Toegepaste farmacologie
Overzichtstabel antibiotica ........................................................................................................... 6
Antimicrobiële stoffen.................................................................................................................. 7
Keuze antibiotica (AB) ................................................................................................................... 7
1 Invloedsfactoren op de werking van een antimicrobiële stof ..................................................... 7
1.1 Gevoeligheid van het micro-organisme .............................................................................. 7
1.2 Groeifase van een micro-organisme .................................................................................. 8
1.3 Natuurlijk afweermechanisme .......................................................................................... 8
1.4 Andere factoren ............................................................................................................... 8
2 Keuze van het antibioticum ..................................................................................................... 8
2.1 Gevoeligheid van de kiem! ................................................................................................ 8
2.2 Toxiciteit van het AB......................................................................................................... 8
2.3 Distributie van het AB....................................................................................................... 8
2.4 Toestand patiënt .............................................................................................................. 9
2.5 Interacties tussen AB ........................................................................................................ 9
2.5.1 Doel van gebruik van meerdere AB ............................................................................. 9
2.5.2 Algemene regel:........................................................................................................10
2.5.3 OEFENINGEN: ...........................................................................................................10
2.6 Bijwerkingen ...................................................................................................................12
2.7 Posologie ........................................................................................................................12
2.8 Eliminatie van GM ...........................................................................................................13
Resistentiemechanismen ..............................................................................................................14
1. Mogelijke resistentiemechanismen........................................................................................14
2. Natuurlijk >< verworven resistentie .......................................................................................14
3. Mutationele resistentie .........................................................................................................14
4. Transfereerbare resistentie ...................................................................................................15
Werkingsmechanisme antibiotica..................................................................................................17
Overzicht werking van antibiotica..............................................................................................17
Groep 1: inhibitoren van de celwandsynthese ............................................................................18
1. Βèta-lactam antibiotica: werkingsmechanisme....................................................................18
2. Βèta-lactam antibiotica: resistentiemechanismen ...............................................................20
3. Soorten bèta-lactam antibiotica: Penicillines.......................................................................20
4. Andere bèta-lactam antibiotica: bij resistentie te gebruiken ................................................21
4.1 Cefalosporines............................................................................................................21
4.2 Carbapenems ..............................................................................................................21
4.3 Monobactams .............................................................................................................21
5. toepassingen: streptokokkeninfecties.................................................................................22
1
, 5.1 Staphylococcus aureus .................................................................................................22
5.2 Staphylococcus aureus – Folliculitis & furonkel..............................................................22
5.3 Staphylococcus aureus – Paronychium..........................................................................22
5.4 Streptococcus pyogenes – Angina pultacea (“witte angine”) ..........................................23
5.3 Streptococcus pyogenes – Peritonsillair abces ...............................................................23
5.4 Streptococcus pyogenes / Staphylococcus aureus – Impetigo.........................................23
5.5 Streptococcus pyogenes/ Streptococcus pneumoniae: Otitis media acuta.......................23
5.6 Staphylococcus aureus / Streptococcus pneumoniae – Conjuctivitis ...............................24
5.7 Staphylococcus aureus / Streptococcus pneumonia: Sinusitis .........................................24
5.8 Streptococcus pneumonia (“pneumokok”) ....................................................................24
5.9 Streptococcus pneumoniae – Meningitis.......................................................................25
5.10 Streptococcus pneumoniae – Pneumonie....................................................................25
5.11 Streptococcus pneumoniae: Vaccinatie .......................................................................26
5.12 Pseudomonas aeruginosa...........................................................................................26
6 Resistentie .........................................................................................................................27
6.1 Resistentie: MRSA .......................................................................................................27
6.2 Resistentie-ontwikkeling bij β-lactam AB.......................................................................28
6.3 Penicillinase of β-lactamasen........................................................................................29
6.4 Breedspectrum β-lactamasen.......................................................................................29
6.5 Extended spectrum β-lactamasen (ESBL).......................................................................29
6.6 Metallo-β-lactamasen of carbapenemasen....................................................................29
6.7 NDM-1: soort van metallo-β-lactamase.........................................................................29
6.8 Behandeling multiresistente gram- bacterie ..................................................................30
6.9 Consequenties, opties, toekomst ..................................................................................30
7 Glycopeptiden ...................................................................................................................30
CASUS: .................................................................................................................................31
