update on antigen detection paul e. verweij, md nijmegen university center for infectious diseases s...
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Update on Antigen Detection
Paul E. Verweij, MDNijmegen University Center for
Infectious Diseases
sEukaryotic cell 2005;4:1308-16
Background
Sandwich ELISA
Detects galactofuranosyl antigen
Detection limit 1 ng/ml
Early marker of invasive aspergillosis
Variable performance reported
Factors affecting performance
Combining surrogate markers
Clinical evaluation
1
2
3
Bifidobacteria
Cross reacting lipoglycans in Gram positive cell wall
Lipoglycans containing a -1,5-galactofuranosyl chain
JCM 2005;43:3925-31
1
Bifidobacteria: reactivity with GM-ELISA
JCM 2005;43:3925-31
Measured in faeces neonates 200 – 36,320
Reactivity in faeces
JCM 2005;43:3925-31
GM and –lactam agents (31 batches analysed)
JCM 2005;43:5214-20
May 2003 – November 2004
1
GM and –lactam agents: impact on patient management
No IA
24
Possible IA
11
probable IA
0
befo
re afte
r
No IA
0
Possible IA
24
probable IA
11
Antifungal therapy
AMX based therapy 5/13
PTZ 18/22
JCM 2005;43:5214-20
J Infect Dis 2004;190:641-9
AML, MDS
Receiving antifungal prophylaxisEffect of exposure to
mould-active antifungals1
Comparative release of surrogate markers in vitro
0
5000
10000
15000
20000
25000
30000
0 2 4 6 8 10 12 14 16 18 24 32 40
time (h)
GM
0
10000
20000
30000
40000
50000
60000
70000
BG GM
BG
- - - - - - - - -- - - - -PCR
Mennink et al, submitted
2
050
100150200250300350400
15/7
22/ 7
29/ 7
19/8 6/
913
/923
/ 94/
1015
/10
11/1
1
29/ 1
1
0
2
4
6
8
10
12
14
BG
GM
GM and BG
ITZ VCZ
JCM 2005;43:5097-5101
GM and PCR
Gm positive samples
Clinical evaluation of diagnostic procedures: CT vs GM
Patients: allo HSCT (65), autol HSCT (30), chemotherapy (66)Prophylaxis: fluconazole
161 episodes in 107 patients
Weekly CT scan, twice weekly GM
CT: major sign (halo, cresent, cavity)minor sign (all other infiltrates)
GM: 0.5 in 2 consecutive samples
CID 2005;41:1143-9
3
No infiltrates
minor major GM+
No IA(109)
76 33 0 20
Possible(32)
3 26 3 21
Probl/prov(20)
1 11 8 16
CT scan
CID 2005;41:1143-9
PTZ
Factors associated with positive GM
CID 2005;41:1143-9
…the decision to administer mould-active treatment should be based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM….
CID 2005;41:1143-9
CT+ CT-
IA+ 8 12
IA- 0 109
GM+ GM-
IA+ 16 4
IA- 20 89
CT
GM
Sensitivity: 40%Specificity: 100%
Sensitivity: 80%Specificity: 81%
Performance
CID 2005;41:1242-50
3
Pre-emptive strategy
88 hematology patients (136 episodes, 4170 samples)
Febrile neutropenia group (117 episodes) ->
9 were treated with AmBisome
41 episodes qualified for empiric
therapy
reduction in use antifungals: 35% to
7.7%
10 non-febrile episodes of febrile episodes with
alternative explanation received antifungal therapyCID 2005;41:1242-50
Pre-emptive strategy
Breakthrough fungal infections:
C. glabrata fungemias (blood culture) – 2 cases
Disseminated zygomycoses – 1 case
CID 2005;41:1242-50
Conclusions
Increased insight in factors that are important for the performance of GM detection
Studies should focus on comparison of markers and on management strategies that incorporate surrogate markers
Differences in performance remains an important problem