The document summarizes key points about invasive fungal infections: 1) It reviews different types of invasive fungi like Candida and Aspergillus species and how their local epidemiology is changing. 2) It discusses risk factors for invasive fungal infections in high risk groups like ICU patients, transplant recipients, and those taking biologics. 3) It describes the clinical manifestations of common fungal infections including candidemia, hepatosplenic candidiasis, aspergillosis, and their associated mortality rates.

1. ‫اللهم إني أستغفرك لكل ذنب‬
‫.. خطوت إليه برجلي .. أو مددت‬
‫إليه يدي‬
‫.. أو تأملته ببصري .. أو أصغيت إليه‬
‫إلي‬
‫بأذني‬

4. Invasive Fungal
Infections Management
Updates
Ahmed Saad MD. FACP.
Ass Prof .Cairo university

5. Review
• Different types of Invasive fungi
• Changing local epidemiology
• Risk factors
• Clinical picture
• Diagnosis
• Treatment & prophylaxis

6. Incidence of Systemic Infections:
Bacterial vs Fungal
225,000
No. of Cases of Sepsis
150,000
Gram-positive bacteria
Gram-negative bacteria
Fungi
75,000
25,000
15,000
10,000
5000
0
1991 1993 1995 1997 1999 2001
Year
Martin GS, et al. N Engl J Med. 2003;348(16):1546-1554.

7. Nosocomial Bloodstream Infections in
US Hospitals: 1995-2002
CoNS, coagulase-negative staphylococci; BSI, blood stream infection.
Surveillance and Control of Pathogens of Epidemiological Importance (SCOPE) study.
Wisplinghoff H, et al. Clin Infect Dis. 2004;39:309-317.

9. Invasive Candidiasis
Mortality Associated with Candidemia
45
40
35
40%
Percent of Patients
30
25
20
25%
15
10
5
0
Patients with Patients with bacterial
candidal bloodstream (non-candidal)
infections bloodstream infections
Adapted from Edmond MB et al Clin Infect Dis 1999;29:239–244.
9

10. Impact of delayed treatment on mortality
Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of Candida bloodstream infection until positive blood
culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 2005;49: 3640–5.

11. Epidemiology of Invasive Mycosis
Pfaller & Diekema, 2007, Clin. Micro. Rev. 20:133-163

12. Review
• Different types of Invasive fungi
• Changing epidemiology
• Clinical picture
• Risk factors
• Diagnosis
• Treatment & prophylaxis

13. Infections Caused by Non-albicans Candida
Are Increasing
100
90
80 C. krusei
70 C. parapsilosis
60 C. tropicalis
50 C. glabrata
40 C. albicans
30 Other
20
10
0
1997-1998 1999 2000 2001 2002 2003
Neither C. glabrata nor C. krusei showed a consistent increase or decrease in isolation rates overall
Increased rates of isolation of C. tropicalis (4.2% to 7.5% increase) and C. parapsilosis (4.6% to 7.3% increase)
over 134,000 consecutive isolates of Candida from cases of invasive candidiasis at 127 medical centers
Pfaller MA, et al. Clin Microbiol Rev. 2007;20(1):133-163.

14. Candida Species:
Incidence vs Mortality
Incidence of Candida albicans, 45.6%; incidence of non-albicans Candida, 54.4%*
%
Candida Species
*This study is based on data for the 2019 patients (pediatric and adult) enrolled from July 1, 2004 through March 5, 2008 from 23
North American centers who received a diagnosis of proven candidemia, including 2.1% other non-albicans Candida [C. lusitaniae,
C. dubliniensis, C. guilliermondii, other (not specified), and unknown].
Horn DL, et al. Clin Infect Dis. 2009;48(12):1695-1703.

15. Incidence of Fungal Infections after
SOT
Invasive Fungal
Aspergillus Candida
Infections
Kidney &
liver
1.4–14% 0–10% 90–100%
Heart 5–20% 77–91% 8–23%
Lungs/Heart-
Lungs
15–35% 25–50% 43–72%
Small
Intestine
40–59% 0–3.6% 80–100%
bardi S. et al. Transplant Int 2007;20:993–1015, Singh N. Clin Infect Dis 2000:31;545–53.

