, consider BAL
• chronic humoral immune defects or cell mediated immune defects with GI
symptoms -consider stool examination with special stains
• urine -typically bacterial infections, often nosocomial but M. tuberculosis
and CMV can be found in urine with dissemination
• ancillary tests –herpesvirus CMV PCR, serum crytococcal antigen, urine
for legionella and histoplasma antigen, antibodies for T. gondii, C. immitis,
hep A-D
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Imaging
• lung most frequently infected organ CXR
• CT scan (head, thorax, solid organs of abdomen)
• MRI (head, bone, thorax, abdomen)
• ?gallium (PJP), Tc bone scan (osteomyelitis),
indium-labelled WBC scanning for intra-abdominal
abscesses ( WBC a problem)
• ?newer modalities -indium labelled IgG
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Pulmonary fungal infection
Halo-Sign
Air-Crescent-Sign
Mucor Aspergillus
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Aspergilloma: Cresent Sign
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Nocardia
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Candida esophagitis in a patient with AIDS
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Rhino-cerebral Mucor
Note bone destruction
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CNS toxoplasmosis
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Hepatosplenic Candidiasis
MRI (T1)-white nodules
CT-hypodense nodules