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Bloodstream Infection at Levanger Hospital, Mid-Norway, 2002-2013 Doctoral Thesis Doctoral

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Bloodstream Infection at Levanger Hospital, Mid-Norway, 2002-2013 Doctoral Thesis Doctoral Doctoral theses at NTNU, 2017:184 Arne Mehl Arne Mehl Bloodstream infection at Levanger Hospital, Mid-Norway, 2002-2013 Doctoral thesis Doctoral Incidence, mortality, antimicrobial resistance, antibiotic treatment, and impact of statin prophylaxis ISBN 978-82-326-2440-9 (printed ver.) ISBN 978-82-326-2441-6 (electronic ver.) ISSN 1503-8181 Doct oral theses at NTNU, 2017:184 oral NTNU Medicine Philosophiae Doctor Thesis for the Degree of the Degree Thesis for Faculty of Medicine and Health Sciences Department of Cancer Research and Molecular Research Department of Cancer Norwegian University of Science and Technology of Science University Norwegian Arne Mehl Bloodstream infection at Levanger Hospital, Mid-Norway, 2002-2013 Incidence, mortality, antimicrobial resistance, antibiotic treatment, and impact of statin prophylaxis Thesis for the Degree of Philosophiae Doctor Trondheim, June 2017 Norwegian University of Science and Technology Faculty of Medicine and Health Sciences Department of Cancer Research and Molecular Medicine NTNU Norwegian University of Science and Technology Thesis for the Degree of Philosophiae Doctor Faculty of Medicine and Health Sciences Department of Cancer Research and Molecular Medicine © Arne Mehl ISBN 978-82-326-2440-9 (printed ver.) ISBN 978-82-326-2441-6 (electronic ver.) ISSN 1503-8181 Doctoral theses at NTNU, 2017:184 Printed by NTNU Grafisk senter Blodbaneinfeksjon ved Sykehuset Levanger 2002-2013 Ved infeksjonar på ulike stader i kroppen (til dømes i lunger, urinvegar gallevegar osb) kan bakteriar, og stundom gjærsopp, koma over i blodbanen, formeira seg der og spreiast til alle delar av kroppen. Slik oppstår ein blodbaneinfeksjon. Mikroorganismar kan også koma direkte inn i blodbanen, til dømes gjennom kanylar eller kateter som går inn i blodårer. Diagnosen blodbaneinfeksjon vert stilt ved at vi påviser bakteriar eller gjærsopp i blodprøve (blodkultur). I perioden 2002-2013 vart det registrert 1995 episodar av blodbaneinfeksjon ved Sykehuset Levanger. Den totale insidensen av blodbaneinfeksjon (episodar pr. 100.000 person-år) auka frå 205 i 2002-2007 til 223 i 2008-2013. Insidensen av blodbaneinfeksjon auka mest hos pasientar som hadde helseteneste-assosiert blodbaneinfeksjon, d.v.s. dei som hadde mykje kontakt med helsetenesta, til dømes pasientar som fekk cellegiftbehandling, dialyse eller som budde på sjukeheim. Insidensen av blodbaneinfeksjon var høgast hos eldre menn. Dei tre vanlegaste mikrobane som gav opphav til blodbaneinfeksjon var Escherichia coli (34,4%), Streptococcus pneumoniae (11,3%) og Staphylococcus aureus (10,9%). Mindre enn 5% av mikrobane vi fann i blodkulturar frå pasientar med blodbaneinfeksjon, var resistente mot den antibiotikakombinasjonen som vert tilrådd av norske helsestyresmakter til behandling av sepsis av ukjent årsak (penicillin pluss gentamicin, med tillegg av metronidazol dersom anaerob infeksjon er mistenkt). Førekomsten av resistente mikrobar var lågare enn det som vert rapportert frå dei fleste andre land. Men i dei siste åra av studieperioden fann vi ein liten auke av E. coli som produserte breispektra beta-laktamase (ESBL). Antibiotikaresistens er eit aukande problem rundt om i verda, men også i vårt land. Skal vi greie å redusere førekomsten av antibiotikaresistens, må vi bruke mindre antibiotika. Å finne andre tiltak som kan førebyggje blodbaneinfeksjon og død som fylgje av blodbaneinfeksjon vil derfor bli viktig framover. Vi undersøkte om det å overleve blodbaneinfeksjon kunne ha samanheng med om pasientane brukte statin, ein type medisin som reduserer kolesterol i blodet, men som også har betennelsesdempande effekt. Det viste seg at blant pasientane som hadde blodbaneinfeksjon med Gram-negativ bakterie, var prosentdel som døydde 50% lågare blant dei som brukte eit statin samanlikna med dei som ikkje brukte statin. Blant dei som hadde blodbaneinfeksjon 3 med Gram-positiv bakterie, var det derimot ingen skilnad mellom dei som brukte statin og dei som ikkje brukte statin. Navn på kandidat: Arne Mehl Disputas: Fredag 16. juni, 2017, HUNT Forskningssenter, Levanger Institutt: Institutt for kreftforskning og molekylær medisin Veiledere: Tom-Harald Edna, Stig Harthug og Bjørn Olav Åsvold Finansieringskilder: x Enhet for anvendt klinisk forsking, NTNU x Samarbeidsorganet mellom Helse Midt-Norge og NTNU x St Olavs Hospital x Norsk overvåkingssystem for antibiotikaresistens hos mikrober (NORM), Tromsø x Fondet for forskning og utvikling, Helse Nord-Trøndelag HF 4 Table of contents LIST OF FIGURES ..................................................................................................................................................... 6 LIST OF TABLES ....................................................................................................................................................... 6 1. ACKNOWLEDGEMENTS .................................................................................................................... 8 2. LIST OF PAPERS ................................................................................................................................. 11 3. ABBREVIATIONS ............................................................................................................................... 13 4. DEFINITIONS ....................................................................................................................................... 17 4.1 Epidemiological and statistical terms................................................................................................... 17 4.2 Infection-related definitions ..................................................................................................................... 19 5. SUMMARY ............................................................................................................................................... 27 6. INTRODUCTION ................................................................................................................................. 31 6.1 Bloodstream infection and sepsis .......................................................................................................... 31 6.2 Causative microorganisms and antibiotic resistance .................................................................... 40 6.3 Treatment and outcome ............................................................................................................................. 41 6.4 Clinical research and surveillance.......................................................................................................... 45 6.5 Diagnosis of BSI ............................................................................................................................................. 52 6.6 Prior statin use and BSI related case fatality ..................................................................................... 56 7. AIMS OF THE STUDY ........................................................................................................................ 65 8. MATERIAL AND METHODS .......................................................................................................... 67 8.1 Literature search strategies ...................................................................................................................... 67 8.1 Study setting and cases included ............................................................................................................ 67 8.2 Microbiology laboratory diagnostics .................................................................................................... 68 8.3 Study design .................................................................................................................................................... 69 8.4 Data sources .................................................................................................................................................... 70 8.5 Definitions of study variables .................................................................................................................. 71 8.6 Statistics ............................................................................................................................................................ 74 8.7 Ethics .................................................................................................................................................................. 75 9. SUMMARY OF RESULTS ................................................................................................................. 77 9.1 Paper I ................................................................................................................................................................ 77 9.2 Paper II .............................................................................................................................................................. 79 9.3 Paper III ............................................................................................................................................................. 80 10. DISCUSSION ....................................................................................................................................... 81 10.1 Strengths and limitations ........................................................................................................................ 81 10.2 Discussion in relation to previous studies ......................................................................................
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