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
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
Pathogens
1) Newly acquired opportunistic
2) Latent organisms
3) Typical community or nosocomial pathogens
Exceptionally broad range
Importance
atypical organisms
atypical therapies
Definitions
immune (specific) vs. non-immune (non-
specific) host defenses
immunosuppressed vs. immunocompromised
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
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
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
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
Principles in Assessment
1) nature of the immune defect
2) severity of the immune defect
3) duration of the immune defect
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
CMV retinitis
Ocular toxoplasmosis
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
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
Ecthyma Gangrenosum
Ecthyma Gangrenosum
Other Skin Lesions in Neutropenia
Disseminated Cryptococcus
Disseminated
Candida in
AML
Diseminated Varicella
Thrush
HSV Esophagitis
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
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
Pulmonary fungal infection
Halo-Sign
Air-Crescent-Sign
Mucor Aspergillus
Aspergilloma: Cresent Sign
Nocardia
Candida esophagitis in a patient with AIDS
Rhino-cerebral Mucor
Note bone destruction
CNS toxoplasmosis
Hepatosplenic Candidiasis
MRI (T1)-white nodules
CT-hypodense nodules