???????(IFI)?????

1
???????(IFI)?????
???????????(IPFI)
2

• IFI?IPFI?????
• IPFI??????
• IPFI?????
• IPFI???
• ???????IPFI????

3
???????(Invasive fungal infection,IFI)?????

• IFI??????????????????,????????????????
  IFI????????????
• IFI????IFI????IFI ???IFI
• ???????,????????(IC)???????(IA)??
• ?????????,?????????????????,??????????(invasive
  pulmonary fungal infections, IPFI)

4
IFI ???
IC????IA?,19962002???????,?2003?????IA?????????
???(?100,000?)
?
??IC?IA??????
NHDS http//www.cdc.gov/nchs/
5
IFI ???
IC???????????,?IA????????
1991?2003???IC?IA????????
Christopher Kibbler. Building Successful
Strategies to Manage Invasive Fungal Infections.
17th European Congress of Clinical Microbiology
and Infectious Diseases and 25th International
Congress of Chemotherapy(NHDS multiple-cause-of-de
ath data from public use files http//www.cdc.gov
/nchs/)
6
IFI??

• ?ICU?????????????
• ??????????
• ??????????????????????????5?21,68????????
• ?????21,?????????26???????????????????

?? ??? ?????????????????????????   2006?
7
IPFI?????
19881997? ???????????
19861998? ????????
20022006? ?????????????
????IPFI???,???????????????????????????????????
??,??????????????????????,2007,20(3)225-229
8
IC?IA???

• IC
• ???????????????,??????????????????????????????????
  ?
• ????????????,??4?,?????
• ???????????,??????????????,??????

• IA
• ????????,????????????????????
• ????????7090
• ????????????????????,????40??????????????????????
  30,?????6090

??,????????????,??????,2005,85(21)1443-1444
9
??????????
????????????1997??????,???????2003?,??????????????
??
M. A. Pfaller, D. J. Diekema, D. L. Gibbs,et al.
Journal of Clinical Microbiology,
2007,45(6)17351745
10
??????????????
???????????????????????
???????????????5????????????????????????????????,
2007 ,7(1)14-18
11
??????
ARTEMIS DISK Surveillance Program ????????????????
???S(??)17 mm SDD(???????)1416 mm R(??)13
mm? ????????P450??Flu?,????????????
Pfaller. J Clin Microbiol 2007
12
??????????????
?????315????????????
Messer et al. J Clin Microbiol 2006
44324326 Pfaller et al. J Clin Microbiol 2005
4354255427
13
??????????

• ?2002??,?81??????????,?10???????????????4????????
  ????????
• 2000??????900?????????????,?????????????2??,2005
  ???????????,10?????????????????
• ???????????????,??????????

Paul E. Verweij, The New Engl and Journal of
Medicine. 35614(2007) 1481-1483G. Chamilos,
D.P. Kontoyiannis. Drug Resistance Updates 8
(2005) 344358
14
? ?

• ???IC????????????,?IA?????????????,IC?????????,???
  ?IC?????
• ????????????,?????????????????????,??????????????
  ??
• ???????????,????????,????
• ????????????????

15

• IFI?IPFI?????
• IPFI??????
• IPFI?????
• IPFI???
• ???????IPFI????

16
IPFI??

• IPFI?? ???????????????,????????????????,?????????
  ???????,??????????,????????????
• IPFI?? ???????

???????????. ???????????????????(??) J .
??????, 2006, 45 (8) 697-701.
17
IPFI????
2002?EORTC??
2007????????????????
?????? ???? ???? ?????
??
???? -
?? - -
?? - -
?????? ???? ???? ?????
??
???? -
?? - -
???????????????????????????,???????????
??IPFI?3???,???(Proven)?????(Probable)???(Possible
)
???????????. ???????????????????(??) J .
??????, 2006, 45 (8) 697-701 Clin Infect Dis
2002 34 7-14 ??????????????????????? 2007?
18
???????
???? ???????
?????????? ??(GM??) ???????,??? gt 85,?????????(50100)
1, 3-ß-D-????? ??(G??) ????????IFI??,????63,????96???????????,????90.9,????100
??DNA?PCR ??(??????????????) PCR ????????,????????5070
???, ???. ??????????????. ????????,2007,6(5)359-3
64 Senn L et al. Clin Infect Dis.
200846878-885
19
GM EIA?qPCR??IPA
GM EIA?qPCR????IPA???????????
Benjamin Musher, et al. Journal of Clinical
Microbiology, 2004, 42(12)55175522.
20

• IFI?IPFI?????
• IPFI??????
• IPFI?????
• IPFI???
• ???????IPFI????

