35 Pneumonia in the Immunocompromised Host Flashcards Preview

Pulm > 35 Pneumonia in the Immunocompromised Host > Flashcards

Flashcards in 35 Pneumonia in the Immunocompromised Host Deck (26)
1

Commonly encountered immunocompromising conditions:
Congenital immunodeficiencies

  • Immuncompromize can be broadly defined as...
  • Frequency
  • Patients usually have...
  • Bruton’s X-linked agammaglobulinemia 

  • Immuncompromize can be broadly defined as...
    • A state in which the response of the host to a foreign antigen is subnormal
  • Frequency
    • Now much less common than acquired causes
    • More frequently observed in patients in pediatric ICUs than in adult ICUs
  • Patients usually have...
    • Repeated infections, especially those affecting the respiratory tract and sinuses
    • “Pure” defects in the response of the host to foreign antigens that are usually specific and well-defined
  • Bruton’s X-linked agammaglobulinemia
    • Associated with a defect in the normal maturation process of immunoglobulin-producing B cells
    • As a result, mature circulating B cells, plasma cells, and serum immunoglobulin are absent
    • Therefore, the patient is susceptible to (encapsulated) organisms that are normally dealt with by immunoglobulin, such as Streptococcus pneumoniae and Haemophilus influenzae

2

Commonly encountered immunocompromising conditions:
Congenital causes of immunodeficiencies

  • T lymphocyte deficiencies
    • ​Di George’s syndrome (thymic aplasia with reduced CD4 and CD3 cells)
  • ​Di George’s syndrome (thymic aplasia with reduced CD4 and CD3 cells)
    • ​Bruton’s X-linked agammaglobulinemia (absence of B cells, plasma cells, and antibody)
    • Selective IgG subclass deficiencies
    • Selective IgA deficiency
  • Mixed T and B lymphocyte deficiencies
    • Common variable immuno-deficiency (leads to various B cell activation or differentiation defects and gradual deterioration of T cell number and function)
    • Severe combined immuno-deficiency (severe reduction in IgG and absence of T cells)
    • Wiskott-Aldrich syndrome (decreased T cell number and function; low IgM; occasionally low IgG)
  • Phagocyte defects
    • Chronic granulomatous disease (defect in NADPH oxidase, phagocytic cells)
    • Chediak-Higashi syndrome (impaired microbicidal activity of phagocytes)

  • T lymphocyte deficiencies
    • Di George’s syndrome (thymic aplasia with reduced CD4 and CD3 cells)
      • Viruses (especially HSV and measles), PJP, fungi or Gram negative bacteria
  • B lymphocyte deficiencies
    • Bruton’s X-linked agammaglobulinemia (absence of B cells, plasma cells, and antibody)
      • H. influenzae, S. pneumoniae
    • Selective IgG subclass deficiencies
      • S. pneumonia, H.influenzae, N. meningitidis
    • Selective IgA deficiency
      • S. pneumoniae, H. influenzae, Giardia
  • Mixed T and B lymphocyte deficiencies
    • Common variable immuno-deficiency (leads to various B cell activation or differentiation defects and gradual deterioration of T cell number and function)
      • S. pneumoniae, H. influenzae, CMV, VZV, PJP
    • Severe combined immuno-deficiency (severe reduction in IgG and absence of T cells)
      • PJP, viruses, Legionella
    • Wiskott-Aldrich syndrome (decreased T cell number and function; low IgM; occasionally low IgG)
      • S. pneumoniae, H. influenzae, HSV, PJP
  • Phagocyte defects
    • Chronic granulomatous disease (defect in NADPH oxidase, phagocytic cells)
      • S. aureus, P. aeruginosa, Aspergillus
    • Chediak-Higashi syndrome (impaired microbicidal activity of phagocytes)
      • S. aureus, H. influenzae, Aspergillus

3

Commonly encountered immunocompromising conditions:
Acquired immunodeficiencies

  • Frequency
  • Four categories of immunocompromized patients

  • Frequency
    • The vast majority of immunocompromized adult patients
  • Four categories of immunocompromized patients
    • (1) patients receiving chemotherapy for hematologic malignancies and solid tumors
    • (2) patients receiving immunosuppressive therapy in the context of solid-organ transplantation
    • (3) patients receiving corticosteroids, methotrexate, monoclonal antibodies to tumor necrosis factor alpha and other disease modifying agents for rheumatoid arthritis, Crohn’s disease and autoimmune disorders
    • (4) patients with human immunodeficiency virus (HIV) infection

