le infezioni fungine in medicina interna2019/10/16 · le infezioni fungine in medicina interna...
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Roberto Luzzati
SC Malattie Infettive,
Ospedale Maggiore, Trieste
Le Infezioni Fungine in Medicina Interna
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Strollo S & NIH, E.I.D. 2017
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Strollo S, E I D 2017
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Strollo S, E I D 2017
Age-adjusted annual rates decreasing during 2002-12 (-4.5%^ per year)
Hospitalization (median lenght) = from 21 days (2002) to 17 days (2012)
Median unadjusted associated cost (inpatient care) = 46,684 US
Overall mortality rate = 22% (average decrease of 3.7% / year)
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Italy: PPS data (49 hospitals) period 2011-2012
Most frequently isolated microorganisms in HAIs (bloodstream
infections) in acute care hospitals in Italy (n=178 microorganisms)
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Country/
City
Period MWs Surgical
wards
ICUs Hematology
wards
References
Italy/
Verona1992-1997 6.3% 24.8% 68.7% --
Luzzati R. et al Nosocomial candidemia in non-neutropenic patients
at an Italian tertiary care hospital. EJCMID 2000; 19(8): 602-7.
France/
Lyon1998-2001 32% 23% 23% 22%
Martin D. et al. Candida species distribution in bloodstream cultures
in Lyon, France, 1998-2001. EJCMID. 2005; 24(5): 329-33
USA2004-2008 66% -- -- --
Horn DL et al. Epidemiology and outcomes of candidemia in 2019
patients: data from the prospective antifungal therapy alliance
registry. CID 2009; 48(12): 1695-703.
Italy Rome/Turin
EOC2004-2008 51.3% 21.3% 27.3% --
De Rosa FG. et al. Mortality in patients with early- or late-onset
candidaemia. JAC. 2013; 68(4): 927-35.
Italy Rome/Turin
LOC2004-2008 41.7% 35.0% 23.1% -- IDEM
Italy/
Genua2008-2010 39.7% 32.1 19.7% 8.4%
Bassetti M. et al. Candidaemia in internal medicine departments: the
burden of a rising problem. CMI. 2013; 19(6): E281-4.5
Italy/
Spain2008-2010 49.7% 24.6% 19.6% 6.1%
Bassetti et al. Epidemiology, species distribution,antifungal
susceptibility, and outcome of candidemia across five sites in Italy
and Spain. JCM 2013; 51(12): 4167
Italy/
Udine2008-2010 57% 17% 16% 10% IDEM
Italy/
Trieste2008-2010 67% 16% 15% 0% IDEM
Spain/
Barcelona2008-2010 32% 27% 32% 8% IDEM
Spain/
Seville2008-2010 28% 17% 43% 10% IDEM
Tascini C , CMI 2015
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Pathogenesis of Invasive Candidiasis.
Kullberg BJ, Arendrup MC. N Engl J Med 2015;373:1445-1456
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Risk Factors for Invasive Candidiasis.
