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Management of Infectious Complications in Immunocompromised Patients

Management of Infectious Complications in Immunocompromised Patients. Abhay Dhand M.D. Director, Transplant Infectious Diseases, Westchester Medical Center, Valhalla, NY. OBJECTIVES.

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Management of Infectious Complications in Immunocompromised Patients

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  1. Management of Infectious Complications in Immunocompromised Patients Abhay Dhand M.D. Director, Transplant Infectious Diseases, Westchester Medical Center, Valhalla, NY

  2. OBJECTIVES 1. To define an immuno-compromised host.2. To understand the role of net immune suppression in mediating the risk of infections in susceptible host.3. To understand the epidemiology and risk factors for infections in immuno-compromised patients.4. To learn the preventative, and diagnostic strategies for management of infections in immuno-compromised patients

  3. CONGENITAL IMMUNOSUPPRESSION ACQUIRED IMMUNOSUPPRESSION IMMUNOCOMPROMISED HOST

  4. ACQUIREDIMMUNOSUPPRESSION • Immunosuppressive Therapy • Microbial Infection • Malignancy • Disorders of biochemical homeostasis • Autoimmune diseases • Trauma

  5. ACQUIREDIMMUNOSUPPRESSION:Immunosuppressive Therapy • Chemotherapy for malignancy- Neutropenia • Treatment of autoimmune disorders • Bone marrow transplant- ablation, graft vs. host disease • Solid organ transplant: induction, maintenance immunosuppression, treatment of rejection

  6. ACQUIREDIMMUNOSUPPRESSION:Microbial Infection • HIV/AIDS • Hepatitis B/C, co-infection with HIV • Herpes infection, Co-infection with HIV • Bacterial infection (super antigens) • Parasitic infections

  7. ACQUIREDIMMUNOSUPPRESSION:Malignancy • Lymphoma • Leukemia • Multiple Myeloma • Solid tumors

  8. ACQUIREDIMMUNOSUPPRESSION:Disorders of biochemical homeostasis • Diabetes Mellius • ESRD/Hemodialysis • Cirrhosis/Hepatic insufficiency • Malnutrition

  9. ACQUIREDIMMUNOSUPPRESSION:Autoimmune diseases • Systemic Lupus Erythematosis • Rheumatoid Arthritis

  10. ACQUIREDIMMUNOSUPPRESSION • Pregnancy • Stress • Functional splenia • Splenectomy • Aging

  11. Immune Defects and Commonly Associated pathogens Immune Defect Pathogen Barrier breakdown: Burns Pseudomonas, S. aureus Trauma Streptococcus pyogenes, S. epidermidis Phagocytic function: Absolute decrease Enteric gram negatives, Pseudomonas, Aspergillus spp., Candida spp. Chemotaxis S. aureus, Enteric gram negatives Microbial killing S. aureus, Enteric gram negatives, Aspergillus spp, Burkholderia

  12. Immune Defects and Commonly Associated pathogens Immune DefectPathogen Humoral Immunity: Hypogammaglobulinemia Streptococcus pneumoniae, Hemophilus IgA deficiency Pyogenic bacteria, Giardia lambia Asplenia Streptococcus pneumoniae, Hemophilus Complement deficiency Pyogenic bacteria, Neisseria spp. Cell mediated immunity: Intracellular organisms (e.g. Listeria) Viruses (e.g. Herpes family) Fungi ( e.g. Candida spp., Cryptococcus) Parasites(e.g. Toxoplasma)

  13. Principles of Infection in Compromised Host: Neutropenia Nosocomial infections in neutropenic cancer patients occur at a rate of : 46.3 episodes per 1000 neutropenic days (48.3 episodes per 100 neutropenic patients) • The risk for infection is correlated with the depth and duration of neutropenia • “Different” presentation • Abscess • Pulmonary Infiltrate

  14. Principles of Infection in Compromised Host • Etiology can be ANYTHING • Polymicrobial Infections can be seen more commonly • Aggressive approach to diagnosis: CT scan, Bronchoscopy, Biopsy • Presumptive treatment

  15. Principles of Infection in Compromised Host • Serologic testing is generally not useful in the acute diagnostic management of immunocompromised patients. • They often fail to generate an adequate antibody response to infection. • Microbiologic testing should include antigen detection and/or nucleic acid detection-based assays as well as cultures.

