????? ??? – ????, ???, ????. ?????? ???/?????

1
??????? ?????? ?????????? ?"? ????
???? ????? ?????? ???????? ???????
2
??????? ????? ????????????? ?????

• ??????? ????? ?????? ?? ????? ?????????.
• ????? ?????? ???????.
• ??????? ?????? ????????????.
• ?????? ????? ?? ?????? ???????????.

3
?????? ??????

• ??? ????? ??? ???? ?????????????
• ??? ???????? ????????
• ???? ????? ???????
• ??? ?????? ????? ???????? ????? ?????? ???? ?????
  ?? ????????????
• ??? ???, ?? ??? ???, ????? ??? ?????? ????
• ??? ?? ?????

4
????? ??????

• ????? ??? ????, ???, ????. ?????? ???/?????
• ??????????? ????? ?????? ???????
• PCR ????? DNA/RNA ??????.
• ?????? ????? ????. ?????? ???? ????? ?????
• ????????? ??????????? ??? ?????- ??? ??????
  ????? ????? ????? ???????? ?? ?????.

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?????? ??????

• ??????? ????? ???? ?????? ???? ???????? ?????.
• MIC ????? ???????????? ????? ????? ????? ?????
  ?????? ???? ????? ?? 18-24 ????.
• ???? ????? ??????
• Disc diffusion
• E-test
• Genetics mec A

9
Disc diffusion
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E-test
11
??????? ??????
12
????? ?????

• ?????? ????
• ???
• ??????? ???? ????? ?? ???? ?????? Ph ???? ????
  -gt ????? ???????? PO ???? ????.
• ????? ??????? ???? ???????- ??????????,
  ????????????, ??????- ???? ?????? ??????????
  (???????) , AG ???????????

13

• ????? ????- ??????? ???? Glucuronide transferase
  ???? ??????-gt????? ?????? ???????????-gt Gray baby
  syndrome.
• ??????????- ??????? ???? ??????? ??????? -gt
  ????????????? ?? ???????
• ?????? ????? ?????? ???? ????? ??????????.

14
?????

• ??? ????? ???? ????-gt ????? ???? ???? ?? ??????-gt
  ???? ?????? ?????.
• ???? ?? ???????? ?????? ?????.
• ??????????, ????????????, ?????????? ??????
  ??????.
• ?????????? ????!!

15
?????? ?????? ????????

• Rapid vs. slow acetylators ???????????? ??
  ?????????? ????? ???????.
• G6PD deficiency- ?????.
• ????? ?? ??????????? IM ?????? ????????

16
????? ????? ????

• ?? ??????? ?????? ???????? -gt ????? ?????.
• ?????? ?? ?? ????? ????? ??? ?????? ?????
  ????????
• ????????, ??????? ??????? AG, ?????????
  ??? ? CN VIII ???????? ????????? (??????)
  ????? ?????? ?????.

17
??? ??????

• ??? ??????
• ?????
• ??? ???
• ???? ????? ????? ?? ?????? ???? ????? ?????
  ???? ????? ? MIC ?? ?????? ????????????.

18

• Meningitis ???? BBB ?????? ??????????.
• Endocarditis ????? ???????
• Osteomyelitis ????? ???? -gt ????????????
• ????? ????? IV ?????.
• Cholangitis ?????? ???????? ???? - Ampicillin

19

• ?????? ??????? AG ?????? ??????????? ?????
  ??????-gt ???? ????? ???????.
• ?????? ??? ?? ??????? ?????? ???????????

20
????? ??????

• ??? ????? ?????? ???? ?????
• ?????
• ????? ???????? ?????? ????? ???????
  ???????????? ????, HIV
• ??????? ??????????????? ?????? ??? (??????????)
• ????? ??? ?????? Neutropenic fever

21

• ????????
• Enterococcal endocarditis,
• Pseudomonas bacteremia
• Trimethprim-Sulfamethoxazole

22
????? ?????? ??????

• ??? ???
• PO
• ???? ????
• ????? ?? ??????
• ????? ?? ?????? ????? (????-??????? ???????
  ?????? ?? ???????????)
• ????? ?? ????/????

23

• IV
• ????? ??????
• ????? ???? ????
• ???? ?????? ???? ?????? - Endocarditis

24
?????

• Time-above MIC ß lactam, ??????????,
  ???????????, ???????? ?????? ????????? ????
  ????? ?????? ??? ? MIC ?????? ???? ??? ????? gt
  ??? ?? ??? ??? ?? ???? ?????.
• Concentration-dependent killing peak/MIC or 24h
  AUC/MIC AG, ???????????. ???? - ??? ???????
  ???? ???

25

• ????

26
Antibiotic -Mechanism of action
Cell wall synthesis Penicillins Cephalosporins Azt
reonam Carbapenem Vancomycin
DNA replication Quinolones
RNA polymerase Rifampine
Folic acid metabolism Trimetoprim Sulfonamide
Protein synthesis 30s Ribosome
Aminoglycoside Tetracycline
50s Ribosome Erythromycin Clindamycin Chloramphen
icol
27
Beta lactam ring antibiotics

• Penicillin
• Cephalosporins
• Carbapenem
• Monobactam

28
Penicillin

• ????? ?"? ?????? ? 1928, ???? ?????? ? 1941.
• ???? ????? ???? ????- ??????.
• ?????? ?????? ????? ???? ?????? ??????? ???? ??
  ?????? (??? ????? ? PBP)
• ??????? ??????
• ??? ???????????? ?"? beta lactamase Staph
  aureus, gram negative
• ????? ?????? ?? ???????????? ????? ??????

