e st T e e patpee, AIDS

1
???µ??e?? st? ??T?e?????????? ???µ??e???pat?p??e
?e?, AIDS

• G?????? T. ??µ?p?????
• ???t??a? ??tat???? Te?ape?a?
• gdimop _at_ med.uoa.gr

2
???µ??e?? st? ??T-??e?µ???a-
3
E?d? ??e?µ???a?

• ??s???µe?a?? ??e?µ???a
• - ??P Hospital Acquired Pneumonia
• Nos???µe?a?? ??e?µ???a p?? s??d?eta?
• µe t? pa???? ?p??es??? ??e?a?
• - HCAP Healthcare Associated Pneumonia
• ??e?µ???a ap? t?? ??ap?e?st??a
• - VAP Ventilator Associated Pneumonia

4

• HAP (Hospital Acquired Pneumonia)
• ? p?e?µ???a p?? eµfa???eta? gt48 ??e? µet?
• ap? t?? e?s?d? t?? as?e???? st? ??s???µe??
• ?CAP (Healthcare Associated Pneumonia)
• ? p?e?µ???a p?? eµfa???eta? se ???e as?e??
• p?? ??s??e????e ??a t??????st?? d?? ?µ??e?
• se ??s???µe?? t?? te?e?ta?e? 90 ?µ??e? ap?
  t??
• eµf???s? t?? ???µ????.
• -as?e?e?? ????? e?????a?, ?s?? ??aßa?
  p??sfata
• a?t?ß??t???, ??µe???e?ape?a, a?µ?d????s?
  ?.?.p.

5
Ep?d?µ??????a t?? ??e?µ???a?
Rello J et al, Crit Care Med 2003,
31(10)2544-2551
6
?a???e?et???? µ??a??sµ??

• ??s??f?s? a???µ???? ???µ?d??? f??t???
• - large inoculum
• ??t??a ???µ????? a?t??
• - virulent organism
• ?p??easµ???? aµ??t???? µ??a??sµ??

7
??s???µe?a?? ??e?µ???a

• ?p?pt?s?
• ? ?????a 30-40 et??
• lt 2 pe??pt?se?? a?? 1.000 e??t???a
• ? ?????a gt 70 et?? (RR 2.1 vs 1.1)
• 16.9 pe??pt?se?? a?? 1.000 e??t???a
• ?????? eµf???s??
• ? ?????a 30-40 et??
• 6? ?µ??a
• ? ?????a gt 70 et??
• 11? ?µ??a (p.02)
• T??t?t??
• ? ?d?a

?anson LC et al, Am J Med 1992 92161-166
8
?p?d?µ??????a ?a? ??t?a VAP

• 2? p?? s???? ???µ???
• gt 25 e?sa????? st? ??T
• 50 t?? s??ta????af?a?
• a?t?ß??t????
• ????µ? ??a???
• p??te? 4 ?µ??e?
• - ?a??te?? ??ßas?
• O???? ???t?t?? 30-70
• - crude mortality
• Ap?d?d?µe?? ???t?t?? 33-50
• - attributable mortality

• P. aeruginosa
• E. coli
• K. pneumoniae
• Acinetobacter spp.
• MRSA
• - as?e?e?? µe S. ?.
• - ???
• - ??T

9
Eµf???s? VAP

• O? ßa???? p?s???te? as?e?e??
• de? t??f??ta? ap? t? st?µa
• ? ?????s? t?? s?e??????? ad????
• ? ?a?a??sµ?? t?? st?µat???? ?????t?ta?
• ep?de????eta? ? st?µat??? ???e???
• ? a???µ?? t?? ßa?t???d???
• p????eta? ? ap????sµ?? st?µat?f?????a

El-Sohl AA et al, Chest 2004, 1261575-1582
10
???d?a?es???? pa?????te?

• S?s?e??? p?? ???s?µ?p?????ta? st? ??s???µe??
• ?e??ß????? (a??a?, ?e?? ?.?.p.)
• ?a??t?ta ??s??, p??t??a ???es? se a?t?ß??t???,
• ?e????????? ep?µßas? ?.?.p.
• ??s??f?s?- ??µ??e?a
• ??sp??? ? ?µes? e?ap??es? µ???????a??sµ??
• ??µat??e??? d?asp???
• ???film

11
?p?pt?se?? t?? VAP

• ? ???t?t?? (30-70)
• d????e?a µ??a????? a?ap????
• pa??tas? ??s??e?a?
• ??st?? ??s??e?a?
• d?af??e? ap? ???a se ???a ?a? e?a?t?ta?
• - ap? t? s?st?µa ??e?a?
• - t?? ??????s? t?? ??s???µe??? ?a? ??T
• - ??? gt 40.000

Fagon et al, Am J Med 1993, 94281-288
12
A??e?t??? pa?????a

• ?nterobacteriaceae (pa?a???? ?SBLs)
• MDR ste???? (?DR multi-drugs resistanse)
• P. aeruginosa, Acinetobacter spp., S.
  maltophilia,
• ?. pneumoniae, B. cepacia ?.?.p.
• ?RSA
• Staphylococcii µ? e?a?s??t?? sta ?????pept?d?a

13
??????s?

• ?? epeµßat???? µ???d??
• - ?a??????e?e?
• - PCR
• - ape?????st???? µ???d??
• ?peµßat???? µ???d??
• - ß?????s??p?s? (BAL, lavage, PBS)
• - FNA, ß????a

14
?d???e? ??a t? ?e?ape?a t?? ???
HAP (severe)1, 2
aminoglycoside or ciprofloxacin antipseudomonal
agent vancomycin or linezolid for MRSA
Caused by MRSA 1. American Thoracic Society.
AJRCCM 19961531711-1725. 2. Wunderink RG et
al. Chest 20031789-1797.
15
?µpe????? ?e?ape?a VAP

• Pseudomonas spp.
• Acinetobacter spp.
• Klebsiella spp.
• Enterobacteriae
• MRSA

• Aµ????????s?d? ?
• a?t??e?d?µ??ad???
• ???????? (Ciprofloxacin,
• ?????? d?se?? Levofloxacin)
• ??t??e?d?µ??ad??? ?efa??sp?????
• (?efta??d?µ?, ?efep?µ?)
• ?µ?pe??µ?,µe??pe??µ?
• ß lactam / ß lactam a?ast???a?
• (piperacillin / tazobactam)
• Linezolid ? Vancomycin

?TS guidelines, 2005
16
Ep?ß??s? se s??s? µe t? d????e?a t??
a?t?µ????ß?a??? ?e?ape?a?
?????e?a ?e?ape?a?
1.0
0.8
8 ?µ??e? 15 ?µ??e?
0.6
???a??t?ta ep?ß??s??
0.6
0.4
0.2
0.0
10
20
30
40
30
60
?µ??e? µet? ap? ß?????s??p?s?
Chastre, Wolf, Fagon et al. JAMA 2003
17
?????e?a ?e?ape?a?
40
80
??af??? 2.9 90 CI, -3.2 ??? 9.1
p 0.038
30
60
20


40
28.9
62.1
26
10
42.1
20
0
0
8 ?µ??e? n 197
15 ?µ??e? n 204
8 ?µ??e? n 197
15 ?µ??e? n 204
?p?t??p? ???µ??e?? t?? a?ap?e?st???? a?????a
µe t? d????e?a t?? ?e?ape?a?
eµf???s? MDR pa???????
Chastre, Wolf, Fagon et al. JAMA 2003
18
G?at? ? p?????? t?? VAP e??a? s?µa?t??? ?

• - ?e??s? ???t?t?ta?
• ?e??s? ???s?? a?t?ß??t????
• ?e??s? a?t????
• ?e??s? d????e?a? ??,??s??e?a?
• ?e??s? ??st??? ??s??e?a?

?? 5 ? !!
Chastre J Resp Care 2005, 50(7)975-984
19
?a??te?a ?a p???aµß??e?? pa?? ?a ?e?ape?e?? !!!!!

• ?p?f??? ap????sµ?? µe pa?????a ??T
• II. ?e??s? ßa?t???a??? f??t???
• ?p????tt?d??? a?a???f?s?
• St?µat??? ???e???
• S?st? ??s? ?efa???