Kullberg BJ, Arendrup MC. N Engl J Med 2015;373:1445-1456
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EJIM 2017
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EJIM 2017
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EJIM 2017
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EJIM 2017
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EJIM 2017
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Int J Clin Pract 2018
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Int J Clin Pract 2018
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+ 1
+ 1
+ 5
+ 2
+ 1
SCORE > 7
(sensitivity 79.2%, specificity 82.6%)
RR 29.8; CI 95% 10.6-93.3
P< 0.001
SCORE
Int J Clin Pract 2018
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Infection 2018
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Infection 2018
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Infection 2018
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Diagn Microb Infect Dis 2019
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Diagn Microb Infect Dis 2019
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Risk Factors for Candidemia
in patients admitted to Internal Medicine wards
Risk factor Falcone 2017 Sozio 2018 Ruiz-R. 2018 Atamna 2019
Severe sepsis/Septic shock X
Recent C. difficile infect. X
Diabetes mellitus X
CVC/PICC X (PICC) X (PICC) X (CVC)
TPN X X X
COPD X
Antibiotic therapy X (glycop) X X X (cephal)
Immunosuppress. therapy X X (steroids)
Neurological disability X
Hospitalization< 3 months X
Urinary catheterisation X
Male sex X
Underweight X
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Infection 2016
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Distribution of candidemia episodes (# 686)
according to hospital wards
21%
25%54%
2011-2013: 686 adult patients (52% males); mean age 70 + 15 yrs
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Severe sepsis and septic shock presentation, and
mortality, according to hospitalization area
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variables Surgery/ICUs
(319 pt)
Medicine wards
(367 pt)OR (95%CI) P-value
Inadeguate antifungal
therapy30/266 (11.27) 83/333 (25) 2.61 (1.66-4.11) <0.001
No antifungal therapy 25/266 (9.3) 48/333 (14.4) 1.62 (0.97-2.71) 0.062
Adeguate therapy + CVC
removal147/212 (69.3) 97/208 (46) 0.39 (0.2 6-0.58) <0.001
Table 4. Comparison of treatment and outcome
according to ward admission
Surgery/ICUs, surgery and intensive care units; OR, odds ratio (misure quantitative OR per unit); CI, confidence interval; NA, not available
Infection, 2016
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Infection 2016
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0
50
100
150
200
<40 41-50 51-60 61-70 71-80 > 80
nu
me
ro p
azi
en
ti
Vivi Morti con candida Morti senza candida
Impatto dell’età avanzata sull’epidemiologia e l’outcome della
candidemia nosocomiale in 642 pazienti
(Candidemia Triveneto study group)
unpublished data, 2019
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VARIABLES ADULT ≤75
(390 patients)
ELDERLY > 75
(293 patients)
ODDS RATIO 95% CI P-VALUE
Age, median (IQ) 63 (53-70) 83 (79-88) <0.0001
Gender (male) 231/390 (59.2) 127/293 (43.3) 1.9 1.4-2.58 <0.0001
Surgery/ICUs 226/390 (57.9) 91/293 (31.1) 3.06 2.22-4.21 <0.0001
Medicine wards 164/390 (42.1) 202/293 (68.9) 0.33 0.24-0.45
