WHY, WHEN AND HOW?

1
WHY, WHEN AND HOW?
2
EARLY PRE-EMPTIVE THERAPY FOR HEMATOGENOUS
CANDIDIASIS
3
DISASTERS
4
CRUCIAL ELEMENTS IN AVOIDANCE OF DISASTERS

• High awareness
• Early recognition
• Knowledge on behavior of the offender
• Early treatment

5
CRUCIAL ELEMENTS IN AVOIDANCE OF DISASTERS

• High awareness
• Early recognition
• Knowledge on behavior of the offender
• Early treatment

6
ENEMY AMONGST US?
7
CRUCIAL ELEMENTS IN AVOIDANCE OF DISASTERS

• High awareness
• Early recognition
• Knowledge on behavior of the offender
• Early treatment

8
SCREEN THEM ALL?
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DIAGNOSTIC TESTS FOR INVASIVE CANDIDIASIS
culture histology
antigen antibody enolase mannan
PCR 1-3-ß-D-glucan
C-Reactive Protein (CRP), procalcitonin
(PCT), interleukin-6 (IL-6)
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RISK FACTORS FOR INVASIVE CANDIDIASISPhilips
1998, Uzun 2001, Mora-Duarte 2002
diabetes renal insufficiency
cvc hyperalimentation
hematol malignancy antibacterials
surgery immunosuppression
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COLONIZATION-INVASION
Initial situation integument damage
invasion
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CRUCIAL ELEMENTS IN AVOIDANCE OF DISASTERS

• High awareness
• Early recognition
• Knowledge on behavior of the offender
• Early treatment

13
RISK FACTORS FOR CANDIDA INFECTIONSEdwards jr JE
et al. Ann Intern Med 1978

• USE OF
• antibiotics
• immunosuppressants
• hyperalimentation
• polyethylene catheters
• prosthetic devices
• heroin
• ABDOMINAL SURGERY

I AM HERE TO HELP YOU!!!
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POST-OPERATIVE CANDIDEMIA RISK FACTORS AND
OUTCOME SOLOMKIN et al, Arch Surg 19821171272-5
antibacterials
51 complex abdominal surgery
i.v. nutrition
63 cases
66 damaged mucosa Candida colonization
42 deaths in hospital
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RISK FACTORS FOR INVASIVE CANDIDOSIS Rex Sobel
Clin Infect Dis 2001 321191

• Risk factor
  Cancer ICU
• Therapy-induced neutropenia
• GvHD, mucosal barrier injury
• Recurrent GI tract perforation (surgery)
• Candida colonization
• Broad-spectrum antibiotics
• Hemodialysis
• Central venous catheter
• Hyperalimentation
• Severity of illness
• Neonatal ICU (H2 blockers, intubation)
• Burns

Risk factor
Cancer ICU Therapy-induced
neutropenia GvHD, mucosal barrier
injury Recurrent GI tract perforation
(surgery) Candida colonization Broad-spectrum
antibiotics Hemodialysis Central venous
catheter Hyperalimentation Severity of
illness Neonatal ICU (H2 blockers,
intubation) Burns, diabetes mellitus
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COLONIZER OR AGGRESSIVE PATHOGEN?
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FACTORS ANNOUNCING OCCURRENCE OF INVASIVE CANDIDA
INFECTIONS
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RISK FACTOR SELECTION
Risk factors
Infection

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INVASIVE CANDIDIASIS AFTER COLONIZATION AND
BACTEREMIAGUIOT et al, Clin Infect Dis 1994
18525-32
53
81 patients
Bacteremia
46
35
YES
NO
20
INVASIVE CANDIDA INFECTIONS IN CRITICALLY ILL
SURGICAL PATIENTSNOLLA et al. ICAAC 2001,
Chicago. Abstr J-1628
Risk factors -prior antibacterials -repeated
surgery -Candida colonization
(non-albicans)
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DEVELOPMENT OF CRITERIA FOR PROPHYLAXIS OF
CANDIDIASIS IN THE ICU PAPHITOU et al. ICAAC,
SAN DIEGO 2002 Abstr M1239
Relative risks new dialysis
6 broad spectrum antibacterials
3 diabetes 3
7 invasive candidiasis 4 persisting fever
337 patients
Total parenteral nutrition diabetes
dialysis 26 invasive candidiasis (16 of all
candidoses)
TPN diabetes dialysis antibacterials 17
invasive candidiasis (50 of all candidoses)
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MODEL FOR INVASIVE CANDIDIASISBlijlevens,
Donnelly, De Pauw. Brit J Haematol 2002117259-64
antibiotics
injury
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OCCURRENCE OF CANDIDIASIS IN RELATION TO
NEUTROPENIAGoodrich et al. J Infect Dis 1991
164731-40
Hepatosplenic candidiasis
candidemia
bacteremia
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CRUCIAL ELEMENTS IN AVOIDANCE OF DISASTERS

