Methicillin-Resistant Staphylococcus aureus (MRSA) Exposure Assessment in Hospital ...

240 Pages·2012·2.01 MB·English

Methicillin-Resistant Staphylococcus aureus (MRSA) Exposure Assessment
in Hospital Environment

by

Nottasorn Plipat

A dissertation submitted in partial fulfillment
of the requirements for the degree of
Doctor of Philosophy
(Epidemiological Science)
in the University of Michigan
2012

Doctoral Committee:

Professor James S. Koopman, Chair
Professor Carol E. Chenoweth
Associate Professor Joseph N. S. Eisenberg
Professor Betsy Foxman
Associate Professor Duane W. Newton
Associate Research Scientist Rick L. Riolo
©Nottasorn Plipat
2012
For Damkerng Plipat and in memory of Anchalee Plipat

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ACKNOWLEDGEMENTS
I owe a debt of gratitude to many people whose help has been essential to the
completion of my dissertation. First and foremost, I would like to express my deep
gratitude to Dr. Jim Koopman, who introduced me to the study of infection transmission
and its potential impact. He made a profound impression and shaped my thinking along
the way. He taught me integrity and determination to pursue science. I greatly appreciate
Dr. Joe Eisenberg for his insightful and timely guidance and suggestions, which helped me
to stay focused and organized. His quest for clarity and direction has always been
valuable. I also had the tremendous fortune to have Dr. Betsy Foxman as a mentor. I very
much appreciate her for her compassion, wisdom, and advice that went beyond the
academic realm, but also for family and life survival skills, which were crucially needed
and always proved helpful. I would like to express my gratitude to Dr. Carol Chenoweth
for her support and expertise in hospital infection control, for providing me with the
opportunity to perform the surveillance study, and for her guidance in finalizing the
manuscript. I am indebted to Dr. Duane Newton for his generous support and time in
getting this project started, for providing access to laboratory data, and for taking the lead
as the principal investigator of the surveillance study. His prompt response to all my
requests is much appreciated. I am also grateful to Dr. Rick Riolo for introducing me to
agent-based modeling. His gentleness and encouraging words have helped appease the
overwhelming confronting tasks. I have been privileged to have six exceptional mentors as
my committee members.
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I would like to acknowledge the financial support from i) the Center for Advancing
Microbial Risk Assessment (CAMRA) by the U.S. EPA: Science to Achieve Results
(STAR) program and by the U.S. Department of Homeland Security University Program
(Grant #R83236201), ii) the U.S. NIH sponsored Interdisciplinary Training Program in
Infectious Diseases (IPID) by the Molecular and Clinical Epidemiology of Infectious
Diseases (MACEPID) (NIH T32 AI049816), and iii) the Risk Science Center. I thank the
Center for the Study of Complex System for computing support and advice.
I would like to offer my sincere thanks to Jijun Zhao for all her work to get the
agent-based model started from the ground up. Jijun taught me a great deal about
designing and implementing models. I appreciate her time and effort that helped shape this
work.
I thank Kathy Welch for the statistical support and all her friendly advice. Ben
Chen, Christy Zalewski, Suma Chandrasekaran, and Craig Meldrum helped with data
extraction and coordination with the intensive care unit personnel.
I want to thank my friends; Ian Spicknall, Sheng Li, Darlene Bhavnani, Meghan
Milbrath, Ethan Romero-Severson, Bryan Mayer, Pete Larson, Laxmi Modali, Nancy
Fleischer and Eileen Rillamas-Sun, who have been supportive and provided an
intellectually stimulating environment.
I want to thank Gai, Koy, and Eed. They have given me tremendous help in caring
for the children and allowing me to complete my work.
During this last stage of the dissertation, I greatly appreciate support and guidance
from Donna Goodin. She has been a dependable friend, who is always there to listen and
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knows when to give her skilled advice. I also thank Jennifer McNeil for her professional
editing help.
I owe much to my father and my late mother for providing me opportunities to
learn a foreign language and to dream beyond my horizon. They have been my endless
source of love and trust. My brothers have always been inspiring, and they set a high bar
to aspire to.
I am so grateful to my husband’s family. Sheri Mark, Abe Slaim, and Joyce Slaim
have been wonderful grandparents. They have shown me what it means that it takes a
whole village to raise children.
Lastly, I am and will always be grateful to my husband, Daniel Slaim, for his love,
unwavering support, and steadfast belief in me. I would also like to acknowledge our
children, Anchalee Slaim and Naphtali Slaim, for being so resilient through our journey
and for filling my life with love and meaning.

