BACTERIOLOGIE
ANDRÉ EMMANUEL
,Inhoudsopgave
H1: inleiding tot de klinische biologie.............................................................7
belang van microbiologie en bacteriologie in menselijke gezondheid.............................7
Belang van microbiologie.............................................................................................7
Doel van klinische laboratoria......................................................................................7
verloop van infectie...................................................................................................... 7
diversiteit van micro-organismen.................................................................................7
Transmissieroutes van bacteriële pathogenen................................................................9
Oorsprong pathogenen................................................................................................. 9
Reservoir en transmissie pathogenen...........................................................................9
Oorsprong en transmissie infectieziektes...................................................................10
Uitbraken....................................................................................................................... 13
Definities.................................................................................................................... 13
Voorbeelden............................................................................................................... 14
Pathogenese van bacteriële infecties............................................................................14
indeling bacteriën....................................................................................................... 14
infectie....................................................................................................................... 15
ontsnappingsroutes van bacteriën.............................................................................16
Risicofactoren voor (ernstiger) bacteriële infecties.......................................................16
Leeftijd....................................................................................................................... 16
Onderliggende gezondheidscondities.........................................................................16
Omgevingsfactoren.................................................................................................... 16
Leefstijlfactoren en risicovol gedrag...........................................................................16
Socio-economische en genetische factoren................................................................16
H2: bacteriologie..........................................................................................18
Bacteriële structuur....................................................................................................... 18
endosymbiont theorie................................................................................................. 18
Celwand...................................................................................................................... 18
Celmembraan............................................................................................................. 22
Bacterieel genoom...................................................................................................... 23
Bacterieel capsule...................................................................................................... 24
Bacteriële sporen........................................................................................................ 25
Bacterieel metabolisme................................................................................................. 26
Bacterieel DNA........................................................................................................... 26
Voedingsuitwisseling.................................................................................................. 26
Efflux pompen............................................................................................................ 26
Bacteriële ademhaling................................................................................................ 27
Bacteriële replicatie.................................................................................................... 27
Transcriptie DNA in mRNA.......................................................................................... 27
Translatie mRNA in proteins.......................................................................................27
Bacterieel microbioom................................................................................................ 28
H3: diagnose van infecties en identificatie van bacteriën...............................29
basic laboratorische technieken: microscopie...............................................................30
Macroscopische examinatie........................................................................................ 30
, Microscopische examinatie......................................................................................... 30
Cultuur en isolatie van bacteriën van klinische specimens............................................35
Incubatie condities..................................................................................................... 35
Identificatie van bacteriën gebruikmakende van biochemische testen.........................36
Biochemische testen en automatie.............................................................................36
gram-positief.............................................................................................................. 37
Antigeen-gebaseerde snelle testen...............................................................................37
Snelle antigeentesten = immunoassays.....................................................................37
Diagnose van clostridium difficile...............................................................................38
Diagnose van legionella pneumophila........................................................................38
Identificatie van bacteriën gebruikmakende van Mass Spectrometry (MALDI-TOF MS). 38
Identificatie van bacteriën gebruikmakende van 16S RNA sequencing.........................39
Ribosomen en 16S rRNA-sequencing..........................................................................39
Disease-specific workflows............................................................................................41
identificatie van mycobacerium tuberculose en antibiotica resistentie mechanismen
................................................................................................................................... 41
Detectie van helicobacter pylori.................................................................................42
H4: drug susceptibility testing en therapeutic drug monitoring......................43
Drug susceptibility testing.............................................................................................43
Phenotypic methods................................................................................................... 47
Alternative methods................................................................................................... 49
Pharmacokinetics – PK................................................................................................... 52
Pharmacodynamics – PD............................................................................................... 53
Therapeutic drug monitoring (TDM)..............................................................................54
balans tussen therapeutische en toxische effecten....................................................54
voorbeelden............................................................................................................... 55
Invloed van CYP-level activiteit...................................................................................56
methoden om antibiotica concentraties in bloed te bepalen......................................59
H5: antibiotica en antimicrobiële resistentie..................................................60
behandeling van syphillis tot de ontdekking van Penicillin............................................60
de systematische studie naar natuurlijke producten.....................................................61
fungal diversity: oneindige bron van kleine inhibitorische moleculen.........................62
belangrijke klassen van antibiotica.............................................................................62
de opkomst van resistentie...........................................................................................63
resistentiemechanismen............................................................................................. 63
drijfveren AMR............................................................................................................ 64
globale antibiotica consumptie...................................................................................64
Belangrijkste mechanismen van resistentie...............................................................65
WHO-prioriteitenlijst................................................................................................... 66
Stille pandemieën van MDRO’s...................................................................................68
actiemechanismen van antibiotica/bacteriën................................................................68
Overzicht antimicrobiële therapie strategieën............................................................68
