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Publicly Accessible Penn Dissertations
Summer 2010
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Sharon B. Meropol
University of Pennsylvania, [email protected]
Follow this and additional works at: https://repository.upenn.edu/edissertations
Part of the Therapeutics Commons
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Meropol, Sharon B., "Evaluating Risks from Antibacterial Medication Therapy" (2010). Publicly Accessible
Penn Dissertations. 424.
https://repository.upenn.edu/edissertations/424
A version of Chapter 3 has been published: Meropol SB, Chen Z, Metlay JP. Reduced antibiotic use for acute
respiratory infections in adults and children. Br J Gen Prac. Oct. 2009; 59(567)3321-328.DOI:10.3399/
bjgp09X472610. E321-328 PMID: 19843412
This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/424
For more information, please contact [email protected].
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ABSTRACT EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY USING AN
OBSERVATIONAL PRIMARY CARE DATABASE Sharon B. Meropol Joshua P. Metlay Virtually everyone in
the U.S. is exposed to antibacterial drugs at some point in their lives. It is important to understand the
benefits and risks related to these medications with nearly universal public exposure. Most information
on antibacterial drug-associated adverse events comes from spontaneous reports. Without an unexposed
control group, it is impossible to know the real risks for treated vs. untreated patients. We used an
electronic medical record database to select a cohort of office visits for non-bacterial acute respiratory
tract infections (excluding patients with pneumonia, sinusitis, or acute exacerbations of chronic
bronchitis), and compared outcomes of antibacterial drug-exposed vs. -unexposed patients. By limiting
our assessment to visits with acute nonspecific respiratory infections, we promoted comparability
between exposed and unexposed patients. To further control for confounding by indication and practice,
we explored methods to promote further comparability between exposure groups. Our rare outcome
presented an additional analytic challenge. Antibacterial drug prescribing for acute nonspecific
respiratory infections decreased over the study period, but, in contrast to the U.S., broad spectrum
antibacterial prescribing remained low. Conditional fixed effects linear regression provided stable
estimates of exposure effects on rare outcomes; results were similar to those using more traditional
methods for binary outcomes. Patients with acute nonspecific respiratory infections treated with
antibacterial drugs were not at increased risk of severe adverse events compared to untreated patients.
Patients with acute nonspecific respiratory infections exposed to antibacterials had a small decreased
risk of pneumonia hospitalizations vs. unexposed patients. This very small measurable benefit of
antibacterial drug therapy for acute nonspecific respiratory infections at the patient level must be weighed
against the public health risk of emerging antibacterial resistance. Our data provide valuable point
estimates of risks and benefits that can be used to inform future decision analysis and guideline
recommendations for patients with acute nonspecific respiratory infections. Ultimately, improved point-of-
care diagnostic testing may help direct antibacterial drugs to the subset of patients most likely to derive
benefit.
DDeeggrreeee TTyyppee
Dissertation
DDeeggrreeee NNaammee
Doctor of Philosophy (PhD)
GGrraadduuaattee GGrroouupp
Epidemiology & Biostatistics
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Joshua P. Metlay, MD, PhD
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anti-infective agents, databases, health services research, prescriptions, respiratory tract infections, drug
toxicity
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Therapeutics
CCoommmmeennttss
A version of Chapter 3 has been published: Meropol SB, Chen Z, Metlay JP. Reduced antibiotic use for
acute respiratory infections in adults and children. Br J Gen Prac. Oct. 2009;
59(567)3321-328.DOI:10.3399/bjgp09X472610. E321-328 PMID: 19843412
This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/424
EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY
USING AN OBSERVATIONAL PRIMARY CARE DATABASE
Sharon B. Meropol
A DISSERTATION
in
Epidemiology
Presented to the Faculties of the University of Pennsylvania
in
Partial Fulfillment of the Requirements for the
Degree of Doctor of Philosophy
2010
Supervisor of Dissertation
Signature
Joshua P. Metlay, M.D., Ph.D.
