Turkish Thoracic Society

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1 Türk Toraks Derneği Turkish Thoracic Society Turkish Thoracic Society Pocket Books Series Diagnosis and of Pneumonia in Immunocompromised Children Short Version (Handbook) in English

2 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: Fax Number: address: Website:

3 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 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 is summarized in Figure 3. If there is diffuse-interstitial infiltration on chest x-ray of a neutropenic patient, approach to diagnosis and 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

4 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 is started based on the chest radiography Focal infiltration, nodule Continue AB Antithrombolytic Normal (Continue AB ) Diuretic 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 Hepatic VOD ECHO: Pulmonary Hypertension Pulmonary VOD HRCT Steroid Positive response No response Bronchoscopy-BAL No response Bronchoscopy-BAL Microbiological studies Microbiological studies POSITIVE RESULT Infection Appropriate POSITIVE RESULT NEGATIVE RESULT Infection Appropriate Hemorrhagic diffuse alveolar hemorrhage NEGATIVE RESULT Follow-up after hours of antibiotics Positive response No response Bronchoscopy-BAL Microbiological studies POSITIVE RESULT Infection Appropriate NEGATIVE RESULT Hemorrhagic diffuse alveolar hemorrhage Idiopathic interstitial pneumonia Steroids Engraftment syndrome Follow-up for hours If no response, CT Fungal infection? Add antifungal Follow-up for 48 hrs Response continue No response bronchoscopy-bal Microbiological Studies (+) (-) Appropriate Biopsy PULMONARY CYTOLYTIC THROMBI Specific Diagnosis Follow-up for hours No response CT Appropriate 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 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

5 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 If no response after hours CT/HRCT COMMUNITY- ACQUIRED PNEUMONIA AB Positive response; BRONCHIOLITIS OBLITERANS Steroid Positive; CT/HRCT BOOP Steroid Positive response; RADIATION PNEUMONIA CT/HRCT Steroid Positive response; Fungal infection? Add antifungal Follow-up for 48 hrs Positive response continue No response; No response; No response; No response; No response; BRONCHOSCOPY - BAL Bronchoscopy BAL Biopsy Diagnostic Not diagnostic Infection Metastasis Relapse Biopsy Appropriate Figure 2. Complications which may be seen in Phase III (> 100 days) in the hematopoietic stem cell transplant recepient; approach to diagnosis and 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

6 Clinical Findings Clinical Findings Clinical Findings Clinical Findings Diagnostic evaluation* 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 hrs Recovery No Recovery Deteriorating Complete to 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 Add Amphotericin B No improvement Reevaluate after 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 in the immunocompromised child with patchy or focal infiltration on chest x-ray 10 11

7 Pulmonary Infiltrates Diffuse or interstitial infiltrates No Neutropenia Neutropenia Diagnostic evaluation Start empiric (TMP-SMX + Macrolide) Re-evaluate after 4 days Stable or Recovering Continue empiric (TMP-SMX) 14 days (Macrolide) 21 days Not Recovering HRCT BAL ± TBB according to the findings HRCT, BAL ± TBB Start broad spectrum antibiotic Not Diagnostic Diagnostic TMP-SMX Add macrolide Improvement Not taking antibiotic Appropriate No improvement Clinical deterioration Cannot tolerate diagnostic attempt Reevaluate after 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 cannot tolerate diagnostic attempt Reevaluate after hours If not improving or no microorganism recovered, TBB, VATS, Open lung biopsy Start Amphotericin B Reevaluate after hours No improvement TBB, VATS, Open lung biopsy Improvement Keep on No improvement Improvement TBB, VATS, Open lung biopsy Continue Modify antibiotics No improvement Improvement TBB, VATS, Open lung biopsy Continue Figure 4. Approach to diagnosis and in the immunocompromised patient with diffuse or interstitial infiltrates on chest x-ray 12 13

8 Abbreviations: * Diagnostic evaluation: chest X-Ray, sputum s smear and sample, blood sample of hospitalized patients, serology, antigen determinations, PCR ** Broad spectrum antibiotics 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 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

9 Türk Toraks Derneği Turkish Thoracic Society