20
?a??te?a ?a p???aµß??e?? pa?? ?a ?e?ape?e?? !!!!!

• ?e??s? ßa?t???a??? f??t???
• ?p????tt?d??? a?a???f?s?
• St?µat??? ???e???
• S?st? ??s? ?efa???

21
E?d?t?a?e?a?? ??a???f?s?
Ae?a????? ?a?a??? ap? e????se?? ?a??? ae??sµ??
?a? ???????s? S?µßat???? ? a????t?? a. ?????µa
t?? ?????µat?? t?? a?ap?e?st??a ß. e?sa????
ap?ste???µ???? ?a?et??a µ??? ???se?? ?. ???e???
?e????, ???s? ?a?t???, µ?s?a ??e?st?? t?p??
p??f???sseta? ap? ??a p?ast??? pe??t????µa
a?t??a??stata? ???e 24 ??e?
?iel Weise BS et al, Infect Control and Hosp
Epid 2007, 28(5)531-536
22
??e??e?t?µata ??e?st?? t?p?? a?a???f?s??
?e? ???eta? ? d??s? t?? PEEP ??? e???e???
ep?µ????s? ??? apa?a?t?t? ? ???? µ?t???
??e????? ????????? ??S??S ?eta-a????s? 8
µe??te? ??e?st?? t?p?? a?a???f?s? se s??s? µe
t?? a????t?? t?p?? s?et??eta? µe t?? ?d?? de??t?
eµf???s?? VAP
?iel Weise BS et al, Infect Control and Hosp
Epid 2007, 28(5)531-536
23
?p????tt?d??? a?a???f?s?

• ?????e?s??f?se?? ep?µ???sµ???? e????se??
• s?ss??e???ta? st?? ?p?f?????a
• d?a????ta? st? pe????? t?? cuff
• ?p????tt?d??? a?a???f?s? µe e?d??? ?a?et??a
• s??e??? a?a???f?s? 20-30 cmH2O
• flush s?st?µat?? ???e 4 ??e?

Davis K et al, J Crit Care 2006, 21 211-228
24
?p????tt?d??? a?a???f?s? ?a? VAP
??e?? t??a??p???µ??e? µe??te? - se as?e?e?? µe
?? gt 72 ??e? - s?µa?t??? µe??s? de??t? VAP M??
meta analysis - ?de??e s?µa?t??? µe??s?
??st???
Mahul P et al, Intens Care Med 1992, 1820-25,
Valles j et al, Ann Intern Med 1995, 122179-186,
Smulders K et al, Chest 2002, 121858-862,
Dezfulian C et al, Am J Med 2005 , 11811-18
25
?a??te?a ?a p???aµß??e?? pa?? ?a ?e?ape?e?? !!!!!

• ?e??s? ßa?t???a??? f??t???
• ?p????tt?d??? a?a???f?s?
• St?µat??? ???e???
• S?st? ??s? ?efa???

26
St?µat??? ???e???

• ?? e??a? ? st?µat??? ???e??? ?
• ? d?ad??as?a µe t?? ?p??a ap?µa????eta?
• ? ?d??t??? p???a ?ai d?at??e?ta? ???? ?
• st?µat??? ?????t?ta ?a? ?? ß?e???????e?
• ep?f??e?e?
• ?d??t??? p???a ? a???s? a???µ?? pa???????
• ? ?at? t? pa?aµ??? t?? as?e??? st? ??T
• 65 ep?f??e?a? ap???sµ??? µe pa?????a
• ?. a?ap?e?st???? vs 16 se ???e?? as?e?e??

Fourier F et al, Crit Care Med 2005, 33(8)
1728-1735
27
?e????? st?µat???? ???e????
?. ??a???f?s? ??. ?efa?? as?e???? st? p???,
?????µa st?µat?? ???. ?p?s??p?s? st?µat????
?????t?ta? ?a? ?st?? ?V. ?a????sµa µe
p?ß?d???-??d??? (20 f???? d?a?e??µ???) V.
?d??t?ß???tsa VI. Epa?????? t? ß?µa IV VII.
??µa ?
?ori et al, Intens Care Med 2006, 32230-236
28
Ep?s??p?s? st?µat???? ?????t?ta?
?ilers et al, Oncol Nurs Forum 1988,15(3)325-30
29
St?µat??? ???e??? - µe??t? se ?a?d???e?????????
??T -
RCT µe??t? 353 as?e?e?? CHG (chlorexidine
gluconate) ?????? de??t?? ??s???µe?a???
p?e?µ???a? ? ?at? 65 (24/180 vs 8/173
plt0.001) S???????? de??t?? ???µ??e??
a?ap?e?st???? ? ?at? 69 (17/180 vs 5/172 p
lt0.05 ???f??a?t??? a???? µe a?t?ß??t??? ? ?at?
43 T??t?t?? ? 1.16 vs 5.56
DeRiso AJ et al, Chest 1996109(6)1556-1561
30
cfu/ml

• Ep?pt?s? VAP
• (epe?s?d?a p?e?µ???a? / 1000
• ?µ??e? µ??a????? a?ap????)
• 3.9 ?µ?da µe??t??
• - 10.4 ?µ?da e?????? p gt 0.001
• ? ep?pt?s??
• p???µ?? ?a? ???µ?? VAP
• RR (relative risk) 0.37
• AR (attributable risk) 3.96
• (95 CI 0.22-0.62)

107
106
105
104
103
102
10
1
Ps. aeruginosa
Candida spp.
MRSA
Gram (-)
????pa?a???t??? a????s?
?ori et al, Intens Care Med 2006, 32230-236
31
St?µat??? ???e??? se ??T- µe??t? se 59 ??T t??
????p?? -

• I. ?????µ? e??t?µat?????? se 9 ????pa???? ???e?
• t? 77 e??e ??a??p???t??? e?pa?de?s?
• t? 93 ??t??se p?? ?ept?µe?? e?pa?de?s?
• t? 88 st?µat??? ??e??? µe????? s?µas?a?
• II. ? efa?µ??? t?? st?µat???? ???e???? ?e??e?t?
• d?s???? ap? t? 68
• ??? e?????st? ap? t? 32
• µ?a f??? t?? ?µ??a (20), d?? ?µe??s??? (31),
• t?e?? f???? t?? ?µ??a (37)
• III. St?µat??? d?a??µata 88, chlorhexidine 61
• IV. ?d??t?ß???tse? (41 ) ??? ??e?t?????

Rello et al, Intens Care Med 2007,33(6)1066-70
32
?a??te?a ?a p???aµß??e?? pa?? ?a ?e?ape?e?? !!!!!

• ?e??s? ßa?t???a??? f??t???
• ?p????tt?d??? a?a???f?s?
• St?µat??? ???e???
• S?st? ??s? ?efa???

33
???a??sµ?? p?? s?et??eta? µe t? ??s? t?? ?efa???

• F?s???????? ?at? t? d????e?a t?? ?p???
• ? ?????p?? a????e? ??se?? a?? 12 min
• ? as?e??? t?? ??T e??a? se ?pt?a ??s? ??a
• µa??? ??????? d??st?µa
• µe??s? FRC ( Functional Residual Capacity)
• µe??s? ß?e??????ss?t?? ???a?s??
• ep??eta? ? s?ss??e?s? ß?????? st? p?e?µ??a

?eane F, Paraplegia 1970 254-258
34
S?st? ??s? ?efa??? ?a? VAP

• S?st? ??s? ?µ??a?est????a (semirecumbent)
• ?ad??ses?µasµ??? t??f? se as?e?e?? se ?pt?a
• (?µ?da ?) ?a? ?µ??a?est????a ??s? (?µ?da ?)
• Se p?s?st? 68 (?µ?da ?) vs 32 (oµ?da ?)
• ? s?????t??s? t??f?? st?? ?? (µet? ap? 5 ??e?)
• ?d??? µ???????a??sµ?? st? a??te?? ?ast?e?te????
• ?a? ?at?te?? a?ap?e?st??? s?st?µa.

?rozso Levi M et al, AJRCCM 1995, 1521387-1390
35
?µ??a?est????a ??s?

