Pneumonia in Compromised hosts

1. Pneumonia in Compromised hosts Dr. M. Shahparianpour

2. Compromised hosts • Patients with damaged defense mechanisms, which leads to severe, life-threatening infections. These conditions are: • acute leukemia (granulocytopenia, changed normal flora, damaged barriers) • lymphoma • transplantation • AIDS • carcinoma, sarcoma (these stop the normal passage) • myeloma, chronic lymphoid leukemia (decreased antibody function) • severe trauma after an accident (damaged barriers) • intravenous drug users (microorganisms pass directly into the blood stream, decreased defense) • any severe underlying disease

3. Main problems • Any microorganism can cause infection • Microorganisms with low virulence may also be involved in severe infections • Infections may present with unusual symptoms • Without a correct microbiological diagnosis, it is too dangerous to treat the patient

4. Case • A 48-year-old male patient (horse breeders),, who had undergone renal transplantation 6 month earlier, was admitted to a surgical unit. The X-ray examination revealed a cavitary infiltrate suspicious of lung tumor. • He had fever and a cough. • A series of biopsies from the lung tissues and blood culture samples (6 pairs of bottles during 3 days) were taken. • The histology did not confirm the suspicion of tumor. Gram staining was carried out on the same samples .

6. Case (cont.) • From all the blood culture bottles and from the tissue samples, the same polymorphic Gram-positive coccobacilli were cultured. Ziel-Nielsen staining showed them to be slightly acid-fast. • Following the susceptibility test results, the patient received amoxicillin/clavulanic acid treatment for 2 weeks and left the hospital. • After 6 month, he visited the hospital with the same symptoms. The same bacterium was isolated from his blood culture. • The same treatment was introduced for 6 weeks. Since then the patient has been free of symptoms of infection.

7. Culture results obtained from the blood and the tissue after 24 h incubation blood agar Lövenstein-Jensen agar

9. Case (cont.) What was the causative agent? Do you think it was a usual pathogen? Rhodococcusequi This is an intracellular pathogen. What other intracellular pathogens can cause, similar pulmonary infection?

10. Multiple simultaneous pulmonary processes are common.These include infectious (eg, viral, bacterial, fungal, parasitic), and noninfectious (eg, pulmonary edema and malignancies) etiologies.Routine chest radiography and sputum sampling may fail to document these concomitant diseases

11. Serologic testing is not generally useful in the acute management of immunocompromised patients. These patients often fail to generate a timely antibody response to infection. Microbiologic testing should include antigen detection or nucleic acid detection-based assays as well as cultures

12. Biopsies with special histopathologic stains (eg, for fungi or mycobacteria) and microbiologic studies (eg, viral cultures, molecular assays) are often essential

13. Awareness of the epidemiology of infection in the community (eg, respiratory viruses, tuberculosis) and the individual (eg, travel) often provide helpful clues

14. The incidence and severity of pneumonia vary with the characteristics of the affected individual, including: the nature of the immune deficits epidemiologic exposures Aspiration remains an important source of pulmonary infection in all compromised patients.

15. Neutropeniais the most important risk factor for pulmonary infection in immunocompromised patients No originating site of infection can be determined in 20 to 50 percent of febrile cancer patients

16. common sources of infection in the febrile, neutropenic patient with hematopoietic malignancy includes the perineal and perirectal areas, the urinary tract, skin (including intravenous lines and wounds) lungs. However, pulmonary infections predominate in series of all non-hematopoietic cancer patients.

17. Nonmyeloablativeconditioning was designed to shorten the duration of neutropenia and mucosal effects of neutropenia, notably when coupled with hematopoietic stem cell transplantation (HSCT).

18. While the length of time a patient is neutropenic has been shortened, the occurrence of late infections after nonmyeloablative conditioning, including fungal infections, have been more common than anticipated

19. Autoimmune and inflammatory conditions: Patients with hematopoietic malignancies, and to a lesser extent, acquired deficiencies (eg, glomerulonephritis with proteinuria or Goodpasture's syndrome) may be susceptible to opportunistic infections similar to those of cancer or transplant patients. Bacterial infections are of greater importance, possibly related to deficiencies in opsonization and phagocytosis

20. Corticosteroid individuals receiving the equivalent of 15 to 20 mg of prednisone per day for more than three weeks were at increased risk particularly for P. carinii/jirovecii pneumonia (PCP)

21. steroid-sparing strategies calcineurin inhibitors sirolimus, costimulatory blockade, and antibody therapies (both antilymphocyte and anti-tumor necrosis factor [TNF] preparations) with concomitant infectious complications.

