IMMUNODEFICIENCY IN PATIENTS WITH CHRONIC MEDICAL CONDITIONS

IMMUNODEFICIENCY IN PATIENTS IMMUNODEFICIENCY IN PATIENTS WITH CHRONIC MEDICAL CONDITIONSWITH CHRONIC MEDICAL CONDITIONS

55thth ESCMID School of Clinical ESCMID School of Clinical Microbiology and Infectious DiseasesMicrobiology and Infectious Diseases

Santander, Spain, 10 - 16 June 2006Santander, Spain, 10 - 16 June 2006

http://www.escmid.org/sites/index.aspx

http://www.escmid.org/sites/index.aspx

The The relevancerelevance of the of the problemproblem

Diabetes: 10%Diabetes: 10% Renal Renal chronicchronic failurefailure: 11%: 11% COPD: 7.5%COPD: 7.5% CardiacCardiac failurefailure: 2.2 %: 2.2 % PsychiatricPsychiatric illnessesillnesses: 6%: 6% DementiaDementia: 2%: 2% Cirrhosis: 0.2%Cirrhosis: 0.2%

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.

1987 USA1987 USA: : – 90 million people with “chronic conditions”.90 million people with “chronic conditions”.– 39 million of whom were living with more than 1 39 million of whom were living with more than 1

chronic condition.chronic condition.


Hoffman C, et al. Persons with chronic conditions. JAMA 1996; 276:1473.

Steinbrook R. Facing the diabetes epidemic. N Engl J Med 2006; 354:545-8.


Number of Persons Diabetes in the United States, 1980–2004

0

2

4

6

8

10

12

14

16

Mil

lio

ns o

f d

iab

eti

cs

Epidemiological evidenceEpidemiological evidence– Increase of infectionsIncrease of infections– Worse prognosisWorse prognosis

Animal models.Animal models. Laboratory dataLaboratory data

– Immune responseImmune response– Host-microorganisms relationships.Host-microorganisms relationships.

ImmunodeficiencyImmunodeficiency in chronic conditions? in chronic conditions?

DiabetesDiabetes

Immunosuppression?Immunosuppression?– Increase of infections Increase of infections immunosuppressionimmunosuppression

25% of diabetics

DiabetesDiabetes

Increase of infections Increase of infections immunosuppressionimmunosuppression

– Organ lesions:Organ lesions: Vascular damageVascular damage NeuropathyNeuropathy

– Glucosuria may promote bacterial growthGlucosuria may promote bacterial growth– Insulin injections: increase nasal carriage of Insulin injections: increase nasal carriage of S. S.

aureus aureus (34% vs 10% )(34% vs 10% )

0

10

20

30

40

50

60

%

Diabetic

Non diabetic

Diabetes:Diabetes:

Memmel H. Infections in diabetic burn patients. Diabetes Care 2004; 27:229.

Burn wound age on admissionWithin 48 h- 49 (40%)- 995 (63%)

0

10

20

30

40

50

60

%

< 24h 48h 72hweek

2-3 weekmonths+

Diabetic

Non diabetic

Diabetes:Diabetes:

Memmel H. Infections in diabetic burn patients. Diabetes Care 2004; 27:229.

OutcomeOutcome Diabetic Diabetic (n=130)(n=130)

Non Non diabetic diabetic (n=126)(n=126)

Bacteremia Bacteremia 12 (9.2%)12 (9.2%) 38 (2.5%)38 (2.5%)

SepsisSepsis 13 (10%)13 (10%) 28 (2.5%)28 (2.5%)

CellulitisCellulitis 35 (27%)35 (27%) 120 (11%)120 (11%)

Burn wound age on admission

Diabetes: Diabetes: immunossupression?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.


“However, many specific infections are more common in diabetic patients, and some occur almost exclusively in them”.


Increased risk of infections?Increased risk of infections?– Selected infectionsSelected infections– Selected microorganismsSelected microorganisms– Global riskGlobal risk

Worse prognosis?Worse prognosis?

DiabetesDiabetes

Diabetes: Diabetes: increase of selected infectionsincrease of selected infections

0 20 40 60 80

Non tiphoidalSalmonellosis

Melioidosis

Zygomicosis

Klebsiellla lungabscess

Klebsiella liverabscess

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.

% Patients with diabetes


0 20 40 60 80

Candida

S. pneumoniae

Enterobacteria

Pseudomonas

GB Strp.

S.aureus

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.

Bacteremia



0 20 40 60 80 100

Lung abscess

Liver abscess

Emphysematous cholecystitis

Perinephic abscess

Necrotizing fasciitis

Malignant otitis external

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.



