Diagnosis and Treatment of Pneumonia in Immunocompromised ...

toraks.org.tr

Diagnosis and Treatment of Pneumonia in Immunocompromised ...

Türk Toraks Derneği

Turkish Thoracic Society

Turkish

Thoracic

Society

Pocket Books Series

Diagnosis and Treatment

of Pneumonia in

Immunocompromised

Children

Short Version (Handbook)

in English

www.toraks.org.tr


This report was prepared and written by

Ugur Ozcelik, Refika Hamutcu Ersu,

Mehmet Ceyhan, Tezer Kutluk, Faik Sarıalioglu,

Leman Yel, Duygu Uckan, Yildiz Camcioglu,

Figen Demirkazik, Mualla Cetin, Nurdan Tacyildiz,

Nuran Salman, Baris Kuskonmaz

The full text of the report is published in Turkish in

Turkish Thoracic Journal 2009;10 (Supplement 4): 6-9

Türk Toraks Derneği

Turkish Thoracic Society

Turkish Thoracic Society

Turan Güneş Boulevard, No: 175/19 Oran-Ankara-Turkey

Telephone Number: +90 312 490 40 50

Fax Number: +90 312 490 41 42

E-mail address: toraks@toraks.org.tr

Website: www.toraks.org.tr


Pneumonia caused by usual microorganisms may show rapid

clinical progress in immunocompromised children. Unusual causes

of pneumonia in healthy children may cause severe disease in

these children.

Table 1. Microorganisms causing pneumonia in children with primary

immunodeficiencies

Affected part of the immune system

Common microorganisms causing lung infections and non-

Infectious conditions which should be considered in the differantial

diagnosis of lung infections in immunocompromised children are

shown in Tables 1 and 2.

Approach to Diagnosis and Treatment

Patient history, physical examination, microbiological methods

and radiological examinations are helpful in diagnosis of pneumonia

in immuno-compromised children.

In hemapoetic stem-cell transplant patients, problems that

emerge depend on the time elapsed after transplantation. Approach

to pneumonia in these patients is shown in Figures 1 and 2.

In neutropenic patients, if chest x-ray shows focal patchy

infiltration, approach to diagnosis and treatment is summarized

in Figure 3. If there is diffuse-interstitial infiltration on chest x-ray

of a neutropenic patient, approach to diagnosis and treatment is

summarized in Figure 4.

Pathogen T-Cell Complement

System

B-Cell Granulocyte TH1-

Macrophage

4 5

Bacteria

Viruses

Fungi

Protozoan

Mycobacterium

Listeria

CMV

EBV

VZV

Respiratory

viruses

Candida

Aspergillus

P. jirovecii

Toxoplasma

Cryptosporidium

Streptococcus

Staphylococcus

H.influenzae

Streptococcus

Staphylococcus

H.influenzae

CMW: Cytomegalovirus, EBV: Epstein - Barr Virus, VZV: Varicella-Zoster Virus

Staphylococcus

Pseudomonas

Nocardia

Candida

Aspergillus

Mycobacterium

Salmonella

Table 2. Non-infectious conditions which should be considered in the differential diagnosis of

pulmonary infections in immunocompromised children

Pulmonary hemorrhage

Pulmonary edema

Metastases of solid tumors

Parenchymal infiltration of lymphoproliferative tumors

Pulmonary toxicity of antineoplastic medicines

Radiation pneumonia

Lung involvement in autoimmune / auto-inflammatory diseases

Acute lung injury, acute respiratory distress syndrome (ARDS)

Lymphoid interstitial pneumonia

Benign pulmonary nodules

Bronchiolitis obliterans

Bronchiolitis obliterans organizing pneumonia (BOOP)

Leukoagglutination reaction

Pulmonary embolism

Pulmonary infarct


PHASE I and PHASE II (0-100 DAYS)

Clinical Findings (fever, cough, dyspnea, etc.)

Complete blood count, SaO 2

, arterial blood gas,

chest radiography, cultures, Galactomannan test, CMV PCR

History of catheter thrombosis

Pulmonary thrombo-embolism?