4

Commonly encountered immunocompromising conditions:
Hematologic malignancies and solid tumors

  • Prolonged neutropenia from chemotherapy
  • Organisms associated with severe neutropenia
  • The severity and duration of neutropenia influence...
  • Aggressive chemotherapy and radiotherapy for Hodgkin’s lymphoma, coupled with splenectomy, significantly impairs humoral defense against...
  • Alemtuzimab and rituximab 
  • Hematopoietic stem cell transplantation carries with it a risk of...

  • Prolonged neutropenia from chemotherapy
    • Carries a significant risk of bacterial and fungal infection
  • Organisms associated with severe neutropenia
    • Gram negative organisms such as Pseudomonas aeruginosa
    • Fungal organisms such as Aspergillus spp.
  • The severity and duration of neutropenia influence...
    • The risk of infection
  • Aggressive chemotherapy and radiotherapy for Hodgkin’s lymphoma, coupled with splenectomy, significantly impairs humoral defense against...
    • Encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis
  • Alemtuzimab and rituximab 
    • Used in treatment of lymphoma’s
    • Can cause a profound T-cell mediated immunocompromized state
  • Hematopoietic stem cell transplantation carries with it a risk of...
    • Graft versus host disease

5

Commonly encountered immunocompromising conditions:
Hematologic malignancies and solid tumors

  • Prophylaxis against, and treatment of, graft versus host disease may involve...
  • Patients receiving therapy for graft versus host disease may be prone to...

  • Prophylaxis against, and treatment of, graft versus host disease may involve...
    • Cyclosporine or tacrolimus
      • Inhibit calcineurin, an enzyme important in the lymphocyte activation cascade
    • Corticosteroids
      • Also have effects on lymphocyte function, as well as depressing functions of activated macrophages
  • Patients receiving therapy for graft versus host disease may be prone to...
    • Fungal infections (PJP, histoplasmosis, cryptococcosis, coccidiomycosis, blastomycosis, Aspergillus)
    • Viral infections (CMV)
    • Mycobacterial infections (tuberculosis and atypical mycobacteria)

6

Commonly encountered immunocompromising conditions:
Solid organ transplantation

  • Solid-organ transplant recipients 
  • In the early post-transplant period, transplant recipients are susceptible to...
  • Solid-organ transplant recipients, by virtue of their iatrogenic immunosuppression (mostly T-cell mediated) are also susceptible to...

  • Solid-organ transplant recipients
    • Uniquely susceptible to infection
    • Undergo significant surgery that breach the defenses provided by the skin
    • Remain in ICUs for prolonged periods of time, requiring intravenous access and mechanical ventilation, breaching cutaneous and pulmonary barriers to infection
    • Receive immunosuppressive therapy to prevent graft rejection
  • In the early post-transplant period, transplant recipients are susceptible to...
    • Nosocomially-acquired bacterial infections, such as pneumonia and central line-associated bloodstream infection associated with general ICU care
    • Wound infections and intra-abdominal infections associated with their surgical procedure
    • Opportunistic infections from the organ graft (ex. cytomegalovirus, histoplasmosis, or West Nile virus)
  • Solid-organ transplant recipients, by virtue of their iatrogenic immunosuppression (mostly T-cell mediated) are also susceptible to...
    • Reactivation of latent infection (such as cytomegalovirus infection, tuberculosis or histoplasmosis)
    • Infections acquired through the hospital environment (such as aspergillosis, legionellosis or tuberculosis)

7

Commonly encountered immunocompromising conditions:
Rheumatoid arthritis and autoimmune disorders

  • Simple therapy
  • Drugs with the potential to cause significant immunocompromize
  • “Anti-cytokine” agents
    • Ex
    • Also treat...
    • Associated risks

