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Samenvatting "antibiotica" - Infectieziekten 2

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Course
Infectieziekten 2

Institution
Universiteit Antwerpen (UA)

Samenvatting van 'antibiotica' als onderdeel van het vak 'Infectieziekten 2' gegeven door prof. Vlieghe in de 2e Bachelor Geneeskunde aan de UA. Volledige samenvatting gebaseerd op college slides én eigen lesnotities.

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Uploaded on August 23, 2024
Number of pages 41
Written in 2023/2024
Type Summary

beta lactam
vancomycine
macrolide
quinolone
kinetiek
resistentie
cloxacilline
amoxicilline
penicilline
meropenem
ceftriaxone
azithromycine
ciprofloxacine
co trimoxazole
nitrofurantoine
fosfomycine
lin

Institution
Universiteit Antwerpen (UA)
Education
Geneeskunde
Course
Infectieziekten 2

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Samenvatting - Infectieziekten 2

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1. Summary - Samenvatting "ziekmakend vermogen" - infectieziekten 2 (deel a)
2. Summary - Samenvatting "antibiotica" - infectieziekten 2
3. Summary - Samenvatting "vaccinatie" - infectieziekten 2
4. Summary - Samenvatting "ziekmakend vermogen" - infectieziekten 2 (deel b)
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Samenvatting + flashcards + overzichtstabel - Infectieziekten 2

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1. Summary - Samenvatting "ziekmakend vermogen" - infectieziekten 2 (deel a)
2. Summary - Samenvatting "antibiotica" - infectieziekten 2
3. Summary - Samenvatting "vaccinatie" - infectieziekten 2
4. Summary - Flashcards antibiotica & parasieten - infectieziekten 2
5. Summary - Overzicht bacteriën & virussen - infectieziekten 2
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INHOUDSTAFEL
Principes van antibiotica resistentie............................................................................................................3
Genetische basis van resistentie................................................................................................................3
Resistentie door spontane mutatie in endogene genen................................................................. 3
Resistentie door verwerving van exogenen....................................................................................3
Mechanismen van resistentiegenen overdracht............................................................................. 4
Mechanisme van resistentie........................................................................................................... 6
Bèta-lactams.............................................................................................................................................. 6
Werkingsmechanisme.................................................................................................................... 6
Resistentiemechanismen............................................................................................................... 7
Glycopeptiden - Vancomycine....................................................................................................................8
Werkingsmechanisme.................................................................................................................... 8
Resistentiemechanisme................................................................................................................. 9
Macroliden..................................................................................................................................................9
Werkingsmechanisme.................................................................................................................... 9
Resistentiemechanismen............................................................................................................... 9
(Fluoro)quinolones................................................................................................................................... 10
Werkingsmechanisme.................................................................................................................. 10
Resistentiemechanismen............................................................................................................. 10
Oorsprong van resistentiegenen.............................................................................................................. 11

Beta-lactams.................................................................................................................................................12
Antibiotica.................................................................................................................................................12
Mechanismen van antibiotica....................................................................................................... 12
Spectrum van antibiotica.............................................................................................................. 12
Kinetiek.........................................................................................................................................13
Veiligheid en allergieën.................................................................................................................14
Beta-lactam antibiotica............................................................................................................................. 14
Resistentiemechanisme............................................................................................................... 15
Bijwerkingen van beta-lactam antibiotica..................................................................................... 16
Penicilline..................................................................................................................................... 17
Cloxacilline................................................................................................................................... 18
Amoxicilline + clavulaanzuur........................................................................................................ 18
Ceftriaxone................................................................................................................................... 19
Meropenem.................................................................................................................................. 19

Non-bèta-lactams......................................................................................................................................... 20
Non-bèta-lactam antibiotica......................................................................................................................20
Gram-negatieve resistentie is booming....................................................................................................20
WHO Global Action Plan (2015)...................................................................................................20
AWaRe......................................................................................................................................... 20
Macroliden................................................................................................................................................21
Azithromycine............................................................................................................................... 22
Fluoroquinolones......................................................................................................................................23
Ciprofloxacine...............................................................................................................................23
Resistentiemechanismen............................................................................................................. 24
Sulfonamides............................................................................................................................................24
Co-trimoxazole............................................................................................................................. 24

