Kompendium i mikrobiologi og infektionsmedicin 2. udgave

Kompendium i mikrobiologi og infektionsmedicin

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KOMPENDIUM I MIKROBIOLOGI OG INFEKTIONSMEDICIN

Kompendium i mikrobiologi og infektionsmedicin 2. UDGAVE

Niels Høiby og Åse Bengård Andersen (red.)

FADL’s Forlag 3

Kompendium i Klinisk mikrobiologi og infektionsmedicin Niels Høiby og Åse Bengård Andersen (red.)

2. udgave, 1. oplag © FADL’s Forlag 2022 ISBN 978-87-94207-05-8 Projektledelse og forlagsredaktion: Joachim Sømark Grafisk opsætning: Graphorama.dk Omslag: Lene Nørgaard, Le Bureau Tryk: AdVerts Printed in Latvia 2022 Mekanisk, fotografisk eller anden gengivelse af denne bog eller dele heraf er kun tilladt ifølge overenskomst mellem Undervisningsministeriet og CopyDan. Enhver anden udnyttelse uden forlagets skriftlige samtykke er forbudt ifølge gældende dansk lov om ophavsret.

FADL’s Forlag Blegdamsvej 26 2200 København N Besøg os på fadlforlag.dk Eller skrive til redaktion@fadlsforlag.dk

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KOMPENDIUM I MIKROBIOLOGI OG INFEKTIONSMEDICIN

Indholdsfortegnelse Forfatterliste .............................. 9 Forord ...........................................11 1 Generel bakteriologi ..........13 Endosporer ...............................................................14 Cellevæg, cytoplasmamembran og cytoskelet ...........................................................15 Den Gram-negative cellevæg ..........................................15 Den Gram-positive cellevæg ............................................17 Den syrefaste cellevæg ........................................................18 L-former..........................................................................................19 Bakteriekapsler og slimlag................................................19 Pili = fimbriae .............................................................................20 Flageller ..........................................................................................20 Bakterielle toksiner ................................................................22 Farvning af bakterier .............................................................22 Metylenblåtfarvningen ........................................................23 Gram-farvningen ......................................................................23 Ziehl-Neelsen-farvningen ..................................................24 Mutationer, insertioner og deletioner .......................26 Mobile genetiske elementer ............................................27 Horisontal genoverførsel ....................................................28 Transformation..........................................................................28 Konjugation ..................................................................................28 R-plasmider .................................................................................29 Transduktion ...............................................................................29 Transposition ..............................................................................30 Molekylær diagnostik og typning ..................30 Molekylær diagnostik ...........................................................30 Molekylær typning ..................................................................32 Helgenomsekventering .......................................33 Bakterievækst ........................................................33 Dyrkning af bakterier ............................................................35 Test til identifikation af bakterier...............................37 Morfologiske karakteristika .............................................39 2. Kolonimorfologi og vækstkarakteristika i halvflydende og flydende medium..............................39 3. Prøver for kulturelle og diverse andre egenskaber ....................................................................39 4. Toleransprøver......................................................................40 5. Oxidations-reduktionsprøver .....................................40

6. Undersøgelse af kulhydratomsætningen ..........40 7. Undersøgelse af proteinomsætningen................40 Taksonomi – klassifikation af bakterier.....41 Antibiotika og kemoterapeutika....................42 Antibiotikas virkningsmekanismer .............................43 Resistensudvikling ...............................................46 Antibiotikakombinationer ................................50 Bestemmelse af bakteriers følsomhed over for antibiotika og resistensbestemmelse ...........................................................51 Koncentrationsmåling af antibiotika i vævsvæsker ...........................................................54 Sterilisation og desinfektion ...........................54 Sterilisation ..................................................................................56 Desinfektion ................................................................................59 Aerobe og fakultative Gram-positive bakterier ...................................................................63 Staphylococcus ..........................................................................63