  • Simple therapy
    • Simple analgesics or non-steroidal anti-inflammatory drugs
  • Drugs with the potential to cause significant immunocompromize
    • Corticosteroids or disease-modifying anti-rheumatic drugs such as azathioprine, cyclosporine, gold salts, hydroxychloroquine, leflunomide, methotrexate or sulfasalazine
  • “Anti-cytokine” agents
    • Ex. etanercept or infliximab
    • Also treat Behcet’s disease, Crohn’s disease, graft-versus-host disease, hairy cell leukemia, psoriasis, pyoderma gangrenosum, sarcoidosis and ulcerative colitis
    • Associated risks
      • Pulmonary tuberculosis
        • The risk is sufficiently high that it is recommended that tuberculin skin testing or interferon gamma release assay be performed for the presence of latent tuberculosis prior to the initiation of these agents
      • Invasive aspergillosis, coccidioidomycosis, cryptococcosis, histoplasmosis and Pneumocystis (PJP) infection
      • As is the case with transplant-associated immunocompromize, such infections may be reactivation of latent infection or new acquisitions of organisms acquired through the environment

8

Commonly encountered immunocompromising conditions:
Human immunodeficiency virus infection

  • Frequency of HIV infection
  • Frequency of acquired immunodeficiency syndrome (AIDS) 
  • Untreated HIV infection 
  • The risk of opportunistic infections causing pneumonia 

  • HIV infection
    • A relatively common infection
  • Acquired immunodeficiency syndrome (AIDS)
    • Less frequently encountered since the advent of highly active antiretroviral therapy
  • Untreated HIV infection 
    • Can be associated with substantial decline in CD4 lymphocyte counts
    • This creates a predisposition to Pneumocystis pneumonia, mycobacterial infection, fungal infection (such as cryptococcal meningitis) and viral infections (such as cytomegalovirus infections)
  • The risk of opportunistic infections causing pneumonia
    • Rises substantially when the CD4 lymphocyte count is less than 200
    • Streptococcus pneumoniae and Mycobacterium tuberculosis can both cause pulmonary infections in HIV-infected individuals with CD4 lymphocyte counts of more than 200

9

The general diagnostic approach to immunocompromised patients with pneumonia

  • Immunocompromized patients are a heterogeneous group, for ex...
  • Even within a particular category of immunocompromize (for example, kidney transplantation), patients may have...
  • In solidorgan transplant recipients, the “net state of immunosuppression”...
  • For example, a renal transplant recipient who is receiving tacrolimus monotherapy twice per week will be...

  • Immunocompromized patients are a heterogeneous group, for ex...
    • The infections commonly encountered by a patient with neutropenia as a consequence of chemotherapy may be quite different from those observed in a patient with rheumatoid arthritis who is receiving infliximab
  • Even within a particular category of immunocompromize (for example, kidney transplantation), patients may have...
    • A different degree of immunocompromize and therefore a different susceptibility to infection
  • In solidorgan transplant recipients, the “net state of immunosuppression”...
    • That is, the cumulative burden of immunosuppression with a special weighting towards recent T cell ablative therapy
    • Influences the risk of infection
  • For example, a renal transplant recipient who is receiving tacrolimus monotherapy twice per week will be...
    • Less susceptible to opportunistic infection than a patient with recent acute cellular rejection treated with alemtuzimab, who has a CD4 lymphocyte count of 20

10

The general diagnostic approach to immunocompromised patients with pneumonia

  • In contrast with HIV infection, CD4 lymphocyte count and HIV “viral load”...
  • Thus, it is important to determine...
  • Those with CD4 counts greater than 200 are likely to be infected with...
  • Those with CD4 counts of <200 may be infected with...
  • A patient with a CD4 count of <50 may develop...

  • In contrast with HIV infection, CD4 lymphocyte count and HIV “viral load”...
    • Are predictive of risk of infection
  • Thus, it is important to determine...
    • The recent CD4 lymphocyte count in patients with HIV infection
  • Those with CD4 counts greater than 200 are likely to be infected with...
    • The usual pathogens such as Strep. pneumoniae and Mycobacterium tuberculosis
  • Those with CD4 counts of <200 may be infected with...
    • Aforementioned organisms and in addition with Pneumocystis
  • A patient with a CD4 count of <50 may develop...
    • CMV pneumonitis

11

The general diagnostic approach to immunocompromised patients with pneumonia

  • Specific environmental exposures may be potentially important for immunocompromized patients
    • A travel history to the southwestern states of the United States may increase the likelihood that an immunocompromized patient has...
    • What's endemic in the Ohio River Valley
  • Environmental risks within the ICU
    • Linked to construction activity within the hospital
    • Waterborne
    • In units caring for transplant recipients or HIV-infected patients
  • Thus, the “net state of immunosuppression” must be considered in the context of...