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TABLE OF CONTENTS

Dedication .......................................................................................................................... ii
Acknowledgements .......................................................................................................... iii
List of Tables .................................................................................................................. viii
List of Figures .................................................................................................................... x
List of Appendices........................................................................................................... xii
Abstract .......................................................................................................................... xiii
Chapter
I. Background and Significance.................................................................................. 1
1.1 History of methicillin-resistant Staphylococcus aureus (MRSA) .......................... 1
1.2 Classification ........................................................................................................... 4
1.3 Burden of healthcare-associated staphylococcal diseases ....................................... 7
1.4 Clinical manifestations ............................................................................................ 8
1.5 Community-associated methicillin-resistant Staphylococcus aureus and its impact
on healthcare-associated infection ................................................................................. 9
1.6 Colonization ........................................................................................................... 13
1.7 Risk factors of acquiring healthcare-associated infection ..................................... 15
1.8 Routes of transmission ........................................................................................... 17
1.9 Current infection control strategy ......................................................................... 20
1.10 Summary .............................................................................................................. 26
II. Selected Transmission Modeling Studies and S. aureus Molecular Typing
Techniques .................................................................................................................. 40
2.1 Previous modeling studies in healthcare setting .................................................... 40
2.2 S. aureus molecular typing methods and their applications .................................. 48
2.3 Summary ................................................................................................................ 54
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III. Supporting Evidence for Environmental Mediated Transmission and Model
Parameterization ........................................................................................................ 58
3.1 S. aureus is shed to the environment continuously and sometimes profusely. ..... 58
3.2 S.aureus survives and remains viable on surfaces and hands for a long period of
time .............................................................................................................................. 69
3.3 S. aureus can be transferred between contacting surfaces .................................... 72
3.4 S. aureus in the environment can lead to infection. .............................................. 76
3.5 Summary ................................................................................................................ 78
3.6 Dissertation goal and outline ................................................................................. 79
IV. Colonization Pressure as a Risk Factor for Methicillin-Resistant
Staphylococcus aureus Acquisition in a Surgical Intensive Care Unit .................. 86
4.1 Introduction ............................................................................................................ 86
4.2 Methods ................................................................................................................. 88
4.3 Results.................................................................................................................... 92
4.4 Discussion .............................................................................................................. 99
V. The Effect of Continual MRSA Shedding on Exposure Patterns and Surface
Contamination.......................................................................................................... 111
5.1 Introduction .......................................................................................................... 111
5.2 Methods ............................................................................................................... 114
5.3 Results.................................................................................................................. 129
5.4 Discussion ............................................................................................................ 143
VI. The Effect of Hand Hygiene at the Entry and Exit of a Patient’s Room Visit
on the Exposure of MRSA to the Uncolonized Patient ........................................ 154
6.1 Introduction .......................................................................................................... 154
6.2 Methods ............................................................................................................... 157
6.3 Results................................................................................................................. 170
6.4 Discussion ........................................................................................................... 182
VII. Conclusions and Future Directions ................................................................ 194
7.1 Summary ............................................................................................................. 194
7.2 Suggestions for future work ................................................................................ 203
Appendices...................................................................................................................... 209

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LIST OF TABLES

Table

1.1: Definitions used for epidemiologic classification of infections with multidrug-
resistant organisms (MDROs) including 1) methicillin-resistant Staphylococcus
aureus, 2) vancomycin-resistant Enterococcus species, 3) multidrug-resistant
gram-negative bacilli, and 4) vancomycin-resistant S. aureus ................................ 5

2.1: Comparison of transmission studies that incorporated environment in their models.
MDRO is multi-drug resistant organisms .............................................................. 46

3.1: Selected literature review of S. aureus dispersal ................................................... 67

4.1: Comparison of variables related to patients who acquired MRSA and those who
did not acquire MRSA. .......................................................................................... 94

4.2: Cox proportional hazard univariate analysis of MRSA acquisition ...................... 96

4.3: Cox proportional hazard multivariate analysis of MRSA acquisition ................... 97

4.4: Characteristics of previous studies of MRSA acquisitions that included
colonization pressure in their analysis ................................................................. 103

5.1: Model parameters and their values. ..................................................................... 116

5.2: A direct contact event between nurses’ hands (NS) and the uncolonized patient
(PT ). NS represents the concentration of MRSA cfu on nurses (MRSA cfu/2000
u
sq.cm.).. ................................................................................................................ 119

5.3: Comparison of the frequency of the two decontamination methods and the affected
surface area. ......................................................................................................... 135

6.1: Model entities and their events ............................................................................ 158

6.2: Model parameters and their values in the baseline scenario. ............................... 162

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7.1: Summary of differences between the deterministic ordinary differential equation
based model in chapter V and the stochastic agent based model in chapter VI. . 199

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