Groep 2: Inhibitoren van de eiwitsynthese .................................................................................31
1 Aminoglycosiden................................................................................................................32
2 Tetracyclines......................................................................................................................32
3 Macroliden ........................................................................................................................33
CASUS: .................................................................................................................................34
Groep 3: AB die de membraanintegriteit verstoren ....................................................................34
1 Polymyxines.......................................................................................................................34
Groep 4: Competitieve inhibitie.................................................................................................34
Groep 5: Inhibitie DNA en RNA synthese....................................................................................35
1 Activiteiten ter hoogte van de DNA-structuur ......................................................................35
1.1 Inhibitoren van DNA gyrase ..........................................................................................35
1.2 Neisseria meningitidis: Meningokokkenmeningitis.........................................................37
2
, 2 activiteiten ter hoogte van de RNA-synthese .......................................................................37
2.1 inhibitoren van DNA transcriptie ..................................................................................37
Tuberculose .............................................................................................................................37
Tuberculostatica ...................................................................................................................38
Tuberculose: voorkomen.......................................................................................................38
Tuberculose opsporen...........................................................................................................38
CASUS: .................................................................................................................................39
Gevoeligheidsbehandelingen en bepaling van resistentie ...............................................................40
1 gevoeligheidsbepalingen ........................................................................................................40
1.1 Keuze antibiotica.............................................................................................................40
1.2 In vitro-testen: Labo MIC-bepaling & dosering ..................................................................40
1.2 Dilutiemethode ...............................................................................................................41
1.2.1 Klassieke MIC bepaling..............................................................................................41
1.2.2 ATB methode............................................................................................................41
1.3 Diffusiemethode .............................................................................................................42
1.3.1 Kirby-Bauer ..............................................................................................................44
1.3.2 Neo-sensitabs-methode (Rosco) ................................................................................44
1.4 Epsilon-test (E-test) .........................................................................................................45
2 Screening en confirmatie ESBL’s .............................................................................................45
2.1 Opsporen ESBL met DDST ................................................................................................46
2.2 Opsporen ESBL met CDDST ..............................................................................................47
2.3 Opsporen ESBL met E-test................................................................................................47
2.4 Cica beta test ..................................................................................................................48
2.5 Sensitiviteit en specificiteit...............................................................................................48
3 ESBL testen van opdracht.......................................................................................................48
3.1 Overzicht β-lactamasen ...................................................................................................48
3.2 VTEK 2 test......................................................................................................................49
3.3 DDS20 & DDS30 ..............................................................................................................50
3.4 ESBL E-test ......................................................................................................................50
Antimycotica ...............................................................................................................................52
1 Soorten mycosen (= schimmelinfecties) ..................................................................................52
2 Werkingsmechanismen antimycotica......................................................................................52
2.1 Polyenen.........................................................................................................................53
2.2 Echinocandinen...............................................................................................................53
2.3 Azoolderivaten................................................................................................................53
2.3.1 Orale candidiosis (spruw) ..........................................................................................53
2.3.2 Luierdermatitis .........................................................................................................54
2.4 Terbinafine .....................................................................................................................54
3
, 2.4.1 Tinea (ringworm) ......................................................................................................54
Antiparasitaire middelen .............................................................................................................55
Introductie...................................................................................................................................55
1 Varkenszweepworm bij IBD....................................................................................................57
2 Kuren met een lintworm? ......................................................................................................57
2.1 Therapie voor lintwormen ...............................................................................................57
3 Vlooienbom...........................................................................................................................58
3.1 Behandeling....................................................................................................................58
