A Prospective Study of Risk Factors For Symptomatic Urinary Tract Infection in Young Women
A Prospective Study of Risk Factors For Symptomatic Urinary Tract Infection in Young Women
A Prospective Study of Risk Factors For Symptomatic Urinary Tract Infection in Young Women
THOMAS M. HOOTON, M.D., DELIA SCHOLES, PH.D., JAMES P. HUGHES, PH.D., CAROL WINTER, A.R.N.P.,
PACITA L. ROBERTS, M.S., ANN E. STAPLETON, M.D., ANDY STERGACHIS, PH.D., AND WALTER E. STAMM, M.D.
A
N estimated 7 million episodes of acute had a chronic illness requiring medical supervision, if they had
cystitis occur annually in the United
States,1 and the annual costs of caring for
these infections in young women are
thought to exceed $1 billion.2 Thus, improved means From the Departments of Medicine (T.M.H., C.W., P.L.R., A.E.S.,
of preventing acute cystitis could lead to important W.E.S.), Biostatistics (J.P.H.), Epidemiology (A.S.), and Pharmacy (A.S.),
reductions in both morbidity and health care costs. University of Washington School of Medicine; and the Center for Health
Studies, Group Health Cooperative of Puget Sound (D.S.) — both in Se-
Factors that may influence the risk of urinary tract in- attle. Address reprint requests to Dr. Hooton at Harborview Medical Cen-
fection include recent sexual intercourse,3-7 use of a ter Madison Clinic, 1001 Broadway (Suite 206), Seattle, WA 98122.
468 Aug u s t 1 5 , 1 9 9 6
used systemic antimicrobial agents within the previous 14 days, or ture-confirmed and probable urinary tract infections were com-
if they had a known anatomical or functional abnormality of the bined for analyses. Contraceptive use was based on data reported
urinary tract. in the diaries, except oral-contraceptive use, which was assumed
At the University of Washington, potentially eligible women to be used daily as prescribed. Because of the differences between
were referred to the study nurse by the family-planning counselor. subjects at the two study sites, all analyses were conducted sepa-
Most such women had not started their new method of contra- rately for women at each site.
ception at the time of study enrollment and began it at the initial Univariate analyses were performed for age, marital status, race
visit with the study nurse. At the Group Health Cooperative, po- or ethnic group, history of urinary tract infections, ABO-blood-
tentially eligible women were identified through a review of an group secretor status, and sexual and contraceptive practices. The
automated pharmacy data base.16 Eligible subjects were sent let- incidence rates of urinary tract infection were determined by di-
ters of invitation, contacted by telephone, and if they agreed to viding the total number of urinary tract infections during follow-
participate, scheduled for a clinic visit. Many of these women had up by the total number of person-years at risk.
begun their new method of contraception at the time of their en- Multivariate analyses of the risk of urinary tract infection were
rollment in the study. For both groups of women, the starting based on data reported in the diaries for the frequency of both
date of the study was considered to be the date of enrollment. contraceptive use and intercourse. The Cox proportional-hazards
The study was approved by the University of Washington and model20 was used to determine the relative contribution of vari-
Group Health Cooperative human-subjects review committees, ous factors to the risk of urinary tract infection. We used the
and all subjects gave written informed consent. counting-process formulation of the Cox model21 in order to in-
clude multiple urinary tract infections per woman, and we used
Evaluation of Subjects the robust variance correction of Lin22 to control for possible cor-
relations within subjects. Time zero for the Cox model was taken
At the initial visit, all subjects were interviewed with a stand- to be the beginning of the study, and real calendar time was used
ardized questionnaire and submitted a midstream urine specimen as the time scale for all analyses. A woman was considered not to
for evaluation of bacteriuria and pyuria as well as blood and saliva be at risk for a new urinary tract infection for five days after the
for blood typing and determination of ABO-blood-group secre- diagnosis of a urinary tract infection.
