ملاحظات
عرض الشرائح
مخطط تفصيلي
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Infection  in Immunocompromised Host
  • Prof. Hamdy Zawam,


  • Prof. of Oncology
  • Cairo University, EGYPT.
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Impaired Immunity in Cancer Patients:
  • The disease it self ; CLL , HD.



  • Treatment modalities ; Cth. ; Rad. & SCT
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Host Defense Impairment :
  • Defects in innate immune system:


  •  Granulocytopenia.
  • Defects in cell mediated immunity.
  • Defects in humoral immune system.
  • Abnormalities in splenic function.


  • Anatomic alternation in host defense.
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I. Defects in Innate IS (Granulocytopenia)

  • Neutropenia : < 500 /mm3
  • Profound granulocytopenia <  100/mm3
  • ↑↑ Bacterial & fungal infection.
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Role of G.CSF      GM.CSF
  • ↑ Phagocytosis
  • ↑ Oxidative metabolism.
  • ↑ Microbicidal activity.
  • ↑ ADCC.
  •  However; Þ Defect of migration
  • ↓ Motility
  • ↓ In vivo migration.
  • ↓Bacterial induced Chemotaxis.
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Defects in Cell-Mediated Immunity (CMI):

  • T- cell is required for macrophage activation.


  • Lymphoma (HD).
  • SCT.
  • AIDS.
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Pathogens Associated with defects in CMI

  • Examples :
    • All viruses.
    • Atypical Mycobacterium ; Legionella , Nocardia , Listeria.
    •  Fungi ( Candida, Cryptococcus , Aspergillus).
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Defect in CMS
  • Prophylactic anti TB.
  • Caution: Disseminated infection due to live vaccines.
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Defects in Humoral Immune System


  • This is achieved by antibodies
  •   (opsonic ; lytic and neutralizing activities).
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Pathogens Associated with defects in humoral IS
  • Defective humoral immunity is responsible for most infection with extra-cellular bacteria.
  • Examples: S. Pneumoniae & H.Influenza
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Defect in Splenic Function


  • Function:
    • Removal of ineffectively opsonised organism.
    • Regulation of alternative complement pathway.
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Pathogens Associated with Asplenic or splenectomized Patients
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Clinical  Presentation
    • Fever only sign for overwhelming infection.
    • Manage as potentially septic.
    • 50% of infection related deaths in the first three M.
    • Vaccination: Pneumococcal; H.Influenza type b & Meningeococcal vaccines.
    • Penicillin prophylaxis.
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II. Anatomic Alternation in the Host Defense
  •  Skin & mucous membranes :


    • Invasion.
    • Infections.
    • Nidus for microbial colonization.
    • Portal of entry.
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Types Of Organisms
  • Site of breakdown
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Indwelling Catheter:
  • Coagulase –ve Staphylococci.
  • Corynebacterium.
  • Bacillus spp.
  • Atypical Mycobacterium.
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"GIT mucosa :"
  •  GIT mucosa :


    • Mainly by cth.
    • Aerobic Gram – ve enteric bacteria.
    • Anaerobic bacteria.
    • Viruses and yeast.
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"Oral Lesions :"
  •  Oral Lesions :


    • HSV reactivation.
    • α- hemolytic streptococci


  • Lower GIT :


    • Bacteroids fragilis.
    • Streptococcus.
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Mechanical Obstruction
  • Respiratory System.
  • GU Tract.
  • Biliary System.
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Measures that will Assist In The Prevention Of Infection
  • Diet Control:
    • Washing ; cooking.
    • Some products inherently certain organism:
    •             - e.g ; blue cheese: Moldes.
    •                       Soft cheese : Listeria.
    •                       Yoghurt: Lactobacillus.
  • Avoid crowded places.
  • Avoid pet animals.
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Environmental Measures
  • Hand washing
  • Infection control of staff and visitors.
  • Contact isolation for patients with Adeno virus; MRSA or Clostridium infection.
  • High-efficiency particulate air filtration (HEPA).
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Febrile Neutropenia
  • Temp > 38.3 C   or   ≥ 38 C over 1 h.
  • ANC > 500 ∕ ml or > 1000 with predicted ↓
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Evaluation of Febrile Neutropenic Patient
  • History :


    • Recent colitis by Clostridium Difficile.
    • Recent invasive fungal infection.
    • Duration of neutropenia.
    • Use of steroids.
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"Physical ex (1):"

  • Physical ex (1):


    • Typical signs may be absent.
    • Mucositis; cth or HSV.
    • Thrush; CMI.
    • Black necrotic region in the palate.
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"Physical ex (2):"
  • Physical ex (2):


    • Ex. Of nasal sinuses.
    • Ophthalmologic ex.
    • Skin & nails.
    • Catheter site.
    • Perianal region.
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"lab :"
  • lab :


    • Routine.
    • Blood
    • Sputum.
    • Urine.
    • Potential site of infection.
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Neutropenic Fever = Medical Emergency
  • Empiric AB
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"Monotherapy"
  • Monotherapy:


    • Ceftazidime.
    • Cefepime.
    • Imipenem.
    • Meropenem.
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"Duo therapy"
  • Duo therapy:


    • Ceftazidime + Aminoglycoside.
    • Cefepime + Aminoglycoside.
    • Anti- Pseudomonal Penicilline + Aminoglycoside.
    • Anti- Pseudomonal Penicilline + Ciproflexacin.
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When to add Vancomycin
  • Clinical instability.
  • C ∕ P Gram +ve pathogen.
  • Sever mucositis (not with carbapeneums).
  • Quinolon prophylaxis.
  • Catheter infection.
  • Prevalence MRSA.
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Duration of AB
  • A febrile within 3 days:


    • Low risk : good general condition; no mucositis.
    •                      - ANC > 1000 & rising → oral AB.
    • High risk: continue parental AB.
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Persistent Fever
  • Modalities of AB according to C∕S.
  • Empiric Anti-fungal.
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Problems with Fungal Infection
  • Difficult to diagnose.
  • High mortality.
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Anti-fungal Drugs
  • AMB


    • Bind to ergosterol.
    • Infusion related reaction.
    • Nephrotoxicity: Azotemia; ↓K ; ↓Mg ; renal tubular acidosis.
    • A.terreus is resistant to AMB.
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Lipid Forms of AMB
  • Three forms.
  • Less nephrotoxicity.
  • Less reaction.
  • Higher doses are used (3-5 mg ∕ kg).
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Anti-fungal Triazoles:
  • Inhibit the conversion of lanosterol to ergosterol.
  • Inhibit cytochrome P-450 → drug interaction.
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Fluconazol :
  • Active against Candida not Aspergillus.
  • Invasive candidiasis; 400-800 mg.
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Itraconazol:
  • Active against yeast & Aspirigillus not Fusarium & Zygomycosis.
  • Absorption is compromised with achlorhydria; antacids H2 antagonists.
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3rd generation Azoles
  • Voriconazol:


    • Active against yeast ; Aspergillus ; Fusarium
    • Drug of choice for IA.
    • Side effects :
    •               - Visual disturbance.
    •               - Hepatotoxicity.
    •               - skin rash.
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"Posaconazol"
  • Posaconazol:


    • Prevention of IA in patient with AML & HSCT recipients
    • Salvage for refractory IA.
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Echinocandius
  • Caspofungin; Micafungin & Anidulafungin.
  • Inhibit 1,3- β glucan.
  • Can be combined with other agents.
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Indication of surgery in IA
  • Pulmonary lesion near major vessels.
  • Skin & soft tissues.
  • Osteomyelitis.
  • Sinusitis.
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