22. anti-TNF antibodies for rheumatoid arthritis, Crohn's disease, and GVHD has been associated with activation of latent tuberculosis, cryptococcosis, aspergillosis, other intracellular organisms

23. ETIOLOGY OF PULMONARY INFILTRATES

24. Infectious • Conventional bacteria 37 percent • Fungi 14 percent • Viruses 15 percent • Pneumocystiscarinii/jirovecii8 percent • Nocardiaasteroides7 percent • Mycobacterium tuberculosis 1 percent • Mixed infections 20 percent

25. Mixed infections combinations of respiratory viruses, CMV, Aspergillusspp gram-negative bacilli are common in neutropenic hosts and after HSCT

26. CMV most common after HSCT, as viral reactivation in seropositive individuals after the completion of prophylaxis (late infection) This contrasts with the risk of CMV pneumonitis in solid organ transplantation which is greatest in seronegativerecipients of seropositive organs

27. Noninfectious  Noninfectious etiologies for pulmonary infiltrates are common in immunocompromised patients, including pulmonary embolus, tumor, radiation pneumonitis, atelectasis with pulmonary edema, drug allergy or toxicity, pulmonary hemorrhage. Often, the resolution of fever in response to a trial of antibiotics is the only suggestive evidence that infection was present.

28. mimics of infection • Alveolar proteinosis • pulmonary infarction • primary connective tissue/collagen vascular diseases • pulmonary-renal syndromes • Sarcoidosis • Acute respiratory distress syndrome • Transfusion-associated leukoagglutinin reactions

29. Radiation-induced injury Clinically apparent injury due to radiation therapy can occur acutely or more than six months after the initial exposure to a dose of over 2000 rads. Vascular damage, mononuclear infiltrates, and edema are seen histologically at three to 12 months

30. Drug-induced injury Acute, drug-induced lung disease may also reflect hypersensitivity to chemotherapeutic agents or to sulfonamides Drug toxicity may be related to the cumulative dose of the agent Synergistic toxicity for the lung is seen with a variety of chemotherapeutic agents and radiation

31. INITIAL EVALUATION OF THE PATIENT

32. Recognition that infection is present in the immunocompromised hosts is often delayed because the usual signs of infection are missing due to the muted inflammatory response Many infections are recognized only when fever, clinical symptoms (eg, cough, pleurisy, confusion), unexplained hypotension, or radiologic abnormalities develop after immune suppression or neutropenia is reversed

33. The first decision to make in an immunocompromised patient with possible infection is whether or not hospital admission is appropriate. Any sign of invasive infection in immunocompromised patients requires at least a brief hospitalization (one to three days) with a careful evaluatio n

34. Certain subgroups of patients are highly susceptible to infection • Aggressive tumors (eg, new leukemia or lymphoma or with uncontrolled metastatic cancer) • Recent HSCT recipients and allogeneic HSCT recipients with significant degrees of graft-versus-host disease (GVHD) • Recent infections, especially due to CMV, or with known colonization with fungi or resistant bacteria • Absolute neutrophil count (ANC) below 500/microL, and especially those below 100/microL, or those in whom the ANC is falling rapidly or expected to fall below 100/microL • High dose corticosteroid therapy or recent intensification of immune suppression • Patients with a history of frank rigors or hypotension • splenectomized patients with fever

35. The initial evaluation for immunocompromised patients with fever with or without pulmonary findings should include: • Rapid assessment of vital signs including oxygen saturation • Complete blood count with differential • Electrolytes, blood urea nitrogen and creatinine • Blood cultures (minimum of two with at least one peripheral and one from any indwelling catheter) • Urine sediment examination and culture • Sputum for Gram's stain, fungal smears, and cultures • Imaging of the lungs (chest radiography or whenever possible, chest computed tomographic [CT] scanning) and imaging of any symptomatic site (eg, abdomen) • Perineal exam to exclude perirectal infection

36. The presence or absence of hypoxemia can assist in the differential diagnosis of pulmonary infiltrates in immunocompromised patients. Hypoxemia with an elevation in lactic dehydrogenase and minimal radiographic findings are common in P. carinii/jiroveciiinfection, the absence of hypoxemia with pulmonary consolidation is more common in nocardiosis, tuberculosis, and fungalinfections until late in the course of disease

