Inhoud
Inhoud ........................................................................................................................................................................................ 1
Antibiotica .................................................................................................................................................................................. 3
1. Inleidende begrippen ......................................................................................................................................................... 3
Bacteriostatisch/ Bactericide .............................................................................................................................................. 4
Antibiogram volgens diffusiemethode ............................................................................................................................... 4
E-test .................................................................................................................................................................................. 5
Synergie/ antagonistisch/ additief effect ........................................................................................................................... 5
Farmacokinetica ................................................................................................................................................................. 5
Resistentie .......................................................................................................................................................................... 6
2. De celwand als doelwit ....................................................................................................................................................... 9
2.1. Biosynthese van peptidoglycaan ................................................................................................................................. 9
Te kennen structuren: .................................................................................................................................................... 9
Synthese van peptidoglycaan ....................................................................................................................................... 10
2.2. Fosfomycine, D-cycloserine, bacitracine ................................................................................................................... 14
Fosfomycine ................................................................................................................................................................. 14
D-cycloserine ................................................................................................................................................................ 14
2.3. Glycopeptide antibiotica ........................................................................................................................................... 15
Vancomycine ................................................................................................................................................................ 15
2.4. Beta-lactam antibiotica ............................................................................................................................................. 15
Penicillines .................................................................................................................................................................... 17
Cefalosporines .............................................................................................................................................................. 17
Carbapenems................................................................................................................................................................ 17
Monobactams .............................................................................................................................................................. 17
3. Polymyxines: verstoring buitenste membraan ................................................................................................................. 18
4. Inhibitoren replicatie en transcriptie ................................................................................................................................ 19
4.1 Quinolonen ................................................................................................................................................................. 19
4.2 Rafamycine ................................................................................................................................................................. 20
5. Inhibitors protein synthesis .............................................................................................................................................. 21
5.1 Bacterieel ribosoom ................................................................................................................................................... 21
1. 30S inhibitors ............................................................................................................................................................ 22
2. 50S inhibitors ............................................................................................................................................................ 24
6. Inhibitoren van metabolisme ........................................................................................................................................... 26
6.1 Inhibitoren foliumzuursynthese ................................................................................................................................. 26
6.2 Metronidazole ............................................................................................................................................................ 27
7. Tuberculostatica ............................................................................................................................................................... 28
Mycobacterium tuberculosis ............................................................................................................................................ 28
Therapie ....................................................................................................................................................................... 28
Isoniazide ...................................................................................................................................................................... 29
Ethambutol/ streptomycin ........................................................................................................................................... 29
1
, Pyrazinamide ................................................................................................................................................................ 29
Rifampicine ................................................................................................................................................................... 30
Multidrug resistente tuberculose (MRD).......................................................................................................................... 30
Extensief-drug resistente tuberculose (XDR) .................................................................................................................... 30
8. Antifungale middelen ....................................................................................................................................................... 31
Polyenen ........................................................................................................................................................................... 31
Allylamines ....................................................................................................................................................................... 31
Azolen ............................................................................................................................................................................... 32
Fluorocytosine .................................................................................................................................................................. 32
Griseofulvine .................................................................................................................................................................... 33
Echinocandin .................................................................................................................................................................... 33
9. Antiparasitaie middelen ................................................................................................................................................... 34
Anti-protozoaire therapie met zware metalen ................................................................................................................. 34
Therapie voor Leishmania ................................................................................................................................................ 34
Therapie van Afrikaanse Trypanosoma ............................................................................................................................ 35
Therapie van Trypanosoma cruzi...................................................................................................................................... 35
Malaria behandeling......................................................................................................................................................... 35
1. Quinine en gerelateerde moleculen ......................................................................................................................... 35
Antifolaat ...................................................................................................................................................................... 36
Artemisinine ................................................................................................................................................................. 36
Preventie ...................................................................................................................................................................... 37
2
,Antibiotica
1. Inleidende begrippen
Curve zakt heel fel = mortaliteit van 25%
( 25% halen 5j niet door infecties, ziekte, slechte
behandeling )
→ Niet genetisch want vroeger bij ons gelijkaardige
piek ( geen antibiotica )
Nu rode piek: veel lagere mortaliteit
Antibiotica:
Een substantie van biologische, semisynthetische (biologisch geproduceerd, maar geoptimaliseerd) of
synthetische oorsprong met een selectieve inhiberende activiteit tegenover bacteriën.