Spiral CT/V-P scintigraphy

Diffuse infiltration

Empiric antibiotic treatment is started

based on the chest radiography

Focal infiltration, nodule

Continue AB treatment

Antithrombolytic treatment

Normal (Continue AB treatment)

Diuretic treatment

Fluid restriction

Positive response

PULMONARY EDEMA

Close follow-up

Sharply-circumscribed

dense infiltrates

History of radiotherapy

PFT: Restrictive findings

RADIATION

PNEUMONIA

HRCT/CT

Steroid

Postive response

Continue treatment

Hepatic VOD

ECHO: Pulmonary

Hypertension

Pulmonary VOD

HRCT

Steroid Treatment

Positive response

Continue treatment

No response

Bronchoscopy-BAL

No response

Bronchoscopy-BAL

Microbiological studies

Microbiological studies POSITIVE RESULT

Infection – Appropriate

Treatment

POSITIVE RESULT

NEGATIVE RESULT

Infection – Appropriate

Treatment

Hemorrhagic – diffuse

alveolar hemorrhage

NEGATIVE RESULT

Follow-up after

42-78 hours of antibiotics

Positive response

Continue treatment

No response

Bronchoscopy-BAL

Microbiological

studies

POSITIVE RESULT

Infection – Appropriate Treatment

NEGATIVE RESULT

Hemorrhagic – diffuse alveolar hemorrhage

Idiopathic interstitial pneumonia – Steroids

Engraftment syndrome

Follow-up for 48-72 hours

If no response, CT

Fungal infection?

Add antifungal

Follow-up for 48 hrs

Response –continue treatment

No response – bronchoscopy-BAL

Microbiological Studies

(+) (-)

Appropriate

Treatment

Biopsy

PULMONARY CYTOLYTIC

THROMBI

Specific

Diagnosis

Follow-up for 48-72 hours

No response

CT

Appropriate

Treatment

Consider to discontinue

Antifungal and Antibiotics

Positive

response

Figure 1. Complications which may be seen in Phase I and Phase II (< 100 days) in the hematopoietic stem cell transplant recipient; approach to diagnosis and treatment

Pulmonary VOD: pulmonary veno-occlusive disease; HRCT: High resolution computerized tomography; CT: Multi-slice computed tomography; PFT: Pulmonary function test; ESR:

Erythrocyte sedimentation rate; CRP: C reactive protein; ECHO: Echocardiography; GVHH: Graft-versus-host disease; AB: Antibiotic


PHASE III ( > 100 DAYS)

Clinical Findings

(dyspnea, cough, etc.)

- Previously developed complication ?

- History of CMV or fungal infection ?

- Acute – chronic GVHH history ?

- Complete blood count – ESR, CRP, cultures ?

- O 2 sat, arterial blood gas, CMV PCR ?

- PFT, chest radiography, ECHO ?

Fever present

Physical examination

findings are

consistent

PFT, Obstructive

findings

CT/HRCT

Chest x-ray:

Fields of air trapping

PFT: Restrictive

findings

No fever

History of radiotherapy

PFT: Restrictive findings

Pulmonary nodule

AB Treatment

If no response after

48 – 72 hours

CT/HRCT

COMMUNITY-

ACQUIRED

PNEUMONIA

AB Treatment

Positive response;

Continue treatment

BRONCHIOLITIS

OBLITERANS

Steroid Treatment

Positive;

Continue treatment

CT/HRCT

BOOP

Steroid Treatment

Positive response;

Continue treatment

RADIATION

PNEUMONIA

CT/HRCT

Steroid Treatment

Positive response;

Continue treatment

Fungal infection?

Add antifungal

treatment

Follow-up for 48 hrs

Positive response –

continue treatment

No response;

No response;

No response; No response; No response;

BRONCHOSCOPY - BAL

Bronchoscopy – BAL

Biopsy

Diagnostic

Not diagnostic

Infection Metastasis

Relapse

Treatment

Biopsy

Appropriate Treatment

Figure 2. Complications which may be seen in Phase III (> 100 days) in the hematopoietic stem cell transplant

recepient; approach to diagnosis and treatment

Pulmonary VOD: pulmonary veno-occlusive disease; HRCT: High resolution computerized tomography; CT: Multi-slice

computed tomography; PFT: Respiratory function test; ESR: Erythrocyte sedimentation rate; CRP: C reactive protein; ECHO:

Echocardiography; GVHH: Graft-versus-host disease; AB; Antibiotic.