N Engl J Med 2003;348:2329


Diabetes: 70%Diabetes: 70% Malnutrition: 25 %Malnutrition: 25 % Alcoholism: 23%Alcoholism: 23% Renal chronic failure: 14%Renal chronic failure: 14% Cirrhosis: 5%Cirrhosis: 5%

BMJ 2005;330:830–3

Elliott D, et al. The microbiology of necrotizing soft tissue infections. Am J Surg 2000; 179:361.


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

Zygomycosis

0102030405060708090

100

1940s 1950s 1960s 1970s 1980s 1990s

Nu

mb

er o

f C

ases

Diabetes No Underlying Deferroxamine

Transplantation Malignancy BMT

5%

60%6%

3%

4%

10%

12%

Diabetes: Diabetes: increase of infectionsincrease of infections

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

8%15%

16%

10%

8%

43%

RhinocecebralSinusSino-orbitalPulmonaryCutaneousGIOther

8%

8%5%

9%

9%

11%

50%Diabetes Malignancy

No underlying condition

N=337 N=154

N=176


85% of Rhino-cerebral zygomicosis in diabetics

Low pHLow pH– Lack of serum activityLack of serum activity– Higher Iron availability Higher Iron availability

Macrophage defectMacrophage defect– Murine modelMurine model


Type 1 DM (n=705)

0

1

2

3

4

5

6

LRTI UTI RecITU B. Skin F. Skin

Od

ds r

ati

o

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


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.

Type 2 DM (n=6712)

0

1

2

3

4

5

6

LRTI UTI Rec ITU B. Skin F. Skin

Od

ds r

ati

o

Control patients with hypertension (n= 18,911)

Diabetes:Diabetes: increase of selected infectionsincrease of selected infections

0

0.5

1

1.5

2

2.5

3

3.5

4

All E.coli Klebsiella

Od

ds r

ati

o

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

Enterobacteria community-acquired bacteremia

Cases n= 1317Controls n=13170

DiabetesDiabetesDiabetes: Diabetes: increase of infectionsincrease of infections

Infection RR (95% CI) Ref

LVAD-related BSILVAD-related BSI 7.7 ( 2.0–29.8)7.7 ( 2.0–29.8) Simon D et al. CID 2005; Simon D et al. CID 2005; 40:110840:1108

Postcardiothoracic Postcardiothoracic (SSI)(SSI) 2.7 (1.64-4.66)2.7 (1.64-4.66) Latham R et al. Infect Control Latham R et al. Infect Control

Hosp Epidemiol. 2001;22:607Hosp Epidemiol. 2001;22:607

Postgastrectomy Postgastrectomy infectionsinfections

6.8 (1.7- 27.1)Yamashita et al. Anesth Analg 2000;91:1176

Campylobacter Campylobacter gastroenteritisgastroenteritis

4.1 (1.1-17) Neal KR et al. Epidemiol Infect; 1997; 119:307

Salmonella Salmonella enteritidisenteritidis 3.1 (1.1-8.6) Telzak EE et al. J Infect Dis

1991; 164:538

NeumoniaNeumonia 1.3 (1.1-1.5)Fine M et al. JAMA 1996; 275: 174

Invasive GASInvasive GAS 11 (8.4-14.0)Sharkawy A et al. CID 2002; 34:454


Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26:510.

*P 0.0001; †P 0.001.

InfectionInfection OR (95% IC)OR (95% IC) Per 100000 pat.Per 100000 pat.

Upper respiratory tractUpper respiratory tract 1.18 (1.17–1.19)* 1.18 (1.17–1.19)* 28,45428,454

Cystitis Cystitis 1.39 (1.36–1.42)* 1.39 (1.36–1.42)* 5,4915,491

Pneumonia Pneumonia 1.46 (1.42–1.49)*1.46 (1.42–1.49)* 4,9194,919

CellulitisCellulitis 1.81 (1.76–1.86)*1.81 (1.76–1.86)* 46264626

Enteric infectionsEnteric infections 1.50 (1.46–1.54)*1.50 (1.46–1.54)* 4,0874,087

Otitis externa Otitis externa 1.14 (1.09–1.18)* 1.14 (1.09–1.18)* 1,7341,734

MycosesMycoses 1.38 (1.32–1.44)*1.38 (1.32–1.44)* 1,3961,396

Genital infections (male)Genital infections (male) 0.89 (0.86–0.89)*0.89 (0.86–0.89)* 13401340

Otitis mediaOtitis media 1.21 (1.15–1.28)* 1.21 (1.15–1.28)* 1,0711,071

Chicken pox/shingles Chicken pox/shingles 1.16 (1.09–1.22)* 1.16 (1.09–1.22)* 816816

Outpatients

Diabetics N= 513,749. 1:1 controls matched for date of birth within 30 days, sex, region, and income quintile.



