Paul Ehrlich(1854~1915)

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2
????
3
????
???? Paul Ehrlich(18541915)
??????????,?????????? ?????????????????????? ??
?? Selman Waksman(18881973)
???????,????????????? ?????????? ? ?????
4
???????????
?????? ? ?????? ? ????????????? ?
?????? ???????? ??????????????
??30????????,????????? ?????????? ? ?????????
5
??????
???? ?????????????,????????????????? ???????
??????(CI)???????????? ???? ????????????
????????ß-?????? ?????????????????
??????????(???????????)????????
6
??????????
??????????????????? ????????????????????
??????????????????????? ?????
?????????????????? ??????? ? ????
???????? ????? ????????????????
??????????????????????
7
?????
????????(MIC) ???????????????????????? ??????(MB
C) ????????????????????? ???????
???MIC?????? ??????????????????? ? ??,????
MIC??????? ? ???????MBC?? ???????
?????????????? ? ??????????? ? ??? d alogP
ß (d??????,P?????) ????????MIC ? ??????
?????,??????,????,???????????MIC PAE(post
antibiotic effect) MIC????????????????,??????????
?? ????,??????????
8
???????
12.5
3.12 mg/mL
6.25
100
50
25
0.05 mg/mL
0.78
0.20
0.10
0.39
1.56
?B
?A
?AMIC 6.25 mg/mL ?BMIC 0.78 mg/mL
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ß?????????
10
????????
Alexander Fleming(18811955)
?????????,????????
Penicillium nonatum ?????????????
?????(1929)
???????(Streptococcus pyogenes) ????(Streptococcus
pneumoniae)
????,????
11
?????????
Howard Florey(18981968) Ernst Chain(19061979)
?????????(1938) ??????????(1941) ?????G(?????????)
?????(1945)
ß?????
?????????(??)
??????(?????,???????) ???????(??,????) ??????(????
???? ??)
12
???????????
??????? (ß???????)
?????????????????????????? 1946? 15 1947? 40
1948? 60
13
???????????
???????(??)
??????(??,??)
??????
????????????????????????????? ???,Proteus
mirabilis,???????? ???????? ??????????
14
??????????
??????(??)
????????????????? Citrobacter,????,Enterobacter,
Serratia, Morganella morganii,Providencia,??? ???
??????????? ????????????
15
?????????????????? ????????????(PBPs)
b-????
16
???????????
????????C
Acremonium chrysogenum
?????????????? ??????????
???
????
17
???????????(?1??)
??????(??)
?????????? ?????????????? ? ???????? ?
???,???? ? ??????????,?????????????
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???????????(?2??)
??????(??)
?1?????????? ??????????????????
???,Citrobacter,Klebsiella,Enterobacter,Proteus,
Morganella morganii,Providencia
rettgeri,????????
19
???????????(?3??)
???????(??)
?2?????????? ????????????,???????
?????????????? ???????,?????????????
20
?3?????????

????????(??)
???3?????????? ?????????????? ????????(1
g?????????7.5 h) ??????,??????,????,??,???, Citro
bacter,Klebsiella,Enterobacter,Serratia,Proteus,Mo
rganella morganii,Providencia,????????,Peptostrept
ococcus,Bacteroides,Prevotella
21
?3?????????
???????(??)
?????? ??????????? ???????????????? ??????,????,?
??,Citrobacter,Enterobacter, Klebsiella,Serratia,
Proteus,Morganella morganii,Providencia
rettgeri, ????????,???,Bacteroides,Prevotella
22
???3??????
?????
????? ?????
??????,??????,????, ??,Moraxella
catarrhalis,???,Citrobacter,Klebsiella,Enterobacte
r, Serratia,Proteus,Morganella morganii, Providenc
ia,????????, Peptostreptococcus,Bacteroides, Prevo
tella,????
?????? ?????
23
(?4??)???????
???????(??)
?3?????????????????? ?????????? ?????,?????,??
??,???,Moraxella catarrhalis,???,Citrobacter,Klebs
iella,Enterobacter,Serratia,Proteus,Morganella
morganii,Providencia,????????,Pseudomonas,???,Burk
holderia cepacia,Stenotrophomonas
maltophilia,Acinetobacter,Peptostreptococcus,Bacte
roides,Prevotella
24
??????????????
??????(??)
??????(????MRSA???),??????,????, ??,Moraxella
catarrhalis ,???,Klebsiella,Proteus,Providencia,Mo
rganella morganii,????????, Peptostreptococcus,Bac
teroides,Prevotella
25
?????????????
??????? (1981)
SQ26823 (1981)
Pseudomonas acidphila
Agrobacterium radiobacter
???????(???)