8 9


Clinical Findings

Clinical Findings

Clinical Findings

Clinical Findings

Diagnostic evaluation*

Treatment according to diagnosis

Not taking antibiotics

Taking antibiotics

At least for 48 hrs

Diagnostic evaluation*

Start broad spectrum

antibiotic **

Number of neutrophils

is increasing

Patient in stable

condition

Clinical

deterioration

Neutropenia

continues

Reevaluate

after 48-72 hrs

Continue treatment

Recovery

No Recovery Deteriorating

Continue treatment

Complete to 10-14 days

HRCT, if he can tolerate

BAL ± TBB

Modify antibiotics **

HRCT, if he can tolerate

BAL ± TBB

Modify antibiotics **

Add Amphotericin B

Informative findings

Informative findings

Available Not available

Available Not available

Treat according

to the results

Continue

treatment

Add Amphotericin B

No improvement

Reevaluate

after 48-72 hrs

Treat according

to the results

Improvement

No improvement

No

improvement

TTB,

VATS,

Open

lung

biopsy

TTB, VATS, Open lung biopsy

Figure 3. Approach to diagnosis and treatment in the immunocompromised child with patchy or focal infiltration

on chest x-ray

10 11


Pulmonary Infiltrates

Diffuse or interstitial infiltrates

No Neutropenia

Neutropenia

Diagnostic evaluation

Start empiric treatment

(TMP-SMX + Macrolide)

Re-evaluate after 4 days

Stable or

Recovering

Continue

empiric

treatment

(TMP-SMX)

14 days

(Macrolide)

21 days

Not

Recovering

HRCT

BAL ± TBB

Treatment

according to

the findings

HRCT, BAL ± TBB

Start broad spectrum

antibiotic

Not Diagnostic Diagnostic

TMP-SMX

Add macrolide

Improvement

Not taking antibiotic

Appropriate

treatment

No

improvement

Clinical deterioration

Cannot tolerate

diagnostic attempt

Reevaluate after

48-72 hours

Diagnostic evaluation

Broad spectrum

antibiotic

TMP-SMX

Start macrolide

Add

Amphotericin B

HRCT, BAL ± TBB

Start Amphotericin B

Not

Diagnostic

TMP-SMX

Add macrolide

Taking antibiotic

(At least for 48 hours)

Diagnostic

Appropriate

treatment

cannot tolerate

diagnostic attempt

Reevaluate after

48-72 hours

If not improving

or no microorganism

recovered, TBB,

VATS, Open

lung biopsy

Continue treatment

Start

Amphotericin B

Reevaluate

after 48-72 hours

No improvement

TBB,

VATS,

Open lung

biopsy

Improvement

Keep on

treatment

No

improvement Improvement

TBB,

VATS,

Open lung

biopsy

Continue

treatment

Modify antibiotics

No improvement

Improvement

TBB, VATS, Open

lung biopsy

Continue

treatment

Figure 4. Approach to diagnosis and treatment in the immunocompromised patient with diffuse or interstitial

infiltrates on chest x-ray

12 13


Abbreviations:

* Diagnostic evaluation: chest X-Ray, sputum’s smear and sample,

blood sample of hospitalized patients, serology, antigen

determinations, PCR

** Broad spectrum antibiotics treatment is treated as a

monotherapy and combination therapy.

In Monotherapy

1) Imipenem/cilastatin, 2) Meropenem, 3) Cefepime can be

used.

In Combination Therapy

1) Pseudomonal broad spectrum anti-penicillin(piperacillin/tazobactam)

+ aminoglycoside (amikacin, tobramycin);

2) Anti-pseudomonal cephalosporins (ceftazidime, cefoperazone,

cefepime) + aminoglycoside;

3) Carbapenem (imipenem/cilastatin,meropenem) + aminoglycoside

can be used.

Initially Glycopeptides (vancomycin, teicoplanin) in the

following cases can be added to monotherapy and combination

therapy:

1) If patients with suspected catheter related infection,

2) If patients had severe mucosal symptoms.

3) If there is penicillin and cephalosporin-resistant pneumococcal

or growth of MRSA for more previous samples of the patient,

4) If patients have hypotension and other symptoms of shock,

5) If there is mastered lung infection while patients have quinolone

prophylaxis.

***Modification of Antibiotic

1) Initially, transition to monotherapy, combination treatment was

started empirically.

2) In clinics which have common MRSA empirically, the addition of

glycopeptide therapy.

3) Initiation of appropriate antibiotic therapy according to the

results obtained from the samples and antibiotic sensitivity.

**** Patients have diffuse/interstitial and infiltration at their

chest radiographs, diagnostic tests should be made for

diagnosis of primarily CMV viral factors, P. jirovecii, Legionella,

Chlamydia, ycoplasma.

HRCT: High-resolution computed tomography. Unable to

hold his/her breath in children Multi-slice computed tomography

should be used.

TBB: Transbronchial biopsy

TTB: Transthoracic biopsy

VATS: Video-assisted thoracoscopy

OLB: Open Lung Biopsy

15


Türk Toraks Derneği

Turkish Thoracic Society

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