• ?e???µ??? ??s? ?efa??? as?e?? ? t?? ??? ?µ?se??
  t?? s?µat?? ?? p??? t? ??????t?? ep?ped? t??
  ??????
• ??te?de????ta? ? a?µ?d??aµ??? ast??e?a,
• ?a??se?? SS
• S?st? ????a ???s?? 30-45?
• ??s???? ?a e??a? ? as?e??? ??? t?? ?µ??a
• S?????? ?? as?e?e?? d????s?a????? se 20? ??s?
  
• µet? ap? t?? a????? t?p???t?s?

Powers J , www. nursingmanagement.com, November
2006
36
A??e? ??se?? t?? ?efa??? p???aµß????? t? VAP

• ?????? ??s?
• ?RDS ße?t???e? t? PaO2 a??? de? µe???e?
• t?? eµf???s? ?a? t? ???t?t?ta t?? VAP
• ???a??? ??se?? ???????
• 2 t??a??p???µ??e? µe??te?
• ? s?et???? ???d???? eµf???s?? ????? stat?st???
• d?af??? ????? ep?d?as? st? ???t?t?ta

Fink MP et al, Chest 1990, 97132-137, Marik PE
et al, Crit Care Med 2002, 302146-48 Choi SC, J
Crit Care 1992, 757-62
37
H s?st? ??s? t?? ?efa??? p???aµß??e? t? VAP
?e??s? t?? ???d???? eµf???s?? VAP se as?e?e?? se
?µ??a?est????a ??s? se s?????s? µ?a?t??? se ?pt?a
??s? RR 0.22 (95 CI 0.05-0.92) Evidence
Based Guidelines CDC (Center for Disease Control
and Prevention) - low-cost, low-risk µe??d??
p??????? t?? VAP T?s? ?efa??? 30-45? se s??s?
µe t? ??eß?t?
Collard HR et al, Ann Inter Med 2003,
138494-451, Drakulovic MB et al, Lancet 1999,
3541851-1858 CDC recommendations Respir Care
2004, 49929-939
38
???µ??e?? st? ??T-????t?a??? ???µ??e??-
39
????te? - ?a????µ?s? ß?se? µ??f?????a? -

• Yeast ??µ?
• Mould ?f??
• Dimorphic ??µ??f??

40
???d?a?es???? pa?????te?

• ?at???e??? ep?d?as?
• ??µe???e?ape?a - ??dete??pe??a
• ??t????e?ape?a
• Ste??e?d?
• ???s??atast???
• ????? pa?????te?
• ??t?ß??t???
• ?e?t????? ?a?et??e?
• ?p????sµ??
• ?a?? ?????
• ?e??ß?????

Dimopoulos G. Clin Intens Care 200213(1)1-12
41
????te? p?? ????? s?µas?a ??a t? ??T
Huh. You guys get all the attention
Fusarium Mucor, other
42
?a?????e?a ???µ??e?? ap? Candida spp.

• ???s?????s? se ep?????a?? ??tta?a
• ???sdes? se p?ast???? ep?f??e?e? (?a?et??e?,
  p??s?et???? ßa?ß?de? ?.?.p.)
• ??e???p???s? Protease
• ??e???p???s? Phospholipase

43
?p????sµ?? Candida score

• ????? pa?e?te???? d?at??f? 0.908
• ?e????????? ep?µßas? 0.997
• ????est?a??? ap????sµ?? 1.112
• S?ßa?? s??? 2.038
• ?? ??dete??pe????? as?e?e?? µe Candida
• score gt2.5 ?a ?fe?????? ap? t?? ???a???
• ??a??? a?t?µ???t?as???? ?e?ape?a?

Leon et al, Crit Care Med 200634730-737
44
?? a????µa t?? Candiduria
???S??S Tet???? ?a??????e?e? ????? ??a
Candida spp. gt106
???a? ???µ??? ? ???d?a??te? se Candidemia ?

• ?p?ßeß??µ??? Te?ape?a
• ??dete??pe??a
• ?etaµ?s?e?s? ?ef???
• ??????????? epeµß?se??

45
?p?d?µ???????? St??f? Candida spp a?? ?t??
(2000-2006)
Dimopoulos et al, Anaesthesia Analgesia (in press)
46
Candida endophthalmitis

??????sµata µ???t?? sta ???a
47

• S?pt??? ???µß?f?eß?t?da
• ?? sfa??t?da?,
• ?p???e?d???,
• ß?a????efa?????
• ap? Candida albicans
• ?a? MRSA

48
?ef???? candidosis
?pat??? candidosis
49
??????? ??a ???µ??e?? ap? Candida spp.

• ?p?f??? ???es??
• ap????sµ??
• µet?d?s? ap? p??s?p???
• ???a??? e?t?p?s? est???
• S?pt??? ???µß?f?eß?t??, a????t??,e?d?f?a?µ?t??
• ??e?µ???a ap? Candida sp???a
• ?µß???asµ?? ???

50
???f??a??

• Meta-analysis
• 9 RCTs (7 d?p??? t?f???)
• 1226 as?e?e?? µe t?a?µa
• Keto- (3 µe??te?), Fluco-(6) vs
• placebo (8) ? µ? ?e?ape?a
• ?p?te??sµata
• ???f??a?? µe azoles
• ? de??t? candidemia
• RR 0.30, 95 CI 0.10-0.82
• ?a? ????? ???t?t?ta
• RR 0.60, 95 CI 0.45-0.81

Crucianni M et al, Intens Care Med 2005,311479-87
51
???f??a?? ??????s? ?? nystatin

• ????pt???, t??a??p???µ???, a????t? µe??t?
• 98 as?e?e?? se ??
• 51 pts st?? ?µ?da µe nystatin / 47 pts control
• ?? nystatin 3x106 U /?µ??a ? µ? ??????s?
• ?p????sµ?? µe Candida
• 25 st?? ?µ?da control vs 0 ?µ?da e??????
  
• ????pa?a???t??? a????s?
• ??e???t?t?? pa?????te? ??a ap????sµ?
• ??s??e?a st? ??T
• (OR 1.05, 95 CI 1.05-1.10, p0.02)

Normand S et al, Intens Care Med 2005,311508-1513
52
???µ??e?? ap? ?spergillus spp.

• ?e???? ep?d?as? st??
• ep?ß??s? st???
• a??s??atasta?µ????? as?e?e??
• ???t? a?t?a ?a??t?? ap?
• ???µ??? st??? as?e?e?? µe
• a?µat??????? ?a????e?a ?a?
• µetaµ?s?e?s? µ?e??? t??
• ?st??

53
Aspergillus st?? a??a
Aspergillus st? ts??
Aspergillus st? s????
Aspergillus st? pe??ß????? t?? ??s???µe???
Aspergillus st? sp?t?
54
Aspergillus
To ???µa p?????eta? ap? t?? a??ast???a t??
?a??????? ?e??a

• ?a p?? ????? ste???? p?? p???a???? ???µ??? st??
• ?????p? ?at? se???? s????t?ta?
• A. fumigatus
• A. flavus
• A. niger
• A. terreus
• A. nidulans

Marr et al, CID 2002, 134(7) 909-917
55
T??e??t?ta µe ???-Hallo Sign-

• Trichosporon,Penicillium,Fusarium
• E?d?µ???? µ???te?
• (coccidioidomyces)
• ?????d?a, Ps. aeruginosa
• TBC,CMV,HSV
• ?????????e??d??? Ca, MALT,
• ?.Wegener