HOST-RELATED FACTORS
Charlson score 3 (1-6) 3 (2-5) 0.73
Solid cancer 132/385 (34.3) 73/293 (24.9) 1.57 1.12-2.21 0.0085
Diabetes mellitus 99/389 (25.4) 74/293 (25.2) 1.01 0.71-1.43 1
Chronic renal failure 50/389 (12.8) 55/293 (18.7) 0.64 0.42-0.97 0.034
Auto-immune diseases 26/385 (6.7) 23/293 (7.8) 0.85 0.47-1.52 0.58
Haematological cancer 18/386 (4.7) 8/293 (2.7) 1.74 0.75-4.06 0.19
Transplantation 15/386 (3.9) 0/293 (0) - - 0.0006
Burns 11/384 (2.9) 6/293 (2.1) 1.41 0.51-3.86 0.5
HIV 3/387 (0.8) 0/293 (0) - - 0.26
Albuminemia 2.6 (±0.6) 2.5 (±0.6) 0.17
Candida colonization 59/347 (17) 29/260 (11.1) 1.63 1.01-2.63 0.043
Concomitant bacteraemia 107/390 (27.4) 79/292 (27) 1.02 0.72-1.43 0.92
HEALTHCARE-RELATED FACTORS
Central venous catheter 302/389 (77.6) 187/290 (64.5) 1.91 1.36-2.68 0.0002
Urinary catheter 242/343 (70.5) 201/253 (79.4) 0.62 0.42-0.91 0.014
Dialysis 36/386 (9.3) 11/292 (3.8) 2.63 1.31-5.26 0.0048
Chemo-radiotherapy 34/381 (8.9) 8/287 (2.8) 3.42 1.56-7.5 0.0012
Immunosuppressive therapy 30/387 (7.7) 5/291 (1.7) 4.81 1.84-12.5 0.0004
Antibiotic therapy 307/326 (94.1) 244/256 (95.3) 0.79 0.38-1.67 0.54
Corticosteroid therapy 70/384 (18.3) 31/288 (10.8) 1.85 1.17-2.91 0.0074
Mechanical ventilation 137/389 (35.2) 53/292 (18.1) 2.45 1.71-3.52 <0.0001
Major surgery 161/387 (41.6) 86/292 (29.4) 1.71 1.24-2.36 0.0011
Peripheral parenteral nutrition 52/381 (13.6) 65/290 (22.4) 0.55 0.37-0.82 0.003
Total parenteral nutrition 212/370 (57.3) 150/281 (53.4) 1.17 0.86-1.6 0.32
TABLE 1. Epidemiologic characteristics of candidemia episodes according to patient age
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VARIABLES ADULT ≤75
(390 patients)
ELDERLY > 75
(293 patients)
ODDS RATIO 95% CI P-VALUE
SEVERITY OF ILLNESSES
Charlson score 3 (1-6) 3 (2-5) 0.73
Severe sepsis and septic shock 229/338 (67.7) 160/258 (62) 1.29 0.92-1.81 0.15
SOURCE CONTROL
CVC removal 237/296 (80) 119/176 (67.6) 1.92 1.26-2.94 0.0024
Time to CVC removal 3 (1-6) 2 (1-5) 0.27
NO ANTIFUNGAL THERAPY 31/339 (9.1) 41/257 (15.9) 0.53 0.32-0.87 0.012
TREATED WITH
ANTIFUNGAL THERAPY
308/339 (90.9) 216/257 (84.1) 1.89 1.15-3.1 0.012
ANTIFUNGAL THERAPY 0.0048
Adequate therapy with azoles 145/308 (47.1) 110/216 (51) 0.86 0.61-1.21
Adequate therapy with
echinocandins
104/308 (33.8) 46/216 (21.3) 1.88 1.26-2.82
Adequate therapy with
amphotericin B
5/308 (1.6) 2/216 (0.8) 1.77 0.34-9.19
Inadequate antifungal therapy 54/308 (17.5) 58/216 (26.8) 0.58 0.38-0.88
ADEQUATE THERAPY + CVC
REMOVAL
180/279 (64.5) 79/166 (47.6) 2 1.35-2.96 0.0005
OUTCOMES AT 30 DAYS <0.0001
Survivor 261/373 (70) 121/270 (44.8) 2.87 2.07-3.98
Died with candidemia 88/373 (23.6) 129/270 (47.8) 0.34 0.24-0.47
Died without candidemia 24/373 (6.4) 20/270 (7.4) 0.86 0.46-1.59
TABLE 2. Clinical characteristics and management of candidemia episodes according to patient age.
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5558
1512
15 13
10 12
6 5
0
10
20
30
40
50
60
70
80
90
100
Adult patients Elderly patients
Candida albicans Candida glabrata Candida parapsilosis Candida tropicalis Other candida non-albicans spp
FIGURE 1 The species distribution (including ratio and number) of candidemia
episodes among adult and elderly patients.
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TABLE 3. Univariate analysis of risk factors for 30-days mortality in patients aged over 75 years.
