Wake Pulm Pneumonia In The Immunocompromised Host

Front 1

Name the 3 types of Immune Deficit

Back 1

1. Neutrophil Defect

2. Immunoglobulin Defect

3. T-cell Defects

Front 2

Circumstances associated with Neutrophil Defect

Back 2

Chemotherapy

Leukemia

Early BMT

Front 3

Circumstances associated with Immunoglobulin Defect

Back 3

Multiple Myeloma

CLL

Asplenia

Chronic variable immundeficiency syndrome (CVID)

Chronic GvHD

HIV

Front 4

Circumstances associated with T-cell Defects

Back 4

Advanced HIV

Solid Organ Transplant

Late BMT

Front 5

Organisms associated with Neutrophil Defect

Back 5

BACTERIA

S. aureus
P. aeruginosa
Aspergillus

Front 6

Organisms associated with Immunoglobulin Defect

Back 6

ENCAPSULATED

S. pneumoniae
H. influenzae

Front 7

Organisms associated with T-cell Defects

Back 7

INTRACELLULAR

P. jeroveci
C. neoformans
Legionella
Aspergillus
M. Tuberculosis
CMV

Front 8

If you get a transplant, where are you most likely to get pneumonia?

Back 8

within the first 12 months patients will get pneumonia and may die

Front 9

What are the phases of opportunistic infections after allogeneic HSCT?

Back 9

First 30 days: NEUTROPENIC DEFECT

30-100 days: IMPAIRED CELLULAR IMMUNITY

>100 days: IMPAIRED HUMORAL AND CELLULAR IMMUNITY

Front 10

Common Interventions To Boost Immune Function and Prevent Pneumonia in Immunocompromised Hosts

Back 10

1. G-CSF and other growth factors
- Only of value in those with expected neutropenia > 7-10 days or prior infection during neutropenia
2. IV Immunoglobulin
- employed in CLL, CVID, Multiple Myeloma, chronic GvHD
- some benefit, though magnitude unclear
3. Prophylactic Antibiotics
- clearly useful in some entities (PCP with TMP-SMX), and of very questionable value in others (S. pneumoniae, P. aeruginosa)
4. Immunizations
- very unclear as to value in many immunocompromised hosts; often need to consider chemoprophylaxis (e.g. for influenza)

Front 11

Bronchoscopic Evaluations of Pneumonia in Immunocompromised

Back 11

1. Wash

2. BAL

3. Protected Brush

4. Biopsy

Front 12

What can you do with a Bronchoscopic Wash?

Back 12

Examination:
- Cytology

- Culture ABF/Fungi

Front 13

What can you do with a Bronchoscopic BAL?

Back 13

Examination:
- Cytology

- Culture (SBF/Fungi/Viral)

- Semi-quantitation for bacteria

Front 14

What can you do with a Bronchoscopic Protected Brush?

Back 14

Examination:
- Semi-quantitation for bacteria

Front 15

What can you do with a Bronchoscopic Biopsy?

Back 15

Examination:
- Pathology

BE CAREFUL: risk of bleeding with BMT and neutropenic patients because of low platelets

Front 16

Is BAL high yield in immunocompromised patients?

Back 16

High yield for HIV patients, but maybe not for BMTs, Solid organ transplants and other immunocompromised pts.

- the degree of yeild decreases significantly with empiric therapy (from over 100% with HIV to ~50%)

Front 17

Can High Res CT Avoid the Need for Bronchoscopy?

Back 17

No because many different organisms image the same way.

Except maybe with high index of suspicion for PCP when non-segmental ground-glass attenuation present.

