longitudinal evaluation of self-reported antibiotic use and its association with vaginal and rectal

117 Pages·2014·0.74 MB·English

by  Meyn, Leslie

LONGITUDINAL EVALUATION OF SELF-REPORTED ANTIBIOTIC USE AND ITS
ASSOCIATION WITH VAGINAL AND RECTAL COLONIZATION BY LACTOBACILLUS
AND VULVOVAGINAL CANDIDIASIS IN NON-PREGNANT WOMEN
by
Leslie Ann Meyn
BS in Biology, University of Alaska – Anchorage, 1991
MS in Biostatistics, University of Pittsburgh, 2000
Submitted to the Graduate Faculty of
Graduate School of Public Health in partial fulfillment
of the requirements for the degree of
Doctor of Philosophy
University of Pittsburgh
2014
UNIVERSITY OF PITTSBURGH

GRADUATE SCHOOL OF PUBLIC HEALTH

This dissertation was presented

by

Leslie A. Meyn

It was defended on

April 7, 2014

and approved by

Committee Chair: Jane A. Cauley, DrPH, MPH
Professor of Epidemiology
Graduate School of Public Health
University of Pittsburgh

Committee Member: Sharon L. Hillier, PhD
Richard Sweet Professor of Reproductive Infectious Disease
School of Medicine
University of Pittsburgh

Committee Member: Maria M. Brooks, PhD
Associate Professor of Epidemiology and Biostatistics
Graduate School of Public Health
University of Pittsburgh

Committee Member: Lee H. Harrison, MD
Professor of Medicine and Epidemiology
School of Medicine
Graduate School of Public Health
University of Pittsburgh

Committee Member: Catherine L. Haggerty, PhD, MPH
Associate Professor of Epidemiology
Graduate School of Public Health
University of Pittsburgh

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Copyright © by Leslie A. Meyn

2014
iii
Jane A. Cauley, DrPH, MPH
LONGITUDINAL EVALUATION OF SELF-REPORTED ANTIBIOTIC USE AND ITS
ASSOCIATION WITH VAGINAL AND RECTAL COLONIZATION BY
LACTOBACILLUS AND VULVOVAGINAL CANDIDIASIS IN NON-PREGNANT
WOMEN
Leslie A. Meyn, PhD
University of Pittsburgh, 2014

ABSTRACT

This dissertation includes three manuscripts describing the use of systemic and intra-vaginal
antibiotics in non-pregnant women. The first manuscript described the scope of antibiotic use
and showed that the antibiotic use rate was high. Nearly half of the antibiotics were used to treat
genitourinary infections. However, one in five antibiotics were used to treat upper respiratory
tract illnesses for which antibiotics are not indicated according to CDC recommendations and
these antibiotics were primarily β-lactam agents.
The second manuscript evaluated whether antibiotic use impacted vaginal and rectal
colonization by hydrogen peroxide (H O )-producing lactobacilli, which are the predominant
2 2
members of the healthy vaginal microbiome. These analyses showed there was a significant
reduction in vaginal colonization by H O -producing lactobacilli following the use of β-lactam
2 2
antibiotics, while other classes of antibiotics had no m easurable effect on Lactobacillus
colonization. A novel finding was that β-lactam use also reduced rectal colonization by
lactobacilli to a similar degree as that observed for the vagina and that the effects persisted for a
longer period of time.
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The third manuscript evaluated whether antibiotic use was associated with acquisition of
vaginal yeast infections. Antibiotic use was associated with increased acquisition of yeast
vaginitis, and while the highest risk was associated with the use of β-lactam antibiotics, the use
of some other classes of antibiotics, including metronidazole, fluoroquinolones, and
nitrofurantoin, were also associated with increased yeast vaginitis.
Each manuscript provided new insights into the public health significance of antibiotic
use in reproductive-aged women. The first confirmed that antibiotic use was common in women
and extended our knowledge by showing that the treatment of genitourinary tract infections was
the primary indication for antibiotic use and that treatment of upper respiratory tract infections
was the major contributor to exposure of women to β-lactam antibiotics. The results of the
second and third manuscripts suggest that decreasing the inappropriate use of β-lactam
antibiotics deserve special attention since β-lactams were associated with decreased colonization
by beneficial lactobacilli and increased yeast vaginitis. This research has provided insights on
how efforts to reduce antibiotic use should be tailored in young women for the greatest public
health benefit.