3.2 Voorkomen.....................................................................................................................58
4 Helminthen in de strijd tegen auto-immuunziekten (vb MS)/allergieën en chronische
inflammaties............................................................................................................................59
4.1 Multiple sclerosis (MS).....................................................................................................59
4.2 Astma en allergieën.........................................................................................................59
Overzicht parasieten en hun behandeling ......................................................................................60
1 Giardia lamblia = Giardiasis ....................................................................................................60
1.1 Bergen outbreak, 2004 (Noorwegen) ................................................................................60
1.2 Symptomen ....................................................................................................................61
1.3 Preventie ........................................................................................................................61
1.4 Behandeling....................................................................................................................61
1.5 Interacties.......................................................................................................................62
2 Entamoeba histolytica = amoebiasis .......................................................................................62
2.1 Behandeling....................................................................................................................63
3 Trypanosoma sp = slaapziekte ................................................................................................63
3.1 Trypanosoma brucei gambiense en rhodensiense ..............................................................63
3.2 Trypanosoma brucei gambiense .......................................................................................63
3.3 Verloop ziekte .................................................................................................................64
3.4 Preventie ........................................................................................................................64
3.5 Behandeling....................................................................................................................64
4 Toxoplasma gondii = toxoplasmose ........................................................................................64
4.1 Symptomen ....................................................................................................................65
4.2 Preventie ........................................................................................................................65
4.3 Behandeling....................................................................................................................65
4.4 Toxoplasma als stille manipulator.....................................................................................66
5 Enterobius vermicularis = aarsmade ........................................................................................66
5.1 Symptomen en preventie.................................................................................................67
5.2 Behandeling....................................................................................................................67
5.3 Interacties & voorzorgen .................................................................................................67
6 Cryptosporidium parvum = Cryptosporidiose ...........................................................................68
4
Overzichtstabel antibiotica ........................................................................................................... 6
Antimicrobiële stoffen.................................................................................................................. 7
Keuze antibiotica (AB) ................................................................................................................... 7
1 Invloedsfactoren op de werking van een antimicrobiële stof ..................................................... 7
1.1 Gevoeligheid van het micro-organisme .............................................................................. 7
1.2 Groeifase van een micro-organisme .................................................................................. 8
1.3 Natuurlijk afweermechanisme .......................................................................................... 8
1.4 Andere factoren ............................................................................................................... 8
2 Keuze van het antibioticum ..................................................................................................... 8
2.1 Gevoeligheid van de kiem! ................................................................................................ 8
2.2 Toxiciteit van het AB......................................................................................................... 8
2.3 Distributie van het AB....................................................................................................... 8
2.4 Toestand patiënt .............................................................................................................. 9
2.5 Interacties tussen AB ........................................................................................................ 9
2.5.1 Doel van gebruik van meerdere AB ............................................................................. 9
2.5.2 Algemene regel:........................................................................................................10
2.5.3 OEFENINGEN: ...........................................................................................................10
2.6 Bijwerkingen ...................................................................................................................12
2.7 Posologie ........................................................................................................................12
2.8 Eliminatie van GM ...........................................................................................................13
Resistentiemechanismen ..............................................................................................................14
1. Mogelijke resistentiemechanismen........................................................................................14
2. Natuurlijk >< verworven resistentie .......................................................................................14
3. Mutationele resistentie .........................................................................................................14
4. Transfereerbare resistentie ...................................................................................................15
Werkingsmechanisme antibiotica..................................................................................................17
Overzicht werking van antibiotica..............................................................................................17
Groep 1: inhibitoren van de celwandsynthese ............................................................................18
1. Βèta-lactam antibiotica: werkingsmechanisme....................................................................18
2. Βèta-lactam antibiotica: resistentiemechanismen ...............................................................20