  16. Principles of Infection in Compromised Host:Risk of Infection • Timing post transplant • Type of immunosuppression • Net state of immunosuppression • Pathogen-pathogen interaction (role of CMV) • Type of transplant

  17. Immunosuppressive Drugs and Mechanism of Action

  18. Morbidity and Mortality in Organ Transplant Recipients - Major Causes • Allograft Loss • life-long requirement - exogenous immunosuppression • major threat - chronic rejection - immunologically mediated, but poorly responsive to immunosuppression • Life threatening infection • ~ 67% transplant recipients develop infection in first year post - transplant; • ~ 25% eventually die of infection • Malignancy • Cardiovascular complications

  19. Infections in Solid Organ Transplantation patients

  20. What are the Risk Factors for Infection in Organ Transplantation? • Exposure to infectious pathogens (endogenous and exogenous) • “Net State of Immunosuppression”

  21. Relationship between Infection and Immunosuppression - MORE REJECTION - LESS INFECTION/ MALIGNANCY - LESS REJECTION - MORE INFECTION/ MALIGNANCY LESS MORE IMMUNOSUPPRESSION

  22. PRE-TRANSPLANT POST-TRANSPLANT INFECTIONS IN RECIPIENT IMMUNO SUPPRESSION TECHNICAL COMPLICATIONS RELATED TO TRANSPLANT PROCEDURE INFECTIONS IN DONOR INFECTIOUS EXPOSURES RISK OF INFECTION

  23. Complications of Transplantation that Predispose to Infection • Contamination of the allograft during harvesting, transport or implantation • Anastomotic leak • Hematoma, infarcted tissue • Presence of vascular access devices • Presence and mismanagement of endotracheal tubes • Presence of urinary, biliary or other drainage catheters

  24. Net State of Immunosuppression • Complex, poorly explained, combination of • exogenous immunosuppression • neutropenia • metabolic abnormalities (protein calorie malnutrition, uremia, etc.) • infection with immunomodulating viruses (Herpes group viruses particularly CMV, EBV, hepatitis viruses, HIV)

  25. Potential Exposures - Post-transplant • Nosocomial organisms (bacteria, fungi) • Opportunistic organisms from environment (e.g. cryptococcus, aspergillus) • Respiratory viruses and bacteria in the community • Organisms in contaminated food and water (e.g. salmonella, listeria)

  26. Immunosuppressive Therapy - what you need to know • What was used for induction immunosuppression • induction with polyclonal, MAB preparations – increased risk for opportunistic infection • What was used as maintenance immunosuppression • How quickly did the patient get to maintenance • What and when was anti-rejection therapy used • The trouble makers

  27. Induction Immunosuppression • Anti-T/B cell preparations • Used in patients with highest risk of rejection, multiple prior transplants • Allows delay in use of nephrotoxic immunosuppression (CyA, Tacrolimus) • Result – Watch out - increase in infection

  28. Maintenance Immunosuppression • Renal • CyA/FK + mycophenolate + prednisone • problem = drug toxicities …organ dysfunction...infection • Other solid organ transplants • FK + mycophenolate + prednisone • problem = drug toxicities …organ dysfunction...infection

  29. Anti-rejection therapy • Aggressive immunosuppression • higher doses of usual immunosuppression (e.g. steroid pulses, etc.) • Polyclonal AB and MABs • Result • significant increase in infection – need for additional prophylaxis

  30. When do Infections Occur in Transplant Recipients? HSV Months post-transplant

  31. First Month, Post-transplantation • Infection that was present pre-transplant (pneumonia, bacteremia/line sepsis, etc.) • Infection from contaminated allograft • Typical bacterial, Candidal infections seen in post-operative patients • NOTE - NO OPPORTUNISTIC INFECTIONS - UNLESS UNUSUAL HAZARD PRESENT

  32. Month 2-6, Post-transplantation • Immunomodulating viruses - particularly CMV, EBV, hepatitis B, C • Opportunistic pathogens - Listeria, PCP, Aspergillus • Residual bacterial, fungal infections from transplant complications • NOTE - MOSTLY OPPORTUNISTIC INFECTIONS