, Tetracyclines.............................................................................................................................................26
Indicaties voor gebruik..................................................................................................................26
Nevenwerkingen...........................................................................................................................27
Urinary antibiotica.....................................................................................................................................27
Nitrofurantoine.............................................................................................................................. 27
Fosfomycine................................................................................................................................. 28
Moeilijk te behandelen gram+ infecties.................................................................................................... 28
Vancomycine................................................................................................................................ 28
Clindamycine................................................................................................................................ 29
Clostridium difficile........................................................................................................................31
Linezolid....................................................................................................................................... 31
Moeilijk te behandelen gram– infecties.................................................................................................... 32
Aminoglycosiden.......................................................................................................................... 32
Gentamicine........................................................................................................................... 33
Amikacine............................................................................................................................... 34
Polymyxines................................................................................................................................. 35
Colistine = polymyxine E........................................................................................................ 35
Nieuwe combinatieproducten....................................................................................................... 36
Alternatieve producten..................................................................................................................36

Antibioticagebruik........................................................................................................................................39
Resistentie terugdringen.......................................................................................................................... 39
Optimaal antibioticagebruik...................................................................................................................... 39

1

,WHO-classification
critical priority Acinetobacter baumannii
● carbapenem-resistent

Pseudomonas aeruginosa
● carbapenem-resistent

Enterobacteriaceae (E. coli)
● carbapenem-resistant
● 3e generatie cephalosporine-resistent

high priority Enterococcus faecium
● vancomycin-resistent

Staphylococcus aureus
● vancomycine-resistent
● methicilline-resistent

Helicobacter pylori
● clarithromycine-resistent

Campylobacter species
● fluoroquinolone-resistent

Salmonella species
● fluoroquinolone-resistent

Neisseria gonorrhoeae
● 3e generatie cephalosporine-resistent
● fluoroquinolone-resistent

medium priority Streptococcus pneumoniae
● penicilline-ongevoelig

Haemophilus influenzae
● ampicilline-resistent

Shigella species
● fluoroquinolone-resistent

2

, Principes van antibiotica resistentie
Genetische basis van resistentie
spontane mutatie in endogene genen = genen die de bacteriën zelf bezitten (species-specifiek)
● structurele genen
○ uitgebreid spectrum van enzymatische activiteit
○ modificatie van target site in de bacterie waarop AB normaal zou binden
○ transport defect
● regulerende genen: verhoogde expressie

verwerving van exogene genen
● meestal regulerende genen die coderen voor inactiverende enzymen of gemodificeerde targets
● mechanismen van DNA-overdracht
○ conjugatie: uitwisseling van plasmiden via cel-cel contact (vooral gram–)
○ transformatie: opname van naakt DNA uit de oplossing/omgeving (vooral gram+)
○ transductie: overdracht van DNA via bacteriofagen (= bacterieel virus)

expressie van resistentie genen: omkeerbare inductie-/repressiesystemen kunnen resistentiefenotypes
beïnvloeden

Resistentie door spontane mutatie in endogene genen
1. populatie van delende bacteriën (elke 20 minuten worden 2 cellen geproduceerd vanuit één
moedercel)
2. groei en deling produceert natuurlijk voorkomende mutanten (loss of function of gain of function)
3. bacteriën blijven multipliceren, af en toe aanleiding gevend tot verschillende mutanten
4. blootstelling aan selectieve druk van antibiotica
5. bacteriën worden gedood of groei wordt voorkomen, behalve voor specifieke resistente mutanten
= uitselectie van resistentie
6. mutanten met de minste fitness-cost prolifereren en verspreiden

Resistentie door verwerving van exogenen
1. twee populaties van verschillende bacteriën groeien in dezelfde omgeving
2. uitwisseling van DNA en mobiele genetische elementen vindt plaats tussen bacteriën met lage
frequentie
3. gevoelige bacteriën verwerven resistentiegenen die aanwezig zijn op een mobiel genetisch element
4. cellen met verworven resistentie prolifereren en gevoelige bacteriën worden gedood of groei
voorkomen

voorwaarde: aanwezigheid van bacterie met resistentiegenen

3

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Samenvatting "antibiotica" - Infectieziekten 2

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