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K.Gohari Moghadam MD. Azar 1394 1- Increased survival of patients by intense immunosuppression . 2-The lung is the most frequently affected organ . 3- Emergence of resistant microorganisms 4- Unusual and subtle clinical manifestations ( absence of fever , sputum ) More complicated clinical course. 5- The changes in immunosuppression regimens , prophylactic regimens and increased graft survival altogether alter the typical clinical presentation . 6- Unusual and subtle radiography ( Normal CXR in neutropenics) 7-Radiologic abnormalities in the background of systemic disease ( SLE , scleroderma ) 8- Progressive and fatal nature of infection in the context of decreased immunity. 9-Need for prompt diagnosis , decision ( often invasive ) and treatment . 10- Concomitant pulmonary diseases , which are not infectious ( edema , atelectasis , emboli , drug toxicity, radiation ) 11-Presence of simultaneous and sequential infections ( CMV,Pneumocystis ,Aspergillus and G- bacteria ) . 12-Limitation of diagnostic assays and procedures 13- Significant adverse reactions to antimicrobial regimens . 14-Invasive Fungal infections are increased in spite of prophylaxis and treatment during recent years . Risk Factors ( Net state of immunosuppression ) Overally , neutropenia is the most important risk factor . Anti TNF ( TB , Fungi) Corticosteroid ( Nocardia , Pneumocystis ,TB) Conditioning and engraftment ( CMV , pneumocystis ,Aspergillus , Nocardia , TB ,Bacterial ) HSCT (Aspergillus ) SOT ( Candida ) T cell depleting Abs ( CMV , EBV , HIV ) Epidemiologic Exposure Net state of immuno suppression Dominant Clinical presentation Epidemiologic Exposure Donor-derived ( CMV , TB , Toxoplasma ) Recipient –derived ( TB , CMV , strongyloides ) Nosocomial : gram negative , S.aureus , HSV , HBV, HCV , HIV . Community acquired ( Aspergillus , Nocardia ) Role of CT scan In patients with febrile neutropenia , Fever and normal CXR with respiratory symptoms Greater confidence in DDx Improve sampling by precise localization Pyogenic bacteria DM : S.aureus , S.pneumoniae, Klebsiella in the form of increased frequency and severity ESRD : Mortality rates from pulmonary infections are higher by a factor of # 20 . A case of SLE following splenectomy TB Lower Lobe TB Mediastinal LAP Extrapulmonary involvement Less cavitation Higher probability of smear negative samples A case of Systemic Sclerosis and LLL cavity ( TB) Miliary TB Nocardia Nocardia has two characteristics: 1- The ability of invasion to any organ ( as TB ) 2-The tendency to relapse or progression despite appropriate treatment ( as Aspergillus ) Lungs are affected in 2/3 of cases. Risk factors are: BMT,steroid use ,CD4< 100 ,DM , Malignancies ,Chronic lung disease ,alcoholism . Lung involvement is usually primary rather than metastatic from skin . Has acute , subacute or chronic presentation . Different radiographic patterns. About 45 days to 1 year delay from clinical onset to diagnosis . Recovery of Nocardia from lung samples is diagnostic . Nocardia in a case of behcet Nocardia in a WG Aspergillus Prolonged and severe neutropenia is the most important risk factor . HSCT ( severity of GVHD ),SOT ( specially in lung transplantation ) Chronic glucocorticoid use Advanced AIDS Chronic Granulomatous disease Uncommon in HIV Hemoptysis ,dyspnea, Pleuritic chest pain in DD of PTE . Fever ,which is unresponsive to broad spectrum antibiotics and even amphotericin is suggestive of Aspergillus infection. Important Radiologic patterns of Aspergillus 1-Halo sign is suggestive . (pseudomonas and in Zygomycosis , neoplasms , Kaposi , WG), 2-Cavitation , crescent sign 3-Wedge shaped peripheral consolidation . The best method of diagnosis is smear and culture from lung tissue . Positive smear and specially culture from BAL specimen in a relevant clinical and radiographic pattern Galactomannan is validated for serum samples .( about 90% sp.,Se, NPV) . BAL GM has more yield. GM in circulation is transient , so it is advised to measure twice a week . Bronchial biopsy. Leukemia and…. © A.J.France 2010 Zygomycosis ( Mucormycosis ) Risk factors include : DM ,Glucocorticoid use ,Leukemia,HSCT,SOT,deferroxamine use ,Iron overload ,AIDS,IV users ,Malnutrition . In comparison to Aspergillus : Numbers of nodules >10 in CT scan , Presence of sinusitis , Pleural effusion and Previous prophylaxis with voriconazole are in a favor of diagnosis of mucormycosis . The most common cause of reverse halo sign is mucor infection . Pneumocystis ( HIV ) Indolent course Diffuse interstitial-alveolar pattern in CXR Patchy or nodular GGO in HRCT HRCT has 100% sensitivity Associated with CD4< 200 as an AIDS defining illness Induced sputum is more diagnostic in HIVs when compared with non HIVs,who have often low burden of organism . Giemsa Gomori PCR ( For Non HIV ) (low burden of microorganism ) Culture : not BAL : 50%-90% Pneumocystis pneumonia. Lung biopsy, silver stain. © A.J.France 2010 Pneumocystis ( Non HIV ) Steroid use Hx specially in tapering or increasing period Transplantation , Sirolimus Hematologic malignancies Progressive course with abrupt respiratory failure Diffuse reticular pattern in CXR and GGO in HRCT Sirolimus cause a noninfectious idiosyncratic pneumonitis mimicing PCP pneumonia . Radiographic patterns Early interstitial GGO Perhilar or central opacities Suspicion of PCP should increase when pneumothorax is obsereved in a HIV patient . Adenopathy and pleural effusion are uncommon . A negative HRCT may allow exclusion of PCP. CMV CMV infection vs. CMV disease CMV infection is defined by : Either finding of virus by culture ,molecular technique or serology CMV disease is defined by : symptoms and signs such as fever , leukopenia , liver , lung ,pancreas ,colon ,meningoencephalitis , chorioretinitis ( AIDS ) CMV DNA by PCR > 500 copies per microgram DNA in peripheral blood is defined as disease . Cytopathic effect in BAL cytology , PP65 quantity (with limitation of WBC<1000) and TBLB . CMV pneumonia in a RTx CMV Pneumonia 1 30/9/91 CMV pneumonia 2/10/91