Won et al Radiology 1998208777-82
56
(No Transcript)
57
????ap?? ?spe??????µata
58
Helsinki University Central Hospital
Maxillofacial Clinic and Laboratory Diagnostics
and Haartman Institute, University of Helsinki,
Finland riina.rautemaa_at_helsinki.fi - a Case of
Maxillary Sinus Aspergilloma -
59
Dimopoulos G et al. Intens Care Med 2003
60
?p?pt?s? ?????t???? Aspergillosis
Haematological malignancy
BMT or PSCT
Organ transplant
Other
Solid tumor
Marr KA, et al., Clin Inf Dis, 2002, 34909
61
?p?d?d?µe?? ???t?t?? se Aspergillosis
CONNEALLY B.M.T. 1990
n 123
DENNING R.I.D. 1990
n 2121
Four different studies of BMT recipients
evaluated for Aspergillus infections
HERTENSTEIN Ann. Hemat. 1994
n 303
MEYERS Sem. Oncol. 1990
n 1500
0
10
20
30
40
50
60
70
80
90
100
Case mortality rate
From B. de Pauw
62
?a?????e?a t?? ?spergillosis
Inactive conidia inhaled
Dissemination to other organs
Hyphae invade blood vessels
Conidia swell and shed outer coat
Conidia germinate to hyphae
BLOCKED BY NEUTROPHILS
BLOCKED BY MACROPHAGES
CHEMOTHERAPY
STEROIDS
63
??????s? ?a? ?e?ape?a Aspergillosis
Treatment
41
40
39
38
Temperature (C)
37
36
Disease likelihood
0
From JP Donnelly
64
O??st??? ??????s?
Bronchoscopy
Sputum
Bronchoalveolar lavage
Fine needle aspirate
Biopsy
Brush
Lung biopsy
65
?e?µat???? ß??ße? ap? Mucormycosis
Pre-treatment
After treatment
Aspergillus lesion
66
????- e??efa???? mucormycosis
?e?µat??? mucormycosis .
67
?e?????????? ???µ??e??
68
?p?d?µ??????a t?? ?e?????????? ???µ??e?? vs t??
pe??t???t?d?? ap? t? ?????t?ta
Roehrborn A, et al. CID 2001331513
69
?? p?? p??a??? µ???????a??sµ??........

• Gram ()
• - Coagulase-negative staphylococci (CoNS)
• - Staphylococcus aureus
• - Enterococci
• Gram (-)
• - Pseudomonas spp
• - Acinetobacter spp
• - ESBL-producing bacteria
• Fungi

70
Gram - positive organisms

• Gram ()
• 50 to 60 t?? pe??pt?se?? ??s???µe?a???
  ßa?t???a?µ?a?
• ?RSA
• Methicillin resistant Staphylococcus aureus

71
???d?a?es???? pa?????te? ??a MRSA ???µ??e??

• S?et???µe??? µe t?? as?e??
• G??st?? ap????sµ??, ??????? f??e??
• ?e????? stad??? ?ef???? ??s??
• ?pat??? a?ep???e?a
• ?a??sa???a
• ???s??atasta?t??? ?e?ape?a
• Sa??a??d?? ??aß?t??
• ?a??se?? SS
• ?????e? a????t?? ß??ße? d??µat??
• ??ep???e?a p????? ???????

72
???d?a?es???? pa?????te? ??a MRSA ???µ??e??

• S?et???µe??? µe t? ?e?ape?a
• ???????µe?? ?e?ape?a µe a?t?ß??t???
• ??s??e?a gt 2 eßd?µ?de?
• ?peµßat???? µ???d??
• ??d?a?????? ?a?et??e?
• ?a?atetaµ??? d????e?a ??
• ?a????????a ??s??e?a ?????

73
???d?a?es???? pa?????te? ??a ???t?t?ta ap? MRSA
???µ??e??
?st?a ???µ???? ??e?µ?? ????st? est?a ???µ????
S?pt??? shock ????µ??? ?????a APACHE III
score gt 60
74
?p?pt?s? MRSA

• ?p?pt?s? ???µ??e?? ap? MRSA gt20
• - ?e??e?ta? ?????
• ??s???µe??
• - ?e?????????? ?a? ?a?d?????a????? ????????
• - ?????te?? ep?pt?s? MRSA (40)
• Ge???af??? ?ata??µ?, t?p??? ep?d?µ??????a

75
VISA and VRSA

• VISA
• Vancomycin Intermediate Staphylococcus aureus
• MIC 8-16 µg/ml
• VRSA
• Vancomycin Resistant Staphylococcus aureus
• MIC gt 32 µg/ml
• mecA ?a? vanA genes

76
Te?ape?a VISA ?a? VRSA

• ? ?e?ape?a ( gentamicin)
• - vancomycin nafcillin ? oxacillin ?
• - vancomycin ampicillin-sulbactam
• ?s?e?e?? a??e?????? st? penicillin
• - vancomycin TMP-SMX gentamicin
• ????a?t???
• - linezolid
• - quinupristin-dalfopristin.

77
VRE

• Vancomycin-resistant enterococci

78
The Role of Enterococci in Intra-abdominal
Infections

• ?????e?t???? µe??t?
• 334 ste???? ap? 131 as?e?e??
• µe ?e?????????? ???µ??e??
• 163 ste???? µete??e???t???
• Gram () ?pe??s??a?
• E. faecalis t? p?? s????e?

Shinagawa N, et al. Jpn J Antibiot. 20045733-69
79
?µpe????? ?e?ape?a

• ???s??atasta?µ???? as?e?e?? µe ??s???µe?a??
  µete??e???t??? pe??t???t?da
• ?s?e?e?? µe severe sepsis µe est?a ap? t? ??????
  ?a? e??a? ??ße? p??????µe?a cephalosporins ? ???a
  e????? f?sµat?? a?t?ß??t??? ??a Enterococcus sp.
• ?s?e?e?? µe peritonitis ?a? ßa?ß?d?p??e?a ?
  p??s?et??? e?da??e?a?? ?a?et??a ?a? ?e?????ta?
  ?????? ???d???? ??a e?d??a?d?t?da

80
Enterococci µe a?t??? st? Gentamicin ?a?/?
Vancomycin
81
????? a?t??? st? Ge?taµ?????

• Gentamicin MIC gt 2000µg/ml
• ??t?? ap? streptomycin

??t??? st? Vancomycin

• Susceptible MIC lt 4 µg/ml
• Intermediate resistance MIC 8-16 µg/ml
• Resistance MIC gt 32 µg/ml

82
???d?a?es???? pa?????te? ??a VRE ???µ??e??

• ???????µe?? ???es? se
• - Vancomycin, 3?? ?. cephalosporins ?a?
  a?t?-a?ae??ß?a
• ?a?atetaµ??? d????e?a ??????s?? vancomycin
• ?a?atetaµ??? p??e??e???t??? ??s??e?a
• ?s?e??? ???t? se ap????sµ??? ap? VRE
• ?a?atetaµ??? ?? ?a? ??s??e?a st? ??T
• G??st?? ap????sµ??

83
???d?a?es???? pa?????te? ??a VRE ???µ??e??

• ?a?????te? p?? ????? s??s? µe t? ??s???µe??
• F??t?? e??as?a?
• ?p?µ????s? pe??ß?????t??
• F??e?? p?? de? e??a? ???st?? ap? t? ?????t?ta
• ??d???s???µe?a?? µetaf???
• ??es? a?t?ß??t????
• F??e?a ap? ??p?a?a
• ?? d?at???s? ?d????? ??a ???e??? ?e????

84
Te?ape?a VRE ???µ??e??

• Ampicillin 18-30g
• Ampicillin Imipenem Genta
• Ciprofloxacin Rifampin Genta
• ß-lactam Vancomycin Genta
• Ampicillin Quinolone

85
?e?te?a a?t?ß??t???

• Linezolid
• Quinapristin-Dalfopristin
• Linezolid Vancomycin
• Linezolid Quinapristin-Dalfopristin
• Quinapristin-Dalfopristin Ampicillin
• Quinapristin-Dalfopristin Vancomycin

86
???sfata a?t?ß??t???

• Daptomycin (Lipopeptide antibiotic)
• Tigecyclin (Glycycycline)

??e???t??? f??µa?a

• Oritavancin (LY 333328)
• Dalbavancin

87
Gram-negative organisms
MDR AcinetobactersMDR multi-drug resistance
88
??t?ß??t??? ??a?t? A. boumannii

• Imipenem
• Meropenem
• Sulbactam
• Ampicillin / Sulbactam
• 6g Sulbactam
• Amikacin
• Colistin

89
S?????e?a in vitro

• Sulbactam plus Rifampin
• Sulbactam plus Azithromycin
• Sulbactam plus Trovafloxacin
• Appleman MD, et. al. AAC 2000441035
• Colistin plus rifampin
• Giamarellos-Bourboulis EJ, et
  al.
• Diagn Microbiol Infect Dis. 200140117

90
MDR Acinetobacter VAP µe IV Colistin

• ????pt??? µe??t? µe 35 epe?s?d?a VAP
• (54 ?e?????????? as?e?e??)
• - 21 MDR ? IV Colistin
• - 14 IPM-sensitive ? IPM
• 57 ep?t???a ?e?ape?a? ?a? st?? 2 ?µ?de?