29
Penicillin
30
Penicillins

• ?Natural Penicillins Penicillin V(Rafapen)

? Penicillase Resistance Cloxacillin (orbenin)

? Aminopenicillins Ampicillin
Amoxicillin (moxypen)
Amoxicillin- clavulonate
(Augmentin)
?Extended spectrum Piperacillin (pipril)
Piperacillin-tazobactam (tazocin)
31
?????? ?????

• ?????? ????????? 0.004-0.4 (???????? G)
• ?????, ??? 4-8 (?????????)
• ?????? 2-5 (?????????)
• ?????????? 1-4 (????????, ?????????...)
• ????? ??????? ??? 1-4 (???????)

32
Drug eruption- penicillin
33
Cephalosporins

• ???? ??????? ? 1945 ??????? Cephalosporium
  acremonium ?????? ????? ?? ????.
• ???? ????? ???? beta-lactam.
• ????? ??? ????? ??????? ??????? ???? ???????,
  ???????????? ??????? ?????-??????.

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Cephalosporins

• First generation
• Cefazoline,Ceforal
• Second generation Cefuroxime (Zinacef/Zinnat)
• Third generation Ceftriaxone (Rocephine)
• Fourth generation Cefepime

Gram negative
Gram positive
36
??????? ??????

• ????? ???? ?????? ?? ???????????? ????? ???
  ?????? (PBP)
• ???? beta-lactamase
• ESBL
• Amp C

37
?????? ????? ???????

• ????????????? 1-5
• ????? 1-4
• ????? ??????? ??? 1-7
• ??????

38
Drug eruption
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Carbapenem

• Imipenem, Meropenem, Ertapenem
• ???? ???? ???? ??????
• ????? ??? ????

40
Carbapenem
41
Carbapenem-Resistant-Enterobacteriacea
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Monobactam

• Aztreonam (Azactam)
• ???? ????? ????? ??? ?? ??????? ??? ??????? ??
  ????????gt ???? ?? ??? ??? ???????.
• ??? ?????? ????? ?? ????-?????? ????? -gt ????
  ??? ??????? ?????????

43
Glycopeptides

• Vancomycin , Teicoplanin
• ?????? ????? ?????? ???? ?? ??????.
• ?????? ??????? ??? ??????? ???? ?????? MRSA
• ???????? VRE

44
Quinolones

• Nalidixic acid ???? ? 1962 ????? ????? ???????
  ??????????.
• ?????? ????? ?????? ? DNA ??????? ?"? ?????
  ?????? ? gyrase, topoisomeraseIV
• ?????? ???? ???? ???? ??????? ??????,
  ???????????.
• ??????? ????? ???? ???? PO.
• ????? ???? ?????? -gt Prostatitis osteomyelitis

45
Aminoglycosides

• ???? ? 1940
• ???? ?????? streptomycin ????? ?"? ???????
  streptomyces.
• ?????? Garamycin Tobramycim Amikacin

46

• ?????? ????? ???? ?????? ?????????? ?? ??????
  ???? ???????? ?????? ?????? ???????.
• ??????- ????? ?????? ? Abx ?????? ????? ????
  ????? ? Abx ????????
• ?????? ????????, ???????????-gt ??? ?? ????,
  ???? ??? ????.

47
Macrolides

• ???? ???????? ????? ????? ????? ????? ??????.
• Erythromycin, Roxithromycin Clarithromyc
  in Azithromycin

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Tetracycline

• ?????? ????? ????? ?????????? ?? ?????? ??????
  ???????? -gt ????? ????? ??????? ?"? ??????.
• ??? ???? ?????????, ???????, ??????, ?????

49
??????

• ??????? ??? ??????? Strep, pneumococci ,
  S.aureus?
• ??????? ??? ??????? ?? ???? ?????? H.influenza
  , Moraxella
• ???????? , ?????????

50

• ??????? ??????- ????? ??????? ?? ??????
  ?????? "????? ?????" ????? ??? ????? ? Abx
  ?"? ????????

51
New arrivals

• Lipopeptide Daptomycin
• Streptogramines Quinupristin/dalfopristin
• Oxazolidinone Linezolid
• Ketolides Telithromycin
• Polymyxins - Colistin

52

• ???

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ANTIBIOGRAM
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E-TEST
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Fever is not an antibiotic deficient state
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Optimal use of Antibiotic

• Does the patient actually need antibiotics?
• What are the likely organism we are aiming at?
• Where is the infection?
• What is /are the best antibiotic (s) for these
  organisms at this site?

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Optimal use of Antibiotic (Cont.)

• Are there any problems in using antibiotics in
  this patients?
• How much, how often, by what route, for how long?
• Is there a response?
• How much does it cost?

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Gram - Positive
Gram - Negative
Outer membrane
Cytoplasmatic Membrane
Peptidoglycan Layer
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???? ????? ???????

• ?????????
• ?????????
• ????????
• ????

64
Mechanism of antibiotic resistance
65
????? ?????

• ??? ????? ???????, ????, ?????? ?????
• ?????? ??????? ????
• ?????/????
• ????? ??????? ?????

66
?????? ??????

• ????? ???? PO
• ????? ??????????? ??? ??????
• ??? ??? PO, IM, IV
• ???????????? ????????????? ??? ????? ?????

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