16. Invasive Aspergillose : Mortality
Denning DW Paterson DL, Singh Lin QY
Clin Infect N Clin Infect
Dis Medicine Dis
till 1995 1987-1997 1995-1999
Bone marrow 90 % 92 % 86.7 %
AIDS/HIV 81 % - 85.7 %
Liver transplant. 93 % 87 % 67.6 %
Kidney transplant. 70 % 75 % 62.5 %
Lung Transplant. 77 % 55 % 62.5 %
Heart transplant. 50 % 78 % 43.6 %
Pancreas
100 % -
transplant

18. Review
• Different types of Invasive fungi
• Our local data
• Clinical picture
• Risk factors
• Diagnosis
• Treatment & prophylaxis

19. Our local data For Candida
fungogram for Candida Isolates (In-patient) March 2011- June 2012
Candida Candida Candida Candica Candica Candida Candida
Albicans Tropicalis Glabrata Parapsilosis Krusei Lusitaniae Dubliniensis
No. of Isolates 73 23 7 5 2 1 5
Caspufugen 100 100 100 100 100 100 100
Amphotericin B 96 98 100 100 100 100 100
Flucytosine 97 100 100 100 50 100 66
Fluconazole 97 89 66 100 0 100 100
Voriconazole 100 100 66 100 100 100 100
Caspofungin 100 100 100 100 100 100 100

20. Dr Erfan & Bagedo Hospital Data
2010
sample Candida Candida Candida Candida Candida
Parapsil Albicans Tropicalis Glabrata Krusie
iosis
Blood 8 6 6 1 1
BAL 9 1
Sputum 4
Urine 1 1
• Aspergillus +ve in 3 sputum samples & 24 environmental

21. No of Candidal isolates
(115) in 18 monthes
Candida albicans
63.5%
Candida dublinensis
4.3%
Candida krusei
1.7%
Candida parapsilosis
4.3%
Candida glabrata
6.1%
Candida tropicalis
20.0%

22. Am
0
20
40
60
80
100
120
ph
o te
ric
in
B
Fl
uc
yt
o si
ne
Fl
uc
on
a zo
le
Vo
r ic
on
az
ol
e
C
as
po
fu
ng
Candida Albicans
in

23. 0
Am
20
40
60
80
100
120
ph
ot
er
ic i
n
B
Fl
uc
yt
os
in
e
Fl
u co
na
zo
le
Vo
ric
on
az
ol
e
Ca
sp
of
u ng
in
Candida tropicalis

24. Am
0
20
40
60
80
100
120
ph
o te
ric
in
B
Fl
uc
yt
os
in
e
Fl
uc
on
az
ol
e
Vo
ric
on
az
ol
e
C
as
po
fu
ng
in
Candida Glabrata

25. Am
0
20
40
60
80
100
120
ph
ot
er
ic
in
B
Fl
uc
yt
o si
ne
Fl
uc
on
az
ol
e
Vo
ric
on
az
ol
e
C
as
po
fu
ng
in
Candida parapsislosis

26. Am
20
40
60
80
0
100
120
ph
ot
er
ici
n
B
Fl
uc
yt
os
in
e
Fl
uc
on
az
ol
e
Vo
ric
on
az
ol
e
Ca
sp
of
un
gi
n
Candida Krusei

27. Am
0
20
40
60
80
100
120
ph
o te
ri c
in
B
Fl
uc
yt
os
in
e
Fl
uc
on
az
o le
Vo
ric
on
az
o le
C
as
po
fu
ng
in
Candida Dubliniensis

28. Review
• Different types of Invasive fungi
• Epidemiology
• Risk factors
• Clinical picture
• Diagnosis
• Treatment & prophylaxis

29. Risk Factors for Invasive Candidiasis In
ICU
∀ ≥3 antibiotics • Neutropenia
• Antibiotics ≥4 d • Immunosuppression
• Time ≥4 d in ICU • Concomitant infection
• Mechanical vent >48 • Diabetes mellitus
• Major Abd surgery • Candida coloniz ≥2 sites
• Candiduria (>100,000
• CVP
colonies)
• TPN
Pappas PG et al. Clin Infect Dis 2004;38:161-189;
Ostrosky-Zeichner L et al. Crit Care Med 2006;34:857-63

30. Invasive Aspergillosis: Risk factors Post
liver transplant
Early IA
< 3 months p
OR (95% CI)
4.9
Renal failure after SOT < 0.0001
(2.4 -9.8)
Hemodialysis after SOT 3.2 0.014
(1.3 - 8.1)
> 1 episode of bacterial 3.2 < 0.006
infection (3.2 - 17.4)
CMV disease 2.3 < 0.029
(1.1 - 4.9)
Reintervention is also risk factor
Gavaldà J et al, Clin Inf Dis 2005; 41:52-9

31. Risk factors of IA after Renal
transplantation
• High doses or prolonged duration of corticosteroids
• Graft failure requiring Hemodialysis
• Potent immunosuppressive therapy for rejection
Singh N et al, Am J Transplant 2009, 9, S180-S191 .