2 Systematisk bakteriologi ...............................63 Pyogene streptokokker ........................................................69 Pneumokokker ...........................................................................71 Listeria, Erysipelothrix, Corynebacterium, Propionibacterium ................................................................... 74 Forgrenede bakterier ...........................................76 Actinomyces, Nocardia, Streptomyces .......................76 Syrefaste bakterier...............................................77 Mycobacteriaceae ....................................................................77 Gram-positive endosporedannende stave: Bacillus og Clostridium ..........................82 Bacillus ............................................................................................82 Clostridium ...................................................................................84 Anaerobe Gram-negative stave.......................90 Bacteroidaceae ..........................................................................90 Aerobe Gram-negative diplokokker og kokkobaciller ....................................................91 Neisseriaceae: Neisseria & Moraxella, .......................91 Neisseria .........................................................................................91 Andre Neisseria-arter..........................................94 Moraxella catharrarlis ..........................................................94

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Små kræsne (eng. Fastidious) Gram-negative stave............................................94 Bordetella, Brucella, Francisella ....................................94 Haemophilus & Pasteurella .............................................98 Gardnerella & Capnocytophaga ......................100 Ikke-fermenterende Gram-negative stave.........................................100 Aerobe kræsne Gram-negative vandbakterier ......................................................103 Fakultative anaerobe Gram-negative stave.........................................................................104 Enterobacteriaceae ..............................................................104 Shigella-arter..........................................................................107 Salmonella-slægten ..........................................................108 Klebsiella-arter .....................................................................111 Proteus-arter ..........................................................................112 Yersinia-arter..........................................................................113 Vibrionaceae .............................................................................114 Vibrio-arter...............................................................................114 Krumme og skrueformede, kræsne bakterier ................................................116 Campylobacter-arter........................................................116 Helicobacteraceae ...............................................................117 Menneskerelaterede spirochaeter .............119 Treponema-arter .................................................................119 Borrelia-arter ..........................................................................121 Leptospira...................................................................................123 Chlamydiales og chlamydia ............................125 Rickettsiales .........................................................127 Mycoplasmatales ...............................................129 Mycoplasma og ureaplasma .........................................129 Normalflora – den humane mikrobiota ..........................................131 Huden ............................................................................................132 Conjunctiva og cavum nasi ............................................133 Cavum oris og fauces .........................................................133 Oesophagus og ventrikel..................................................133 Tyndtarmen...............................................................................133 Colon- og fæcesfloraen.....................................................134 Prøvetagning, forsendelse og prøvebehandling .................................................135

3 Klinisk bakteriologi, infektionshygiejne og antibiotikabehandling ....... 135 Hurtigmetoder .....................................................139 Infektion, smittekilder, smitteveje og smittemåder ...................................................139 Udbredelse af endemier, epidemier og pandemier .......................................................145 Infektionshygiejnens opgaver og organisation .........................................................146 Sygehusinfektioner og

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infektionshygiejne.............................................148 Hospitalsepidemiologi.......................................................151 Sygehusinfektioner: urinvejsinfektioner ...........................................152 Sygehusinfektioner: luftvejsinfektioner.............................................153 Sygehusinfektioner: infektioner relateret il brug af intravaskulære katetre ...............154 Sygehusinfektioner: postoperative sårinfektioner ......................................................155 Forholdsregler..........................................................................157 Sygehusinfektioner: gastroenteritis .....................................................158 Sygehusinfektioner: hudinfektioner..........159 Almene infektionshygiejniske forholdsregler ......................................................159 Håndhygiejne ...........................................................................160 Uniformshygiejne..................................................................162 Isolationsforanstaltninger .............................163 Kontrol af trykforhold på slusestuer .......................164 Antibiotikaprofylakse ......................................164 Infektionspatogenese ......................................165 Biofilminfektioner ................................................................168 Principper for antibiotikabehandling ....... 171 Indikationer og prøvetagning .......................................172 Grundlaget for rationel antibiotikaterapi ................................................172 Administration, proteinbinding, fordeling og effekt af antibiotika ..............................172 Behandlingens varighed..................................175 Empirisk antibiotikabehandling .................176 Farmakogenetik ..................................................180 Biofilm og fremmedlegemeinfektioner ....180 Hvad er virus?......................................................181 Inddeling ................................................................181

4 Generel virologi ................. 181 Replikation ...........................................................182 Infektionsforløbet..............................................184 Infektionspatogenese ved virusinfektioner .......185 Diagnostik af virusinfektioner .....................187 Direkte påvisning af virus ...............................................188 Antiviral kemoterapi ........................................192 De virale børnesygdomme ..............................199 Morbilli (mæslinger)...........................................................199