37. DIAGNOSIS

38. Historical clues • Travel and employment: Exposures to mycobacteria, endemic fungi (eg, H. capsulatum, Coccidioidesimmitis), R. equi (horse breeders), or C. neoformans (spelunkers and pigeon breeders), or exposure to soil (eg, Aspergillus spp. or Nocardia spp. in gardeners) • Prolonged duration of neutropenia(higher risk for gram-negative infection, Aspergillus or Fusarium sp.) • Past history of frequent antimicrobial exposure (increased risk for organisms with resistance to various antimicrobials used previously) • Potential or witnessed aspiration (risk for anaerobic infection) • Presence of potential pulmonary pathogens in prior cultures particularly molds (Aspergillus, Fusarium), Pseudomonas, or Stenotrophomonas • Cardiac abnormalities (endocarditis), indwelling catheters or intravascular clot(bacteremic seeding of the lungs) • Metastatic tumorparticularly intrathoracic malignancies • Diabetes with sinopulmonary infection (Zygomycosis [more commonly called mucormycosis])

39. Radiographic evidence of pneumonitis may appear only with immune reconstitution, notably marrow engraftment after neutropenia.

40. Chest radiograph • A focal or multifocal consolidation of acute onset will probably be caused by a bacterial infection. • subacute to chronic progression are more commonly due to fungal, tuberculous, or nocardial infections. • Large nodules are usually a sign of fungal or nocardial infection in this patient population, particularly if they are subacute to chronic in onset. • Subacute disease with diffuse abnormalities, either of the peribronchovascular type or miliary micro nodules, are usually caused by viruses (especially CMV), P. carinii/jirovecii, or rejection in the lung transplant patient

41. The presence of cavitationsuggests a necrotizing infection which can be caused by fungi, Nocardia, mycobacteria, and certain gram-negative bacilli (most commonly Klebsiellapneumoniae and Pseudomonas aeruginosa • The appearance of invasive pulmonary aspergillosisis heterogeneous with patchy infiltrates, nodules, cavitation and pleural-based wedge-shaped lesionsmost common. • In neutropenic patients, the initial appearance may be pleural-based lesions with surrounding attenuation (the "halo sign")followed by cavitating nodules ("air-crescent sign") after the return of neutrophils.

42. The depressed inflammatory response of the immunocompromised transplant patient may greatly modify or delay the appearance of a pulmonary lesion on radiograph, especially if neutropenia is present. fungal invasion, which excites a less exuberant inflammatory response than does bacterial invasion, will often be very slow to appear on conventional chest radiography

43. Chest CT  CT frequently reveals abnormalities even when the chest radiograph is negative or has only subtle findings

44. Cavitary CT lesions are suggestive of infections with mycobacteria, Nocardia, Cryptococcus, Aspergillus, and some gram-negative bacilli (Pseudomonas, Klebsiella). • Rapidly expanding pulmonary lesions with cavitation and/or hemorrhageare associated with the zygomycetous fungi (eg, Mucor), especially in diabetics. • Opacified secondary pulmonary lobules in the lung periphery are suggestive of bland pulmonary infarcts or septic or hemorrhagic Aspergillus infarcts (if cavitated).

45. Peribronchial distribution of CT opacities is suggestive of fluid overload, viral or P. carinii/jirovecii infection and, in the lung transplant recipient, allograft rejection. • Dense regional or lobar consolidation on CTis usually seen in bacterial pneumonia or invasive fungal infection.

46. Lymphadenopathy is not a common finding in immunosuppressed patients other than in those with lymphoma or PTLD associated with Epstein-Barr virus (EBV). • Lymphadenopathy may be observed with acute viral infections (CMV, EBV), sarcoidosis, and infections due to mycobacteria, Cryptococcus, and with drug reactions (eg, TMP-SMX).

47. CT scans frequently will detect multiple simultaneous patterns, in contrast to conventional radiographs, which can raise the possibility of : . dual infection . sequential infection of the lungs

48. Common Viral Infections in Immunocompetent and Immunocompromised Adults

49. In patients who have AIDS, the pattern and progression of abnormality should be correlated with the clinical scenario, including the CD4 count; in patients who have undergontransplants, the amount of time that has elapsed since institution of chemotherapy or transplant is important.

50. CD4+ greater than 200 × 106 cells/L: bacterial pneumonia, TB (reinfection) • CD4+ 50 to 200 × 106 cells/L: bacterial pneumonia, primary TB, PCP, fungal infections • CD4+ less than 50 × 106 cells/L: bacterial pneumonia, atypical appearances of TB, PCP, fungal infections, MAC, CMV