32. Risk factors of IA after Heart
transplantation
• Isolation of Aspergillus from respiratory tract cultures
• Reintervention
• CMV disease
• Hemodialysis
Munoz P et al, Curr Opin Infect Dis 2006; 19: 365-370
Singh N et al, Am J Transplant 2009, 9, S180-S191 .

33. Fungal Infection Post Biologics

34. Fungal Infection Post Biologics

35. Fungal Infection Post Biologics
• Till 2007 ,281 reports of invasive fungal infections (IFIs)
associated with the 3 anti-TNF- alpha agents, ie,
infliximab, etanercept, and adalimumab
• 226 (80%) were associated with infliximab, 44 (16%)
with etanercept, and 11 (4%) with adalimumab
• Histoplasmosis (n=84 [30%]), candidiasis (n=64 [23%]),
and aspergillosis (n equals 64 [23%]).
• Infl iximab induces apoptosis memory T cells, whereas
etanercept is antiapoptotic

36. Review
• Different types of Invasive fungi
• Epidemiology
• Clinical picture
• Risk factors
• Diagnosis
• Treatment & prophylaxis

37. SPECTRUM OF INVASIVE
CANDIDA INFECTIONS
organ infection
candidemia
acute ‘hepato-
candidemia disseminated splenic’
candidiasis candidiasis

38. Candida: Infection sites
C. parapsilosis
C. parapsilosis C. tropicalis
C. tropicalis
C. albicans
C. albicans
C. krusei
C. krusei
C. glabrata
C. glabrata

39. Candida: Hepatosplenic
candidiasis
FEVER
FEVER
ALKALINE PHOSPHATASE
ALKALINE PHOSPHATASE
NEUTROPHILS
NEUTROPHILS
DISSEMINATION MICROCOLONIES ‘BULLS EYE’
DISSEMINATION MICROCOLONIES ‘BULLS EYE’

41. Renal candidiasis

42. Esophageal Candidiasis
Baseline After caspofungin
Courtesy of John Rex, MD

43. Candida Retinitis

44. Candida Endocarditis

46. Interaction of Aspergillus with the host
A unique microbial-host interaction
Frequency of aspergillosis
Frequency of aspergillosis
Acute IA
ABPA
Allergic sinusitis
Subacute IA
Aspergilloma
Chronic cavitary
Chronic fibrosing
Immune dysfunction Immune hyperactivity
. www.aspergillus.man.ac.uk
www.aspergillus.man.ac.uk

47. Timeframes
IPA days/1-4 weeks
Subacute IPA weeks/2-3 months
CCPA months/years
Aspergilloma months/years

48. Aspergilloma
Patient RT
December 2002
Cough (mild) &
tired
Wythenshawe Hospital

49. Aspergilloma – may be mobile in the cavity
Upright Prone
Severo on www.aspergillus.man.ac.uk

50. Aspergilloma
Severo on www.aspergillus.man.ac.uk

51. Fungal Sinusitis

52. Fungal Sinusitis

53. Aspergillus Endocarditis

54. Zygomycosis in SOT
• Rhinocerebral form
• 76% diabetes and corticosteroids
• 56% mortality

55. Review
• Different types of Invasive fungi
• Epidemiology
• Clinical picture
• Risk factors
• Diagnosis
• Treatment & prophylaxis

57. Invasive aspergillosis diagnosis
• Radiology: chest X-ray and CT
• Microbiology
– Respiratory secretions: BAL/biopsy
• Direct microscopy
• culture
• PCR
Ergin et al. Transplant International 2003; 16: 280-286

58. IA in solid-organ transplant
recipients

59. Diagnosis of Pulmonary Aspergillosis
•Pulmonary Infection
– Peripheral infiltrates
– "halo" sign on chest CT scan
– Broncho-alveolar lavage ++
• Direct exam, Culture, Ag, PCR
Halo sign ??

