10-28-c.txt

• Saying someone is immunocompromised does not really help, you need to know the type of deficit!:
• Each type of immune deficiency is associated with a special set of organisms that are dependent on the corresponding branch of the immune system for eradication of the organisms

• Cell-mediated immunity:
• Humoral Immunity:
• Innate immunity: neutrophils, complement, antimicrobial peptides
• (skin, mucosal epithelium)

• AIDS:
• Many types of lymphomas and transplant patients suffer from defects in cell-mediated immunity:
• Organ transplant recepients, patients on corticosteroid therapy: and lymphomas are at high risk for these infections
• Severity and the rapidity of the presentations may differ

• Type of transplant: (renal, cardiac, lung, liver, and bone marrow) and
• The type and frequency of these infections varies with the type of transplant:
• Different immunosuppressive regimens will give different responses

• Common pathogens include
• Listeria:
• Salmonella:
• M. tuberculosis:
• Nocardia:
• Cryptococcus, histoplasmosis, coccidiomycosis, and
• Pneumocystitis: poster child for immune-mediated immune responses
• Cytomegalovirus and varicella-zoster virus: can also get reactivation

• Not all HIV patients have the same risk of infection
• CD4 > 200 S. Pneumoniae, H. influenzae, M. Tuberculosis, S. aureus (IDU), Influenza:
• CD4 count 50-200 Above + P. jiroveci, Cryptococcus, histoplasmosis, coccidioidomycosis, nocardia, M. kansasii, Kaposi’s sarcoma:
• CD4 count <50 Above + P. aeruginosa, aspergillus, MAC, CMV:

• Opportunistic pathogen:
• Compromised host:
• T-cell immune defect: Pneumocystis jiroveci (pneumocystis carinii)
• Originally classified as a protozoan, molecular studies clearly place it as a fungus:
• Cell wall lacks eldosterol

• High risk HIV: central role for the CD4 cell, dormant for years
• Immunosuppressive therapy:glucocorticoids:
• Organ transplantation:
• Children with primary immunodeficiency
• Premature malnourished infants

• Dyspnea:
• Fever:
• Nonproductive cough:
• In non-HIV associated changes in the glucocorticoid dose

• Tachypnea, tachycardia, and hypoxia are prominent: like regular bacterial pneumonia
• Chest examination: is frequently normal but no rales.
• ABG’s show hypoxia ans respiratory alkalosis
• LDH values are frequently elevated in HIV infected individuals: NON-SPECIFIC, NOT A SENSITIVE INDICATOR
• Disease progression in HIV is generally slower than in other forms of immunosupression
• Organisms can be seen on silver stain, but..
• ***FLUORESCENT MONOCLONAL ANTIBORY IS MUCH MORE SENSITIVE:
• Sputum for DFA is the best diagnostic choice: can also be done on lung tissue

• Diffuse bilateral infiltrates in the perihilar region: classic look of pneumocystis
• Other findings may be seen and failure to see a classic CXR does not rule out the disease
• Patients with HIV increased pneumothorax

• Trimethoprim-sulfamethoxazole: first drug of choice, second line
• Second line clindamycin/primaquin, atovaquone, dapsone/primaquin, pentamidine, trimetrexate
• Patients with HIV frequently develop worsening of their symptoms on initiation of antibiotic therapy:
• PAO2 of 70 mmHg or an A-a gradient of 35 mmHg benefit from corticosteroids within 72 hours!: IN PATIENTS WITH SEVERE DISEASE, GIVING STEROIDS MAY HELP WITH THE COMPLICATIONS OF TREATMENT

• Primary prophylaxis: prevention of 1st episode; in HIV and patients at known high risk – use cut-off of 200 to decide who’s at high risk
• Secondary prophylaxis is indicated ifor HIV – prior history of PCJ
• Regimens: TMP/SMX preferred: dapsone or dapsone pyrimethamine
• Inhaled pentamidine:
• Or atovaquinone are alternatives

• Higher bacteria, somewhat intermediate between bacteria and fungi
• Microbiology: worldwide in soil
• Epidemiology: e.g. 53 y o patient with a non-Hodgkins lymphoma, think T- cell mediated disease
• Risk is associated with deficient cell-mediated immunity – AIDS, lymphoma, transplantation

• Nocardia may spread locally in the chest cavity to adjacent structures but has a predilection for extrapulmonary spread to the brain.
• Pulmonary and CNS disease in a patient with deficient T-cell immunity should raise the suspicion of Nocardia!!: when see lung and brain involvement, and T-cell mediated immunity deficiency, think Nocardia!!
• Transcutaneous inoculation leads to a cutaneous form of Nocardia

• The lab should be alerted
• Organism may take more time to grow and may be difficult to differentiate
• Branching Gram-positive hyphae that is acid-fast on a MODIFIED acid-fast stain!!!: if on exam, think Nocardia!

• Sulfonamides:
• Minocycline, imipenem others second choice
• Patients with pulmonary disease and impaired T-cell immunity should probably have a CT or MRI to inverstigate the CNS as dissemination is common:!! Look for it

• Severe hypogammaglobulinemia(unable to produce antibodies): encapsulated bacteria – streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningititus
• Asplenia: (can’t remove Ab labeled cells) encapsulated bacteria - Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningititus

• Seen mainly in pts with cancer chemotherapy
• Severe neutropenia, early: gram-negative rods
• Pseudomonas aeruginosa, Enterobacteraceae, Staphylococcus aureus, esp with catheters, Aspergillus
• Severe neutropenia, Late: think Fungi
• Aspergillus, Mucomycosis – because have been treated with many antibiotics by this point

• Gram-negative pathogens, including Pseudomonas aeruginosa are common
• Classic skin manifestation – ecthyma gangrenosum

• Infections may rapidly progress and rapid institution of appropriate antibiotic therapy is essential in preventing overwhelming sepsis in the absence of the primary pagocytic cell line: risk of death is very high, so give antibiotics, which should cover pseudomonas
• A recent increase in gram positive infections has been associated with highly active gram-negative therapy and IV acess lines

But the antibiotics have to cover pseudomonas

• White candida is a common pathogen outside of the pulmonary tract, it is an uncommon agent of pneumonia:
• Bone marrow translplants have a high degree of marro suppression and are at risk for many opportunist pathogens with a wide variety of clinical syndromes:

• Chronic granulomatous disease: STAPH AUREUS, Aspergillus, Nocardia, Gram-negative rods, and other catalase-positive bacteria
• Other neutrophil defects – diabetes?

Terminal complement deficiencies (C6-C9) high frequency of Neisserial infections, especially Neisseria meningitides