Carnacho-Montero J, et al. CID 2003361111
91
MDR Acinetobacter ?e?ape?a

• Ampicillin/sulbactam
• 6g Sulbactam
• Colistin
• Tigecyclin

92
Pseudomonas aeruginosa
93
?p?????? ??a ?e?ape?a

• Ceftazidime
• Ciprofloxacin
• Ticarcillin/clavulanate
• Piperacillin/tazobactam
• Imipenem
• Meropenem
• Colistin

94
??t??? st?? -pe??µe?

• OprD- mutants
• MexA-MexB-OprM

95
Aztreonam ?

• plasmid VIM metallo-ß-lactamases (IPM-)
• ?d?????? ß-lactams e?t?? ap? Aztreonam

Colistin ?
21 as?e?e?? µe pan-resistant P. aeruginosa 39
µe pan-resistant Acinetobacter spp 60-300mg, IV
se 2-3 d?se?? St? 58 t?? as?e??? ?a?? ??ßas?
??? ?a?? ??ßas? se as?e?e?? µe pneumonia - ????
t? 25 e??a? ?a?? ??ßas?
Levin AS, et al. CID 1999281008
96
S?????e?a a?t?ß??t???? in vitro

• Antipseudomonal ß-lactams
• antipseudomonal aminoglycosides
• Colistin
• Ceftazidime against multi-resistant P.
  aeruginosa

Gunderson BW, et al. AAC 200347905
97
S??e??? vs ??ape?p??sa? ??????s??

• ????pt???, t??a??p???µ??? µe??t? se as?e?e?? µe
  p?e?µ???a
• 90 se ??
• 40 ???µ??? ap? P. aeruginosa
• CAZ 2g tid (n18) vs 3g/day Continuous Infusion
  (CI) (n17) plus tobramycin once daily
• Cure Improvement 83 vs 94 (pNS)
• Time to afebrile 5.2 d vs 3.1 d (p0.015)

Nicolau DP. Intern J Antimicrob Agents 200117497
98
Extended spectrum ß-lactamases (ESBL)

• Fluoroquinolones and aminoglycosides
• - ß?se? e?a?s??s?a?
• ß-lactam/ß-lactamase a?ast???a
• Cefamycins cefoxitin or cefotetan
• - de? s?st????ta?
• Carbapenems
• - a?t?ß??t??? e??????

99
?pat?p??e?e?
100
?e?t??????? ??at?µ?a ?pat??
101
?pat??? ??ß??

• ? ßas??? ?e?t??????? µ???da t?? ?pat??
• ?????d???? d?µ?, µ????? a??et?? ?????st?? ?a?
  d?aµ?t??? 0.8 2 mm
• ?? a????p??? ?pa? ap?te?e?ta? ap? 50000-100000
  ??ß?a.

102
?e?t?????e? ?pat??

• A-lbumin
• B-ilrubin
• C-oagulation
• D-rug
• E-limination
• F-at
• G-lucose metabolism
• H-ormone metabolism
• I-mmunologic function

103
??t?µ?s? ?pat???? ?e?t?????a?

• ???e??????? ????
• ?????, ?µes?, ?µµes?
• ???e??????? ?a? ?????????????? ?????
• ?µ???t?a?sfe??se? ????
• AST, ALT
• ???a???? f?sfat?s? ???? (ALP)
• ?- G???taµ??-t?a?spept?d?s? ???? (?GT)
• 5-?????e?t?d?s? ???? (5-NU)
• Ga?a?t??? af?d??????s? ???? (LDH)
• ???te??e? ????
• ?e???µat???, sfa????e?, pa?????te? p????
  I, II, V,
• VII, IX, X ? PT)
• ?µµ???a a?µat??

104
?pe?????st???? ??e???? ?pat??

• MRI ?????a?
• ?R a??e????af?a
• ?ad???s?t?p???? ??e????
• ERCP / MRCP
• SPECT / PET

• ??t?????????? ??e????
• ?????a? (/- s??a??af???)
• ?pe???????f?µa ?????a?
• CT ?????a?

105
???e? e?et?se??

• ??ade?µ??? ß????a ?pat??
• µe ? ????? ?a??d???s? ECHO / CT)
• ??asfa??t?d??? ß????a ?pat??
• ??s?fa???ast??s??p?s? ??????s??p?s?
• ?apa??s??p?s?

106
(No Transcript)
107
????? ??????? ???????????? S???????? ?????

• ????????? ? - 0-8
• ????????? ? - 3-47
• ??????S???G?? ????????????S (?????????F????S)
  2-56
• ???? F?????? ? ??????S 5-18
• ???? ????? 1-14
• ?G?OS?? ????? 19-44

108
????? ??????? ?????????? ???????S
?????OS??S/????????S

• ?pat??? e??efa??p??e?a
• ???efa???? ??d?µa
• ??ata?a?e? t?? p????
• ?pat??ef???? s??d??µ?
• ?etaß?????? d?ata?a???
• ?p?????a?µ?a, ????s?, a?????s?, ?p??a?µ?a
• S???

109
HIV / AIDS
110
??????e? ?a? ?a?d?? p?? ?p??????eta? ?t? ???? µe
HIV ???µ??? t? 2005
Eastern Europe and Central Asia 1.4
million
Western/ Central Europe 720,000
North America 1.3 million

• East Asia
• 680,000

North Africa and Middle East 440,000
Caribbean 330,000
Southern and Southest Asia 7.6 million
Sub-Saharan Africa 24.5 million
Latin America 1.6 million
Oceania 78,000
UNAIDS, 2006. Available at http//www.unaids.org.

111
S??????? d??????ta HIV ????et??? ?t?µa ?at? ?t??
d???s?? ?a? f???p??? ????, 12/2005
S????? HIV/AIDS ap? 1984-2005 (5898 ? 1433
G)7371
2005 data ??? ?a? 30-6-05, p??? www.keel.org.gr
access 30-11-05
112
???????ta HIV ????et??? ?t?µa st?? ?? (a??
e?at?µµ.p???) 2002
113
? ?et?????? ????p????? ?e?et???? ??????? St?d??
a?t?st??f?? µeta??af?? RNA ??? µeta???feta?
se DNA (p?????) e?s?µat??eta? st? ?e?et???
????? t?? ??tt???? t?? ?e??st??
A?t?st??f? µeta??af?s? apa?a?t?t? ????µ? ??a
t?? a?t?st??f? µeta??af?? ?et? ap? e?s?µ?t?s?
t?? p????? st? DNA t?? ??tt???
p???ap?as???eta? µ?s? t?? ?e??st?

• Virus- HIV (?e???? p??s????s?)

114
reverse transcriptase needed to make copy
viral RNA
viral DNA
CD4 receptor sites
incorporated into cells DNA using integrase
REPLICATION
human DNA
protease needed to cut strands
assembly
budding
115
???s??????? ?p??t?s? t?? ???
CD4
CD8
HIV/CD4
NK
B
M
116
?????? ap? t?? ???es? µ???? t? ??s?
117
(No Transcript)
118
????µ?? CD4 ?eµf???tt???? se HIV () as?e??
119
E?d???se?? ap? t? ??ap?e?st???
????µ?? CD4/µl
?a?????a ap? t? ?????t?ta (???e?e?? ???µ??e??,
???p?, ßa?t???d?a??? ???µ??e??, ?t?pe?
p?e?µ???e?
800-1000/µl
?e?p??sµata s????µa Kaposi Non-Hodkin
??µf?µa ???µese? ??e?µ???p??e?e? ???µ??? ap? M.
tuberculosis M???te?
250-1000/µl
lt 250 /µl
???a???a??? ???µ??e?? PCP CMV Cryptococcus Histop
lasma capsulatum ???e?
120
??s?? HIV ?a? CD4 ?eµf???tta?a st? ?????
Bacterial skin infection, Herpex simplex, zoster,
Oral, skin fungal infections
800
600
Thrombocytopenia Lymphadenopathy
Kaposis sarcoma
500
300
400
400
CD4 cell count /mm3
200
Hairy leukoplakia Tuberculosis
Lymphoma
PCP
200
Cryptococcosis Toxoplasmosis
100
CMV
MAC
0
Years
Months
121
?f?? ??e? te?e? ? d?????s? p?? pa?a??????e?ta?
? as?e??? ?
122
?ï?? (viral) RNA

• ??t??s? st? a?µa
• Se s??d?asµ? µe a???µ? CD4 ?a?
• t? ??????? ?at?stas? t?? as?e???
• ?p?fas??eta?
• ? ??a??? t?? a?t??et?????? ?e?ape?a?
• ??t?µ?ta?
• ? ap?te?esµat???t?ta t??
• ? a?t??? sta f??µa?a ?a? ? ap?t???a t?? ?e?ape?a?
• ? p???d?? t?? ??s??

