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IMMUNODEFICIENCY IN PATIENTS WITH CHRONIC MEDICAL CONDITIONS

IMMUNODEFICIENCY IN PATIENTS WITH CHRONIC MEDICAL CONDITIONS. 5 th ESCMID School of Clinical Microbiology and Infectious Diseases Santander, Spain, 10 - 16 June 2006. Diabetes: 10% Renal chronic failure : 11% COPD: 7.5% Cardiac failure : 2.2 % Psychiatric illnesses : 6% Dementia : 2%

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IMMUNODEFICIENCY IN PATIENTS WITH CHRONIC MEDICAL CONDITIONS

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  1. IMMUNODEFICIENCY IN PATIENTS WITH CHRONIC MEDICAL CONDITIONS 5th ESCMID School of Clinical Microbiology and Infectious DiseasesSantander, Spain, 10 - 16 June 2006

  2. Diabetes: 10% Renal chronicfailure: 11% COPD: 7.5% Cardiacfailure: 2.2 % Psychiatricillnesses: 6% Dementia: 2% Cirrhosis: 0.2% The relevance of the problem Lora-Gomez RE et al. Am J Kidney Dis 2003, 41:1–12; Halbert RJ, et al. Eur Respir J 2006, 12; Redfield MM, et al. JAMA 2003, 289:194-202; Ansseau M, et al. Eur Psychiatry 2005, 20:229-35; Wimo A, et al. Dement Geriatr Cogn Disord 2006, 21:175-81.

  3. The relevance of the problem • 1987 USA: • 90 million people with “chronic conditions”. • 39 million of whom were living with more than 1 chronic condition. Hoffman C, et al. Persons with chronic conditions. JAMA 1996; 276:1473.

  4. The relevance of the problem Number of Persons Diabetes in the United States, 1980–2004 Steinbrook R. Facing the diabetes epidemic. N Engl J Med 2006; 354:545-8.

  5. Immunodeficiency in chronic conditions? • Epidemiological evidence • Increase of infections • Worse prognosis • Animal models. • Laboratory data • Immune response • Host-microorganisms relationships.

  6. Diabetes • Immunosuppression? • Increase of infections immunosuppression 25% of diabetics

  7. Diabetes • Increase of infections immunosuppression • Organ lesions: • Vascular damage • Neuropathy • Glucosuria may promote bacterial growth • Insulin injections: increase nasal carriage of S. aureus (34% vs 10% )

  8. Diabetes: Burn wound age on admission Within 48 h - 49 (40%) - 995 (63%) Memmel H. Infections in diabetic burn patients. Diabetes Care 2004; 27:229.

  9. Diabetes: Burn wound age on admission Memmel H. Infections in diabetic burn patients. Diabetes Care 2004; 27:229.

  10. Diabetes: immunossupression? • “Contrary to common belief, the association between diabetes mellitus and increased susceptibility to infection in general is not supported by strong evidence”. Joshi N, et al. Infections in patients with diabetes mellitus. N Eng J Med 1999; 341: 1906.

  11. Diabetes: immunossupression? • “However, many specific infections are more common in diabetic patients, and some occur almost exclusively in them”. Joshi N, et al. Infections in patients with diabetes mellitus. N Eng J Med 1999; 341: 1906.

  12. Diabetes • Increased risk of infections? • Selected infections • Selected microorganisms • Global risk • Worse prognosis?

  13. Diabetes: increase of selected infections % Patients with diabetes Wang JH, et al. CID 1998; Wang JL CID 2005; Roden MM et al. CID 2005; Farley et al. N Engl J Med 1993; Hohmann EL. CID 2001; 32:263–9; Simpson JH, et al. CID 2003.

  14. Diabetes: increase of selected infections Bacteremia % Patients with diabetes Vidal F et al. Arch Intern Med 1998; Chi et al . JAGS 2006; Thompsen RW et al. CID 2005; Kao et al. CID 1999; Khatit R et al. CID 2005.

  15. Diabetes: increase of selected infections % Patients with diabetes Edelstein H et al. Medicine 1988; Wang JL et al. CID 2005, et al. Mentzer RM, et al. Am J Surg 1975; Grandis JR et al. Lancet Inf Dis 2004; Paty R et al. Urol Clin N Am 1992.