Associate Professor of Medicine & Epidemiology
Graduate Group Chairperson
Signature
Daniel F. Heitjan, Ph.D., Professor of Biostatistics & Statistics
Dissertation Committee
Jalpa A. Doshi, Ph.D., Research Assistant Professor of Medicine
A. Russell Localio, Ph.D. Associate Professor of Biostatistics
Paul R. Rosenbaum, Ph.D. Professor of Statistics
Brian L. Strom, M.D., M.P.H., Professor and Chair, Biostatistics & Epidemiology
EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY
USING AN OBSERVATIONAL PRIMARY CARE DATABASE©
2010
Sharon B. Meropol
Dedication
For Neal, Dan and Hannah
iii
Acknowledgement
I thank the faculties of the University of Pennsylvania Department of Biostatistics and
Epidemiology and the Center for Clinical Epidemiology and Biostatistics for their mentorship and
consistently open doors and minds. I’m particularly grateful to Brian Strom for providing me the
opportunity to be part of this exceptional community, to Josh Metlay for his scholarship, lucidity,
patience, and endless optimism, and to the members of my Committee for giving me the gifts of
their time, support, intellect, and inspiration. Special thanks go to Neal, Dan, and Hannah for
their continual support and love.
Zhen Chen provided statistical support for the early part of this work, especially Chapter
3. All authors have no competing interests to disclose
This work was supported in part by a Ruth L. Kirschstein National Research Service
Award (grant number F32-AI-073015-01A1) from the National Institute for Allergy and Infectious
Diseases, an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and
Research on Therapeutics cooperative agreement (grant number U18-HS-016946) from the
Agency for Healthcare Research and Quality, by an NIH Clinical and Translational Science Award
(grant UL1-RR02-4134) and by a grant from CDC EPIC, London, U.K.. The content is solely the
responsibility of the authors and does not necessarily represent the official views of the Agency
for Healthcare Research and Quality.
This work was presented, in part, at the Pediatric Academic Societies Annual Meeting,
May 4, 2008, Honolulu, HA, and the 4th Annual International Conference on
Pharmacoepidemiology & Therapeutic Risk Management, August 20, 2008, Copenhagen,
Denmark.
The limited dataset used in this study is covered by a data use agreement between the
Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania and EPIC
Database Research Company. EPIC is a licence holder of an historical part of the GPRD
dataset. GPRD is owned by the Secretary of State for Health and is managed on his behalf by the
GPRD Group at the MHRA. The name GPRD is a trade mark of the GPRD group.
iv
This study was granted exempt status by the University of Pennsylvania
Institutional Review Board, and approval by both the University of Pennsylvania THIN User
Committee and EPIC Database Research Company in the U.K.
v
ABSTRACT
EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY
USING AN OBSERVATIONAL PRIMARY CARE DATABASE
Sharon B. Meropol
Joshua P. Metlay
Virtually everyone in the U.S. is exposed to antibacterial drugs at some point in their lives. It is
important to understand the benefits and risks related to these medications with nearly universal
public exposure. Most information on antibacterial drug-associated adverse events comes from
spontaneous reports. Without an unexposed control group, it is impossible to know the real risks
for treated vs. untreated patients. We used an electronic medical record database to select a
cohort of office visits for non-bacterial acute respiratory tract infections (excluding patients with
pneumonia, sinusitis, or acute exacerbations of chronic bronchitis), and compared outcomes of
antibacterial drug-exposed vs. -unexposed patients. By limiting our assessment to visits with
acute nonspecific respiratory infections, we promoted comparability between exposed and
unexposed patients. To further control for confounding by indication and practice, we explored
methods to promote further comparability between exposure groups. Our rare outcome
presented an additional analytic challenge. Antibacterial drug prescribing for acute nonspecific
respiratory infections decreased over the study period, but, in contrast to the U.S., broad
spectrum antibacterial prescribing remained low. Conditional fixed effects linear regression
provided stable estimates of exposure effects on rare outcomes; results were similar to those
using more traditional methods for binary outcomes. Patients with acute nonspecific respiratory
infections treated with antibacterial drugs were not at increased risk of severe adverse events
compared to untreated patients. Patients with acute nonspecific respiratory infections exposed to
antibacterials had a small decreased risk of pneumonia hospitalizations vs. unexposed patients.
This very small measurable benefit of antibacterial drug therapy for acute nonspecific respiratory
infections at the patient level must be weighed against the public health risk of emerging
antibacterial resistance. Our data provide valuable point estimates of risks and benefits that can
be used to inform future decision analysis and guideline recommendations for patients with acute
vi
nonspecific respiratory infections. Ultimately, improved point-of-care diagnostic testing may help
direct antibacterial drugs to the subset of patients most likely to derive benefit.
vii
Description:propensity to have received treatment, or propensity score matching is . was obtained and/or ingested by the patient of interest; data on which