5 Systematisk virologi ....... 199 Parotitis (fåresyge) ..............................................................201 Rubella (røde hunde) .........................................................203 Erythema infectiosum (lussingesyge)....................204 Influenzavirus og andre respirationsvejsvirus ........................................206 Influenzavirus (orthomyxovirus)................................206 Influenza A-virus...................................................................206

KOMPENDIUM I MIKROBIOLOGI OG INFEKTIONSMEDICIN

Influenza B-virus...................................................................210 Respiratorisk syncytial-virus og øvrige luftvejsvirus...............................................................210 Respiratorisk syncytialvirus (RSV)............................211 Humant metapneumovirus ...........................................211 Parainfluenzavirus ...............................................................212 Adenovirus .................................................................................212 Rhinovirus ..................................................................................212 Coronavirus................................................................................213 Diagnostik af luftvejsvirus .............................................215 Papilloma- og polyomavirus .........................................215 Polyomavirus............................................................................215 Humant papillomavirus (HPV) ....................................216 Picornavirus..........................................................217 Enterovirus.................................................................................218 Parechovirus .............................................................................220 Viral gastroenteritis ..........................................220 Adenovirus .................................................................................221 Astrovirus....................................................................................222 Calicivirus (Norovirus, Norwalk-virus) ...................223 Rotavirus .....................................................................................225 Patogenese ................................................................................226 Hepatitis-virus ....................................................226 Viral hepatitis ..........................................................................226 Hepatitis A-virus (HAV)....................................................227 Hepatitis B-virus (HBV)....................................................229 Hepatitis C-virus (HCV) ....................................................232 Hepatitis D-virus (HDV) ...................................................234 Hepatitis E-virus (HEV) . ..................................................235 Herpesvirus-familien (herpesviridae) .......236 Ơ-herpesvirus ..........................................................................236 ơ-herpesvirus...........................................................................237 Ƣ-herpesvirus ...........................................................................237 Herpes simplex-virus (type 1 og type 2) .............237 Varicella-zoster-virus.........................................................239 Cytomegalovirus (CMV) ....................................................241 Epstein-Barr-virus ................................................................243 HHV-6 ...........................................................................................244 HHV-7 ...........................................................................................245 HHV-8 (Kaposis sarcomaassociated herpesvirus (KSHV)) ............................................................245 Retrovirus ..............................................................246 HTLV-1 og -2............................................................................246 HIV-1 og -2................................................................................247 Eksotiske virus ....................................................252 Flaviviridae ...........................................................252 Flaviviridae genus flavivirus .........................253 Tick-borne encephalitisvirus (TBEV) ......................253 Centraleuropæisk encephalitis-virus .....................253 Dengue-virus ............................................................................253 Gul feber-virus ........................................................................255 Japansk encephalitis-virus (JEV) ................................256 Zikavirus ......................................................................................256 West Nile encephalitis-virus.........................................257

Togaviridae ...........................................................257 Eastern equine encephalitisvirus (EEEV) .............258 Sindbis-virus og Ockelbo-virus ...................................258 Bunyaviridae ........................................................258 Bunyavirus (California encephalitis-virus (CE)), Nairavirus, fx Crimean-Congo hæmoragisk feber-virus (CCHFV), Phlebovirus, fx Rift Valley feber-virus, Sandfly feber-virus, Hantavirus, fx Hantaanvirus, Sin Nombre-virus, Puumala-virus...............258 Nairovirus (CrimeanCongo hæmoragisk feber-virus (CCHFV)) ..........................................................258 Phlebovirus (Rift Valley febervirus, Sandfly feber-virus) ............................................................259 Hanta-virus (Hantaanvirus, Puumala-virus, Sin Nombre-virus)...........................259 Filoviridae..............................................................260 Ebolavirus og Marburgvirus (Zaire, Sudan, Reston, Elfenbenskysten) ..............................260 Arenaviridae .........................................................260 Lassa-virus .................................................................................261 Junin-virus og argentinsk hæmoragisk feber (AHF) ................................................................................261 Rabies-virus ..........................................................261 Struktur........................................................................................261 Poxvirus ..................................................................263 Prioner og prionsygdomme ............................264 Generel mykologi................................................267

