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Roberto Luzzati
SC Malattie Infettive,
Ospedale Maggiore, Trieste
Le Infezioni Fungine in Medicina Interna
Strollo S & NIH, E.I.D. 2017
Strollo S, E I D 2017
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)
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)
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
Pathogenesis of Invasive Candidiasis.
Kullberg BJ, Arendrup MC. N Engl J Med 2015;373:1445-1456
Risk Factors for Invasive Candidiasis.
Kullberg BJ, Arendrup MC. N Engl J Med 2015;373:1445-1456
EJIM 2017
EJIM 2017
EJIM 2017
EJIM 2017
EJIM 2017
Int J Clin Pract 2018
Int J Clin Pract 2018
+ 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
Infection 2018
Infection 2018
Infection 2018
Diagn Microb Infect Dis 2019
Diagn Microb Infect Dis 2019
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
Infection 2016
Distribution of candidemia episodes (# 686)
according to hospital wards
21%
25%54%
2011-2013: 686 adult patients (52% males); mean age 70 + 15 yrs
Severe sepsis and septic shock presentation, and
mortality, according to hospitalization area
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
Infection 2016
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
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
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.
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.
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
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
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)
Recommended