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TABLE OF CONTENTS
ACKNOWLEDGEMENT ........................................................................................................... xi
1.0 INTRODUCTION.............................................................................................................. 1
2.0 LITERATURE REVIEW ................................................................................................. 5
2.1 ANTIBIOTIC CONSUMPTION .................................................................................. 5
2.1.1 Regional variations in antibiotic consumption .......................................................... 5
2.1.2 Distribution of antibiotic classes consumed ............................................................... 6
2.1.3 Indications for antibiotic use ....................................................................................... 7
2.1.4 Antibiotic use in women ............................................................................................... 8
2.2 ANTIBIOTIC SUSCEPTIBILITY OF VAGINAL LACTOBACILLI .................... 9
2.2.1 Antibiotic susceptibility of vaginal lactobacilli in vitro ........................................ 9
2.2.2 Vaginal colonization by lactobacilli following antibiotic use ............................ 12
2.2.2.1 Vaginal colonization by lactobacilli following self-reported antibiotic use . 13
2.2.2.2 Vaginal colonization by lactobacilli following penicillin use ......................... 15
2.2.2.3 Vaginal colonization by lactobacilli following macrolide use........................ 17
2.2.2.4 Vaginal colonization by lactobacilli following fluoroquinolone use ............. 17
2.2.2.5 Vaginal colonization by lactobacilli following tetracycline use ..................... 18
2.2.2.6 Vaginal colonization by lactobacilli following metronidazole and
clindamycin use ................................................................................................................ 18
2.3 ASSOCIATION OF ANTIBIOTIC USE WITH VULVOAGINAL CANDIDIASIS . 24
2.4 SUMMARY........................................................................................................................ 32
3.0 SPECIFIC AIMS AND POWER ANALYSES .................................................................. 34
4.0 MANUSCRIPT 1: LONGITUDINAL EVALUATION OF ANTIBIOTIC USE IN NON-
PREGNANT, REPRODUCTIVE-AGED WOMEN ............................................................... 37
4.1 ABSTRACT ....................................................................................................................... 38
4.2 INTRODUCTION ............................................................................................................. 39
4.3 METHODS ........................................................................................................................ 40
4.3.1 Study population ......................................................................................................... 40
4.3.2 Covariates .................................................................................................................... 41
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4.3.3 Statistical analysis ....................................................................................................... 42
4.4 RESULTS ........................................................................................................................... 43
4.5 DISCUSSION .................................................................................................................... 47
4.6 ACKNOWLEDGEMENTS .............................................................................................. 50
4.7 TABLES ............................................................................................................................. 51
5.0 MANUSCRIPT 2: ASSOCIATION OF CLASS-SPECIFIC ANTIBIOTIC USE WITH
VAGINAL AND RECTAL COLONIZATION BY LACTOBACILLUS ............................... 56
5.1 ABSTRACT ....................................................................................................................... 57
5.2 INTRODUCTION ............................................................................................................. 58
5.3 METHODS ........................................................................................................................ 59
5.3.1 Study population ......................................................................................................... 59
5.3.2 Antibiotic use and Lactobacillus identification ........................................................ 60
5.3.3 Covariates .................................................................................................................... 61
5.3.4 Statistical analysis ....................................................................................................... 61
5.4 RESULTS ........................................................................................................................... 62
5.5 DISCUSSION .................................................................................................................... 66
5.6 ACKNOWLEDGEMENTS .............................................................................................. 69
5.7 TABLES ............................................................................................................................. 70
6.0 MANUSCRIPT 3: ASSOCIATION OF CLASS-SPECIFIC ANTIBIOTIC USE,
MULTPLE SEX PARTNERS, AND HORMONAL CONTRACEPTION WITH
VUVOVAGINAL CANDIDIASIS ............................................................................................ 75
6.1 ABSTRACT ....................................................................................................................... 76
6.2 INTRODUCTION ............................................................................................................. 77
6.3 METHODS ........................................................................................................................ 78
6.3.1 Study population ......................................................................................................... 78
6.3.2 Vulvovaginal candidiasis and antibiotic use ............................................................ 79
6.3.3 Covariates .................................................................................................................... 79
6.3.4 Statistical analysis ....................................................................................................... 80
6.4 RESULTS ........................................................................................................................... 80
6.5 DISCUSSION .................................................................................................................... 83
6.6 ACKNOWLEDGEMENTS .............................................................................................. 87
6.7 TABLES ............................................................................................................................. 88
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7.0 DISCUSSION ........................................................................................................................ 93
7.1 SUMMARY OF FINDINGS ............................................................................................ 93
7.2 FUTURE RESEARCH ..................................................................................................... 96
7.3 PUBLIC HEALTH SIGNIFICANCE ............................................................................. 97
BIBLIOGRAPHY ..................................................................................................................... 100

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LIST OF TABLES

Table 2.1 Summary of studies evaluating the association between vaginal Lactobacillus
colonization and antibiotic use…………………………………………………………………...22
Table 2.2 Characteristics of studies evaluating antibiotic use for vulvovaginal candidiasis in non-
pregnant women………………………………………………………………………….............30
Table 4.1 Antibiotic use by class………………………………………………………………...51
Table 4.2 Antibiotic use by class and indication………………………………………………...52
Table 4.3 Independent risk factors for receiving antibiotics for bronchitis, rhinosinusitus, or non-
specific upper respiratory tract infection (N=229 women)…………..…………………………..53
Table 4.4 Antibiotic use rates by demographic and behavioral characteristics (N=699
prescriptions)……………………………………………………………………………………..54
Table 4.5 Independent risk factors for antibiotic use, excluding use for upper respiratory tract
infections (N=516 prescriptions)………………………………………………………………...55
Table 5.1 Antibiotic use by class………………………………………………………………...70
Table 5.2 A ssociation of demographics and contraceptive methods with vaginal and rectal
colonization by hydrogen peroxide-producing Lactobacillus…………………………………...71
Table 5.3 A ssociation of antibiotic use with vaginal and rectal colonization by hydrogen
peroxide-producing Lactobacillus……………………………………..………………………...72
Table 5.4 Independent risk factors for vaginal and rectal colonization by hydrogen peroxide-
producing Lactobacillus………………………………………………………………………....73
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Table 5.5 Vaginal and rectal colonization by Lactobacillus spp. and antibiotic use among women
in the tetanus-diphtheria vaccine arm – multinomial logistic regression model (N=330
women)………………………………………………………………………………..................74
Table 6.1 Association of enrollment characteristics with vulvovaginal candidiasis………….....88
Table 6.2 Antibiotic use by class………………………………………………………………...89
Table 6.3 Association of antibiotic use, contraceptive methods, sexual activity, and vaginal
Lactobacillus colonization with vulvovaginal candidiasis……………………………………...90
Table 6.4 Independent risk factors for vulvovaginal candidiasis, both clinician and self-
diagnosed events (N=5599 Visits, n=205 events)……………………………………………….91
Table 6.5 Independent risk factors for vulvovaginal candidiasis, restricted to clinician-diagnosed
events (N=5599 Visits, n=164 events)…………………………………………………………...92

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