123
?a?a???????s? ?ï??? f??t???

• St?? a??? d?? µet??se??
• ?et? ap? 2-4 eßd?µ?de? ap? t?? ??a???
• ? µetaß??? t?? a?t??et?????? ?e?ape?a?
• ???e 3-4 µ??e?

124
?a?a???????s? CD4 ??tt????
?R? a?t??et????? ?e?ape?a
125
Highly Aggressive ART HAART

• S??d?asµ?? a?t??et??????
• ??se?
• CD4
• ????? f??t???
• ???????? ?at?stas??
• ep???µ?a? as?e????

126
????? t?? HAART

• µ???st? ?atast??? ???
• s??e??? ?atast???? ???
• a??a?? fa?µ???? ep? a?t????
• p??a?? ?a µ?? ap??atast?se?
• t?? a??s??????? ?e?t?????a e?d???
• ?ta? ? ??s?? ??e? p??????se?

127
??a??? ?e?ape?a?

• CD4 gt 500 HIV RNA lt 5000 ?
• CD4 gt 500 HIV RNA gt 5000
• CD4 200 500 HIV RNA gt 5,000
• CD4 lt 200

128
?a????µ???ta? a?????a µe t? s?µe?? t??
?????? a?apa?a????? t?? ??? p?? p??sß?????? se
?. ??ast??e?? t?? a?t?st??f?? t?a?s???pt?s??
(RT) No???e?s?d??? a?????a ??
??????e?s?d???? a?ast??e?? ?. ??ast??e?? t??
p??te?s?? (PI)

• ??t??et????? f??µa?a

129
??t??et????? f??µa?a

• Non-nucleoside RTIs
• Nevirapine (Viramune)
• Delaviridine (Rescriptovir)
• Efavirenz (Sustiva)
• Protease Inhibitors
• Saquinovir (Fortovase)
• Indinavir (Crixivan)
• Ritonavir (Norvir)
• Nelfinavir (Viracept)
• Amprenavir (Agenerase)

• Nucleoside RTIs
• Zidovudine (ZDV,AZT,Retrovir)
• Didanosine (ddI, Videx)
• Zalcitabine (ddC, HIVID)
• Stavudine (d4T, Zerit)
• Lamivudine (3TC, Epivir)
• Abacavir (Ziagen)
• Combivir (ZDV 3TC)
• Adefovir (Preveon)

130
Te?ape?a

• ???st?
• 2 NRTIs 1 PI
• ??a??a?t???
• 2 NRTIs 1 NNRTI

131
?? e??a? a?t???

• ?p??e?a t?? e?a?s??s?a? t?? HIV st??
• a?asta?t??? d??s? t?? fa?µ????
• ?a?a?t???st??? t?? HIV
• ?p?t??esµa t?? µetaß???? t?? ?e?et????
• ?????? t?? ???
• ?????te?? a?t?a ap?t???a?

132
???a??? a?t?e? a?t????

• ??epa???? ?e?ape?a
• ????? ???? f??t?? e?a????
• Fa?µa????????? pa?????te?
• ?a?? ap????f?s? ?a? ß??d?a?es?µ?t?ta
• ?a?? d?e?sd?s? fa?µ????
• ?a?? s?µµ??f?s? as?e????

133
???µ?de?? - d?????s? - ?e?ape?a -
p??f??a???? ???µ?de??

• ??d???se?? t?? HIV ap? t? ??ap?e?st??? S?st?µa
  !!!!

134
???µ??e?? t?? ??ap?e?st????

• ?a?t???a???
• ????ßa?t???d?a???
• ???a???a???
• ????t?as????
• ???t???a
• ???e?e??
• ???e?

135
???µ??e?? t?? ??ap?e?st????

• ?a?t???a???
• Strep pneumoniae
• Haemophilus influenzae
• Staph aureus
• Legionella pneumophila
• Gram (-) ß???????
• Nocardia
• Rhodococcus Equi

136
- ?a a?t?a e??a? ta ?d?a µe a?t? st??? as?e?e??
µe f?s???????? a??s??????? ?e?t?????a- ??
??V () as?e?e?? s?µpe??f????ta? ?p?? ??
as?e?e?? µe asp????a ? s???e?? ?p?-
?aµµasfa????a?µ?a- ?a?t?????? ???µ??? µe
e??a???a?? pa?????a de? e??a? as??????

• ?a?t???a??? ???µ??e??
• ??e?µ???a

137
?a?t???a?? p?e?µ???a

• Strep pneumoniae

• Haemophilus influenzae

138
Str. Pneumoniae ??e?µ???a

• ??ß?d?? ?ata??µ?
• ?????? ???d????
• ?????e? ??s??
• Asp????a
• HIV/AIDS
• ??????µ????
• ?µß???asµ??

139
Str. Pneumoniae ??e?µ???a

• CD4 lt 200
• eµß????
• S. pneumoniae pneumonia
• 100 f???? p?? p??a?? se as?e?e?? µe HIV

140
??e?µ???a ap? t? ?????t?taHIV (-) vs HIV ()
???ste? ??s???
?????? ap? t? p??t? ßa?t???a?? p?e?µ???a s?µf??a
µe a???µ? CD4

• ALIVE cohort, Baltimore N 3889
• ???e?e? 75
• HIV () 24
• ?ap??st?? 85
• ? ???d???? ? CD4
• 3-fold ? HIV IDUs CD4 gt 500
• vs HIV-negative IDUs
• 20-fold ? CD4 lt 200
• vs HIV-negative IDUs

HIV negative
HIV/CD4 500
HIV/CD4 200-499
HIV/CD4 100-199
HIV/CD4 lt 100
1.00
0.75
Pneumonia-Free Probability
0.50
0.25
0.00
0
5
10
15
20
Years of Follow-up
Stein K, et al. IAC 2006. Abstract MOAB0303.
141
??e?µ???a ap? t? ?????t?taHIV (-) vs HIV ()
???ste? ??s???

• HAART associated with 0.50 RH (95 CI 0.26-0.94)
  for CAP

HIV negative
14
45
HIV positive
40
HAART
12
35
10
30
8
25
of Study Visits on HAART
Pneumonia Cases/100 PYs
20
6
15
4
10
2
5
0
0
1989
1991
1993
1995
1997
1999
2001
2003
Calendar Year
Stein K, et al. IAC 2006. Abstract MOAB0303.
142
CXR
143
MRSA ap? t? ?????t?ta

• 40.4 /1000 PY HIV () 2005
• 18-fold ? ap? HIV (-)

• ???d?a?es???? pa?????te? ??a
• MRSA
• ???????µe?a ß-lactam
• OR 2.46 P .001
• ?st????? s?f???d??
• OR 4.40 P .01
• CD4 cell count
• OR per 100 CD4 cells 0.84 P .03
• Maximum log10 HIV viral load
• OR 4.52 P lt .001

18
16
MRSA Prevalence 1993-2005
14
12
10
Number of Cases
8
6
4
2
0
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
Year
Crum-Cianflone N, et al. IAC 2006. Abstract
MOAB0304.
144
MRSA ap? t? ?????t?ta

• 2006
• 435 HIV () as?e?e??
• 29 (6.7) community-acquired MRSA

• ??a?s??s?a se
• vancomycin and minocycline
• 28/29 (97) e?a?s??s?a TMP- SMX
• 4/29 (14) e?a?s??s?a erythromycin

Crum-Cianflone N, et al. IAC 2006. Abstract
MOAB0304.
145
??e?µ???a ap? ?t?pa

• Mycoplasma, Legionella, Chlamydia
• ?s??????
• ???p?e?µ?????? e?d???se??
• CXR s???? f?s???????? e?d??? st??
• a???
• ?? f?s????????
• ??????s? ?????????, ?g ?????
• Te?ape?a
• macrolides, quinolones

146
?a??a???????p?t? ? - s????t?ta eµf???s?? 70 -
ap? ta p??ta st?d?a t?? ??s?? - ?p?t??p??????
(??? ?a? 80) - s?????? p??sß?????ta? ta
??µ??e?a - Str. pneumoniae - ?????e?a a?????
3-4 eßd?µ?de?