  • Specific environmental exposures may be potentially important for immunocompromized patients
    • A travel history to the southwestern states of the United States may increase the likelihood that an immunocompromized patient has...
      • Coccidioidomycosis
    • What's endemic in the Ohio River Valley
      • Histoplasmosis
  • Environmental risks within the ICU
    • Linked to construction activity within the hospital
      • Outbreaks of invasive pulmonary aspergillosis
    • Waterborne
      • Outbreaks of legionellosis and many fungal and bacterial infections
    • In units caring for transplant recipients or HIV-infected patients
      • Tuberculosis transmission
  • Thus, the “net state of immunosuppression” must be considered in the context of...
    • Recent environmental exposures

12

The general diagnostic approach to immunocompromised patients with pneumonia

  • Ockham's razor
  • Given all the patient’s symptoms, signs and non-invasive laboratory test results,...
    • Immunocompetent
    • Immunocompromized
  • For example, a neutropenic patient may have...
    • Immunocompetent
    • Immunocompromized

  • Ockham's razor
    • Caution must be exercised in use of the diagnostic principle which follows “Ockham’s razor” (“entities are not to be multiplied without necessity”)
  • Given all the patient’s symptoms, signs and non-invasive laboratory test results,...
    • In the immunocompetent patient, one unifying diagnosis usually explains all
    • Immunocompromized patients may have more than one infection simultaneously
  • For example, a neutropenic patient may have...
    • Bacterial pneumonia and invasive pulmonary aspergillosis simultaneously in an immunocompetent patient
    • An immunocompromized patient with HIV infection may have Pneumocystis pneumonia and pulmonary infiltrates due to complications from HHV-8 infection (Kaposi’s sarcoma)

13

The general diagnostic approach to immunocompromised patients with pneumonia

  • The potential for multiple diagnoses underscores the need for...
  • For example, patients with unexplained severe community-acquired pneumonia may be best managed by...
  • Bronchoalveolar lavage could be sent for...
  • The bronchoalveolar lavage should be...

  • The potential for multiple diagnoses underscores the need for...
    • Early, invasive testing in immunocompromized patients with severe infection
  • For example, patients with unexplained severe community-acquired pneumonia may be best managed by...
    • Early bronchoalveolar lavage prior to antimicrobial therapy aimed at numerous pathogens
  • Bronchoalveolar lavage could be sent for...
    • Gram stain (Most bacteria)
    • Ziehl Neelsen stain (Mycobacteria)
    • Modified acid-fast stain (Nocardia)
    • Calcofluor stain (fungi)
    • Direct fluorescent antibody tests (Legionella)
    • Methenamine silver stain (Pneumocystis)
    • Cytologic analysis to enable rapid diagnosis of infection
  • The bronchoalveolar lavage should be...
    • Inoculated onto solid media and appropriate cell lines to enable culture of pathogens cultivable by such techniques
    • Molecular diagnostic testing may be appropriate in some instances

14

The diagnostic approach for severe infections in immunocompromised patients:
History-taking and review of prior records

  • Likely degree of immunocompromize
  • Prophylaxis against opportunistic infections
  • Family history
  • Potential environmental exposures

  • Likely degree of immunocompromize
    • Recent CD4 lymphocyte count and HIV “viral load"
    • Time since transplantation
    • Recent acute cellular rejection or graft versus host disease, and treatment thereof
    • Current or recent receipt of immunosuppressive medications
    • Current or recent receipt of antiretroviral medications
  • Prophylaxis against opportunistic infections
    • Receipt of antimicrobial prophylaxis against Pneumocystis, herpes simplex virus or cytomegalovirus
    • Vaccination status (pneumococcus, influenza, N. meningitidis)
  • Family history
    • Personal or family history of tuberculosis or chickenpox
  • Potential environmental exposures
    • Travel history to southwestern United States
    • Exposure to hospital construction activity (aspergillosis)
    • Exposure to hospital water supply (legionellosis, aspergillosis)
    • Exposure to patients with tuberculosis or chickenpox
    • Donor and recipient serostatus for CMV or Toxoplasma gondii