60. Fungal Pneumonia

61. Serology
• 1,3-,D-glucan is a component of fungal
cell walls that can be detected by serology
• One way to effectively use the 1,3-,D-glucan
or galactomannan assays may be to serially
screen patients who are at high risk for IFIs
and/or use them to monitor response to
therapy .

62. Review
• Different types of Invasive fungi
• Epidemiology
• Clinical picture
• Risk factors
• Diagnosis
• Treatment & prophylaxis

63. Antifungal Agents

65. Cell Membrane Active Antifungals
Cell membrane
• Polyene antibiotics
- Amphotericin B, lipid
formulations
• Azole antifungals
- Ketoconazole
- Itraconazole
- Fluconazole
- Voriconazole
-Posaconazole

66. DNA/RNA synthesis Inhibitors
Cell membrane
• Polyene antibiotics
• Azole antifungals
DNA/RNA synthesis
• Pyrimidine analogues
- Flucytosine
Cell wall
• Echinocandins
-Caspofungin acetate
(Cancidas)

67. Cell Wall Active Antifungals
Cell membrane
• Polyene antibiotics
• Azole antifungals
DNA/RNA synthesis
• Pyrimidine analogues
- Flucytosine
Cell wall
• Echinocandins
-Caspofungin acetate
- micafungin
Atlas of fungal Infections, Richard Diamond Ed. 1999
Introduction to Medical Mycology. Merck and Co. 2001

68. Amphotericin B (Fungizone™)
• Binds ergosterols in fungal cell membrane forming pores
in the membrane & interferes with permeability and
transport functions.
• Broad spectrum antifungal
• Lipid formulations facilitate drug insertion within the
fungal cytoplasmic membrane while reducing uptake in
human cells, so limiting toxicity.

69. Lipid Amphotericin B Formulations
Abelcet ® ABLC Ambisome ® L-AMB
Amphotec ABCD ®
Ribbon-like particles Disk-like particles Unilaminar liposome
Carrier lipids: DMPC, Carrier lipids: Cholesteryl Carrier lipids: HSPC,
DMPG sulfate DSPG, cholesterol(1:9)
(1:1) Particle size (µm): 0.12- Particle size (µm) : 0.08
Particle size (µm): 1.6- 0.14
11
DMPC-Dimyristoyl phospitidylcholineHSPC-Hydrogenated soy phosphatidylcholine
DMPG- Dimyristoyl phospitidylcglycerol
DSPG-Distearoyl phosphitidylcholine

70. Lipid AMB Formulations-
Summary
• Efficacy
– Lipid formulation > AMB-deoxy
• Nephrotoxicity
– L-AMB < ABLC < ABCD << AMB-deoxy
• Infusion related toxicity
– L-AMB < ABLC < ABCD < AMB-deoxy
• Product cost (AWP)
– L-AMB > ABLC > ABCD > AMB-deoxy

71. Amphotericin B - Nephrotoxicity
• Renovascular and tubular mechanisms
– Vascular-(decrease in renal blood flow) leading to drop
in GFR, azotemia
– Tubular-distal tubular ischemia, wasting of potassium,
sodium, and magnesium
• Sodium loading-> blunt the vasoconstriction and
tubular-glomerular feedback
– Administration of 500 ml of NaCl before and after
amphotericin B infusion

72. Azole Antifungals for Systemic
Infections
• Itraconazole (Sporanox)
• Fluconazole (Diflucan) Triazoles (3N)
• Voriconazole (Vfend)
“2nd generation
triazole”
Fluconazole Ketoconazole

73. Azoles - Mechanism
• Azoles bind to (fungal P450 enzymes)
lanosterol 14α-demethylase inhibiting
the production of ergosterol
– Some cross-reactivity is seen with
mammalian cytochrome p450
enzymes
• Drug Interactions
• Impairment of steroidneogenesis
(ketoconazole, itraconazole)

74. Fluconazole
Advantages Disadvantages
• Well tolerated • Fungistatic
• IV/PO formulations • Resistance is
• Favorable increasing
pharmacokinetics • Narrow spectrum
• Good activity against • (Drug interactions)
C. albicans and • Not in biofilm
Cryptococcus

75. Key Biopharmaceutical Characteristics of
the Triazole Antifungals
Fluconazole Voriconazole
Spectrum vs. C. albicans, C. tropicalis +/- Broad, includes most
Candida and Candida spp.,
Aspergillus No Aspergillus Aspergillus, Fusarium
sp. Not Zygomycoses
Oral formulation Tablet (>90%) Tablet (>90%)
(% bioavailibility)
Intravenous Available, no solubilizer Available, cyclodextrin
formulation
R.E. Lewis 2002. Exp Opin Pharmacother 3:1039-57.