• ?a?t???a??? ???µ??e??
• - ???te?? ??ap?e?st???

147
???????

• ?µß???asµ??
• ???f??a?? µe a?t?ß??t???
• ????????? s?µpe??f???
• ?p?µ???s? pas???t??
• ?paf? µe e?d??? ???t?a

148
A??s?p???s?

• ???a??? ??????s?
• ?d?a??p???µ??a eµß???a e?t?? ap? MMR
• S?st??eta? eµß???asµ?? ??a?t?
• ??e?µ??????????
• Influenza
• Hepatitis B
• MMR e?? e??a? as?µpt?µat????

149
???µ??e?? t?? ??ap?e?st????

• ?a?t???a???
• ????ßa?t???d?a???
• ???a???a???
• ????t?as????
• ???t???a
• ???e?e??
• ???e?

150
- Se as?e?e?? µe TB t? p?s?st? ????et???t?ta?
??a ??V 20-30- Se as?e?e?? µe HIV 4-5- St??
?ït? t? p?s?st? a?af??eta? 50- ?µfa???eta?
????? ??ass??? ??????? s?µe?a- S????te?a µe
e??p?e?µ?????? e?d???se??- S???? e??a? ? p??a?a
?a? µes????a???? ?eµfade??p??e?a

• ????ßa?t???d?a??? ???µ??e??

151
F?µat??s?

• Mycobacterium tuberculosis
• ?p??e?a ???µ???
• ??????? ß??a? /- a?µ?pt?s?
• ???et??
• ?p??e?a ß?????
• ???te????? ?d??te?
• ???d???? 100 f???? ?????te??? se HIV/AIDS

152
??????s? F?µat??s??

• ?t?e?a (t??????st?? 3 de??µata)
• /- ??????s??p?s? (BAL)
• K/ a ap? ???a ????? (p?e???t??? ????, ??? ??p)
• ??e???? a?t????
• Mantoux

153
CXR se F?µat??s?

• S???? ?t?p? e????a
• ?st?a??? d????se??
• ?????t?te?/Sp??a?a e?d??? st??? ??? ??ß???
• ???a?a ?eµfade??p??e?a
• ??e???t??? s??????
• ???????? CXR se HIV

154
- ?a?t?????? ?? ?a? ???? ???µ??? (PCP, CMV
?.?.p.)- N? ??µf?µa- ?t?p? a?t?????????
e????a- Mantoux (-)- ?? a????e?s? ??e??t????
ßa?????? sta pt?e?a- ????t???? ?/a ??a
????ßa?t???d??

• ??t?e? µ? ???a???? d?????s?? F?µat??s?? se HIV
  as?e??

155
??t?a ???stas?a? - ?p?µ???s? - ??te???ta
?t?µa T??????????????

• ??t?µet?p?s?

156
??? RIF PZA ??a 2 µ??e? ??? RIF ??a 7
µ??e? ??? 300 mg / ?µ??a ??RIF 600 mg /
?µ??a ????? 25-30 mg / kgr ?µ??a
?????p?e?µ?????? ??d???se???d?? s??µa a???
??aµß??t??? (25 mg /kg / ?µ??a)

• Te?ape?a

?????e?a 9 -12 µ??e? (??a p??????)
157
9-12 µ??e??a??d??? a?t?d?as? - ep?pt?s? 2 -
ep?de???s? s?µpt?µ?t?? µe t?? ??a??? a?t?-?? -
s???d???eta? µe µe??s? t?? ????? f??t??? -
a?t?µet?p?s? µe ???t???e?d? ??a ???e? ?µ??e??
??faµp????? ? ep?p?d?? PI ?a? ??RTIs st? a?µa
µe ap?t??esµa t?? a?epa??? a?t??et??????
?e?ape?a ?a? t?? a??pt??? a??e?t???? ste?e???
t?? ??? - ??a??a?t??? Rifamputin (300 mg/
?µ??a)

• ?????e?a Te?ape?a?

158
?e??s? ?p?pt?s?? TB HAART ?a? INH

• HIV ? ep?pt?s? TB
• HAART isoniazid prophylaxis ? TB ep?pt?s?
• Observational study
• gt 11,000 as?e?e?? st? Rio de Janeiro, Brazil

Golub JE, et al IAC 2006. Abstract MOPE0395.
159
???e?t??? TB ?a? T??t?t?ta

• South African clinic
• ?p?d?µ?a a??e?t???? ??
• ????µ??? ???t?t??

n 544 (33) culture positive for TB
N 1538 HIV pts
n 53 (24 of MDR) resistant to all TB drugs
tested (XDR TB)
n 221 (41) resistant to isoniazid and
rifampin (MDR TB)
52/53 died Median time to death 16 days
Gandhi NR, et al. IAC 2006. Abstract THLB0210.
160
F?µat??s? p??f??a??

• PPD gt 5 mm
• ??e?????? µe CXR (-)
• Se ???es?
• 1 ?t?? Isoniazid 300 mg / ?µ??a
• e?t?? ?a? e?? e?t????a? se
• MDR-TB

161
1. PZA Cipro ? ?floxacin PZA 25-30 mg
/Kgr PO /?µ??a Cipro- 750 mg x 2 PO /
?µ??a Ofloxacin 400 mg x 2 PO / ?µ??a2.
PZM SM ? ?micacin ? Capreomycin 3.
Paraaminosalicylic acid, Ethionamide,
Cycloserine4. PZA EMB PZA 25-30 mg
/Kgr PO /?µ??a EMB 15-25 / kgr. PO /
?µ??a

• ??a??a?t??? s??µata p??????? ?DR TB

162
Mycobacterium Avium-Intracellular Complex
(MAC)Ep?pt?s? 40-50?safe?? f?s???? ?a?a?t??e?
?p?d?µ??????a a?????a ap? ???a se
???a?µfa???eta? ?ta? CD4 lt 100/mm3?? e?d???
??????? ?a? a?t????????? e???µata?t?e?a () se
p?s?st? 16?/a () se 25?/a a?µat?? () e??
?a? 85

• ???µ??? ap? ?t?pa ????ßa?t???d?a

163
(No Transcript)
164
Non tuberculous mycobacteria
M KANSASII

• Infection of respiratory compromised hosts
• Present like pulmonary tuberculosis
• Treatment resistant to anti TB drugs

M SCROFULACEUM

• Infection of cervical lymph nodes
• Presents as cervical lymphadenopathy
• Treatment surgery

165
Non tuberculous mycobacteria
M avium intracellulare
Immuno competent host

• Infection of cervical lymph nodes

• Presents as cervical lymphadenopathy

• Treatment surgery

Immuno deficient host
M avium intracellulare

• severe RTI
• severe GI infection
• septicaemia

AIDS
166
Non tuberculous mycobacteria
M ulcerans

• Burundi ulcer

• Prolonged incubation required for growth

M fortuitum / M chelonei

• Injection related abscesses
• Associated with sternal wound infections
• following cardo-thoracic surgery

167
??s? t?? ?e?ape?a? ap?te???? ??
?????????SS??d?????ta? µe ???? ??a
pa?????ta?p?t???a t?? ?e?ape?a? -
a???t???p???s? ?/a se d??st?µa 4-12
eßd?µ?d????a?????µ????? 1-2 gr / 24 h ?
A?????µ????? 500 mg / ?µ??a???fa??µ???
50-100 mg/ ?µ??a ?? ? ??faµp????? 600 mg/ ?µ??a
?? ? ?µ??as??? 7.5 mg/kgr /12 h IM ? ?V

• Te?ape?a

168
?e?te??pa??? p??f??a?? - d?a ß??? -
??????µ????? 1250 mg / eßd?µ?da ? -
??a?????µ????? 250 mg / ?µ??a

• ???f??a??