15

The diagnostic approach for severe infections in immunocompromised patients:
Physical examination

  • Skin
  • Mouth and other mucous membranes
  • Respiratory system
  • Cardiovascular system
  • Abdominal examination
  • Neurologic examination

  • Skin
    • Presence of cutaneous nodules consistent with cryptococcosis, nocardiosis etc
    • Presence of cutaneous manifestations of graft versus host disease
    • Kaposi’s sarcoma
    • Line insertion site erythema or pus
    • Peripheral embolic phenomena
    • Scars consistent with prior surgery (splenectomy)
  • Mouth and other mucous membranes
    • Presence of candidiasis
  • Respiratory system
    • Presence of signs of focal versus multilobar pneumonia
  • Cardiovascular system
    • Murmurs, prosthetic heart sounds
  • Abdominal examination
    • Signs of peritonitis
    • Hepatomegaly or splenomegaly
    • Tenderness of renal allograft
  • Neurologic examination
    • Nuchal rigidity
    • Cranial nerve signs

16

The diagnostic approach for severe infections in immunocompromised patients

  • Non-invasive laboratory tests
  • Invasive laboratory tests

  • Non-invasive laboratory tests
    • White blood cell count and differential
    • Blood and urine cultures
    • Serum cryptococcal antigen
    • Serum galactomannan antigen (aspergillosis)
    • Serum and urine Histoplasma antigen
    • Urinary Legionella antigen
    • Throat and/or nasal swab for PCR (influenza, para-influenza, RSV, adenovirus, metapneumovirus)
  • Invasive laboratory tests
    • Bronchoalveolar lavage +/- bronchoscopic biopsy
    • Pleural fluid aspiration
    • Percutaneous CT guided lung biopsy
    • Video assisted thoracoscopic (VATS) lung biopsy
    • Open lung biopsy

17

Major manifestations of pneumonia in the immunocompromized patient

  • Pneumonia 
  • Infectious microorganisms gain access to the respiratory tract through...
    • Usually
    • Other ways
  • Mechanical defenses 
  • Inhaled particles above 10μm in diameter 
  • Most bacteria 
  • First line of defense in the alveoli
  • Subsequently, there is an inflammatory response comprising...
  • Finally,...

  • Pneumonia
    • A significant cause of morbidity and mortality in immunocompromised patients
    • Unlike in the normal host, the impaired responsiveness of the immune system means that the disease presents in unusual ways, which may lead to challenges in establishing a diagnosis
  • Infectious microorganisms gain access to the respiratory tract through...
    • Usually
      • Inhalation
    • Other ways
      • Hematogenous spread
      • Direct inoculation
      • Pathogenic transformation of normal airway flora
  • Mechanical defenses
    • Remove the bulk of potentially harmful agents from the lungs
  • Inhaled particles above 10μm in diameter
    • Usually get trapped in the upper airways or are removed by coughing or mucociliary clearance
  • Most bacteria
    • Range from 0.5 to 2μm in size
    • Are able to reach the terminal airways/alveoli and potentially cause infection
  • First line of defense in the alveoli
    • The alveolar macrophages are the first line of defense
  • Subsequently, there is an inflammatory response comprising...
    • Polymorphonuclear neutrophils
  • Finally,...
    • Specific T and B cell immune responses are essential for successful defense against many pathogens

18

Major manifestations of pneumonia in the immunocompromized patient

  • While it may be possible to pinpoint a major immunological deficiency, most immunocompromized individuals...
  • For example, an organ transplant recipient who is on immunosuppressed from corticosteroids and tacrolimus may also be...
  • In solid-organ transplant recipients, specific etiologies of pulmonary infection are most frequent...
  • In a similar manner, specific etiologies of pulmonary infection are more frequent...