Front 18

CVID

Back 18

2nd most common cause of immunodeficiency in adults… low B cells .: low Ig

Front 19

Bacterial Pneumonia in Immunocompromised

Back 19

Still very common, don’t immediately think zebras in immunocompromised
Typical organisms (S. pneumoniae, H. influenzae, P. aeruginosa) and atypical (Legionella, Nocardia, Typical and Atypical AFB [TB])

HIV patients with bacterial pneumonia; Dx’d either w/sputum or BAL

Front 20

Barotrauma

Back 20

blow out of lung from infection (collapse)

Front 21

ABG: #/#/#

What are the number signs?

Back 21

pH/pCO2/pO2

Front 22

multiple cysts on silver stain (GMS) stain and --- (+) by fluorescence (Direct Fluorescence Antibody) suggest...

Back 22

pneumocystis jiroveci pneumonia

Front 23

Pneumocystis jiroveci Pneumonia
Treatment

Back 23

Therapy
- Trimethoprim/sulfamethoxazole
- Trimethoprim/dapsone
- clindamycin/primaquine
- pentamadine
- atovaquone

Adjunctive steroids for:
- PaO2 < 70 b/c the cells lyse --> burst of inflammation --> become more hypoxic

Front 24

If there is an HIV patient with a pneumothorax, what do we suspect?

Back 24

Pneumocystis jiroveci Pneumonia

Front 25

Pneumocystis jiroveci Pneumonia
Prevention

Back 25

- TMP/SMX

- dapsone

- inhaled pentamadine

- atovaquone

Front 26

Pneumocystis jiroveci Pneumonia

Unusual Presentations

Back 26

- pneumothorax; especially w/inhaled pentamidine b/c drug lacks good spread to the edges of the lung, build up of infxn at pleura

- dyspnea on exertion

- recurrent pneumonia with steroid tapers

Front 27

Pneumocystis jiroveci Pneumonia

Clinical clues

Back 27

- Epidemiology

- Diffuse infiltrate on CXR

- increased LDH

- Marked hypoxemia

Front 28

Pneumocystis jiroveci Pneumonia became more prevalent in the mid 1980s with...

Back 28

HIV and introduction of cyclosporine (and other immunosuppressive drugs)

Front 29

Relative risk for PCP

Back 29

- HIV w/CD4 < 200

- Solid Organ Transplant w/in 6 months

- Allo BMT, esp w/GvHD

- High dose steroids (infxn is suppressed with steroid use and comes back with stopping)

Front 30

Aspergillus Imaging and Labs

Back 30

CXR: multiple nodular infiltrates

Chest CT shows
- wedge shaped infiltrates
- "halo" or "air crescent" sign

Serum aspergillus galactomannan assay (+)

Front 31

Common Fungal Pneumonias

Back 31

Aspergillus spp.

Cryptococcus neoformans

Geographic fungi in specific regions
- Histoplasma capsulatum (rivers)
- Coccidiodes immitis (arid)

Front 32

Rare Fungal Pneumonias

Back 32

Zygomycetes (Mucor)

Blastomyces dermatides
- can present as ARDS

Pseudoallescheria boydii
- Amphotericin B resistant

Candida spp.
- Only consider a true pathogen if at risk for disseminated candidiasis

Front 33

Which populations are most at risk for Invasive Aspergillosis?

Back 33

Hematologic

BMT/Allogenic Transplants

Front 34

What is the most common site of infection for Invasive Aspergillosis?

Back 34

Pulmonary

Front 35

Radiographic Presentation of Aspergillus Pneumonia and Evolution Over Time

Back 35

Halo transitory: <5 days

Increased volume for 1 week --> stabilization

--> air crescent

Front 36

Galactomannan Assay for Diagnosis of Aspergillosis

Back 36

Galactomannan is part of the aspergillus cell wall
- this is specific ONLY for aspergillus

- FDA approved as aid to diagnosis of aspergillosis for adult patients with neutropenia and/or BMT
Sensitivity 80.7%, specificity 89.2% (in trials – MORE LIKELY 40% SENSITIVITY and 90% SPECIFICITY IN REAL LIFE)

