Hospital antibiotic use in Norway PhD thesis

121 Pages·2014·11.74 MB·English

by  Jon Birger Haug

Hospital antibiotic use in Norway

Epidemiology and surveillance methodology

PhD thesis

Jon Birger Haug

Oslo 2014

Institute of Clinical Medicine
Faculty of Medicine, University of Oslo, Oslo, Norway

Department of Pharmacology and Department of Infectious Diseases
Oslo University Hospital Trust, Oslo, Norway
© Jon Birger Haug, 2014

Series of dissertations submitted to the
Faculty of Medicine, University of Oslo
No. 1823

ISBN 978-82-8264-834-9

All rights reserved. No part of this publication may be
reproduced or transmitted, in any form or by any means, without permission.

Cover: Inger Sandved Anfinsen.
Printed in Norway: AIT Oslo AS.

Produced in co-operation with Akademika Publishing.
The thesis is produced by Akademika Publishing merely in connection with the
thesis defence. Kindly direct all inquiries regarding the thesis to the copyright
holder or the unit which grants the doctorate.
INSPIRATIONS

Some experts say we are moving back to the pre-antibiotic era.
No.
This will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is
virtually dry. A post-antibiotic era means, in effect, an end to modern medicine as we know it.
Things as common as strep throat or a child's scratched knee could once again kill.
Margaret Chan, WHO Director (1947- )

If you cannot measure it,
you cannot improve it.
Lord Kelvin, scientist (1824-1907)

Progress is made by lazy men
looking for easier ways to do things.
Robert A. Henlein, sci-fi author (1907-1988)

Give me six hours to chop down a tree
and I will spend the first four sharpening the axe.
Abraham Lincoln, American president (1809-1865)

Table of contents
Acknowledgements ..................................................................................................................... i
List of publications .................................................................................................................. iii
1. General background .......................................................................................................... 1
1.1. Antibiotics and modern medicine ................................................................................ 1
1.2. An antibiotic paradox ................................................................................................... 1
1.3. The antibiotic resistance challenge .............................................................................. 2
1.4. Antibiotic resistance in hospitals ................................................................................. 5
1.5. Resistance surveillance ................................................................................................ 6
1.6. The antibiotic stewardship program ............................................................................. 6
1.7. Legislative and strategic measures ............................................................................... 8
2. Epidemiology of antibiotic use ........................................................................................ 10
2.1. Antibiotic use in the community (outpatient use) ...................................................... 10
2.2. Antibiotic use in hospitals .......................................................................................... 12
3. Antibiotic surveillance methodology .............................................................................. 16
3.1. Sources for data on antibiotic use .............................................................................. 16
3.1.1. Wholesalers’ data............................................................................................................ 17
3.1.2. Pharmacy sales to hospital wards ................................................................................... 18
3.1.3. Electronic hospital charts with prescription data ........................................................... 18
3.2. Overview of measurement units and terms ................................................................ 19
3.2.1. The numerators: measures of drug amounts used ........................................................... 19
3.2.2. The denominators: units against which antibiotic use is related ..................................... 22
3.3. “Standards of reporting” of antibiotic use .................................................................. 25
3.4. Methods for surveying antibiotic use ......................................................................... 26
3.4.1. Prevalence surveys .......................................................................................................... 26
3.4.2. Incidence surveys ............................................................................................................ 27
4. Aims of the thesis ............................................................................................................. 30
5. Material and methods ...................................................................................................... 31
5.1. Data on antibiotic use ................................................................................................ 31
5.2. Administrative data and patient-related factors ......................................................... 34
5.3. Hospitals’ antibiotic resistance .................................................................................. 35
5.4. Statistical analyses ..................................................................................................... 36
6. Synopsis of the studies ..................................................................................................... 39
6.1. Paper I ....................................................................................................................... 39
6.2. Paper II ...................................................................................................................... 40
6.3. Paper III ..................................................................................................................... 42
6.4. Paper IV..................................................................................................................... 43
7. Discussion of antibiotic surveillance methods ............................................................... 44
7.1. Reliability of pharmacy sales data ............................................................................. 44
7.2. Bed days versus discharges as denominator unit ....................................................... 45
7.3. WHO DDDs versus hospital adjusted DDDs ............................................................ 46
7.4. Factors decisive for hospital antibiotic use ................................................................ 48
8. General discussion ........................................................................................................... 51
8.1. Utilization of antibiotics in hospital – temporal trends.............................................. 51
8.2. Antibiotic use in relation to resistance ...................................................................... 53
8.3. Strengths and limitations ........................................................................................... 55
9. Conclusions ...................................................................................................................... 57
10. Implications and future research ............................................................................... 58
11. References .................................................................................................................... 61
ACKNOWLEDGEMENTS