  • While it may be possible to pinpoint a major immunological deficiency, most immunocompromized individuals...
    • Have an assortment of deficiencies in host defense working together
  • For example, an organ transplant recipient who is on immunosuppressed from corticosteroids and tacrolimus may also be...
    • Intubated and diabetic
    • All these factors will contribute to the overall degree of immunity, each paving the way for its peculiar array of susceptibilities to pulmonary infection
  • In solid-organ transplant recipients, specific etiologies of pulmonary infection are most frequent...
    • At certain times post-transplantation
  • In a similar manner, specific etiologies of pulmonary infection are more frequent...
    • At different CD4 lymphocyte counts for patients with HIV infection

19

Occurrence of pulmonary infection after solid organ

  • Organisms < 1 month after transplant
  • Organisms 1-6 months after transplant
  • Organisms > 6 months after transplant

  • Organisms < 1 month after transplant
    • Methicillin resistant Staph. aureus
    • Gram negative bacilli
    • Legionella
    • Aspergillus
  • Organisms 1-6 months after transplant
    • Cytomegalovirus
    • Aspergillus
    • Legionella
    • Gram negative bacilli (if still mechanically ventilated)
  • Organisms > 6 months after transplant
    • Nocardia
    • Mycobacteria
    • Cryptococcus
    • Coccidiodes immitis

20

Etiology of pulmonary infections in patients infected with human immunodeficiency virus infection, stratified by CD4 lymphocyte count

  • > 200 CD4 cells / mm3
  • < 200 CD4 cells / mm3

  • > 200 CD4 cells / mm3
    • S.pneumoniae
    • M.tuberculosis
  • < 200 CD4 cells / mm3
    • S.pneumoniae
    • Pneumocystis
    • M.tuberculosis

21

Major manifestations of pneumonia in the immunocompromized patient

  • A normal chest radiograph 
  • While some diseases have very suggestive radiologic findings...
  • Computerized tomography (CT)
  • The differential diagnosis of pulmonary nodules 
  • The differential diagnosis of cavitary lesions 
  • The broad differential diagnosis of pulmonary infection in immunocompromized patients mandates...

  • A normal chest radiograph
    • Does not necessarily rule out pulmonary infection in immunocompromised patients
  • While some diseases have very suggestive radiologic findings...
    • For example, apical cavitations in tuberculosis
    • Most radiographic findings need to be interpreted in the light of all other data available
  • Computerized tomography (CT)
    • Sometimes CT may be required, for example, in the evaluation of pulmonary nodules
  • The differential diagnosis of pulmonary nodules
    • Infections due to fungi (especially Cryptococcus neoformans, Coccidioides immitis, Aspergillus fumigatus), Nocardia, mycobacteria, Rhodococcus equi and Bartonella
    • Additionally, carcinomas and post-transplant lymphoproliferative disorder may present with pulmonary nodules
  • The differential diagnosis of cavitary lesions 
    • Mycobacteria, invasive pulmonary aspergillosis, legionellosis and infection with Rhodococcus equi
  • The broad differential diagnosis of pulmonary infection in immunocompromized patients mandates...
    • Early and aggressive diagnostic strategies, such as bronchoscopy with bronchoalveolar lavage, sent for a comprehensive battery of microbiologic investigations

22

Therapeutic difficulties in the immunocompromized patient:
Empiric therapy

  • Empiric antibiotic therapy in suspected bacterial infections should be...
  • There is a clear link between microbiologically adequate empiric therapy and...
  • In settings such as severe pneumonia in the immuncompromized patient,... 
    • Empiric regimens comprising...
    • ...may be necessary to cover potentially lethal infection with...
  • Preferred empiric antifungal therapy for suspected fungal pneumonia
  • Role for combination empiric therapy with antifungal agents
  • The decision to start empiric mycobacterial therapy 
  • Empiric therapy for disseminated Strongyloides infection