3. Soorten bèta-lactam antibiotica: Penicillines.......................................................................20
4. Andere bèta-lactam antibiotica: bij resistentie te gebruiken ................................................21
4.1 Cefalosporines............................................................................................................21
4.2 Carbapenems ..............................................................................................................21
4.3 Monobactams .............................................................................................................21
5. toepassingen: streptokokkeninfecties.................................................................................22
1
, 5.1 Staphylococcus aureus .................................................................................................22
5.2 Staphylococcus aureus – Folliculitis & furonkel..............................................................22
5.3 Staphylococcus aureus – Paronychium..........................................................................22
5.4 Streptococcus pyogenes – Angina pultacea (“witte angine”) ..........................................23
5.3 Streptococcus pyogenes – Peritonsillair abces ...............................................................23
5.4 Streptococcus pyogenes / Staphylococcus aureus – Impetigo.........................................23
5.5 Streptococcus pyogenes/ Streptococcus pneumoniae: Otitis media acuta.......................23
5.6 Staphylococcus aureus / Streptococcus pneumoniae – Conjuctivitis ...............................24
5.7 Staphylococcus aureus / Streptococcus pneumonia: Sinusitis .........................................24
5.8 Streptococcus pneumonia (“pneumokok”) ....................................................................24
5.9 Streptococcus pneumoniae – Meningitis.......................................................................25
5.10 Streptococcus pneumoniae – Pneumonie....................................................................25
5.11 Streptococcus pneumoniae: Vaccinatie .......................................................................26
5.12 Pseudomonas aeruginosa...........................................................................................26
6 Resistentie .........................................................................................................................27
6.1 Resistentie: MRSA .......................................................................................................27
6.2 Resistentie-ontwikkeling bij β-lactam AB.......................................................................28
6.3 Penicillinase of β-lactamasen........................................................................................29
6.4 Breedspectrum β-lactamasen.......................................................................................29
6.5 Extended spectrum β-lactamasen (ESBL).......................................................................29
6.6 Metallo-β-lactamasen of carbapenemasen....................................................................29
6.7 NDM-1: soort van metallo-β-lactamase.........................................................................29
6.8 Behandeling multiresistente gram- bacterie ..................................................................30
6.9 Consequenties, opties, toekomst ..................................................................................30
7 Glycopeptiden ...................................................................................................................30
CASUS: .................................................................................................................................31
Groep 2: Inhibitoren van de eiwitsynthese .................................................................................31
1 Aminoglycosiden................................................................................................................32
2 Tetracyclines......................................................................................................................32
3 Macroliden ........................................................................................................................33
CASUS: .................................................................................................................................34
Groep 3: AB die de membraanintegriteit verstoren ....................................................................34
1 Polymyxines.......................................................................................................................34
Groep 4: Competitieve inhibitie.................................................................................................34
Groep 5: Inhibitie DNA en RNA synthese....................................................................................35
1 Activiteiten ter hoogte van de DNA-structuur ......................................................................35
1.1 Inhibitoren van DNA gyrase ..........................................................................................35
1.2 Neisseria meningitidis: Meningokokkenmeningitis.........................................................37
2
, 2 activiteiten ter hoogte van de RNA-synthese .......................................................................37
2.1 inhibitoren van DNA transcriptie ..................................................................................37
Tuberculose .............................................................................................................................37
Tuberculostatica ...................................................................................................................38
Tuberculose: voorkomen.......................................................................................................38
Tuberculose opsporen...........................................................................................................38
CASUS: .................................................................................................................................39
Gevoeligheidsbehandelingen en bepaling van resistentie ...............................................................40
1 gevoeligheidsbepalingen ........................................................................................................40
1.1 Keuze antibiotica.............................................................................................................40
1.2 In vitro-testen: Labo MIC-bepaling & dosering ..................................................................40
1.2 Dilutiemethode ...............................................................................................................41
1.2.1 Klassieke MIC bepaling..............................................................................................41
1.2.2 ATB methode............................................................................................................41
1.3 Diffusiemethode .............................................................................................................42
1.3.1 Kirby-Bauer ..............................................................................................................44
1.3.2 Neo-sensitabs-methode (Rosco) ................................................................................44
1.4 Epsilon-test (E-test) .........................................................................................................45