21
IFI????

• ????
• ?????0.5109/L,??10d
• ????????????????gt4d
• ??gt38??lt36?,?????????
• ?60d ????????gt10d
• ?30d ???????
• ??????????
• AIDS
• ????????????,????3 ?

• ????
• ?????lt0.1109/L,??3 ?
• ?????lt0.5109/L,??5 ?
• ????????
• ???????????????????,????????????,????gt1mg/kg??????
  lt0.1109/L,??1 ?,????gt2mg/kg ??gt2 ?
• ??????

????, ??????????????????. ????????,
2007,5(1)7-11 Clin Infect Dis 2002 34 7-14
22
IA????
IA ??????????Logistic????
?????? ?????? ??IA?? ??IA??
OR (95????) P OR (95????) P
??????B????? 31.4 (12.181.9) 0.001 27.8 (6.7109.7) 0.001
???? 2.7 (1.26.9) 0.01 3.3 (1.111) 0.04
???? 0.2 (0.10.6) 0.006 0.191 (0.0460.789) 0.02
Juan José Castón,et al. Chest 2007131230-236
23
IC????
???? ?????????
??????? ??????
??????? ????
?? ????
?? ????
???? ????
??????? ??????
???? ?????
???? ??????
?????? ??????????
??????? (lt500/mm3) ????
????(???) ???????????
???? ????
?????/?? ?????????
???? ????
????/ICU?? ?????
??????? ??????????
M. A. Pfaller, D. J. Diekema. Clinical
Microbiology Reviews, 2007,20(1) 133163
???????
24
??????

• Wenzel ???4????????(????????????
  ??Hickman???????)???ICU??1?2.5?5?????????,????L
  ogistic????,?????????????????????
• Leon?????????( Candida score )???ICU???????????
  ???2?,????1?,??????1?,?????????1????2.5???,??????gt
  2.5????????? 2.5 ????7.75???????????????81?74?

M. A. Pfaller, D. J. Diekema. Clinical
Microbiology Reviews, 2007,20(1) 133163
25
IPFI????
44 ?COPD ?????????????Logistic ???????
?? ?2 P OR? OR?95CI
???? 9.090 0.003 8.333 2.10033.067
????? 7.027 0.008 3.513 1.3878.895
??? 6.475 0.011 1.765 1.76579.714
??????? 4.811 0.028 2.684 1.1116.484
?????? 0.037 0.848 1.080 0.4932.364
???? 0.291 0.590 0.450 0.4501.574
????????????????????????????COPD ???????????
???,????????????????????????????,????????,2005,25(
6)516-517
26
? ?

• IPFI???????????????,????????????????,?????????????
  ???
• ?????4?????????????????????????
• ??IPFI?3???,???????????
• ????????????,?????????????????
• ??????????????????????????
• ??????????????????????????

27

• IFI?IPFI?????
• IPFI??????
• IPFI?????
• IPFI???
• ???????IPFI????

28
IPFI??????
?????????? ??IPFI
? ? ? ?
????
???????
?????
??????????
??? DNA??
??????? ??????
???????
?????????
????
?????
??
??
????
????
???????????. ???????????????????(??) J .
??????, 2006, 45 (8) 697-701.
29
???????
?? ???? ???? ????
??? ????B ??????????,?????? ????,?????????
?? ??????????????????????? ??????P450 ???14-a-????????,???????????????? ????????????,?????????,???????????,??????????,????????
5-???? 5-???? ??????????? ????,?????????
???? ?????????????? ??????ß-1 ?3-D-?????,????????? ????,?????,?????
???, ???. ??????????????. ????????,2007,6(5)359-3
64 Christopher Kibbler. Building Successful
Strategies to Manage Invasive Fungal Infections.
17th European Congress of Clinical Microbiology
and Infectious Diseases and 25th International
Congress of Chemotherapy .
30
IPFI????

1. ?????????????????????,???????????????IPFI????????
   ????????????,????????????
2. ???????????????????????????????????????
   IDSA????????????????( 10?)?????????(?????????????
   ??)IA???????2009??????IDSA?????????(?????)????????
   ??????
3. ?????????????????????????
4. ?????????????????????????????????????????????????
   ????????????????????