  16. Diabetes: increase of selected infections N Engl J Med 2003;348:2329

  17. Diabetes: 70% Malnutrition: 25 % Alcoholism: 23% Renal chronic failure: 14% Cirrhosis: 5% Diabetes: increase of selected infections BMJ 2005;330:830–3 Elliott D, et al. The microbiology of necrotizing soft tissue infections. Am J Surg 2000; 179:361.

  18. Diabetes: increase of selected infections Zygomycosis Roden MM, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634.

  19. Diabetes: increase of infections N=337 N=154 Diabetes Malignancy No underlying condition N=176 Roden MM, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634.

  20. Diabetes: increase of infections Low pH Lack of serum activity Higher Iron availability Macrophage defect Murine model 85% of Rhino-cerebral zygomicosis in diabetics

  21. Diabetes: increase of infections Control patients with hypertension (n= 18,911) Muller LM, et al. Increased Risk of Common Infections in Patients with Type 1 and Type 2 Diabetes Mellitus. Clin Infect Dis 2005; 41:281-8

  22. Diabetes: increase of infections Control patients with hypertension (n= 18,911) Muller LM, et al. Increased Risk of Common Infections in Patients with Type 1 and Type 2 Diabetes Mellitus. Clin Infect Dis 2005; 41:281.

  23. Diabetes:increase of selected infections Enterobacteria community-acquired bacteremia Cases n= 1317 Controls n=13170 Thomsen RW, et al. Diabetes Mellitus as a Risk and Prognostic Factor for Community- Acquired Bacteremia Due to Enterobacteria. Clin Infect Dis 2005;40:628

  24. Diabetes Diabetes: increase of infections

  25. Diabetes Diabetes: increase of infections Outpatients *P 0.0001; †P 0.001. Diabetics N= 513,749. 1:1 controls matched for date of birth within 30 days, sex, region, and income quintile. Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26:510.

  26. Diabetes Diabetes: increase of infections Outpatients *P 0.0001; †P 0.001. Diabetics N= 513,749. 1:1 controls matched for date of birth within 30 days, sex, region, and income quintile. Shah BR, et al. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26:510.

  27. Diabetes Diabetes: increase of infections Inpatients *P 0.0001; †P 0.001. Diabetics N= 513,749. 1:1 controls matched for date of birth within 30 days, sex, region, and income quintile. Shah BR, et al. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26:510.

  28. Diabetes: immunossupression? • “Contrary to common belief, the association between diabetes mellitus and increased susceptibility to infection in general is not supported by strong evidence”. Joshi N, et al. Infections in patients with diabetes mellitus.N Eng J Med 1999; 341: 1906.

  29. Diabetes: increase of infections? • “The association between diabetes mellitus and increased susceptibility to infection is well supported”.

  30. Diabetes: prognostic factor • Uncontrolled diabetes was reported to be associated with a fatal outcome of infectious diseases in diabetic patients. Leibovici L, et al. Influence of diabetes mellitus and glycaemic control on the characteristics and outcome of common infections. Diabet Med 1996;13:457.

  31. Diabetes: prognostic factor Enterobacteria bacteremia: prognostic factors n = 225 n = 1092 90 days the mortality: -Diabetics: 23.3% -Non diabetics 19.5%. Thomsen RW, et al. Diabetes Mellitus as a Risk and Prognostic Factor for Community- Acquired Bacteremia Due to Enterobacteria. Clin Infect Dis 2005;40:628

  32. Diabetes: prognostic factor Staphylococcus aureus bacteremia: prognostic factors 293 patients with episodes of SAB, 68 died (23.2%) Mylotte MA, et al. Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort. Clinical Infectious Diseases 2000; 31:1170.

  33. Diabetes: prognostic factor Deep neck infection in diabetic patients Huang TT. Deep neck infection in diabetic patients. Otolaryngol Head Neck Surg 2005;132:943.

