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Developments in the Diagnosis and Treatment of Pneumonia in

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									Developments in Diagnosis and
Treatment of Pneumonia in
Immunocompromised Patients


   Dr.Özlem Özdemir Kumbasar



                                1
   The development of pulmonary
    symptoms and infiltrates is a frequent
    and life-threatining complication in
    immunocompromised patients.

   Early diagnosis and optimal treatment
    are important for survival.

                                             2
   Number of immunocompromised patients has
    increased over the past decade.

   Pulmonary physicians have been more
    involved in the care of these patients.
    Because pulmonary complications are most
    common and serious complications in these
    patients.

                                                3
   Diagnosis of pulmonary complications in
    immunocompromised patients is difficult:
       List of differential diagnosis of pulmonary
        infiltrates is broad and includes both infectious
        and noninfectious etiologies.
       More than one infectious agent can be found in
        the same patient.
       Infectious and noninfectious complications may
        coexist.


                                                            4
   Sometimes invasive diagnostic approach
    is required to obtain etiologic diagnosis.
   Patients condition may not allow
    invasive diagnostic tests.
   Usually, empiric therapy and diagnotic
    tests are started simultaneously


                                             5
Diagnostic Approach
   Medical history
   Physical examination
   Imaging methods
   Basic laboratory tests
   Arterial blood gases
   Microbiological investigations
   Antigens or nucleic acids specific to microorganisms
   Antibodies specific to microorganisms
   Invasive diagnostic tests

                                                           6
Recent developments in diagnostic tests

   Aspergillus galactomannan antigen:
       It is a fungal cell wall constituent
       Host factors predisposing to IPA+
        compatible clinical and radiologic findings+
        two consecutive positive serum
        galaktomannan assays            probable IA




                                                   7
   BAL-galactomannan
       Cut-off value >/=1
            Sensitivity 100%
            Specifity 90.8%
            Positive predictive value 41.7%
            Negative predictive value 100%




                                               8
   Serum B-glucan
       A fungal cell wall constituent
       In patients with AML, MDS it was found highly
        sensitive and specific in detecting early fungal
        infections (candidiasis, fusariosis, aspergillosis and
        trichosporonosis)
       More research is required to define the utility of
        this assay in nonneutropenic patients at high risk
        for invasive fungal infections


                                                             9
   PCR
       PCR based detection of aspergillus applied
        to blood and BAL is another promising tool
        for early diagnosis.
       Specific primers vary in published series,
        and will require standardization and
        validation .


                                                 10
   PCP
       Pneumocystis is a member of fungi
        Each mammalian host is infected by a
        specific Pneumocystis that cannote infect
        other hosts.
       Some auuthorities use P.jirovecii to refer
        the species Pneumocystis that causes
        human diseases.
       PCP= Pneumocystis pneumonia

                                                     11
   Newer methods to diagnose PCP
       PCR assays
            BAL
            Induced sputum
            Oral wash specimens
       In general, PCR assays have been more
        sensitive, but less specific for Pneumocystis
        pneumonia compared to traditional
        microscopic methods.

                                                   12
   PCR assay in serum and blood samples
    to diagnose PCP
       Results are contradictory
       It did not seem to be of value for PCP
        diagnosis.
       Positive results may reveal transient blood
        passages of Pneumocystis organisms.


                                                      13
   PCP-PCR
       Drug resistence-dihydropteroate synthase
        (DHPS) gene mutations ??
       Colonization of Pneumocystis in
        immunocompromised and
        immunocompetent persons. Is colonization
        important ??
       Viability of organisms

                                               14
   Serum indicators for the diagnosis of
    PCP
       LDH
       B-D glucan-a fungal cell wall constituent
       KL-6-a high molecular weight mucin like
        glycoprotein, a sensitive indicator of
        various interstitial pneumonitis


                                                    15
   Serum indicators-PCP
       B-D glucan- most reliable indicator for
        detecting P.jirovecii infection
       LDH-correlated with oxygenation
        impairment




                                                  16
   CMV
       Detection of pp65CMV antigen on
        peripheral blood leukocytes
       Quantitative PCR of viral DNA/RNA in
        serum
       Both assays have a sensitivity for diagnosis
        of active infection of greater than 80%.


                                                   17
   BAL
       BAL is a succesful method to diagnose infections
        in immunocompromised patients
            Traditional microbiological methods
            Cytology
            PCR
                  PCP
                  CMV
                  Legionella
                  Mycobacteria
                  M.pneumoniae
                  C.pneumoniae
            Aspergillus antigen test

                                                           18
Recent developments in treatment

   New antifungal agents
       Echinocandins-salvage therapy in IA
            Caspofungin
            Mycafungin
       Voriconazole-effective as an initial therapy
        in IA. pe/oral
       Posaconazole-safe and effective
       Combination therapy

                                                       19
Recent developments in treatment

   Strengthening the host immun response
       CSF
       Granulocyte transfusions
       IFN-g-reduces infections in patients with
        CGD; adjunctive therapy in IA in case
        reports. Recommendations about its use
        cannot be made, safety ??


                                                    20
   Strengthening the host immun response
       Toll like receptors-enhance innate and
        antigen specific immunity against fungi
       Pentraxin 3 (PTX3)-is an innate pathogen
        recognition protein. It binds selected
        microbial agents and activates several
        effector pathways to oppose pathogen
        infectivity.

                                                   21
Diagnostic approach
   Medical history
       Type of immunosuppression
       Behavior of the clinical picture
            Acute
            Subacute or chronic
   Radiological pattern of infiltrates
       Focal/segmental
            nodule
                  halo sign
            cavity
       Diffuse

                                           22
   Acute / focal infiltrates
       Empiric antibiotic treatment according to
        type of immunosuppression
            Antipseudomonal combination for neutropenic
             patients
       Consider noninfectious mimics of
        pneumonia (PTE, BOOP…)
       Workup for bacterial pneumonia

                                                           23
   Acute / focal infiltrates
       No response to empiric antibitics
       No specific diagnosis from first
        investigations
            CT of the thorax
            Serum galactomannan
            Bronchoscopy-BAL
            Antifungal treatment?


                                            24
   Subacute / focal infiltrates
       Empiric antibiotic treatment according to patients’
        condition and type of immunosupression
       Consider aspergillus, nocardia, BOOP, tb…
       Serum galactomannan
       AFB
       CT of the thorax
       Bronchoscopy
       Antifungal treatment?
       Open lung biopsy

                                                          25
   Acute / diffuse infiltrates
       Consider PCP, pulmonary edema, DAH, drug
        toxicity
       Serum LDH
       ABG
       CT of the thorax
       Serum B-D glucan
       Oral washing specimens
       Induced sputum
       Bronchoscopy-BAL
       Empiric treatment for PCP

                                                   26
   Subacute, chronic / diffuse infiltrates
       Consider viral pneumonia, drug toxicity,
        BOOP
       Detection of pp65CMV antigen
       Quantitative PCR for CMV DNA/RNA
       Bronchoscopy-BAL
       Open lung biopsy


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