- Noninvasive (serum), rapid result

Front 37

What are the caveats for Diagnosis with Galactomannan Assay

Back 37

Questions of utility in other populations
- Non-neutropenia
- Patients receiving mold-active agents
- Children
- Suspected cases
- Solid organ transplants

False positives may be more frequent in patients with mucositis and those on Piperacillin-tazobactam

Front 38

Therapy for Invassive Aspergillosis

Back 38

Voriconazole is superior to Amphotericin B > Echinocandins

(b/c of better mortality... 70.8% V to 57.(% AmB)

- combination therapy may be best... but it has not yet been shown

Front 39

What is the gold standard for diagnosis for Aspergillus Pneumonia?

Back 39

Biopsy showing invassive disease

Front 40

What organisms does Fluconazole not treat?

Back 40

C glabrata dose-dependent

C krusei

all molds

Front 41

What organisms does Amphotericin B not treat?

Back 41

C lusitaniae

Aspergillus terreus

Fusarium

Scedosporium

Front 42

What organisms does Echinocandins not treat?

Back 42

Cryptococcus

Zygomycetes (Agents of mucormycosis)

Fusarium

Scedosporium

Front 43

What organisms does Voriconazole not treat?

Back 43

Zygomycetes (Mucor)

Front 44

Viral Causes of Pneumonia in Immunocompromised Hosts

Back 44

Cytomegalovirus
- particularly in allogeneic BMT patients

Varicella Zoster or Herpes simplex
- usually as part of dissemination... not just pneumonia, but skin signs also

Community acquired
- Respiratory Syncytial Virus (RSV)
- Influenza
- Parainfluenza

Front 45

Risk of CMV Illness with Transplant
(D/R)

Back 45

D-/R-:
CMV Infection: 0
CMV Dz: 0

D-/R+:
CMV Infection: 70
CMV Dz: 20

D+/R+: (reactivation of virus)
CMV Infection: 70
CMV Dz: 20

D+/R-:
CMV Infection: 80
CMV Dz: 70

Anti-lymph Rx (eliminates virus killing cells):
CMV Infection: 80
CMV Dz: 60

Front 46

Which transplants put patients at the most risk for CMV pneumonia?

Back 46

AlloBMT
Lung Transplant

Whatever organ is transplanted is more likely to have infxn (it is a priveleged site…immuno system does not work as well) probably b/c you cannot present antigen as well with worse HLA subtype recognition

Front 47

CMV Pneumonia

Diagnosis

Back 47

Diagnosis is usually clinical, but BAL cytology (owl's eye cell) and culture helpful

Very often found in presence of another pathogen (most common: fungi including PCP and Pseudomonas) b/c CMV is immunosuppressive

Front 48

CMV Pneumonia

Therapy

Back 48

Ganciclovir alone in non-BMT patients

Ganciclovir with IVIG in BMT patients

- often you do not need to treat CMV, you just need to treat the other infection b/c CMV is a continuously shedding virus

Front 49

Non-infectious Causes of Fever and Pulmonary Infiltrates in Immunocompromised Hosts

Back 49

Idiopathic pneumonia

ARDS

Alveolar Hemorrhage

Leukemic Infiltration

Lymphoma

Pulmonary Emboli

Aspiration

Drug Induced Lung Injury: bleomycin, cyclophosphamide, busulfan, ifosfamide, methotrexate, BCNU, doxorubicin

Front 50

Unusual Causes of Pneumonia in the Immunocompromised Host

Back 50

Strongyloides stercoralis

BOOP

Rhodococcus equii
- looks like TB illness, except gram (+) rods

Radiation pneumonitis

Cytokine release syndrome
- OKT3 causing leaky cpillaries

Leukoagglutination

Front 51

Strongyloides stercoralis

Back 51

common in SE USA, hyperinfection syndrome possible in immunocompromised host

presents with diffuse infiltrates and perhaps with gram negative sepsis (streak across plate from worm)