76. Voriconazole –Dose & Side Effects
• Dose 6mg/kg 1st day 6mg/kg bid then 4mg/kg
bid
• Visual disturbances (~ 30%)
– Decreased vision, photophobia, altered color
perception and ocular discomfort
– IV > oral
– No evidence of structural damage to retina

77. The Fungal Cell Wall
mannoproteins
Echinocandins inhibition
of ß-(1,3)glucan synthase
osmotic fragility
β1,3
β1,6
glucans
Cell β1,3 glucan chitin
membrane synthase
ergosterol
Atlas of fungal Infections, Richard Diamond Ed. 1999
Introduction to Medical Mycology. Merck and Co. 2001

78. Echinocandins - spectrum
Highly active Very active
Candida albicans, Candida parapsilosis
Candida gulliermondii
Candida glabrata, Aspergillus fumigatus
Candida tropicalis, Aspergillus flavus
Candida krusei
Low MIC ,with Low MIC, but without fungicidal
fungicidal activity and activity in most instances.
good in-vivo

79. Echinocandins
Caspofungin Micafungin Anidulafungin
Absorption Not orally absorbed. IV only
Metabolism spontaneous degradation, Chemical degradated
hydrolysis and N-acetylation Not hepatically
metabolized
Elimination Limited urinary excretion. Not dialyzable
Half-life 9-23 hours 11-21 hours 26.5 hours
Dose 70 mg IV on day 100 mg IV 200 mg IV on day 1,
1, then 50 mg IV once daily then 100 mg IV
daily thereafter daily thereafter
Dose Child-Pugh B None None
Adjustment 70 mg IV on day 1,
then 35 mg IV daily
thereafter

86. Review
• Different types of Invasive fungi
• Changing epidemiology
• Risk factors
• Clinical picture
• Diagnosis
• Treatment &prophylaxis
• Updated guidelines

87. Candidemia
• If species is unknown, either fluconazole (800mg loading dose, 400 mg
daily) or an echinocandin is appropriate initial therapy for most adult
patients (AI)
• An echinocandin is favored if
– Moderately severe to severe illness.
– Recent azole use for treatment or prophylaxis (AIII), or
– Isolate is known to be C. glabrata or C. krusei (BIII)
• Fluconazole for patients who are
– less critically ill and
– who have no recent azole exposure (AIII).
• Remove or exchange intravenous catheters
• Treat for two weeks after clearance of bloodstream
IDSA Guidelines 2010.

88. Treatment options
of blood candidal infections in adults
Treatment options of invasive fungal infections in adults 2010

89. Candidemia: catheter removal
• Removal of central venous line
– is a consensus recommendation for the
non-hematological patients II A
- in hematology patients the quality of
evidence is lower IIIB
- removal is always recommended when
C parapsilosis is isolated II A
IDSA Guidelines 2010.

90. Duration of antifungal therapy in
candidemia : recommendations
Non-neutropenic adults: at least 14 days after the last +ve
blood culture and resolution of signs and symptoms : III B
Neutropenic patients: at least 14 days after the last +ve
blood culture and resolution of signs and symptoms and
resolved neutropenia: III C
IDSA Guidilines 2010.

91. Invasive pulmonary aspergillosis :1st line
Agent Grade Comments
Voriconazole IA 2 x 6 mg/kg D1 then 4 mg/kg BID
Ambisome IB 3 – 5 mg/kg
Caspofungin IC
Amphotericin B ID
IDSA Guidelines 2010.