???????????. ???????????????????(??) J .
??????, 2006, 45 (8) 697-701. Thomas J. Walsh,
et al. Clinical Infectious Diseases 2008
46327-60 2009 IDSA Guidelines for Invasive
candidiasis. D. H. Dockrell. Salvage therapy for
invasive aspergillosis. Journal of Antimicrobial
Chemotherapy (2008) 61, Suppl. 1, i41-i44
31
IC?????
ECIL,2007ICAAC 2007 (2009 IDSA Guidelines)
32
IC???????
?? ??????????????????
???? ?????????????B?????
????? ????B??????????????? ????
?????? ??????????????????B?????
????? ??????????????????B?????
????? ???????????????????B
?????? ??????????????????
?????? ??????????????????
???????????. ???????????????????(??) J .
??????, 2006, 45 (8) 697-701.
33
2004 IDSA???????????
?? ???? ???? ??
?????
????? ???? AmB Flu 800 mg/d ????????????????14?
AmB ????????????????14?
Flu 400 800 mg/d ????????????????14?
?????? ???? Flu 6 mg/kg/d ???????????????,????????????14?
AmB?L-AmB ???????????????,????????????14?
????????? AmB?L-AmB ???? Flu 6 mg/kg/d 3 6??,???????????
Clinical Infectious Diseases 2004 3816189
34
2009 IDSA????IC??(????)

• ????????????,??????(?????)???????/??IC????????????
  ????????????,???????(?????)????????
• ?????????????(?????)
• ?????,?
• ????????????
• ????????????????
• ???????????
• ????,?
• ???????????

John H. Rex. 2009 IDSA Candidiasis Guidelines
35
2007 ???????????
??????? ????
???
????? Flu IV Flu??
?????? Flu5-FC
????
?????????? AmB(???????????????)
?????,????
???
????? ?? Flu 400 mg/d IV
???????????????
?????????, AmB?L-AmB
?????? AmB?L-AmB/-5-FC Flu??
Flu AmB?L-AmB 56? Flu??
??????????
??????????????????????? 2007?
36
IPA???????

• ?????????B,????????????B????
• ??????????
• ???????????????????????2????????
• ???????????
• ??????,??????????????????,????????????????????????
  

???????????. ???????????????????(??) J .
??????, 2006, 45 (8) 697-701.
37
2008 IDSA????IPA??
???? ???? ??
???????(IPA) ????(???????) ????B?????????????????? ????????,??????????? ???????????????????????? ????????????50mg/m2/d
??????IA(???IPA ) ?? ?? ???????,????????
??????? ?????????? ?? ?????????????? ?? ???????????
Thomas J. Walsh, Clinical Infectious Diseases
2008 4632760
38
2007 ??????IPA???
???? ???? ????
????
?? VCZ 6 mg/kg iv bid twice 4 mg/kg bid VCZ 6 mg/kg iv bid twice 4 mg/kg bid
?? AmB 1 mg/kg/d AmB 1 mg/kg/d
L-AmB 3 5 mg/kg/d L-AmB 3 5 mg/kg/d
ITRZ 200 mg bid twice 200 mg/d ITRZ 200 mg bid twice 200 mg/d
????
Caspo 70 mg/d 50 mg/d Caspo 70 mg/d 50 mg/d
VCZ(???????)??????? VCZ(???????)???????
L-AmB 3 5 mg/kg/d L-AmB 3 5 mg/kg/d
?????IPA Caspo VCZ Caspo VCZ
Caspo L-AmB Caspo L-AmB
??????????????????????? 2007?
39
2008 IDSA???????
????????? ????
L-AMB 3 mg/kg/d
???? 70 mg/d 50 mg/d
???? 200 400 mg/d
???? 6 mg/kg q12h 3 mg/kg q12h
Clinical Infectious Diseases 2008 46 327-60
40
??????????
??????????????
?? 12h????? 12h????? P
??????() 100 98 0.55
??????(?) 00 7.015.6 0.016
??????(?) 0.41.3 9.419.4 0.019
??????(?) 40.218.1 31.429.7 0.056
???????????????
Matthew Morrell,et al. Antimicrobial Agents and
Chemotherapy, 2005, 49(9) 36403645
41
??????????
????????,?????????
Garey et al. Clin Infect Dis. 20064325-31.
42
?????????

• IDSA??IA?????????612?????????,??????????????????
  ?

??????????????????
???????????
Morgan et al. Infect Control Hosp Epidemiol. 2005
43
? ?