???????????????????????
26
?????????????
??????? (1976)
Streptomyces cattleya
??????? ?????????
??????????? I ? ???????
1 1
?????????? I???
???????????(??)
????????(????) ????????(????,Bacteroides) ?????,?
???????????????????
27
??????????

?????(??)
4-??????????,???????????????????? ??????,??????,?
???,????,????, Moraxella catarrhalis,???,Citrobact
er,Klebsiella,Enterobacter, Serratia,Proteus,Provi
dencia,????????,Pseudomonas, ???,Burkholderia
cepacia,Bacteroides,Prevotella ??????,??????
28
b-????????????
b-??????
??????
??????
Streptomyces clavuligerus
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b-???????????????????
2 1
?????????????(??)
??????????????,Klebsiella,Proteus
vulgaris,Bacteroides?????
2 1
????????????(??)
??????,???,Proteus,????????
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b-????????????????
4 1
????????????(??)
??????????????? ??????,??????,????,????, Moraxel
la catarrhalis,???,Citrobacter,Klebsiella,Enteroba
cter, Serratia, Proteus,Providencia, ????????,???,
Acinetobacter
31
b-???????????????
1 1
?????????????(??)
??????,???,Citrobacter,Klebsiella,Enterobacter,Ser
ratia, Proteus,Providencia rettgeri,Morganella
morganii,????????,???,Acinetobacter,Bacteroides,Pr
evotella
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ß?????????
??????????,??????? ?????(????????)
????????????? ?????,??????????? ?????
????,?????,???? ????????? ??????(???????)
??,????,????,????? ????????(?????????)
?????????????,??,??,?? ???????K???
33
???????????
34
??????????
???????(1955)
Streptomyces orientalis
MRSA???(??) Clostridium difficile??????(??) ???
???,???? ????,??????????? ?????????(?????)
(?,?,????????,???) ???? ??????????????? D-Ala-D-
Ala ???????? ? ????,??????
35
???????????
???????(??)
Actinoplanes teichomyceticus
MRSA??? ???????? ???,???? ????,???????????
?????(??????)???
36
????????????
37
????????????
Selman Waksman (1888-1973)
???(Mycobacterium tuberculosis)
??? ????? ? ??????
????????? (1944)
Streptomyces griseus
??? ?????????????????????? ???,????(Yersinia
pestis), ????(Francisella tularensis), ??????????
?????30S??????????, ???????????? ???????,???
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?????????
2-??????????? (??????????)
??????(??)
Streptomyces kanamyceticus
???,??????????????????????????? ?????30S???50S
??????????,???????????? ???,??????????????????
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????????????
???????(??)
?????(??)
Streptomyces tenebraius
????????????? ??????????????? ???????????????????
????????????? ???????????????
40
???????????
R1 , R2 H or CH3
???????(??,??)
Micromonospora purpurea
?????????????,????? ???(????????,????) ????,??????
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?MRSA????????
??????(??)
?MRSA? ??????????????? ?????????????? ????????????
???????
42
???????????????
?????????,???????????? ???????????????????????
??????????? ???????? ????(?????????),?MRSA?
(??????) ???????????????????????????
???,??????? ??????????? ???????????PAE(postant
ibiotic effect) ????????????????????????? ?
?????? ???????? ?????????,??????,?????
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??????????
44
???????????
???????? (1952)
Saccharopolyspora erythraea
?????????????(14??) ?????50S??????????,????????
???? ??????,???????,???????,????? ???????? ?
????? ???,???
45
???????????
?????????(??)
????????(??,??)
??????? ??????,??????,????, Moraxella
catarrhalis ,????????,Legionella, Peptostreptococc
us,???????,????? ????????(????????????????PPI)
46
?????????????
?????50S??????????,???????????? ??????,???????,?
??????,???????? ?????????,???????????????????? ?
?????,?????????? ????????? ?????,????????(??????
???)
47
????????
48
???????????
????????(??,??)
??????,????????????????(??) ?????50S??????????,??
?????????? ????????????????? ???Clostridium
difficile?????????
49
?????????????
30 70
???????????????(??)
?????????Enterococcus faecium(VREF)???
50
????????????
???????
????????(1953)
Streptomyces viridofaciens
??,?? ?????,?????????????? ????????????
Legionella pneumophila, ?????,?????????
??,?? ??????,???????????? ???????? ?????,?????,??
???????? ?????30S??????????, ????????? ?????
51
??????????????
??????????(??)
Streptomyces venezuelae
????????????(???,?????) ? ???????? ??Salmonella
???(????,???????) ?????50S??????????,????????????
?????? ?????? ? ??????? Gray??????(???)????