Viral hepatitis Viral hepatitis 1.49 (1.39–1.60)*1.49 (1.39–1.60)* 682682

Pyelonephritis Pyelonephritis 1.95 (1.78–2.13)*1.95 (1.78–2.13)* 486486

Tuberculosis Tuberculosis 1.12 (1.03–1.23)† 1.12 (1.03–1.23)† 344344

Osteomyelitis Osteomyelitis 4.39 (3.80–5.06)* 4.39 (3.80–5.06)* 340340

Genital infections (female)Genital infections (female) 1.16 (1.04–1.30)†1.16 (1.04–1.30)† 234234

Mononucleosis Mononucleosis 1.60 (1.39–1.85)* 1.60 (1.39–1.85)* 159159

Rectal abscessRectal abscess 1.97 (1.67–2.32)*1.97 (1.67–2.32)* 144144

Infectious arthritisInfectious arthritis 1.72 (1.42–2.08)* 1.72 (1.42–2.08)* 9898

Herpes simplex virusHerpes simplex virus 0.92 (0.84–1.02) 0.92 (0.84–1.02) 253253

HIVHIV 0.96 (0.78–1.18)0.96 (0.78–1.18) 5757*P 0.0001; †P 0.001.

Outpatients


Shah BR, et al. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26:510.



SepsisSepsis 2.45 (2.23–2.68)*2.45 (2.23–2.68)* 539539

Postoperative infectionsPostoperative infections 2.02 (1.80–2.27)*2.02 (1.80–2.27)* 283283

Biliary tree infectionsBiliary tree infections 1.60 (1.39–1.83)*1.60 (1.39–1.83)* 173173

PeritonitisPeritonitis .94 (1.58–2.37)*.94 (1.58–2.37)* 193193

AppendicitisAppendicitis 1.19 (0.96–1.47)1.19 (0.96–1.47) 6262

*P 0.0001; †P 0.001.

Shah BR, et al. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26:510.

Inpatients



“Contrary to common belief, the association between diabetes mellitus and increased susceptibility to infection in general is not supported by strong evidence”.


Diabetes: Diabetes: increase of infectionsincrease of infections??

“The association between diabetes mellitus and increased susceptibility to infection is well supported”.

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.

Diabetes: Diabetes: prognostic factorprognostic 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

Mylotte MA, et al. Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort. Clinical Infectious Diseases 2000; 31:1170.


293 patients with episodes of SAB, 68 died (23.2%)

Staphylococcus aureus bacteremia: prognostic factors


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

Deep neck infection in diabetic patients

Oursler KK. Survival of patients with pulmonary tuberculosis: clinical and molecular epidemiologic factors. Clinical Infectious Diseases 2002; 34:752.


139 patients with tuberculosis 29 (21%) died (Baltimore).

Tuberculosis: prognostic factors

Diabetes Renal failure

Hyperglycemia: Hyperglycemia: prognostic factorprognostic factor

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

Infection related

Diabetes: Diabetes: worse prognosisworse prognosis

Bertoni AG, et al. Diabetes and the risk of infection-related mortality in the U.S. Diabetes Care 2001; 24:1044.

Diabetic

Non- Diabetic

n=9,208

Increase risk of infectionsIncrease risk of infections Worse prognosisWorse prognosis

Diabetes: Diabetes: ““epidemiological” conclusionsepidemiological” conclusions

Diabetes: Diabetes: altered immunityaltered 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


Immunity HumoralHumoral CellularCellular

Innate Complement ↓ PMNs ↓=

Cytokines without stimulation

↑ Monocytes ↓

Cytokines after stimulation

↓=

Adaptative Immunoglobulins = T lymphocytes ↓

Adherence ↑

Geerlings SE, et al. FEMMS 1999; Calvet HM, Inf Dis Clin N Am 2001


Normal PMN

ActivatedResting PMN

TolerantResting PMN

Stimulus

Oxidative burstDegranulationFree radial productionAdhesion molecules

Risk of infection

Calvet HM. Infect Dis Clin N Am 2001;

Diabetes

Oxidative burstDegranulationFree radial productionAdhesion molecules

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.

Uroepithelial cell adherence


0

2

4

6

8

10

12

14

Bacte

ria p

er

cell

Negative P fimbriae Type 1fimbriae

Nofimbriae

Non diabeticsDiabetics


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.

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.