Overzicht resistentiemechanismen.............................................................................69
celwand inhibitoren....................................................................................................... 70
, Werking ß-lactam-antibiotica en vancomycine...........................................................70
DNA en mRNA synthese inhibitoren..............................................................................80
Quilonolen.................................................................................................................. 81
Peptide synthese inhibitoren......................................................................................... 82
macroliden.................................................................................................................. 83
Lincosamide............................................................................................................... 83
Aminoglycosides......................................................................................................... 84
Tetracyclines.............................................................................................................. 84
andere antibiotica......................................................................................................... 85
Bactrim....................................................................................................................... 85
metronidazole............................................................................................................. 86
alternatieven van antibiotica: fagen..............................................................................86
H6: antibacterial vaccines and vaccine-preventable diseases.........................88
Inleiding: early discoveries............................................................................................ 88
soorten vaccins........................................................................................................... 88
Vaccins in Belgë............................................................................................................ 89
DtaP.............................................................................................................................. 90
Drifterie...................................................................................................................... 90
Tetanus...................................................................................................................... 91
Kinkhoest.................................................................................................................... 91
Haemopohilus influenzae type B...................................................................................93
Neisseria mengitidis...................................................................................................... 94
Streptococcus pneumoniae...........................................................................................95
overall effect van vaccins op bacteriële meningitis.......................................................97
Salmonella enterica subsp. Eneterica serovar Typhil.....................................................98
H7: skin and soft tissue infections...............................................................100
normale huid en zijn microbioom................................................................................100
ziekten geassocieerd met dysbiosis............................................................................102
meest voorkomende bacteriën in huidinfecties...........................................................102
ziektes veroorzaakt door toxines.................................................................................104
infecties geassocieerd met barriere doorbreking........................................................104
Superficial bacterial skin infections.............................................................................107
follikel gerelateerde huid infecties..............................................................................109
zachte weefsel infecties..............................................................................................109
Health-care associated infections (HAI).......................................................................111
niet-bacteriële infecties met huidmanifestaties...........................................................111
zeldzame bacteriële huidinfecties...............................................................................112
niet-tuberculose mycobacteriële huidinfecties............................................................113
syphillis: huidmanifestaties......................................................................................... 114
ANDRÉ EMMANUEL
,Inhoudsopgave
H1: inleiding tot de klinische biologie.............................................................7
belang van microbiologie en bacteriologie in menselijke gezondheid.............................7
Belang van microbiologie.............................................................................................7
Doel van klinische laboratoria......................................................................................7
verloop van infectie...................................................................................................... 7
diversiteit van micro-organismen.................................................................................7
Transmissieroutes van bacteriële pathogenen................................................................9
Oorsprong pathogenen................................................................................................. 9
Reservoir en transmissie pathogenen...........................................................................9
Oorsprong en transmissie infectieziektes...................................................................10
Uitbraken....................................................................................................................... 13
Definities.................................................................................................................... 13
Voorbeelden............................................................................................................... 14
Pathogenese van bacteriële infecties............................................................................14
indeling bacteriën....................................................................................................... 14
infectie....................................................................................................................... 15
ontsnappingsroutes van bacteriën.............................................................................16
Risicofactoren voor (ernstiger) bacteriële infecties.......................................................16
Leeftijd....................................................................................................................... 16
Onderliggende gezondheidscondities.........................................................................16
Omgevingsfactoren.................................................................................................... 16
Leefstijlfactoren en risicovol gedrag...........................................................................16
Socio-economische en genetische factoren................................................................16
H2: bacteriologie..........................................................................................18
Bacteriële structuur....................................................................................................... 18
endosymbiont theorie................................................................................................. 18
Celwand...................................................................................................................... 18
Celmembraan............................................................................................................. 22
Bacterieel genoom...................................................................................................... 23
Bacterieel capsule...................................................................................................... 24
Bacteriële sporen........................................................................................................ 25
Bacterieel metabolisme................................................................................................. 26
Bacterieel DNA........................................................................................................... 26
Voedingsuitwisseling.................................................................................................. 26
Efflux pompen............................................................................................................ 26
Bacteriële ademhaling................................................................................................ 27
Bacteriële replicatie.................................................................................................... 27
Transcriptie DNA in mRNA.......................................................................................... 27
Translatie mRNA in proteins.......................................................................................27
Bacterieel microbioom................................................................................................ 28
H3: diagnose van infecties en identificatie van bacteriën...............................29