,??,??,?????
52
????????
???????(??,??)
Streptomyces fradiae
?????,????????????? ?????,???,???,Salmonella,Serr
atia,Proteus, Morganella morganii,Providencia
rettgeri,???,Campylobacter ?????????????????N-????
????????????
53
????????
???????(??)
Streptomyces roseosporus
MRSA???(??????????) ???????????
54
????????
?????(??)
Pseudomonas fluorescens
MRSA?????? ???????????? ? ????? ??????-tRNA???????
55
????????
56
??????????
?????????
????
????????(1978)
?????? (1962)
??????????????????? ???????????PAE(postantibiotic
effect) DNA???????? ???????
??????? ? ?????
57
???????(??)
??????????????? Acinetobacter,Peptostreptococcus??
?
?????????(??,??)
??????????????? Acinetobacter,Peptostreptococcus??
?
????????
?????(2?)
58
???????????????
????????(??,??)
??????,??????,????,????,???, Peptostreptococcus,??
?? ??,???,Moraxella catarrhalis,Acinetobacter,Leg
ionella, ????, Q??????,???,???,Salmonella,Citrobac
ter,Klebsiella,Enterobacter,Serratia,Proteus,????,
Providencia,Morganella morganii, ????,????????,Cam
pylobacter,Brucella ??????????,???????,?????????
59
???????????
???????(??)
????????(??)
??????,??????,????, Moraxella catarrhalis,???, Kle
bsiella,Enterobacter,????????, Legionella
pneumophila, ???????,????????? ????????,1?1???
??????,???????????? Burkholderia
cepacia,Stenotrophomonas maltophilia,Bacteroides??
???? ??????? ?????????
60
????????????
??????????,???????(35) ??????????,?????,??
??,?? ??????,??,???? ?????????,????,??,??,
??,?? ?????? ????????,???????? ?????????? ???
??????????????????????? ?????????,???????? ????
????????????(NSAIDs)????(GABA????)
???????,????????????????? ???????
?????????
61
???????
62
????????
Gerhard Domagk (1895-1964)
?????(Streptococcus pyogenes)????????????????
??????????
?????? (1935)
63
ST??
5 1
??????????????????
?????????????,???(??) ???,?????(?????) ?????(??)
?????????,????????
64
???????????
??????
???????
????????
65
????
66
????
??? Mycobacterium tuberculosis
??????????????
??????(??,??)
???,??????? ?????????????? ??????,??????
(?????????)
67
????
???,??????? ????????,????? ????DNA???RNA????????
??????,???? ?????????P450????,???? ????????,??
????????? ??????,?????,???????, ?????????,??????(
?HIV?) ??????(?HIV?) ???????(????) ???????(????) ?
?????(???????)
???????(??)
68
????
???????(??)
??????(??)
???,??????? ???????? ????????????????? ???????
???,??????? ????????????????? ????? ?
???????? ??????,???
69
????
?????????(??)
30S????????????????? ?????????,???
70
????????
?????? ??????? ?????? ??????? or
????????? 2??
?????? ??????? 4??
????????
???,?????????,??????????,??????????
???????????????????????????????????
71
?????????
72
?MRSA,VRE?
?????(??,??)
MRSA,VREF???????????? ?????70S????????? ?
????????? ???????????Enterococcus faecium(VREF)
??????????????(MRSA) ???????????????,??,????,
?????
73
?????
????????
????(??)??????? PPI ??????(??,??) ?????????
???????????????????,DNA?????? ???????,?????,???
??????,???? ????(???)
74
??????????
???(????????)????? ß-????? ??????????????????(??
)?? ???????? ???????D-Ala-D-Ala????? ? ??,????
??????? ??????N-???????????????? ??????????
??????? 50S???????? ???????? 50S????????
?????????? 50S???????? ????????? 30S????????
????????? 30S(???50S)???????? DNA?????????
????? DNA??????,???????????? ???????
????? p-???????????,????????????????
??????? ????????????
75
?????????????
ß-???? ß-??????????? ???????????????????????????(
MRSA) ???????? ??????????????? ?????????????????
(???) ?????? rRNA??????????????? ??????????????
??? ???????? ??????????????? ????????????? ????
??? ???????????? ??????????????? ??????? ???????
????????????????(VRE) ?????,??????? ?????????????
???? ???? DNA?????????????????? ????????????????
??
76
??????????????
???????????????? ??????????,?????? ?????????
????,??? ?????????????????????
?????????????? ??????????????? ?????????????
??,??? ????????????
77
??????
????????,???,??????????? ?????,???????,?????????
????????????,????? ?????????,???????? ?????????
???????????? ß-????? ?????????????????????
?????