Restoration of phagocytic activity

0102030405060708090

100

Before After

% a

cti

vit

y o

f c

on

tro

l v

alu

es

VaccinationVaccination InfluenzaInfluenza S. pneumoniaeS. pneumoniae OthersOthers

Relevance of glycemic controlRelevance of glycemic control During infectionDuring infection Long termLong term

Diabetes: Diabetes: clinical consecuencesclinical consecuences

Chronic liver diseaseChronic liver disease: : increase of infections?increase of infections?

0 20 40 60 80

Non tiphoidal Salmonellosis

Group B Strp bacteremia

Zygomicosis

Klebsiellla lung abscess

Klebsiella liver abscess

Vibrio vulnificus

Liver diseaseDiabetes

% 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.


Spontaneous bacterial peritonitis: 60% of severe infections

Prolonged Bacteremia

Bacterial traslocation

SBPBacterascitisSterile ascitis

Impaired clearing bacteria

Intestinal hipomotility

Intestinal oedema

Chronic liver disease: Chronic liver disease: immunossupression?immunossupression?

Gomez F, et al. Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis. N Engl J Med 1994; 331:1122.

51Cr erythrocytes (RhD+) from patients sensitized with human IgG anti-RhD antibodies.


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.

Mild

ModerateSevere


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.

*Standardized incidence ratio

Danish National Registry of Patients:•7033 cases of bacteremia•1339 patients with liver cirrhosis

-117 cases of bacteremia and cirrhosis

Bacteremia

*SIR (95% CI) Bacteremia*SIR (95% CI) Bacteremia

Liver CirrhosisLiver Cirrhosis

AlcoholicAlcoholic 13.9 (10.8-17.6)13.9 (10.8-17.6)

Non-alcoholicNon-alcoholic 7.8 (5.7-10.4)

TotalTotal 10.5 (8.8-12.7) 10.5 (8.8-12.7)


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.

Standardized incidence ratio of 15.4 (9.6–23.6).

Danish National Registry of Patients:•22764 cases of liver cirrhosis•665 patients with liver abscess

-21 cases of liver abscess and cirrhosis

Liver abscess

*SIR (95% CI) Bacteremia*SIR (95% CI) Bacteremia

Liver CirrhosisLiver Cirrhosis

AlcoholicAlcoholic 15.5 (8.2-26.5)15.5 (8.2-26.5)

Non-alcoholicNon-alcoholic 15.7 (6.8-30.9)

TotalTotal 15.4 (9.6-23.6) 15.4 (9.6-23.6)


Runyon BA. Gastroenterology 1986;91:1343; Runyon BA. Hepatology 1988;8:632-5

0

2

4

6

8

10

12

14

16

%S

BP

Protein Opsoniccapacity

HighLow

Cut points:-Albumin 1 g/dL-Opsonic: 0.2 log Kill


Haq SM, et al. Am J Gastroenterol. 2005;100:1195-9. Falcon, L. M. et al. N Engl J Med 2005;353:1604

Vibrio vulnificus septicemia

PredisposingPredisposing %%

Liver CirrhosisLiver Cirrhosis 8080

Other immunossupressionOther immunossupression 1515

Consume of raw oystersConsume of raw oysters 9797

PresentationPresentation %%

FeverFever 9797

Skin lesionsSkin lesions 6565

DiarrheaDiarrhea 4747

Mortality Mortality 5353


Haq SM, et al. Am J Gastroenterol. 2005;100:1195-9. Falcon, L. M. et al. N Engl J Med 2005;353:1604

Vibrio vulnificus septicemia

PredisposingPredisposing %%

Liver CirrhosisLiver Cirrhosis 8080

Other immunossupressionOther immunossupression 1515

Consume of raw oystersConsume of raw oysters 9797

PresentationPresentation %%

FeverFever 9797

Skin lesionsSkin lesions 6565

DiarrheaDiarrhea 4747

Mortality Mortality 5353

Shunting of bacteriaShunting of bacteria AchlorhydriaAchlorhydria Increase of Iron serumIncrease of Iron serum

Hor LI, et al. Survival of Vibrio vulnificus in whole blood from patients with chronic liver diseases: association with phagocytosis by neutrophils and serum ferritin levels. J Infect Dis 1999;179:275.


0100200300400500600700800900

Healthy Chronichepatitis

Cirrhosis Hepatoma

Ferr

itin

(n

g/m

L)

0102030405060708090

100


Cirrhosis Hepatoma

0

0.5

1

1.5

2

2.5

3

3.5

4


Cirrhosis Hepatoma5.6

5.8

6

6.2

6.4

6.6

6.8

7


Cirrhosis Hepatoma

Ferritin Phagocytosis

Vibrio survival E. coli survival

Chronic liver diseaseChronic liver disease

Hsu RB . Risk factors for nosocomial infective endocarditis in patients with methicillin-resistant staphylococcus aureus bacteremia . Infect Control Hosp Epidemiol 2005; 26:654.

