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what are the basic principles involved with immunocompromised patients?

1. may be unable to tell you they are sick and they feel fine because their immune system isn't strong enough to mount a response

2. often have more extensive disease than is apparent

3. may require longer treatment than individuals with a “normal” immune system

4. acquire infections with organisms that usually are not pathogens, “environmentals” or “comensals”

5. the type of organism causing the infections correlates with the type of immunodeficiency (not all immunodeficiencies are equal)


what are the common features of lung infections in immunocompromised individuals?

1. abnormal frequency of infections

recurrent pneumonia in HIV and diabetics

2. abnormal/severe presentation of infections

pneumococcal septic shock in splenectomized patients, disseminated histoplasmosis in HIV patients, fulminant acute pulmonary aspergillosis in stem cell transplant

3. unusual infections

- Pneumocystis jiroveci

- Burkholderia cepacia

- Nontuberculous mycobacteria

- Aspergillus

- Nocardia


35 y/o man with AML (acute myeloid leukemia) had induction chemotherapy and total body radiation in preparation for stem cell transplant. He is now on day 7 post-stem cell infusion. Absolute neutrophil count is 0. He has been on levofloxacin and fluconazole for prophylaxis.
He develops fever 102F, mild shortness of breath, pleuritic chest pain and dry cough.
Sputum Gram stain and culture is obtained, xray shows a faint right lower lobe infiltrate.
He is started on piperacillin/tazobactam and vancomycin.

Blood culture is growing a NON lactose fermenting Gram negative rod. The most likely organism causing pneumonia in this patient is:

A. Proteus

B. Legionella

C. Salmonella

D. Pseudomonas

E. Klebsiella



what are the risk factors for developing pseudomonas pneumonia?

1. neutropenia

2. solid organ and stem cell transplant

3. hospital acquired, critical care, intubated

4. tracheostomy

5. CF and bronchiectasis

6. frequency COPD exacerbations, steroid use

7. recent antibiotic use


what is neutropenia?

mild – < 1000 PMN/μl

moderate <500 PMN/μl

severe <100 PMN/μl

it matters how immunocompromised you are and for how long!


which antibiotics work on pseudomonas?

1. quinolones = ciprofloxacin and levofloxacin

2. penicillins = piperacillin/

3. cephalosporins = cefepime, ceftazidime, ceftolozane/tazobactame, ceftazidime/avibactam

4. carbapenems = imipenem, meropenem, doripenem -- NOT ertapenem

5. aminoglycosides = gentamicin, tobramycin, amikacin --> these should NOT be used alone because they're don't have good distribution to tissues from the blood

6. polymyxins = colistin, polymyxin B


what do you give to critically ill patients with pseudomas pneumonia?

combination therapy!! until you know what the organism is and what it's susceptible to; then you can cut down to 1 drug

if the resistance is more than 10% in that area/hospital give 2 drugs!!


Our patient improves after 7 days of treatment with piperacillin tazobactam, fever resolves, and he is switched back to prophylactic antibiotics

5 days later ANC is now 20, platelets 10 and he develops a new fever. He is started again on IV piperacillin-tazobactam, but 48h later he is still febrile and his respiratory status is deteriorating. New sputum and blood cultures are obtained.

chest CT shows 2 peripheral masses. What is the next step in management?

A. add voriconazole

B. change piperacillin-tazobactam to meropenem

C. add trimethoprim sulfamethoxazole

D. obtain a lung biopsy

E. continue current antibiotics, awaiting culture

A. add voriconazole

there's lots of things you can do with a patient like this so none of these are really wrong but you should recognize that this patient has 2 infiltrates and one of them has a halo around it which is specific for aspergillosis

can't do a biopsy because his platelets are super low and he'd bleed to death

so you would add an anti-fungal and anti-staphylococcal coverage


where does aspergillum come from?

1. holy water sprinkler

2. vacuum cleaner (aerosolizes dust)

3. mulching


what are the risk factors for aspergillosis?

1. severe* and prolonged* neutropenia

2. receipt of high doses of glucocorticoids

3. other drugs or conditions that lead to chronically impaired cellular immune responses like immunosuppressive regimens administered to treat autoimmune diseases and to prevent organ rejection, AIDS


what do you see in aspergillosis microscopy?

thin septated hyphae that are the same thickness everywhere without bumps

narrow angle branching

looks like coral on microscopy and dandelions on cultures


what is the radiographic appearance of aspergillosis?