→ Selectieve toxiciteit: O.b.v. verschillen tussen gastheer en infectieus agens wordt het toxisch voor B gemaakt,
maar niet voor eukaryote gastheer. Moet penetratievermogen hebben en een grote specifiteit en affiniteit voor
microbieel doelmolecule.
(Controle van fungale en protozoaire pathogenen moeilijker omdat verschillen met eukaryoten kleiner zijn (vaak
ook toxisch voor gastheer)
→ Ontdekking van pencilline mbv staphylococcus
Spectrum: Tegen welke B is antibiotica actief
Breed: tegen veel B (zowel gram + als - )
Eng: tegen minder B ( bv enkel gram -)
3
, Bacteriostatisch/ Bactericide
Bacteriostatisch: Inhibeert groei (B NIET kapot) Verdere opruim door immuunsysteem
Bactericide: Afdoden en kapot maken van B
= Kijken vanaf welke [antibioticum] er geen
B groei meer is.
= Kijken vanaf welke [antibioticum] B
afgedood worden
= hier is MBC kleiner omdat B al afgedood
wordt bij een [antibioticum]= 1/4
MIC (minimale inhibitorische concentratie): Minimale concentratie antibiotica nodig om Bgroei te inhiberen.
MBC (minimale bactericide condentratie ): Minimale concentratie antibiotica nodig om B af te doden.
BPC (breekpunt concentratie): Specifieke grenswaarden van antibioticum concentraties internationaal vastgelegd. Werd
bepaald door normale dosis toe te dienen aan patiënt en kijken welke [antibioticum] er terug gevonden wordt.
→ Gevoelig: B geremd door BPC
→ Intermediair: B niet geremd door BPC wel door maximale [antibioticum]
→ Resistent: B niet geremd door BPC
Antibiogram volgens diffusiemethode
1. Uitplaten over agarbodem ([agar] moet gelijk verdeeld zijn)
2. Papierschijfjes met antibiotica
3. Diameter van opklaringszone bepaald gevoeligheid (R, I, S)
4. MIC-waarde bepaald met standaardcurve
4
Inhoud ........................................................................................................................................................................................ 1
Antibiotica .................................................................................................................................................................................. 3
1. Inleidende begrippen ......................................................................................................................................................... 3
Bacteriostatisch/ Bactericide .............................................................................................................................................. 4
Antibiogram volgens diffusiemethode ............................................................................................................................... 4
E-test .................................................................................................................................................................................. 5
Synergie/ antagonistisch/ additief effect ........................................................................................................................... 5
Farmacokinetica ................................................................................................................................................................. 5
Resistentie .......................................................................................................................................................................... 6
2. De celwand als doelwit ....................................................................................................................................................... 9
2.1. Biosynthese van peptidoglycaan ................................................................................................................................. 9
Te kennen structuren: .................................................................................................................................................... 9
Synthese van peptidoglycaan ....................................................................................................................................... 10
2.2. Fosfomycine, D-cycloserine, bacitracine ................................................................................................................... 14
Fosfomycine ................................................................................................................................................................. 14
D-cycloserine ................................................................................................................................................................ 14
2.3. Glycopeptide antibiotica ........................................................................................................................................... 15
Vancomycine ................................................................................................................................................................ 15
2.4. Beta-lactam antibiotica ............................................................................................................................................. 15
Penicillines .................................................................................................................................................................... 17
Cefalosporines .............................................................................................................................................................. 17
Carbapenems................................................................................................................................................................ 17
Monobactams .............................................................................................................................................................. 17
3. Polymyxines: verstoring buitenste membraan ................................................................................................................. 18
4. Inhibitoren replicatie en transcriptie ................................................................................................................................ 19
4.1 Quinolonen ................................................................................................................................................................. 19
4.2 Rafamycine ................................................................................................................................................................. 20
5. Inhibitors protein synthesis .............................................................................................................................................. 21
5.1 Bacterieel ribosoom ................................................................................................................................................... 21
1. 30S inhibitors ............................................................................................................................................................ 22
2. 50S inhibitors ............................................................................................................................................................ 24