  33. > 6 Months, Post-transplantation • 80% patients - good allograft function, minimal immunosuppression - usual community acquired ID • 10% patients - chronic viral infections ….. Progress to end organ failure, sepsis, etc. • 10% patients - continuing acute, chronic rejection, more immunosuppression, continuing risk of opportunistic infection

  34. What Type of Infections Occur in Transplant Recipients? • Sources of infection • limitless, but usually follow a timetable • bacterial > viral > fungal • Presentation of infection • infection difficult to recognize - signs blunted because of impaired immune response • unusual presentations • chronic or relapsing infection • Therapy challenging • prolonged courses • adverse interactions with immunosuppressive agents

  35. CMV and Solid Organ Transplantation • CMV is still among the most important infectious complications after transplant • In the absence of prophylaxis, CMV reactivation can occur in over 75% of solid organ transplant recipients depending on other risk factors • Once CMV infection is established, then its replication is highly dynamic with rapid increases in viral load

  36. Risk of Symptomatic CMV Disease • Serologic status of donor and recipient • Type of organ transplanted • Type of immunosuppression

  37. CMV Infection: Risk Categories in Solid Organ Transplant Recipients * D+/R+ generally at higher risk than D-/R+

  38. CMV Disease in SOT Percent with CMV Disease

  39. Indirect Effects of CMV Infection Indirect Effects Altered host immune response • Graft rejection; graft dysfunction • Opportunistic infections: Bacterial fungal superinfection • Decreased graft and patient survival • Herpesvirus interactions: EBV/PTLD

  40. Strategies for Prevention of Infection in Transplant Patients • Pre-transplant • Peri-transplant • Post-transplant

  41. Strategies for Prevention of Infection in Transplant Patients:PRE-TRANSPLANT • Evaluate for active infection • Evaluate for colonization with MDROs • Evaluate for latent infections • Vaccination

  42. Strategies for Prevention of Infection in Transplant Patients:PERI-TRANSPLANT Antibiotic prophylaxis: • Goal: decrease the risk of surgical site infection, donor derived infection, disseminated infection, active treatment of latent/occult infection • Type of transplant, h/o colonization, active localized infection, infection/colonization in the donor, antibiotic allergies

  43. Strategies for Prevention of Infection in Transplant Patients:POST-TRANSPLANT Prophylaxis: Antibiotics: bactrim, ciprofloxacin Anti-viral: herpes viruses (CMV): valganciclovir Anti-fungal: candida, aspergillus, endemic funguses

  44. Candida Prophylaxis • Liver transplant: Atleast 2 risk factors: re-transplantation, Cr>2mg/dl, choledochojejunostomy, prolonged intra-operative time, use of >40 U of blood products, fungal colonization 2 days before and 3 days after transplant. • Heart/Kidney: not required • Pancreas, Small bowel

  45. Aspergillosis Prophylaxis • Heart transplant recipients: Isolation of aspergillus in airway cultures Repeat thoracic surgery CMV disease Posttransplant renal replacement therapy • Liver transplant recipients: Retransplantation, renal replacement therapy Repeat intra-abdominal or thoracic surgery 4 weeks post transplant Transplant for fulminant hepatic failure

  46. Prevention of Nosocomial Infections

  47. “Ventilator Bundle” *Institute for Healthcare Improvement Reduction in VAP from 6.6 to 2.7 (59%) per 1000 ventilator-days with > 95% compliance Head of bed elevation > 30 degrees* Daily “sedation vacation” and assessment of readiness to extubate* Oral care (chlorhexidine) Peptic ulcer disease prophylaxis* Deep vein thrombosis prophylaxis*

  48. Hospital-Acquired UTI 40% of healthcare-associated infections 80% due to indwelling urethral catheter Potential Strategies Insertion/care Catheter reminders/automatic stop orders Bladder US scanners Condom catheters Antimicrobial catheters Clin Infect Dis 2008;46:243-50

  49. Zero Central Line Associated Bloodstream Infections: …how to get there… • Multimodal intervention • Bundle approach • The “last mile” may require the use of some technical device (chlorhexidine patch, coated catheters, antibiotic impregnated device, lock solutions…)

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