6 Mykologi .............................. 267 Systematisk mykologi ......................................274 Gærsvampe ................................................................................274 Genus Candida ........................................................................275 Genus Cryptococcus ............................................................279 Skimmelsvampe..................................................280 Genus Aspergillus .................................................................281 Dermatofyter............................................................................282 Epidermophyton floccosum...........................................283 Genus Microsporum ............................................................283 Microsporum canis ..............................................................284 Microsporum audouinii ....................................................284 Genus Trichophyton.............................................................284 Trichophyton interdigitale..............................................284 Trichophyton mentagrophytes ....................................285 Trichophyton rubrum .........................................................285 Trichophyton verrucosum ...............................................285 Andre svampe i hud og negle.......................................287 Dimorfe svampe ..................................................288 Svampetoksiner ..................................................288 Allergi og “buildingrelated symptoms” ....289 Antimykotika .......................................................290 Polyener .......................................................................................290 Echinocandiner .......................................................................291 Azoler.............................................................................................291

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Azoler til lokal applikation (miconazol, econazol, clotrimazol og ketoconazol) ......................................................................292 Resistensbestemmelse ....................................294 Genus pneumocystis .........................................294 Forekomst og epidemiologi ...........................................294 Livscyklus ...................................................................................295 Patogenese ................................................................................295 Klinik ..............................................................................................296 Diagnostik ..................................................................................296 Behandling.................................................................................296 Protozoer ...............................................................299

7 Parasitologi......................... 299 Protozoer i mavetarm-kanalen mv.............300 Entamoeba histolytica og andre intestinale amøber...............................................................300 Fritlevende opportunistiske amøber .......................302 Giardia intestinalis...............................................................302 Cryptosporidium-arter .......................................................303 Trichomonas vaginalis.......................................................305 Toxoplasma gondii ...............................................................305 Plasmodium spp.

(Malariaparasitter) ...........................................308 Malign malaria forårsaget af P. falciparum .......314 Leishmania-arter...................................................................316 Trypanosoma cruzi...............................................................320 Trypanosoma brucei gambiense og T. b. rhodesiense .....................................................................321 Helminther ............................................................323 Trematoder (ikter) .............................................323 Schistosoma (blodikter) ...................................................324 Cestoder (bændelorm) .....................................326 Taenia-arter (tintebændelorm) og T. saginata (oksetintebændelorm) ...........................326 T. solium (svinetintebændelorm) ..............................328 Echinococcus-arter (hunden og r ævens dværgbændelorm) ...............................................329 Echinococcus multilocularis .........................................330 Diphyllobothrium latum (fiskebændelorm) .................................................................331 Nematoder (rundorm) ......................................331 Intestinale nematoder .....................................331 Enterobius vermicularis (børneorm)........................331 Ascaris spp. (spolorm) .......................................................332 Trichuris trichiura (piskeorm) ......................................333 Necator americanus og Ancylostoma duodenale (hageorm) .........................................................334 Strongyloides stercoralis .................................................335 FILARIER .................................................................336 Wuchereria bancrofti og Brugia-arter (lymfatisk filariasis, elefantiasis)..............................336

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Onchocerca volvulus (flodblindhed) .......................338 Loa loa (Afrikansk øjeorm) ............................................338 Andre nematoder ...............................................339 Trichinella spp. (trikiner).................................................339 Larva migrans ..........................................................................340 Visceral larva migrans .......................................................340 Arthropoder ..........................................................341 Lus ...................................................................................................341 Lopper ...........................................................................................342 Flåter ..............................................................................................342 Sarcoptes scabiei ..................................................................342 Myiasis ..........................................................................................343 Parasitologisk diagnostik ...............................343 Parasitter i fæces ..................................................................344 Parasitter i urin ......................................................................346 Parasitter i blod .....................................................................346 Parasitter i spinalvæske...................................................346 Parasitter i knoglemarv, lever og milt....................346 Parasitter i hud.......................................................................346 Parasitter i øjne......................................................................347 Infektionsmedicin..............................................349