6. Inhibitoren van metabolisme ........................................................................................................................................... 26
6.1 Inhibitoren foliumzuursynthese ................................................................................................................................. 26
6.2 Metronidazole ............................................................................................................................................................ 27
7. Tuberculostatica ............................................................................................................................................................... 28
Mycobacterium tuberculosis ............................................................................................................................................ 28
Therapie ....................................................................................................................................................................... 28
Isoniazide ...................................................................................................................................................................... 29
Ethambutol/ streptomycin ........................................................................................................................................... 29
1
, Pyrazinamide ................................................................................................................................................................ 29
Rifampicine ................................................................................................................................................................... 30
Multidrug resistente tuberculose (MRD).......................................................................................................................... 30
Extensief-drug resistente tuberculose (XDR) .................................................................................................................... 30
8. Antifungale middelen ....................................................................................................................................................... 31
Polyenen ........................................................................................................................................................................... 31
Allylamines ....................................................................................................................................................................... 31
Azolen ............................................................................................................................................................................... 32
Fluorocytosine .................................................................................................................................................................. 32
Griseofulvine .................................................................................................................................................................... 33
Echinocandin .................................................................................................................................................................... 33
9. Antiparasitaie middelen ................................................................................................................................................... 34
Anti-protozoaire therapie met zware metalen ................................................................................................................. 34
Therapie voor Leishmania ................................................................................................................................................ 34
Therapie van Afrikaanse Trypanosoma ............................................................................................................................ 35
Therapie van Trypanosoma cruzi...................................................................................................................................... 35
Malaria behandeling......................................................................................................................................................... 35
1. Quinine en gerelateerde moleculen ......................................................................................................................... 35
Antifolaat ...................................................................................................................................................................... 36
Artemisinine ................................................................................................................................................................. 36
Preventie ...................................................................................................................................................................... 37
2
,Antibiotica
1. Inleidende begrippen
Curve zakt heel fel = mortaliteit van 25%
( 25% halen 5j niet door infecties, ziekte, slechte
behandeling )
→ Niet genetisch want vroeger bij ons gelijkaardige
piek ( geen antibiotica )
Nu rode piek: veel lagere mortaliteit
Antibiotica:
Een substantie van biologische, semisynthetische (biologisch geproduceerd, maar geoptimaliseerd) of
synthetische oorsprong met een selectieve inhiberende activiteit tegenover bacteriën.
→ Selectieve toxiciteit: O.b.v. verschillen tussen gastheer en infectieus agens wordt het toxisch voor B gemaakt,
maar niet voor eukaryote gastheer. Moet penetratievermogen hebben en een grote specifiteit en affiniteit voor
microbieel doelmolecule.
(Controle van fungale en protozoaire pathogenen moeilijker omdat verschillen met eukaryoten kleiner zijn (vaak
ook toxisch voor gastheer)
→ Ontdekking van pencilline mbv staphylococcus
Spectrum: Tegen welke B is antibiotica actief
Breed: tegen veel B (zowel gram + als - )
Eng: tegen minder B ( bv enkel gram -)
3
, Bacteriostatisch/ Bactericide
Bacteriostatisch: Inhibeert groei (B NIET kapot) Verdere opruim door immuunsysteem
Bactericide: Afdoden en kapot maken van B
= Kijken vanaf welke [antibioticum] er geen
B groei meer is.
= Kijken vanaf welke [antibioticum] B
afgedood worden
= hier is MBC kleiner omdat B al afgedood
wordt bij een [antibioticum]= 1/4
MIC (minimale inhibitorische concentratie): Minimale concentratie antibiotica nodig om Bgroei te inhiberen.
MBC (minimale bactericide condentratie ): Minimale concentratie antibiotica nodig om B af te doden.
BPC (breekpunt concentratie): Specifieke grenswaarden van antibioticum concentraties internationaal vastgelegd. Werd
bepaald door normale dosis toe te dienen aan patiënt en kijken welke [antibioticum] er terug gevonden wordt.
→ Gevoelig: B geremd door BPC
→ Intermediair: B niet geremd door BPC wel door maximale [antibioticum]
→ Resistent: B niet geremd door BPC
Antibiogram volgens diffusiemethode
1. Uitplaten over agarbodem ([agar] moet gelijk verdeeld zijn)
2. Papierschijfjes met antibiotica
3. Diameter van opklaringszone bepaald gevoeligheid (R, I, S)
4. MIC-waarde bepaald met standaardcurve
4