basic laboratorische technieken: microscopie...............................................................30
Macroscopische examinatie........................................................................................ 30
, Microscopische examinatie......................................................................................... 30
Cultuur en isolatie van bacteriën van klinische specimens............................................35
Incubatie condities..................................................................................................... 35
Identificatie van bacteriën gebruikmakende van biochemische testen.........................36
Biochemische testen en automatie.............................................................................36
gram-positief.............................................................................................................. 37
Antigeen-gebaseerde snelle testen...............................................................................37
Snelle antigeentesten = immunoassays.....................................................................37
Diagnose van clostridium difficile...............................................................................38
Diagnose van legionella pneumophila........................................................................38
Identificatie van bacteriën gebruikmakende van Mass Spectrometry (MALDI-TOF MS). 38
Identificatie van bacteriën gebruikmakende van 16S RNA sequencing.........................39
Ribosomen en 16S rRNA-sequencing..........................................................................39
Disease-specific workflows............................................................................................41
identificatie van mycobacerium tuberculose en antibiotica resistentie mechanismen
................................................................................................................................... 41
Detectie van helicobacter pylori.................................................................................42
H4: drug susceptibility testing en therapeutic drug monitoring......................43
Drug susceptibility testing.............................................................................................43
Phenotypic methods................................................................................................... 47
Alternative methods................................................................................................... 49
Pharmacokinetics – PK................................................................................................... 52
Pharmacodynamics – PD............................................................................................... 53
Therapeutic drug monitoring (TDM)..............................................................................54
balans tussen therapeutische en toxische effecten....................................................54
voorbeelden............................................................................................................... 55
Invloed van CYP-level activiteit...................................................................................56
methoden om antibiotica concentraties in bloed te bepalen......................................59
H5: antibiotica en antimicrobiële resistentie..................................................60
behandeling van syphillis tot de ontdekking van Penicillin............................................60
de systematische studie naar natuurlijke producten.....................................................61
fungal diversity: oneindige bron van kleine inhibitorische moleculen.........................62
belangrijke klassen van antibiotica.............................................................................62
de opkomst van resistentie...........................................................................................63
resistentiemechanismen............................................................................................. 63
drijfveren AMR............................................................................................................ 64
globale antibiotica consumptie...................................................................................64
Belangrijkste mechanismen van resistentie...............................................................65
WHO-prioriteitenlijst................................................................................................... 66
Stille pandemieën van MDRO’s...................................................................................68
actiemechanismen van antibiotica/bacteriën................................................................68
Overzicht antimicrobiële therapie strategieën............................................................68
Overzicht resistentiemechanismen.............................................................................69
celwand inhibitoren....................................................................................................... 70
, Werking ß-lactam-antibiotica en vancomycine...........................................................70
DNA en mRNA synthese inhibitoren..............................................................................80
Quilonolen.................................................................................................................. 81
Peptide synthese inhibitoren......................................................................................... 82
macroliden.................................................................................................................. 83
Lincosamide............................................................................................................... 83
Aminoglycosides......................................................................................................... 84
Tetracyclines.............................................................................................................. 84
andere antibiotica......................................................................................................... 85
Bactrim....................................................................................................................... 85
metronidazole............................................................................................................. 86
alternatieven van antibiotica: fagen..............................................................................86
H6: antibacterial vaccines and vaccine-preventable diseases.........................88
Inleiding: early discoveries............................................................................................ 88
soorten vaccins........................................................................................................... 88
Vaccins in Belgë............................................................................................................ 89
DtaP.............................................................................................................................. 90
Drifterie...................................................................................................................... 90
Tetanus...................................................................................................................... 91
Kinkhoest.................................................................................................................... 91
Haemopohilus influenzae type B...................................................................................93
Neisseria mengitidis...................................................................................................... 94
Streptococcus pneumoniae...........................................................................................95
overall effect van vaccins op bacteriële meningitis.......................................................97
Salmonella enterica subsp. Eneterica serovar Typhil.....................................................98
H7: skin and soft tissue infections...............................................................100
normale huid en zijn microbioom................................................................................100
ziekten geassocieerd met dysbiosis............................................................................102
meest voorkomende bacteriën in huidinfecties...........................................................102
ziektes veroorzaakt door toxines.................................................................................104
infecties geassocieerd met barriere doorbreking........................................................104
Superficial bacterial skin infections.............................................................................107
follikel gerelateerde huid infecties..............................................................................109
zachte weefsel infecties..............................................................................................109
Health-care associated infections (HAI).......................................................................111
niet-bacteriële infecties met huidmanifestaties...........................................................111
zeldzame bacteriële huidinfecties...............................................................................112
niet-tuberculose mycobacteriële huidinfecties............................................................113
syphillis: huidmanifestaties......................................................................................... 114
