The use of Antibiotics and Implications for Antimicrobial Resistance Development
Harald-Jan van Loon
Cover: Shaded Blue; are we at the end of the antibiotic era ? Printed by Ponsen & Looijen bv grafisch bedrijf, Wageningen ISBN 90-6464-935-9 Copyright © 2004 by H.J. van Loon
The use of Antibiotics and Implications for Antimicrobial Resistance Development. Het gebruik van antibiotica en implicaties voor antimicrobiële resistentie. (met een Nederlandse samenvatting)
Proefschrift ter verkrijging van de graad van Doctor aan de Universiteit Utrecht op gezag van de Rector Magnificus, Prof. Dr W.H. Gispen, in gevolge het besluit van het College voor promoties in het openbaar te verdedigen op vrijdag 03 december 2004 des morgens om 10.30 uur door Harald-Jan van Loon geboren op 15 februari 1974 te Brummen
Promotores:
Prof. Dr Chr. van der Werken Prof. Dr J. Verhoef
Co-promotor:
Dr A.C. Fluit
Financial support for publication of this thesis was provided by: Aventis
Pharma,
Ortomed
BV,
Stichting
Bevordering
Wetenschappelijk Onderzoek in de Microbiologie and Chirurgisch Fonds Universitair Medisch Centrum Utrecht.
For family, friends and colleagues
Contents Chapter I
Introduction
9
Chapter II
Short versus Prolonged Antimicrobial Treatment During Open Management of the Abdomen.
27
Chapter III
Predicting for Recurrence of Abdominal Sepsis and Mortality in Patients Undergoing Open Management of the Abdomen.
47
Chapter IV
Antibiotic Rotation and Development of Gramnegative Antibiotic Resistance in ICU.
67
Chapter V
Cross-Transmission of Microorganisms in a Surgical Intensive Care Unit.
97
Chapter VI
A Highly Epidemic Enterobacter cloacae Clone.
113
Chapter VII
The Evolution of Pseudomonas aeruginosa During Antibiotic Rotation in a Medical Intensive Care Unit.
129
Chapter VIII
Evaluation of Genetic Determinants Involved in β-lactam- and Multi-Resistance in a Surgical ICU.
151
Chapter IX
General Discussion and Summary
167
Chapter X
Summary in Dutch
179
Aknowledgements
187
Curriculum vitae auctoris
191
Summary in Dutch
lactameses waargenomen die een enzym bevatten dat indicatief was voor het chromosomaal gecodeerde AmpC van Pseudomonas aeruginosa. Er bleek geen sprake van een bijdrage van ‘horizontal gene transfer’ aan de (interspecies) verspreiding van resistentie determinanten en de verspreiding van mogelijk pathogene microorgansimen van patiënt naar patiënt. Dit proefschrift heeft gedemonstreerd dat veranderingen in antibiotisch beleid een verandering in antibiotisch resistentie niveau teweeg brengt en dat de behandelingsduur met antibiotica continu gemonitord dient te worden. Alleen het aanpassen of alterneren van verschillende antibiotische beleiden zal niet volstaan. Een goed samenspel met factoren zoals, correct antibioticum gebruik, toegenomen infectie preventie maatregelen en een verscherpt detectie systeem voor epidemische verspreiding zullen noodzakelijk zijn om toekomstige kolonizatie met (multi-) resistente microorganismen in perspectief te houden. De komende decennia zal toename van interspecies resistentie-genoverdracht potentiële gevaren opleveren, waarvan de overdracht van het vanA gen uit een Enterococcus spp. naar een Staphylococcus aureus die daardoor vancomycine-resistent wordt, slechts het begin is.
185
Chapter X
186
Acknowledgements & Curriculum Vitae Auctoris
Acknowledgements
The research described in this thesis was not the single effort of one author. It was accomplished with the support of many people, who were indispensable for the realization of this dissertation. I would like to acknowledge them in full for their support, comments, discussions, time and energy. Prof. Dr Chr. van der Werken and Prof. Dr J. Verhoef, promotores of this thesis. Dear Sirs, I would very much like to thank you both for the continuous support, trust and guidance I received. You both kept my drive and focus going and I am proud that I was given the opportunity to grow and evolve under both your wings. Dr A.C. Fluit, co-promotor of this thesis. Dear Ad, thank you for your guidance and help performing experiments in the field of molecular biology. You opened a new door for me and took me by the hand. All experiments described in this thesis were thanks to your creative thoughts and experience. Dr M.R. Vriens. Menno, thank you for all the hard work you performed for the set-up and start-up of the CYCLONE-trial. You paved the way. Prof. Dr M.J.M. Bonten. Marc, thank you for the commitment and effort you put in helping me analyzing and editing the research described in chapter IV. Thanks to you it became a clearer and more thorough article. Dr K. Bosscha. Koop, thank you for your support and editoral work concerning OMA. Your creative thoughts were inspiring. Dr A. Algra. Ale, thank you for introducing me into the world of epidemiology and statistics. You took me by the hand and showed me some basics. Thank you for being there when I needed help with statistical analysis. There still remains a lot I need to learn. I am grateful for your help in chapters II and III.