8 Infektionsmedicinske principper og strategier – alment ................................... 349 Infektionsmedicin .......................................... 349 Feber ........................................................................350 Udredning og undersøgelse ved febersygdomme...................................................351 Håndtering af infektionspatienter.............352 Langvarig feber .......................................................................353 Sepsis.............................................................................................354 Vurdering af mikrobiologiske prøver ........355 Empirisk behandling.........................................356 Adjuverende og immunmodulerende behandling ............................................................357 Immunglobuliner som post-exposure profylakse eller understøttende behandling ............................................................357 Cytokiner .....................................................................................358 Hæmopoietiske vækstfaktorer ....................359 Ændret sygdomspanorama.............................359

Appendix: Plancher ........... 363 Bakterier ............................................................. 364 Virus ...................................................................... 366 Antibiotika ......................................................... 368 Svampe ................................................................ 369 Parasitter ............................................................. 370

Register .................................. 373

KOMPENDIUM I MIKROBIOLOGI OG INFEKTIONSMEDICIN

Forfatterliste

REDAKTØRER Niels Høiby Professor, overlæge, dr.med.

Institut for Immunologi og Mikrobiologi Københavns Universitet & Klinisk Mikrobiologisk Afdeling Rigshospitalet Åse Bengård Andersen Professor, overlæge, dr.med.

Infektionsmedicinsk Afdeling Rigshospitalet

BAKTERIOLOGI Niels Høiby Professor, overlæge, dr.med.

Institut for Immunologi og Mikrobiologi Københavns Universitet & Klinisk Mikrobiologisk Afdeling Rigshospitalet Oana Ciofu Professor, dr.med., ph.d.

Institut for Immunologi og Mikrobiologi Københavns Universitet

Claus Moser Professor, overlæge, ph.d.

Institut for Immunologi og Mikrobiologi Københavns Universitet & Klinisk Mikrobiologisk Afdeling Rigshospitalet Leif Percival Andersen Overlæge, Klinisk Mikrobiologisk Afdeling Rigshospitalet Michael Kemp Professor, overlæge dr. med.

Syddansk Universitet & Den Regionale Mikrobiologiske Afdeling, Region Sjælland

VIROLOGI Allan Randrup Thomsen Professor, dr.med.

Institut for Immunologi og Mikrobiologi Københavns Universitet Jan Gerstoft Professor, overlæge, dr.med.

Infektionsmedicinsk Afdeling Rigshospitalet & Københavns Universitet

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Claus Bohn Christiansen Overlæge, ph.d.

Mikrobiologisk Afdeling Lunds Universitetshospital Sverige

MYKOLOGI

PARASITOLOGI Thor Grundtvig Theander Professor, dr.med.

Institut for Immunologi og Mikrobiologi Københavns Universitet

Ditte Marie Saunte Lektor, overlæge, ph.d. Dermatologisk afdeling Sjællands Universitetshospital i Roskilde & Institut for Klinisk Medicin Københavns Universitet

Jørgen Anders Lindholm Kurtzhals Professor, overlæge, ph.d.

Institut for Immunologi og Mikrobiologi Københavns Universitet & Klinisk Mikrobiologisk Afdeling Rigshospitalet

Maiken Cavling Arendrup Fagchef, professor, overlæge, ph.d., dr.med. Afdeling for mikrobiologi og infektionskontrol Statens Serum Institut & Institut for Immunologi og Mikrobiologi, Københavns Universitet

INFEKTIONSMEDICIN

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Åse Bengård Andersen Professor, overlæge, dr.med.

Infektionsmedicinsk afdeling Rigshospitalet

KOMPENDIUM I MIKROBIOLOGI OG INFEKTIONSMEDICIN

Forord Dette kompendiums 2. udgave er skrevet af de samme forfattere, som er ansvarlige for lærebogen Klinisk mikrobiologi og infektionsmedicin, 5. udgave, FADLs Forlag 2021. Kompendiet imødekommer et behov hos de studerende for en komprimeret tekst og mnemotekniske oversigtsskemaer, som kan bruges til at få overblik over pensum i forbindelse med eksamensforberedelserne.

Kompendiet er derfor ikke en generel lærebog i mikrobiologi, klinisk mikrobiologi og infektionsmedicin, hvor der i stedet er den velillustrerede og pensumdækkende Klinisk mikrobiologi og infektionsmedicin, som dækker behovet.

Niels Høiby og Åse Bengård Andersen

FORORD

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