2 Screening en confirmatie ESBL’s .............................................................................................45
2.1 Opsporen ESBL met DDST ................................................................................................46
2.2 Opsporen ESBL met CDDST ..............................................................................................47
2.3 Opsporen ESBL met E-test................................................................................................47
2.4 Cica beta test ..................................................................................................................48
2.5 Sensitiviteit en specificiteit...............................................................................................48
3 ESBL testen van opdracht.......................................................................................................48
3.1 Overzicht β-lactamasen ...................................................................................................48
3.2 VTEK 2 test......................................................................................................................49
3.3 DDS20 & DDS30 ..............................................................................................................50
3.4 ESBL E-test ......................................................................................................................50
Antimycotica ...............................................................................................................................52
1 Soorten mycosen (= schimmelinfecties) ..................................................................................52
2 Werkingsmechanismen antimycotica......................................................................................52
2.1 Polyenen.........................................................................................................................53
2.2 Echinocandinen...............................................................................................................53
2.3 Azoolderivaten................................................................................................................53
2.3.1 Orale candidiosis (spruw) ..........................................................................................53
2.3.2 Luierdermatitis .........................................................................................................54
2.4 Terbinafine .....................................................................................................................54
3
, 2.4.1 Tinea (ringworm) ......................................................................................................54
Antiparasitaire middelen .............................................................................................................55
Introductie...................................................................................................................................55
1 Varkenszweepworm bij IBD....................................................................................................57
2 Kuren met een lintworm? ......................................................................................................57
2.1 Therapie voor lintwormen ...............................................................................................57
3 Vlooienbom...........................................................................................................................58
3.1 Behandeling....................................................................................................................58
3.2 Voorkomen.....................................................................................................................58
4 Helminthen in de strijd tegen auto-immuunziekten (vb MS)/allergieën en chronische
inflammaties............................................................................................................................59
4.1 Multiple sclerosis (MS).....................................................................................................59
4.2 Astma en allergieën.........................................................................................................59
Overzicht parasieten en hun behandeling ......................................................................................60
1 Giardia lamblia = Giardiasis ....................................................................................................60
1.1 Bergen outbreak, 2004 (Noorwegen) ................................................................................60
1.2 Symptomen ....................................................................................................................61
1.3 Preventie ........................................................................................................................61
1.4 Behandeling....................................................................................................................61
1.5 Interacties.......................................................................................................................62
2 Entamoeba histolytica = amoebiasis .......................................................................................62
2.1 Behandeling....................................................................................................................63
3 Trypanosoma sp = slaapziekte ................................................................................................63
3.1 Trypanosoma brucei gambiense en rhodensiense ..............................................................63
3.2 Trypanosoma brucei gambiense .......................................................................................63
3.3 Verloop ziekte .................................................................................................................64
3.4 Preventie ........................................................................................................................64
3.5 Behandeling....................................................................................................................64
4 Toxoplasma gondii = toxoplasmose ........................................................................................64
4.1 Symptomen ....................................................................................................................65
4.2 Preventie ........................................................................................................................65
4.3 Behandeling....................................................................................................................65
4.4 Toxoplasma als stille manipulator.....................................................................................66
5 Enterobius vermicularis = aarsmade ........................................................................................66
5.1 Symptomen en preventie.................................................................................................67
5.2 Behandeling....................................................................................................................67
5.3 Interacties & voorzorgen .................................................................................................67
6 Cryptosporidium parvum = Cryptosporidiose ...........................................................................68
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