VARIABLES DIED (128 pts) SURV (121 pts) OR 95% CI P-value
Age 85 (81-88) 83 (79-87) 0.14
Gender (male) 58/128 (45.3) 49/121 (40.5) 1.22 0.74-2.01 0.44
HOSPITALIZATION AREA 0.0023
Surgery/ICUs 28/128 (21.9) 48/121 (39.7) 0.43 0.24-0.74
Medicine wards 100/128 (78.9) 73/121 (60.3) 2.35 1.35-4.09
HOST-RELATED FACTORS
Solid cancer 34/128 (26.6) 31/121 (25.6) 1.05 0.6-1.85 0.86
Diabetes mellitus 29/128 (22.6) 39/121 (32.2) 0.62 0.35-1.08 0.09
Haematological cancer 3/128 (2.3) 3/121 (2.5) 0.94 0.19-4.77 1
Charlson score 3 (2-6) 2.5 (2-5) 0.035
Albuminemia 2.5 (± 0.6) 2.5 (± 0.6) 0.98
Concomitant bacteraemia 37/127 (29.1) 31/121 (25.6) 1.19 0.68-2.09 0.54
HEALTHCARE-RELATED FACTORS
Central venous catheter 79/128 (61.7) 80/119 (67.2) 0.79 0.47-1.33 0.37
Dialysis 6/128 (4.7) 5/121 (4.1) 0.88 0.26-2.95 0.82
Prior antibacterial exposure 105/110 (95.4) 102/109 (93.6) 1.44 0.44-4.69 0.54
Corticosteroid therapy 18/126 (14.3) 10/120 (8.3) 1.83 0.81-4.15 0.14
Mechanical ventilation 21/128 (16.4) 27 /121 (22.3) 0.68 0.36-1.29 0.24
Major surgery 31/128 (24.2) 45/121 (37.2) 0.54 0.31-0.93 0.026
Peripheral parenteral nutrition 33/128 (25.8) 19/120 (8.3) 1.85 0.98-3.47 0.054
Total parenteral nutrition 71/123 (57.7) 65/116 (56) 1.07 0.64-1.79 0.79
CVC removal 36/66 (54.5) 66/83 (79.5) 0.31 0.15-0.64 0.0011
Adequate antifungal therapy 57/108 (52.8) 71/111 (64) 0.63 0.37-1.08 0.093
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TABLE 4. Univariate analysis of risk factors for 30-days mortality in patients aged over 75 years.
VARIABLES DIED
(128 patients)
SURVIVOR
(121 patients)
ODDS
RATIO
95% CI P-
VALUE
CANDIDA SPP DISTRIBUTION 0.04
Candida albicans 81/127 (63.8) 67/119 (56.3) 1.37 0.82-2.28
Candida glabrata 15/127 (11.8) 17/119 (14.3) 0.8 0.38-1.69
Candida parapsilosis 9/127 (7.1) 22/119 (18.5) 0.34 0.15-0.76
Candida tropicalis 13/127 (10.2) 10/119 (8.4) 1.24 0.52-2.95
Other candida non-albicans spp 9/127 (7.1) 3/119 (2.5) 2.95 0.78-11.2 0.097
ANTIFUNGAL THERAPY 0.065
No 25/108 (23.2) 15/111 (13.5) 1.93 0.95-3.9
Yes 83/108 (76.8) 96/111 (86.5) 0.52 0.26-1.05
ANTIFUNGAL THERAPY 0.21
Azoli 40/83 (48.2) 48/96 (50) 0.93 0.52-1.67
Echino 16/83 (19.3) 24/96 (25) 0.72 0.35-1.46
Anfo 1/83 (1.2) 1/96 (1) 1.16 0.07-18.8
ANTIFUNGAL THERAPY 0.27
Inadequate 26/83 (31.3) 23/96 (24) 1.45 0.75-2.8
Adequate 57/83 (68.7) 73/96 (76) 0.69 0.36-1.34
SEVERITY OF SEPSIS
Sepsis 37/113 (32.7) 49/108 (45.4) 0.59 0.34-1.02 0.054
Severe sepsis 42/113 (37.2) 48/108 (44.4) 0.74 0.43-1.27 0.27
Septic shock 34/113 (30.1) 11/108 (10.2) 3.8 1.81-7.97 0.0002
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Variable OR ( 95% CI) P value
Medical Ward 4.13 (1.67 – 10.19) 0.0020
Septic Shock 3.21 (1.18 – 8.74) 0.0221
TABLE 5. Multivariate analysis of risk factors for 30-days mortality in patients aged
over 75 years.
§ AUC (area under the ROC curve) = 0.701 (95% CI 0.61-0.78)
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