• High awareness
• Early recognition
• Knowledge on behavior of the offender
• Early treatment

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INVESTMENT IN THE FUTURE
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TISSUE INVOLVEMENT IN RELATION TO DURATION OF
CANDIDEMIA IN BMT Goodrich et al. J Infect Dis
1991 164731-40
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MORTALITY OF CANDIDEMIA IN BMT Goodrich et al. J
Infect Dis 1991 164731-40
yes no
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RESPONSE RATES DEPENDING ON TIME OF INTERVENTION
Abele-Horn et al. Infection 1996 24426-32
74 51
Within 1 week after onset of symptoms More
than 1 week
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TIMING OF THE INTERVENTION
Peter Donnelly Ben dePauw
prophylaxis
empirical
pre-emptive
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PREVENTION
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PROPHYLAXIS WITH FLUCONAZOLEIN BONE MARROW
TRANSPLANTATIONGOODMAN et al. N.ENGL.J.MED 1992,
326 845
PLACEBO n 177
FLUCONAZOLE n 179
SYSTEMIC FUNGUS SYSTEMIC CANDIDIASIS SUPERFICIAL
FUNGUS SYSTEMIC AMPHO-B FATAL FUNGUS
3 0 8 56 1
16 10 33 66 6
32
FLUCONAZOLE 400 mg/day AS PROPHYLAXISIN LIVER
TRANSPLANT RECIPIENTSWINSTON et al.
Ann.Intern.Med. 1999131729-37
PLACEBO n 117
FLUCONAZOLE n 119
SYSTEMIC FUNGUS SUPERFICIAL FUNGUS COLONIZATIO
N OVERALL SURVIVAL FUNGAL DEATH RATE
6 4 70 --gt 28 11 2
23 28 60 --gt 90 14 13
C. glabrata prevalent species
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FLUCONAZOLE vs PLACEBO AS PROPHYLAXISAGAINST
CANDIDIASIS IN SURGICAL PATIENTS PELZ et al. Ann
Surg 2001 233542-8
PLACEBO n 130
FLUCONAZOLE n 130
SURGERY MEAN ICU DAYS PRE-EXISTENT CANDIDA
COLONIZATION CANDIDA INFECTIONS CANDIDEMIA DEAT
H OVERALL CANDIDA RELATED
91 1 78 9 0 11 n.a.
92 1 89 15 2 12 n.a.
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RESULTS OF CANDIDA PROPHYLAXIS IN ICU
PATIENTS Garbino et al, Intensive Care Med
2002281708-17
n 220 Fluconazole 100 mg/d Placebo
35
TOTAL INCIDENCE OF CANDIDEMIA IN US ICUS Trick
et al CID 2002 35 627-32.
NNIS data from 1116 ICUs/ 311 hospitals. From
data for 3,041,585 patients
Candidemia per 10,000 CVC days
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
year
1989
1990
91
92
93
94
95
96
97
98
1999
36
COLONIZATION-PROPHYLAXIS-INVASION
Initial situation prophylaxis
integument damage invasion
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EVOLVING CANDIDEMIAS IN US ICUS Trick et al CID
2002 35 627-32.
NNIS data from 1116 ICUs/ 311 hospitals. From
data for 3,041,585 patients
Candidemia per 10,000 CVC days
C. albicans
C. krusei
C. parapsilosis
C. tropicalis
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EMPIRICAL ????
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EARLY EMPIRICAL ANTIFUNGAL THERAPY IN FEBRILE
NEUTROPENICS EORTC. Am J Med 1989 86668-72
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THE BASIS FOR EMPIRICAL ANTIFUNGAL THERAPY IN
FEBRILE NEUTROPENICS PIZZO et al Am J Med 1982
72101-10
fungal infections
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IMPACT OF EARLY ANTIFUNGAL THERAPY IN FEBRILE
NEUTROPENICS PIZZO et al Am J Med 1982 72101-10
Persisting FUO and neutropenia (n50)
add 0.5 mg/kg/day amphotericin n18
continue n16
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6
fungal infections
4 candidiasis
no candidiasis
42
CANDIDATES FOR EARLY PROTECTION
Clinically ill Damaged gut epithelium Colonized
by Candida strains Neutropenic Central venous
line Receiving antibacterials No
prophylaxis Diabetes mellitus Recent
corticosteroids
43
EMPIRICAL