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