Acknowledgements
My motivation for this PhD project has been a long-lasting interest in hospital epidemiology,
initially triggered by my assignment in the early 1990’s at the National Institute of Public Health.
I was working with a pioneer in national infection control, professor Arve Lystad, who was the
creator of MSIS. This simple and brilliant surveillance national notification system for infectious
diseases has for decades been of great importance for Norwegian health care. For Arve’s early
inspiration, I am very grateful.
My most special thanks goes to my main supervisor, professor Åsmund Reikvam. To him I
wish to express a sincere gratitude. Without his scientific experience, extensive knowledge in
pharmacoepidemiology and eminent writing skills this thesis would have been very much harder
to complete. He represents great working capacity with a remarkable persistence and sufficient
patience blended in, and the combination has benefited me tremendously. Above all, he is a
colleague I have come to respect and like a lot. Åsmund, thank you for all your help and support.
A new employment at the Aker university hospital almost 10 years ago fuelled an interest for
antibiotic stewardship that had been pre-existing, but dormant. At this excellent – now
unfortunately extinct – hospital Signe Ringertz and Dag Berild were important catalysts for this
PhD thesis: Signe always encouraging in the initial planning phase, and Dag a perpetual source
of good ideas, always blending in his sound common sense and tons of good humour. I wish to
thank them both for their support, Dag especially for trying – but not succeeding – in being the
“stern” co-supervisor. Nevertheless, he has been a strong motivating force for me especially in
times of trouble. Moreover, he generously left me in charge of the Helse Sør-Øst Regional
Competence centre for hospital antibiotic use at an early stage, thus providing some precious
time for my scientific work.
It was during the Aker period that I met Randi Myhr, one of the many resourceful and
knowledgeable pharmacists in our hospital system that are “overly underused” in the clinic. She
did a large part of the hard work for the Paper I, and never faltered in in her aid to bring that
particular work to a satisfactory completion.
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ACKNOWLEDGEMENTS

My other co-supervisor, Mette Walberg, has provided the sound practical views and good
advices to help find the best path when an overwhelming amount of data seemed to cloud the
way forward.
Several individuals have helped in various ways to complete this thesis, and deserve my most
sincere thank you. The bulk of national data on antibiotic consumption would have been far more
difficult to acquire without the relentless support from the efficient and patient Skule Ingeberg,
chief of analytics at the Hospital Pharmacy Regional Health Enterprise. Three statisticians have
been my consultants for the choices of statistical methods and have aided in the interpretation of
the results. I wish to extend my gratitude to Lien My Diep and Leiv Sandvik for their
contributions to Paper I, and Tron Moger for a critical review of the regression analyses in Paper
IV.
Main companions in my investigations of antibiotic use epidemiology have been the products of
Bill Gates, in particular Microsoft Access and Excel – especially in the process of data mining
and presentation.
Although I wish to express a minor praise to Bill, I am not sure my family shares this entirely.
PhD activities and an intimate relationship to the computer keyboard have often been given
priority over family life. A deeply felt praise go to the love of my life, Nina, who has endured
all of this with great patience. My three wonderful children Linn, Jonas and Mathias have been
very supportive but have during this process become, I suspect, more certain than ever that the
father’s choice of profession was not theirs to follow.
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PUBLICATIONS

List of publications

1. Pharmacy sales data versus ward stock accounting for the surveillance of broad-
spectrum antibiotic use in hospitals.
Haug JB, Myhr R, Reikvam Å.
BMC Medical Research Methodology 2011; 11(1): 166.
http://www.biomedcentral.com/1471-2288/11/166

2. Increased antibiotic use in Norwegian hospitals despite a low antibiotic resistance rate.
Haug JB, Berild D, Walberg M, Reikvam Å.
Journal of Antimicrobial Chemotherapy 2011; 66(11): 2643-6. doi:10.1093/jac/dkr361

3. WHO defined daily doses versus hospital adjusted daily doses: impact on surveillance
results of antibiotic use.
Haug JB, Reikvam Å.
Journal of Antimicrobial Chemotherapy 2013; 68(12): 2740-2747. doi:10.1093/jac/dkt268

4. Explanatory factors for differences in hospital antibiotic use: analysis of national data
from 2006 to 2011.
Haug JB, Berild D, Walberg M, Reikvam Å.
Submitted.

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