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Immunocompromised Host: LABORATORY APPROACH. Prof. Dr.Özay Arıkan Akan Ankara University Medical School Ibni Sina Hospital Central Microbiology Laboratories. Lower respiratory tract microbiology. Diagnosis (mimicking clinical presentations)
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Immunocompromised Host:LABORATORY APPROACH Prof. Dr.Özay Arıkan Akan Ankara University Medical School Ibni Sina Hospital Central Microbiology Laboratories
Lower respiratory tract microbiology Diagnosis (mimicking clinical presentations) Establishing the agent (Clinical/radiological findings are nonspecific) Success of the therapy(atypical microorganisms, antimicrobial resistance) Collecting the epidemiological data
Laboratory diagnosis Microbiological approach Microscopy Culture (blood, sputum and respiratory tract secretions) Serologic tests Nucleic asit amplification tests (eg: PCR)
Microbiology Laboratory Rapid Reliable Reproducible results Continuous care
QUALIFIED SERVICE Right specimen Right area Right technique Right time Right amount • Right transportation
There is lung involvement in at least 75% of febrile neutropenic patients, but etiological agents can be microbiologically documented in only 50% of them. Limits of diagnosis
Specimen collection is difficult PMNLs are absent in neutropenic patients Normal flora Bacteria can cause infection Fastidious and resistant bacteria can be observed Serological antibody response is not sufficient Diagnostic problems in immunosuppressed patients
Etiological agents Bacteria I.group S.pneumoniae H.influenzae M.catharralis Gram negative bacilli Enterobactericeae Acinetobacter Pseudomonas aeruginosa Stenotrophomonas maltophilia S.aureus Nonfermenter bacteria Bacteria II group. Nocardia, Legionella, M.pneumoniae Chlamydophila pneumoniae, Mycobacterium tuberculosis Mycobacteria other than M.tbc Fungi: Candida, Aspergillus, Cryptococcus, Zygomycetes grubu , Pneumocystis jirovecii Dematiaceous molds Fusarium- Scedosporium- Geothricum candidum.- Trichosporon spp. Viruses: RSV- influenza-parainfluenza Adenovirus Coronavirus, Metapneumovirus, Herpes viruses Parasites: Strongloides stercoralis Toxoplasma gondii Enterocytozoon bieneusi
ONE WHO DOES NOT KNOW WHAT HE IS LOOKING FOR, CANNOT UNDERSTAND WHAT HE HAS FOUND
15-30 % positive in pneumonia of immunosupressed patients Especially conditions in which bacteria predominates; Febrile neutropenia, Early phases of Heart and Lung transplants. Blood cultures CollinBA, Clin Infect Dis N Am 1998
Comparison of Manuel and Automated blood culture results Clinical study, 1442 blood culture sets. 16,14 %specimen positivity Time (hours) Saleh, A.F. et al. 8th ECCMID 1997
Urinary antigen L.pneumophilaserogroup 1 Sensitivity 70-90 %, Specificity 99-100 % S.pneumoniae Sensitivity 72%, Specificity %90 Histoplasmosis and blastomycosis by ELISA
Nasopharyngeal swab, aspirats Sputum In the diagnosis of viral infections, M.pneumoniae and Chlamydophilia Respiratory tract specimens
Standard sputum evaluationGram stain an Cultura Advantages Easy Rapid Cheap Disadvantages Nonproduction of sputum Upper Respiatory tract contamination (20-25%) Insufficient with some organisms Experts for evaluation • Appropriate specimen and transport • Rejection criteria • Induced sputum for P. jirovecii , M. tbc and various bacteria • Endotracheal aspirates can replace sputum in immunsupressed patients.
Baughman RP et al In:Pulmonary infections in immunocompromised patients, 2009
Bronchoscopic Standard bronchial lavage BAL PSB (protected specimen brush) Nonbronchoscopic Tracheal /transtranscheal aspiration Blind protected brush Blind protected bronchial lavage lavaji Distal lung aspiration with teleschopic catheter Biopsi (plevral, transthoracic, toracoschopic ve torachotomic) Advantages Reaches distal airways High sensitivity and specificity? Diagnostic standardization with quantitative cultures Disadvantages Hard to perform High cost Antibacterial effect of local anestetics Indications Reproducibility ? (Point to borderline results) complications Invazive techniques in the diagnosis of pneumonia
Diagnosis of pneumonia in immunocompromised patient Baughman RP et al In:Pulmonary infections in immunocompromised patients, 2009
Mycobacterium tuberculosis Direct smear (AFB) Culture: classical (4-8 weeks), BACTEC Serology ? PCR With 2 consecutive sputumspecimens Diagnosis rate: 95% Value of examining three acid-fast bacillus sputum smears for diagnosis of pulmonary tuberculosis. J Clin Microbiol 2000; 38:4285
Diagnosis in invazive aspergillozis • Galactomannan antigen (serum and BAL) • (1-3)-B-D-glucan • PCR : sensitivity for aspergillozis 45-93 % • specificity 72-100 % • Galactomannan • GMI >0.5 sensitivity 100 % specificity 97.5% • meta analysis: sensitivity % 79 specificity % 86 • frequency: 2 times /week • Patient population :neutropenia in hematological malignancy and allogeneic SCT • Sensitivity is higher in BAL compared to serum (85 -100% vs %73-83) Wheat LJ, Walsh T. Eur J Clin Microbiol Inf Dis 2008 Klont R CID 2004
Beta glucan • Panfungal? -Zygomycosis and Cryptococcosis- • Cannot differentiate between Aspergillus -Candida • ECIL 2010 • High cost • False positive reactions