  • Empiric antibiotic therapy in suspected bacterial infections should be...
    • Tailored to the individual patient in order to maximize the chance that empiric therapy is microbiologically adequate
  • There is a clear link between microbiologically adequate empiric therapy and...
    • Successful outcome from infections in the ICU
  • In settings such as severe pneumonia in the immuncompromized patient,...
    • Empiric regimens comprising...
      • Vancomycin, ciprofloxacin, meropenem, amphotericin, ganciclovir and trimethoprim/sulfamethoxazole
    • ...may be necessary to cover potentially lethal infection with...
      • MRSA, Pseudomonas aeruginosa, Legionella, fungi, CMV and Pneumocystis
  • Preferred empiric antifungal therapy for suspected fungal pneumonia
    • Amphotericin, since it has activity against zygomycetes, which neither voriconazole nor the echinocandins possess
  • Role for combination empiric therapy with antifungal agents
    • No established role
  • The decision to start empiric mycobacterial therapy
    • Advise against it, unless there is a clear risk factor for tuberculosis
  • Empiric therapy for disseminated Strongyloides infection
    • May have a place in immunocompromized patients coming from an endemic area and with the classic presentation of this parasitic disseminated infection

23

Therapeutic difficulties in the immunocompromized patient:
Pathogen-directed therapy

  • The importance of appropriate specimen collection 
  • With immunocompromized patients, antimicrobial therapy is often complicated by...
  • Patients most at risk
  • Why these patients are most at risk
  • Significant interactions may occur between...
  • Aggressive treatment of infections in immunocompromized hosts (for example, with amphotericin, pentamidine or foscarnet) may be associated with...
  • Frequent antimicrobial causes of neutropenia

  • The importance of appropriate specimen collection
    • Empiric therapy can be streamlined if cultures or other diagnostic tests are positive
  • With immunocompromized patients, antimicrobial therapy is often complicated by...
    • Drug interactions or adverse drug reactions
  • Patients most at risk
    • Transplant recipients taking calcineurin inhibitors (for example, cyclosporine or tacrolimus)
    • HIV-infected patients taking protease inhibitors
  • Why these patients are most at risk
    • Because these drugs may be metabolized by the cytochrome P450 system
  • Significant interactions may occur between...
    • Rifampin, macrolide antibiotics or azole antifungal drugs, and the calcineurin inhibitors
  • Aggressive treatment of infections in immunocompromized hosts (for example, with amphotericin, pentamidine or foscarnet) may be associated with...
    • Renal dysfunction, compounding the nephrotoxic effects of the calcineurin inhibitors
  • Frequent antimicrobial causes of neutropenia
    • Ganciclovir
    • Potentially adds further host defense defects

24

Therapeutic difficulties in the immunocompromized patient:
Prevention

  • The most significant problem an immunocompromized patient will face
  • Immunocompromized patients may...
  • Primary importance
  • Pneumonia can be readily prevented by a number of strategies
    • Ventilator-associated pneumonia 
    • Opportunistic pneumonia with Pneumocystis 
    • Environmental exposure to Legionella, Aspergillus and Mycobacterium tuberculosis 

  • The most significant problem an immunocompromized patient will face
    • Infection
  • Immunocompromized patients may...
    • Present with severe infection 
    • Acquire infection while critically ill for other reasons
  • Primary importance
    • Prevention of infection in the ICU environment
  • Pneumonia can be readily prevented by a number of strategies
    • Ventilator-associated pneumonia
      • May be prevented by semi-recumbent posturing and use of sucralfate (rather than H2 blockers) for stress ulcer prophylaxis
      • The role of aspiration of subglottic secretions and selective digestive tract decontamination are still controversial
    • Opportunistic pneumonia with Pneumocystis
      • Can be prevented by use of prophylaxis with trimethoprim/sulfamethoxazole, dapsone or inhaled pentamidine
    • Environmental exposure to Legionella, Aspergillus and Mycobacterium tuberculosis
      • Can be prevented by ensuring water purification techniques (for example, copper-silver ionization)
      • Can also be prevented by preventing exposure of patients to construction activity or infected patients

25

Which association is incorrect between immunocompromise and organism?

  • A. PJP and HIV infection
  • B. Aspergillus and CGD
  • C. CMV and liver transplant
  • D. Candida and splenectomy
  • E. Pseudomonas and neutropenia

26

Which association is incorrect?

  • A. Nocardia and pulmonary nodules
  • B. TB and cavitary lesions
  • C. Coccidiodomycosis and travel to SW USA
  • D. Aspergillus and construction activity
  • E. PJP prevention and valganciclovir

Decks in Pulm Class (47):