169
???µ??e?? t?? ??ap?e?st????

• ?a?t???a???
• ????ßa?t???d?a???
• ???a???a???
• ????t?as????
• ???t???a
• ???e?e??
• ???e?

170
E??a???a??? ???µ??e??

• Pneumonocystis Carinii (PC)
• CMV
• MAC
• Cryptococcus spp.
• Cocciodioides spp.
• Fungii
• HZV complex

171
???µ??? ap? Pneumocystis carinii

• ? p?? ????? e??a???a?? ???µ??? se as?e?e?? µe HIV
  ?a? CD4 200 ? ????te??
• ?p?pt?s? ??? ?a? 60
• ?s?e?e?? ????? p??f??a?? 80

172
Pneumocystis carinii (PCP) p??f??a??

• ?st????? PCP
• CD4 lt 200/mm3
• ?µµ????sa? ?f?e?, d?s???? ?at?p?s?
• FUO gt 2 eßd?µ?de?
• TMP/SMX ?
• Dapsone, Pentamidine

173
Pneumocystis carinii ? Pn. jirovecii

• Unicellular eukaryote-Fungus
• ?a???sµ?a ?e???af??? ?ata??µ?
• ????a?e? ???µ??e?? se as?e?e?? µe d?ata?a??? sta
  T- ?eµf???tta?a
• AIDS
• ?p?f???d?t???? d?ata?a??? ?eµf???tt????
• CLL
• ?et? ap? µetaµ?s?e?s? µ?e???
• ?a?atetaµ??? ??????s? ???t???e?d?? ?a? ?. Cushing

174
???????? e?d???se??

• S?µpt?µata
• Stad?a?? eµf???s? (eßd?µ?de?)
• ?? pa?a??????? ß??a?
• ??sp???a
• ???et??

• S?µe?a
• ?????s??
• ?a??p???a
• S???? ????? e???µata ap? t??? p?e?µ??e?
• St?µat??? ????

175
(No Transcript)
176
??t???????a PCP

• ?µf?te??p?e??a ?e??p??a?a ?????µata
• F?s???????? µ??e??? ?a?d???
• ?e??stas?a?? ??e?µ????a?

177
PCP radiology
178
??????s? PCP

• ???ast???a??
• ABG ?p??????a?µ?a
• ?? LDH
• CD4 lt200

• ?st???????
• ?t?e?a
• ??????s??p?s? ?a? BAL
• ?????a ??e?µ????
• ?e?????a

179
?st?????a t?? PCP

• F?s????????? ???e??de?

PCP
180
?st?????a silver methenamine
181
?e?????a se PCP
182
Te?ape?a t?? PCP

• Trimethoprim/ sulfamethoxazole
• Dapsone/clindamycin
• Pentamidine iv
• Steroids

183
F??µa?a -??se??
184
(No Transcript)
185
(No Transcript)
186
(No Transcript)
187
???f??a?? ??a PCP

• ??de??e??
• CD4 lt 200
• ???????µe?? epe?s?d?? PCP
• St?µat??? candidiasis

• TMP/SMX daily
• Dapsone daily
• ??sp?e?µe?? Pentamidine / a?? µ??a

188

• ???f??a??

189
???f??a?? ??a ???e? ??s???

• CD4 ?????e?ta? p??f??a?? ??a
• Mycobacterium avium complex (MAC)
• Toxoplasma gondii
• Herpes simplex
• ????t?as???? ???µ??e??
• Cytomegalovirus (CMV)

190
F??µa?a, d?se?? ??a p??f??a??
191
(No Transcript)
192
???f??a??

• PCP, toxoplasmic encephalitis, MAC, CMV
• p??f??a?? d?a ß???
• Salmonella septicemia
• ??a µ??e?

193
Fungal pneumonia

• E?d?µ???? ????te?
• Histoplasmosis 1
• Blastomycosis 0.1
• Cryptococcosis 7-13
• Aspergillus spp.
• Candida spp.

194
(No Transcript)
195
?????t? Aspergillosis
196
??????s? ?a? Te?ape?a

• ??????s??p?s?
• ?????a ?st??
• ??t?µ???t?as???
• Amphotericin
• Imidazoles
• Caspifungins
• ????t???? pa?????te?
• ?p?st????t??? µ?t?a

197
???µ??e?? t?? ??ap?e?st????

• ?a?t???a???
• ????ßa?t???d?a???
• ???a???a???
• ????t?as????
• ???t???a
• ???e?e??
• ???e?

198
???e?e?? ???µ??e??

• Influenza
• Cytomegalovirus (CMV)
• Herpes simplex virus (HSV)

199
Influenza virus

• Orthomyxovirus
• ssRNA virus
• Influenza A,B,C
• haemagglutinin (HA) neuramindase (NA)

200
Flu ??????? ?a? ?e?ape?a

• Amantidine /Ramantidine
• Targets envelope protein
• Used in prev. and Rx
• NA inhibitors
• Oseltamivir or ranamivir
• Use at onset of Sx
• Reduce Sx by 1 day

• Vaccination
• Adequate immune response takes 2 weeks
• Immunity weans in few months
• Contraindication with egg allergy and allergy to
  other vaccine components

201
CMV p?e?µ???a

• ?a?e?? ???µ???
• ????s?st?µat???
• Sta te?e?ta?a st?d?a t?? ??s??
• ? d?????s? PCR ß????a
• Te?ape?a
• Ganciclovir-quanine
• 5mg/kgr a?? 12 ??e? ??a 2 eßd?µ?de?
• ?a?e????e?e? ??dete??pe??a

202
???µ??e?? t?? ??ap?e?st????

• ?a?t???a???
• ????ßa?t???d?a???
• ???a???a???
• ????t?as????
• ???t???a
• ???e?e??
• ???e?

203
????p??sµ?s?

• ?a?as?t?s?
• 5-15
• CD4 lt 100
• ??e?µ???a ?a? e??efa??t?da
• () anti-Toxoplasma IgG a?t?s?µata
• ????µe?aµ??? s???fad?a????
• ?e???ß?????

204
?? ???µ?de?? e?d???se?? ap? t? ??ap?e?st??? se
as?e?e?? µe HIV ???µ???
205
?a????e?a - S????µa Kaposi - Non-Hodgkin
??µf?µa ???µes? ??e?µ???p??e?a -?eµf???tta????
(LIP) -?? e?d??? ?eµf???tta???? ???e??d?t??
206
20.000 f???? s????te?a ap?t? st? ?e????
p????sµ?t? 15-20 t?? as?e??? ?a a?apt??e? S?t?
95 af??? ??d?e? (?µ?- ? aµf?f???f?????)Te??e?ta
? - µ? ?a?????? ?pe?p?ast??? ß??ß? t?? a??e?a???
ep???????- de?µat??? e?t?p?s? s?????ste??-
p?e?µ????? e?t?p?s? ???d?a ?a? d?af?a?µat????
d????se??- s?µpt?µata µ? e?d??? t??
a?ap?e?st????- d?????s? scanning Ga 67 -
ß????a ???st??? d?????s?- ??µe???e?ape?a

• S????µa Kaposi

207
60 f???? s????te?? ap?t? st? ?e???? p????sµ?-
p?????????? ?pe?p?as?a- µ??????????
?a????e?a-e?tetaµ??? ??s?? µe e???eµfade?????
e?t?p?se??- p??et??, ap??e?a ß?????, ?d??te?-
d?????s? p?e?µ?????? e?t?p?s?? ß????a-
??µe???e?ape?a

• ??n-Hodgkin ??µf?µa