SARM nosocomial endocarditis: risk factors

0

5

10

15

20

25

30

35

40

45

Diabetes Renal CF Cirrhosis IDU Dyalisis

Endocarditis n=31

Non-endocarditis n=142

**

*


Johnson DH, Cunha BA. Infections in cirrhosis. Infect Dis Clin North Am 2001;15:363-71.

ABNORMALITIESABNORMALITIES

Impaired Impaired rethiculoendothelial systemrethiculoendothelial system

Impaired hepatic clearance for bacteriaImpaired hepatic clearance for bacteria

Impaired killing Impaired killing

Splenic hypofunctionSplenic hypofunction

Complement defectComplement defect Acquired C3 defectAcquired C3 defect

Neutrophil defectNeutrophil defect Defective chemotaxisDefective chemotaxis

Presence of chemotatic inhibitorsPresence of chemotatic inhibitors

T and B defectT and B defect Decreased Lympocyte response to Decreased Lympocyte response to PHAPHA

Delayed type hypersensitivityDelayed type hypersensitivity

Immunoglobulin defectImmunoglobulin defect Policlonal gammapathyPoliclonal gammapathy

Chronic conditionsChronic conditions: : increase of infections?increase of infections?

0 20 40 60 80 100

Group B Strpbacteremia

Zygomicosis

Klebsiellla lungabscess

Klebsiella liverabscess

Vibriovulnificus

AnyRenal failureAlcoholismLiver diseaseDiabetes

% 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. CID 2001; 32:263–9; Simpson JH, et al. CID 2003.


Peralta G et al. Risk factors for bacteremia in patients with limb cellulitis. Eur J Clin Microbiol Infect Dis (in press)

02468

1012141618

Bacteremic

Non-bacteremic

N=308 (Bacteremic 18.5%)


Peralta G et al. Risk factors for bacteremia in patients with limb cellulitis. Eur J Clin Microbiol Infect Dis

0

2

4

6

8

10

12

No AB Proximal >1Comorb.

< 2 days

Mo

rtali

ty (

%)


Charlson ME, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 1987; 40: 373.

CONDITIONSCONDITIONS POINTSPOINTS

Myocardial infarctMyocardial infarct 11

Heart failureHeart failure 11

Peripheral vascular Peripheral vascular dis.dis.

11

DementiaDementia 11

COPDCOPD 11

Connective tissue dis.Connective tissue dis. 11

Ulcer diseaseUlcer disease 11

Mild liver diseaseMild liver disease 11

DiabetesDiabetes 11

HemiplegiaHemiplegia 11

CONDITIONSCONDITIONS POINTSPOINTS

Moderate-severe renal Moderate-severe renal diseasedisease

22

Diabetes + organ Diabetes + organ damagedamage

22

TumorTumor 22LeukemiaLeukemia 22LymphomaLymphoma 22Moder-severe liver dis.Moder-severe liver dis. 33MetastaticMetastatic 66AIDSAIDS 66

Charlson index

Chronic conditionsChronic conditions: : prognosisprognosis

0

5

10

15

20

25

30

SARM TTP <12h Charlson >3

Od

ds r

ati

o

Marra AR et al. Time to blood culture positivity as a predictor of clinical outcome of Staphylococcus aureus bloodstream infection. J Clin Microbiol 2006; 44:1342.

n = 91

Chronic conditionsChronic conditions: : prognosisprognosis

Murray SB, et al. Charlson Index is associated with one-year mortality in emergency department patients with suspected infection. Acad Emerg Med 2006;13:530.

0

10

20

30

40

50

0 1 2 3 4 >5

Charlson score

Mo

rtali

ty (

%)

n = 3102

Global risk of infection associated with chronic Global risk of infection associated with chronic illnesses.illnesses.

Interaction among chronic illnesses.Interaction among chronic illnesses. Clinical presentation of infections.Clinical presentation of infections. Specific immune and non-immune Specific immune and non-immune mechanismsmechanisms.. Potential restoration of immunity.Potential restoration of immunity. Prevention in high risk situations.Prevention in high risk situations.

Infections in patients with chronic medical conditions? What we don't to know?

Infections in patients with chronic medical conditions? What we don´t to know?

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IMMUNODEFICIENCY IN PATIENTS WITH CHRONIC MEDICAL CONDITIONS

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