tor status. At both sites, the subjects were provided with a daily
diary and instructions to indicate in the diary the days on which
the following occurred: sexual intercourse; use of contraception,
with the type indicated; postcoital voiding within one hour of co-
itus; and vaginal and urinary symptoms. The university subjects
were asked to return to the clinic for a directed history taking,
diary review, and urine culture each month or whenever urinary TABLE 1. CHARACTERISTICS OF THE STUDY
symptoms developed during follow-up. The HMO subjects were SUBJECTS WHO MADE AT LEAST ONE
seen every two months for a history taking and midstream urine FOLLOW-UP VISIT.*
collection. At the initial visit, the HMO subjects were also in-
structed in the use and handling of Oxoid dipslides (Unipath,
Ogdensburg, N.Y.). At each clinic visit, the diary was examined UNIVERSITY HMO
by the research nurse to encourage compliance. In alternate SUBJECTS SUBJECTS
months, each subject was interviewed by telephone to collect in- CHARACTERISTIC AT ENROLLMENT (N 348) (N 448)
formation about episodes of urinary tract infection since the last percent
visit, and she was asked to return a urine dipslide to the clinic for
the determination of bacteriuria. The HMO subjects were asked Age
to see their primary care providers for evaluation and treatment 18–22 yr 62 11
if they had urinary symptoms. Subjects at both sites were followed 23–30 yr 31 49
for six months. 31–40 yr 7 40
Marital status
Laboratory Studies Married 10 61
Never married 85 30
Midstream urine specimens for cultures of aerobic bacteria Other 4 9
were collected from the subjects according to previously de- Race or ethnic group
scribed methods.17 The microbiologic procedures used to isolate White 79 88
Black 2 6
and identify organisms from urine cultures have also been de-
Asian or Pacific Islander 10 3
scribed previously.17 ABO-blood-group secretor status was deter- Other† 9 3
mined in a blinded fashion according to standard methods.18
History of any urinary tract 28 58
infection
Definition of Urinary Tract Infection
History of 2 urinary tract 14 38
Subjects were considered to have a culture-confirmed urinary infections
tract infection if they had dysuria, frequency, or urgency (or all ABO-blood-group secretor 75 76
three) and 102 colony-forming units of a uropathogen per mil- Contraceptive method started
liliter of midstream urine.19 Subjects were considered to have a at study enrollment
probable urinary tract infection if they had dysuria, frequency, or Oral contraceptive 52 29
urgency (or all three) and they had been given a diagnosis of a Diaphragm and spermicide 30 46
Cervical cap 15 15
urinary tract infection by their provider in the absence of a urine
Spermicide alone‡ 3 9
culture or, in the absence of provider documentation of a urinary
tract infection, there was documentation of treatment with a uri- *Because of rounding not all categories total 100
nary antimicrobial agent. percent.
†This category includes Native Americans, His-
Statistical Analysis panics, and other groups.
Only subjects who returned to the clinic for at least one follow- ‡Spermicide alone refers to the use of spermicide
up visit were included in the analyses. Except where specified, cul- in the absence of a diaphragm or cervical cap.