• ????????????????????????????
• ????????????IC??, IDSA????????????????????????
• ???????????IC??, IDSA???????(?????)???????
• ??IA,?????????????????????,??????????????????,????
  ?????????????????????
• ??????????????????????
• IDSA??IPA?????????612?

44

• IFI?IPFI?????
• IPFI??????
• IPFI?????
• IPFI???
• ???????IPFI????

45
????????

• ???????????????????????
• ????
• ????(??????????B????????)
• ??????(????????????????)?????????
• ????
• ?????
• ????????????????????

Johan Maertens. International Journal of
Antimicrobial Agents 27 (2006) 457467.
46
?????????
6 ????????????MIC ???(µg/ mL)
????? MIC MIC MIC
????? ?? MIC50 MIC90
???? 0.194 0.50 1.00
??? 192.00256 256.00 256.00
??? 0.5012 6.00 32.00
????B 0.09432 0.50 2.00
????? 0.00432 0.094 0.25
5-???? 0.38032 32.00 32.00
???????????????????
???, ???, ????,?????????,2007,17(10)1309-1311
47
?????????
?????6 ???????MIC ???(µg/ mL)
????? ??? ??? ???
???? 0.4770.379 0.6670.289 2.6671.528
??? 256 234.7036.90 256
??? 8.508.660 1.000.50 16.67013.61
????B 0.7270.836 2.251.639 0.1740.180
????? 0.0810.045 0.2100.035 0.0900.089
5-???? 32 32 21.58018.04
???????????????????
???, ???, ????,?????????,2007,17(10)1309-1311
48
?????????????

• ???????????????????

??????????????????4???????????,
MIC1µg/mL?,99????
M. A. Pfaller, L. Boyken,R. J. Hollis, et al.
Journal of Clinical Microbiology, 2006, 44(3)
760763
49
?????????????????

• ?????315????????????????????

M. A. Pfaller, D. J. Diekema. Clinical
Microbiology Reviews, 2007,20(1) 133163
50
?????,?????
?? ?? ?? ??
??? 2007 18?IA?? ??????????? ??????38.9 (7/18) 10 ?IPA? ??,5 ??????????
Maertens et al, 2004 90?IA?? ????28?(???) ??????45 64?IPA???, ????AmpB????? 50????,?????
Maertens J et al, 2006 53?IA??, ??????????? ??????55, 84???49 81?IPA ?1???????????????
Aliff, et al 2003 30??Amp ???? AmpB ????????60, ??20???? ???IPFI?? 24?(???) 20?????????????? IPA?????????75
Anttila et al, 2003 52?????? ????65? ??????,???????,???? IPA?? ???,??20??AST?????
Candoni et al, 2005 32????? ????20? ????????56,??12/18?? ??IPFI?? (???) ????,6/18????,2?????
Taccone et al, 2003 47?????? ????15? AmpB????????????????? IPA?ALL?? ???????????IA???????? ???,?6???????????????
51
?????,?????
?? ?? ?? ??
Sallmann et al,2003 13?CGD?? ????29???? ????3???????? ??IPA AmpB 21?
Carby et al, 2004 23???-??? ????7? ????????????,?????? ??IPA??
Ifran et al, 2005 35?AML?? ????27? ??????,???????????? ??IA?? (???)
Aimee K et al, 2006 122???IC?? ???? ??????????????83,??? 104????? ????75????????????? 93????77?????100?????
Jorge, et al 2002 239?IC?? 73.4?????? MITT????????AmpB???????? 61.7??AmpB ?73.4?61.7,?????????,??? ??AmpB?????????80.7? 64.9? ???????????????????AmpB?
52
?????????????
2007??????????????

???? Ba,b,c B-I
????
Ca,c B-I
a ????????b ??????(??,??,??) c
?AmB?????10????(????FDA??),?????????,??????,??IFI
??????? ??????????????
Marchetti O, Cordonnier C, Calandra T. EJC.
2007Suppl 53242. National Comprehensive Cancer
Network. www.nccn.org. Accessed 30 March
2008. RAFAEL DE LA CAMARA. 34th Annual Meeting of
the European Group for Blood and Marrow
Transplantation, 2008 Alison Freifeld. Clinical
practice guideline for the use of antimicrobial
agents in neutropenic patients with cancer2007
update.
53
? ?

• ?????????,???????????????????????????
• ??????????????
• ?????????????????????????,?????,???????
• ????????????????IA,???????????????
• ??????????????????????????