CXR are nonspecific and can even be normal in immunocompromised patients so do a CT

1. nodular lesions, can be peripheral, close to pleura

2. halo sign

3. crescent sign

4. frequently involves both lung and brain so get brain MRI


what is an aspergilloma?

something previous has caused a cavity in the lungs and now asperillus has formed a ball-shaped colony in the cavity that isn't invading into the lung tissue

usually pretty benign; can resect surgically but ONLY if there's symptoms


what is chronic pulmonary aspergillosis?

go look at the CT

chronic invasive asperigillosis

really hard to treat; give 2 months of anti-fungals


how do you diagnose aspergillosis?

risk factors + clinical picture + radiology + tissue dx!! put it all together because sometimes someone can have positive cultures but they're fine

can be difficult – can colonize respiratory tract; BC never positive...

tissue diagnosis is the gold standard!! but with someone who is immunocompromised it's hard to get a piece of lung

aspergillus galactomannan (from BAL more sensitive than from blood) and beta-D glucan can be suggestive but are not specific


what are zygomycetes?

a mold that under microscopy looks like broad, ribbon-like nonseptated right angle branching that's bumpy coral

often seen in diabetics or transplants

they invade lung and sinuses and get to the brain and can kill people in days

treat with mphotericin B, newer azoles (posa-, isavuconazole) and surgical excision


how do you treat aspergillosis?

empirical and as soon as suspected in high risk pts

1. aoriconazole, IV then PO

2. posaconazole

3. isavuconazole

4. liposomal Amphotericin B

5. echinocandins (caspofungin, micafungin, anidulafungin) -- not first line; more of a salvage therapy

combination therapy is frequently used

give prophylaxis in pts with high risk hematologic malignancies


what is nocardiosis?

like aspergillosis, it can affect skin, lung, brain.

it's an agent of mycetoma in immunocompetent host; you can have chronic foot infections that lead to sinus tract infections

can disseminate; blood cultures can be positive

often seen in solid organ transplant, chronic steroids, ETOH, DM, CGD, anti-TNF, less common AIDS


how do you treat nocardiosis?

treat with Bactrim, carbapenems (imipenem), aminoglycosides (amikacin) in COMBINATION

penems are needed when there's brain involvement

you have to know the species before you give specific treatment


what does the nocardia gram stain look like?

gram stain shows weakly acid fast positive bacteira

looks like really thin tangled weeds



what does a nocardia pneumonia CT look like?

you'll have lung and brain involvement; looks a lot like aspergillosis

you'd have to get blood cultures and with nocardia you're more likely to get positive blood cultures than in aspergillosis


what are the 4 B's of nocardiosis?






40 year old man with a history of splenectomy is brought in by family to ED with fever for 2 days, productive cough – greenish sputum with blood streaks, confusion. In ER hypotensive, altered, requires intubation, fluids and pressors.

Blood cultures are drawn and he is started on broad spectrum antibiotics

What test should be used to confirm the suspected etiology of this pneumonia, given that blood cultures may take several days to grow?

A. Lung biopsy

B. urine antigen

C. PCR from blood

D. procalcitonin

E. sputum gram stain and culture

B. urine antigen


E. sputum gram stain and culture


what is invasive pneumococcal disease?

an infection in the lungs causing pneumonia and meningitis too - sometimes you can also have endocarditis

can present post-influenza


how do you prevent invasive pneumococcal disease?

PCV13/PPSV23 vaccines is crucial


what are the risk factors for invasive pneumococcal disease?

1. hyposplenism and splenectomy

2. B cell defects: multiple myeloma, SLE, transplant (HSCT with GVHD

3. HIV


how do you diagnose invasive pneumococcal disease?

1. sputum gram stain and culture

rate of pathogen detection varies from 10-80%

2. pneumococcus urine antigen (70% sensitive, 90% specific)

3. blood cultures are indicated for the patients that require admission to the ICU; the sicker the patient , the higher the likelihood of positive blood cultures

low sensitivity in milder infections


what is asplenia?

no spleen

congenital absence is very rare; most asplenics had it surgically removed


what are the indications for a splenectomy?

1. trauma

2. idiopathic thrombocytopenia purport (ITP)

3. spherocytosis, thalassemia major, hairy cell leukemia

4. malignancies involving the spleen like Hodkigns and non-Hodgkin's lymphoma

5. abscess


what are examples of functional hyposplenism?

so they have a spleen but it just doesn't work well

1. Graves

2. SLE

3. Sjogren

4. vasculitis

5. neoplasia = Hodgkin's, CML, Sezary

6. amyloidosis, sarcoidosis

7. alcoholism

8. sickle cell disease

9. malaria

10. elderly, neonates, prematures