Age
18–22 yr 92 61 0.7 20 10 0.5
23–30 yr 45 35 0.8 86 44 0.5
31–40 yr 9 2 0.2 70 28 0.4
Marital status
Married 15 7 0.5 109 36 0.3
Never married 126 88 0.7 52 32 0.6
Other 5 3 0.6 15 14 0.9
Race
White 116 84 0.7 156 68 0.4
Nonwhite 31 14 0.5 21 14 0.7
History of urinary tract
infection
No previous urinary tract 107 53 0.5 74 21 0.3
infections
1 urinary tract infection in 20 12 0.6 36 16 0.4
lifetime
2 urinary tract infections 20 33 1.6 64 42 0.7
in lifetime
ABO-blood-group secretor
Yes 109 74 0.7 131 59 0.4
No 37 24 0.6 40 22 0.6
Oral-contraceptive use† 75 33 0.4 49 18 0.4
No. of days with intercourse
in past 7 days†
0 40 10 0.2 54 6 0.1
1 30 14 0.5 42 18 0.4
2 26 17 0.6 27 19 0.7
3–7 36 45 1.2 26 25 1.0
No. of days diaphragm and
spermicide used in past
7 days†
0 108 56 0.5 116 44 0.4
1 12 5 0.4 18 12 0.7
2 7 7 1.0 9 7 0.8
3–7 6 18 3.0 6 5 0.8
No. of days cervical cap used
in past 7 days†
0 121 74 0.6 136 59 0.4
1 4 5 1.2 5 3 0.6
2 4 6 1.5 3 0 0.0
3–7 4 1 0.2 3 6 2.0
No. of days spermicide alone
used in past 7 days†
0 124 79 0.6 136 53 0.4
1–7 9 7 0.8 12 15 1.2
*For comparison, the incidence among women who were taking oral contraceptives; did not have
intercourse or use a diaphragm and spermicide, a cervical cap, or spermicide alone in the past 7 days;
and had a history of one or fewer urinary tract infections was 0.05 (20.8 person-years) in the univer-
sity cohort and 0.09 (11.8 person-years) in the HMO cohort.
†This information was obtained from the subjects’ diaries. The categories marked with a dagger
are not mutually exclusive.
470 Aug u s t 1 5 , 1 9 9 6
University cohort
10.0 10.0
HMO cohort
P0.001
P0.001
Relative Risk
Relative Risk
P 0.04
P 0.002
1.0 1.0
0.1 0.1
0 1 2 3 4 5 0 1 2 3 4 5
Days with Intercourse in Past 7 Days Days Diaphragm and Spermicide Used
in Past 7 Days
2.0
10.0
Relative Risk
Relative Risk
P 0.08
1.0
P 0.53
P 0.35
1.0
P 0.04
0.5
0.1
0 1 2 3 4 5 20 25 30
as we did with the use of a diaphragm with spermi- fection decreased from 2.1 in the full analysis to 1.4
cide, cervical cap, and intercourse. in this subanalysis (P0.25).
Other potential risk factors, including blood-group
secretor status, race or ethnic group (white vs. oth- DISCUSSION
er), parity, time of voiding after intercourse, and The overall incidence of symptomatic urinary
having a new sexual partner since the last visit, were tract infections in the two populations studied was
not statistically significant when added to the model 0.5 per person-year in the HMO cohort and 0.7 per
shown in Table 3 and Figure 1 (P0.20 for each person-year in the university cohort. Although the
variable at each site). incidence among the young, largely unmarried uni-
versity students was higher than among the older,
Multivariate Analyses with Only Culture-Confirmed largely married HMO members, the difference was
Urinary Tract Infections
not dramatic and suggests that neither the incidence
Using the model shown in Table 3 and Figure 1, of nor risk factors for urinary tract infection seen in
we repeated the analyses using only the subgroup of university women are unique. We are not aware of
patients with culture-confirmed urinary tract infec- other prospective studies with which these incidence
tions. These analyses yielded essentially the same re- data can be compared. Although the HMO popula-
sults as those described above (data not shown), tion at the Group Health Cooperative is representa-
except that in the HMO cohort, the relative risk as- tive of all women in the Puget Sound region,15 our
sociated with a history of recurrent urinary tract in- study subjects were not randomly selected and had
472 Augus t 1 5 , 1 9 9 6
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between diaphragm use and urinary tract infection. JAMA 1985;254:240-5.
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The conclusions and generalizability of our find- and urinary tract infection. JAMA 1979;241:2525-6.
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Diet, clothing, and urination habits. Am J Public Health 1985;75:1314-7.
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14. Hooton TM, Roberts PL, Stamm WE. Effects of recent sexual activity
gion. Further studies should address how sexual and and use of a diaphragm on the vaginal microflora. Clin Infect Dis 1994;
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