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Acknowledgements
Dr D.T. Tsukayama. Dean, thank you for letting me participate in the RADAR-trial. Your positive attitude really inspired me and you were a great guest to travel with sightseeing Holland. I hope you will visit again. All experimental work described in this thesis was performed in both the clinical and experimental laboratories for medical microbiology. I would like to thank all technicians and post-docs who assisted me, especially Adrienne, Armand, Mabel, Maartje, Ali, Alice and Willem. Many thanks to all healthcare workers at the surgical ICU for enduring the different study-protocols enforced on them and maintaining high level patient care during the different study periods. The department Hospital Hygiene and Infection Prevention is acknowledged for their help in continuous monitoring and surveillance of the different hospital wards and analyses of possible epidemic outbreaks. Surgeons and fellow-residents surgery of the Amphia Hospital Breda, The Netherlands. The fantastic work climate you create is the reason why I drive those miles every day with a smile on my face. Thank you for your interest, support and the fun we have every day. Martijn Lolkema and Miquel Ekkelenkamp, my paranymphs. I am proud to have you by my side on such a special day. Martijn, we go back to the first year of medicine. We had a lot of fun and over the years you have remained a true friend, thank you. Miquel, doing research was sometimes frustrating. Drinking coffee, near the elevator on G4, while blowing off steam was good therapy. I was honored to review your first novel. It was great! Thanks you for being a colleague and a friend.
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Acknowledgements
My parents, my brother and my sister. Olav, when I was twelve you already showed me Amsterdam during my holiday visits, which made it clear to me that I had to study in Amsterdam. Your stories about Medicine, absolutely fascinated me. During my study you always looked out for me, kept me on the right track and gave me advise on how to get where I am now. I admire the courage you had to move to the UK and I am proud of what you have accomplished. Marishka, your perseverance and creativity in dance have always inspired me. Even though your whole world evolved round ballet, you never lost sight of your little brother, who has grown up now and is very proud of such a wonderful sister. Mum and dad, thank you for your unconditional love, trust and guidance. Without your continuous support and care I would not even be half the man I am today. Even though France is a little bit further than Oisterwijk, you taught us no matter what, la famiglia rimane famiglia and I know you are always there for us. Dearest Annechien, with your love and support I was able to make this thesis to what it is. You strengthen and complete me. I love you. Pepijn, my daily sunshine, at this moment you are too young to understand, but in the future I hope you will be proud.
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Curriculum vitae
Curriculum vitae The author of this thesis was born on the 15th of February 1974 in Brummen, The Netherlands. Having lived two years in the Eastern part of the country his family moved to Schoorl (NH), were he enjoyed a careless youth. During his adolescence the family lived in Oisterwijk (NB), were he attended highschool at the Maurick College in Vught. After graduating in 1992 he started medical school at the University of Amsterdam that same year. During medical school he started research in the field of palliative radiological therapy for esophagus cancer, and the familial aspects of stomach cancer at the Department of Gastro-Enterology, Antoni van Leeuwenhoek Hospital Amsterdam, The Netherlands (Dr B.G. Taal). He graduated from medical school in 1999. That year he started as a resident at the Department of Surgery, ISALA clinics, location Weezenlanden in Zwolle (Dr M. Lopez-Cardozo), where he won the “work horse” prize for his research on patient positioning during subclavian vein puncture (Dr E.G.J.M. Pierik). In 2001 the research described in this thesis was initiated at the Departments of Surgery (Prof. Dr Chr. van der Werken) and Medical Microbiology (Prof. Dr J. Verhoef), University Medical Center Utrecht, The Netherlands. In July 2003 he enrolled into the residency program for general surgery, region Utrecht (Prof. Dr I.H.M. Borel Rinkes). Currently he and his own family live in Hilversum and he is following the first part of his residency program at the Amphia Hospital, location Langendijk in Breda, The Netherlands (Dr F.J.M. van Geloven). The entire program will be completed in 2009.
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