92. Treatment options
of aspergillus infections
Treatment options of invasive fungal infections in adults 2010

93. Aspergillosis
• Surgery (CIII) in case of
– Lesion near to a large vessel
– Hemoptysis from a single lesion
(embolization is an alternative)
– Localized extrapulmonary lesion including
central nervous system lesion
– Fungal sinusitis

94. Timing of Intervention
Directed
infection Empiric
specific symptom
Pre-emptive
refractory fever
Prophylactic
nonspecific symptom ± early markers
suppressive Rx
basic disease
Progression

95. Different antifungal strategies for treatment in invasive fungal
infections based on diagnostic stage.
Prophylactic treatment preventive administration of an antifungal agent to patients at risk of IFI
without attributable signs and symptoms.
Empiric treatment is defined as the initiation of antifungal treatment in patients at high risk of IFIs
and established clinical signs and symptoms, but without microbiological documentation.
Preemptive therapy aims to treat a suspected early IFI but uses radiologic studies, laboratory
markers, applied when the decision of treatment is based on early diagnostic test. (Radiographic
imaging,( Halo sign, air crescent) Serology: Galactomannan B-D-Glucan, histopathology
Targeted therapy needs a pathogen identification to be defined.
1.Zaragoza R et al. Therapeutics and Clinical Risk Management 2008:4(6) 1261–1280.

96. Treatment of Suspected Invasive
Candidiasis (Definitions)
• Prophylactic therapy: given to everyone in a given class (ex.
BMT patients who are at very high risk for IC).
• Preemptive therapy: patients at risk are monitored closely
and therapy is initiated with early evidence suggesting infection
(ex. positive Candida cultures at non-sterile sites, clinical
suspicion) to prevent disease.
• Empirical therapy: (ex. therapy is started because a cancer
patient has remained febrile after 4days of broad-spectrum
antibiotics).
• Directed therapy: is based on a clinical or laboratory finding
indicating that an infection is present (ex. positive blood culture
for Candida species).

97. Empirical antifungal treatment in ICU
Clinical Prediction Rule (CPR)
• All of
– [(day 1–3 of ICU stay): mechanical ventilation,
– broad spectrum antibiotics
– And central venous catheter CVC
• And ONE of
– TPN (total parentral neutrition) (d1-3)
– Dialysis (d1-3)
– Major surgery (d-7-0),
– Pancreatitis (d-7-0),
– Steroids (d-7-3),
– Other immunosuppressive agents (d-7-0)].
sensitivity of 90%, a specificity of 48%
Ostrosky-Zeichner L, et al. 2007. Eur J Clin Microbiol Infect Dis, 26:271–6.
Ostrosky-Zeichner L, et al. Mycoses. 2011 Jan;54

98. Empirical antifungal treatment in ICU
The Candida Score
• Parenteral nutrition ................................................. (+1)
• Prior surgery ............................................................ (+1)
• Multifocal Candida colonization *........................... (+1)
• Severe sepsis ........................................................... (+2)
The authors concluded that a “Candida score” of 2.5 could accurately
select patients who would benefit from early antifungal treatment
Leon C, et al. 2006. Crit Care Med, 34:730–7.
Leon C, et al. 2009 Crit Care Med 37:1624–1633.

99. Prophylaxis of high-risk patients after Liver
transplantation
(Recommendations of the AST Infectious disease Community of Practice)
• Lipid formulation of AmB (II 2)
– 3-5 mg/kg/day
• Or an Echinocandin (II 3)
• Duration 3-4 weeks or until resolution of risk
factors
Singh N et al, Am J Transplant 2009, 9, S180-S191 .

100. Prophylaxis for high-risk patients after Lung
transplantation (recommendations of the AST Infectious disease Community of
Practice)
• Inhaled lipid formulations of amphotericin B
– Nebulized L-AmB
• 25 mg three times per week x 2 months
• In high-risk patients
– Voriconazole* : 400 mg/day x 4 months
Singh N et al, Am J Transplant 2009, 9, S180-S191 .

101. Prophylaxis for high-risk patients after Heart
transplantation
(Recommendations of the AST Infectious disease Community of Practice)
• Voriconazole
– 200mg BID for 50-150 days
Singh N et al, Am J Transplant 2009, 9, S180-S191 .

102. Fluconazole Prophylaxis: ? Pre Emptive Approach
HCT & AML Monitor with Serum galactomannan Thrice wkly
Antifungal use if Asp GM x consecutive 2 positive •
CT abnorm & BAL (+) Aspergillus •
antifungal use reduced by 78%
Survival with IFI, 64%
Maertens J et al, Clin Infect Dis 2005;41:1242

103. Antifungal prophylaxis in
haematology patients
CLINICAL MICROBIOLOGY AND INFECTION April 2012
3rd European Conference on Infections in Leukaemia (ECIL-3)