  34. Diabetes: prognostic factor Tuberculosis: prognostic factors Diabetes Renal failure 139 patients with tuberculosis 29 (21%) died (Baltimore). Oursler KK. Survival of patients with pulmonary tuberculosis: clinical and molecular epidemiologic factors. Clinical Infectious Diseases 2002; 34:752.

  35. Hyperglycemia: prognostic factor Van den Berghe, G. et al. N Engl J Med 2001;345:1359

  36. Diabetes: worse prognosis Infection related Diabetic • n=9,208 Non- Diabetic Bertoni AG, et al. Diabetes and the risk of infection-related mortality in the U.S. Diabetes Care 2001; 24:1044.

  37. Diabetes: “epidemiological” conclusions • Increase risk of infections • Worse prognosis

  38. Diabetes: altered immunity • Leukocyte function • Adherence • Chemotaxis • Phagocytosis. • Antioxidant systems involved in bactericidal activity • Intracellular killing of microorganisms • May improve with better glycemic control. Joshi N. Infections in patients with diabetes mellitus. N Eng J Med 1999; 341: 1906

  39. Diabetes: altered immunity Geerlings SE, et al. FEMMS 1999; Calvet HM, Inf Dis Clin N Am 2001

  40. Diabetes: altered immunity Normal PMN Diabetes Oxidative burst Degranulation Free radial production Adhesion molecules Activated Resting PMN Tolerant Resting PMN Oxidative burst Degranulation Free radial production Adhesion molecules Risk of infection Stimulus Calvet HM. Infect Dis Clin N Am 2001;

  41. Diabetes: altered immunity Uroepithelial cell adherence Geerlings SE, et al. Adherence of type 1-fimbriated Escherichia coli to uroepithelial cells: more in diabetic women than in control subjects. Diabetes Care 2002; 25:1405.

  42. Diabetes: altered immunity Geerlings SE, et al. Adherence of type 1-fimbriated Escherichia coli to uroepithelial cells: more in diabetic women than in control subjects. Diabetes Care 2002; 25:1405.

  43. Diabetes: altered immunity Restoration of phagocytic activity Gin H, et al. Influence of glycaemic normalisation by an artificial pancreas on phagocytic and bactericidal functions of granulocytes in diabetic patients. J Clin Pathol 1984;37:1029.

  44. Diabetes: clinical consecuences • Vaccination • Influenza • S. pneumoniae • Others • Relevance of glycemic control • During infection • Long term

  45. Chronic liver disease: increase of infections? % Patients Wang JH, et al. CID 1998; Wang JL CID 2005; Roden MM et al. CID 2005; Farley et al. N Engl J Med 1993; Hohmann EL et al. CID 2001;Simpson JH, et al. CID 2003.

  46. Chronic liver disease: increase of infections? Spontaneous bacterial peritonitis: 60% of severe infections Impaired clearing bacteria Prolonged Bacteremia Sterile ascitis Bacterascitis SBP Bacterial traslocation Intestinal hipomotility Intestinal oedema

  47. Chronic liver disease: immunossupression? 51Cr erythrocytes (RhD+) from patients sensitized withhuman IgG anti-RhD antibodies. Gomez F, et al. Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis. N Engl J Med 1994; 331:1122.

  48. Chronic liver disease: immunossupression? Severe Moderate Mild Gomez F, Ruiz P, Schreiber AD. Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis. N Engl J Med. 1994 Oct 27;331(17):1122-8.

  49. Chronic liver disease: increase of infections? Bacteremia • Danish National Registry of Patients: • 7033 cases of bacteremia • 1339 patients with liver cirrhosis • -117 cases of bacteremia and cirrhosis *Standardized incidence ratio Thulstrup AM, et al. Population-based study of the risk and short-term prognosis for bacteremia in patients with liver cirrhosis. Clin Infect Dis 2000;31:1357.

  50. Chronic liver disease: increase of infections? Liver abscess • Danish National Registry of Patients: • 22764 cases of liver cirrhosis • 665 patients with liver abscess • -21 cases of liver abscess and cirrhosis Standardized incidence ratio of 15.4 (9.6–23.6). Molle I, et al. Increased risk and case fatality rate of pyogenic liver abscess in patients with liver cirrhosis: a nationwide study in Denmark. Gut 2001;48:260.

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