ORIGINAL STUDY
A Comparison of Single-Dose Versus Multidose
Metronidazole by Select Clinical Factors for the
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Treatment of Trichomonas vaginalis in Women
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Christina A. Muzny, MD, MSPH,* Leandro A. Mena, MD, MPH,† Rebecca A. Lillis, MD,‡
Norine Schmidt, MPH,§ David H. Martin, MD,‡§ and Patricia Kissinger, PhD§
Background: In a randomized controlled trial of 2 g (single-dose) metro-
nidazole (MTZ) versus 500 mg twice daily for 7 days (multidose) for Trich-
omonas vaginalis treatment, multidose was superior. We examined if the ef-
fect was similar by select clinical factors to determine if treatment recom-
mendations could be targeted.
Methods: The primary outcome was T. vaginalis repeat infection at test-
of-cure (TOC) 4 weeks after completion of therapy. Analyses were stratified
by T. vaginalis history, baseline genital symptoms, and concurrent diagno-
sis of bacterial vaginosis (BV) per Nugent score at baseline.
Results: Women who returned for TOC (n = 540) were included. At base-
line, 52.9% had a self-reported history of T. vaginalis; 79.3%, genital symp-
toms; 5.8%, a gonorrhea diagnosis; and 47.5%, BV. During follow-up,
97.4% took all MTZ as instructed and 34.5% had interval condomless
sex with a baseline partner. At TOC, 14.8% tested positive for T. vaginalis.
In stratified analysis, women randomized to single-dose MTZ had a higher
rate of TOC T. vaginalis positivity than those randomized to multidose if
they were symptomatic at baseline (21.4% vs. 10.8%, P = 0.003) or had a re-
ported history of T. vaginalis (24.1% vs. 12.6%, P = 0.01). Test-of-cure T.
vaginalis positivity was higher for women receiving a single dose (18.9%)
versus multidose (10.8%), irrespective of baseline BV status ( P > 0.06). In
multivariable analysis, only a history of T. vaginalis and single-dose MTZ
were independently associated with a positive TOC for T. vaginalis.
Conclusions: Although multidose MTZ is recommended for all women
with T. vaginalis, it is especially important for women with a T. vaginalis
history and, given high posttreatment infection rates, a TOC should
be performed.
From the *Division of Infectious Diseases, University of Alabama at
Birmingham, Birmingham, AL; †Division of Infectious Diseases and
Department of Population Health Science, University of Mississippi
Medical Center, Jackson, MS; ‡Section of Infectious Diseases,
Louisiana State University Health Sciences Center; and §Department
of Epidemiology, Tulane University School of Public Health and
Tropical Medicine, New Orleans, LA
Acknowledgments: This study was funded by grant 1R01AI097080-01A1
from the National Institute of Allergy and Infectious Diseases (Patricia
Kissinger, PhD: principal investigator). The authors would like to
thank Jane Schwebke, Stephanie Taylor, Laura Beauchamps,
Hanne Harbison, Saralyn Richter, Rhonda Whidden, Meghan
Whitfield, Christen Press, Jim Alosi, Ann Dillashaw, Charles
Rivers, Keonte Graves, Cheri Aycock, Melverta Bender, Jennifer
Brumfield, Catherine Cammarata, Judy Burnett, Denise Diodene,
Lauren Ostrenga, and Scott White for their assistance in performing
the overall study. Study data were collected and managed using
the Research Electronic Data Capture tools, hosted by Tulane
University. Research Electronic Data Capture is a secure, Web-
based application designed to support data capture for research studies,
providing (1) an intuitive interface for validated data entry, (2) audit
trails for tracking data manipulation and export procedures, (3) auto-
mated export procedures for seamless data downloads to common sta-
tistical packages, and (4) procedures for importing data from external
sources.
Sexually Transmitted Diseases • Volume 49, Number 3, March 2022
Copyright © 2022 by the American Sexually Transmitted Diseases Association. Unauthorized reproduction of this article is prohibited.
T richomonas vaginalis is estimated to be the most common
nonviral sexually transmitted infection worldwide.1 It is asso-
ciated with poor birth outcomes,2 reproductive morbidity,3 and
amplified HIV transmission.4 The 2015 US Centers for Disease
Control and Prevention (CDC) Sexually Transmitted Diseases
(STD) Treatment Guidelines previously recommended a 2 g dose
(single-dose) of oral metronidazole (MTZ) or tinidazole (TDZ) as
first-line treatment for HIV-negative women, with a 7-day course
of oral MTZ 500 mg twice daily (multidose) as an alternative.5
The multidose MTZ regimen was recommended as first-line treat-
ment for HIV-infected women, based on data from a prior random-
ized controlled trial (RCT), which found that women receiving
multidose MTZ were half as likely to be T. vaginalis positive at test
of cure (TOC) compared with women receiving a single dose.6
The 2021 CDC Sexually Transmitted Disease (STI) Treat-
ment Guidelines and the 2020 practice bulletin on the manage-
ment of vaginitis in nonpregnant women by the American College
of Obstetricians and Gynecologists have recently expanded the
recommendation to use multidose oral MTZ for all women with
T. vaginalis.7,8 This change in national guideline recommenda-
tions was informed by several studies that have shown that
single-dose MTZ is insufficient to treat T. vaginalis in women be-
yond HIV-infected populations.9,10 The first is a meta-analysis of
6 studies, including 5 studies of HIV-negative women and 1 study
of HIV-infected women, which found that women receiving
single-dose MTZ were 1.87 times more likely to experience treat-
ment failure than those receiving multidose MTZ (95% confidence
Conflict of Interest and Sources of Funding: C.A.M. is a consultant for
Lupin Pharmaceuticals, BioFire Diagnostics, Cepheid, and PhagoMed.
She has also received research funding support from Lupin Pharmaceuticals
and Abbott Molecular as well as speaker honoraria from Abbott
Molecular, Cepheid, Roche Diagnostics, and Becton Dickinson. L.A.M.
has received honoraria for his role as a consultant to Gilead Sciences,
ViiV Healthcare, Roche, and Merck. He has received research grants
from Gilead Sciences, ViiV Healthcare/GSK, Janssen, Binx Health
(Atlas Genetics), Becton Dickinson, Rheonix, Click Diagnostics, Roche,
Evofem, Westat, and Lupin Pharmaceuticals. R.A.L. has conducted
clinical trials for Cepheid and Hologic and is a consultant for Roche and
Merck. N.S., D.H.M., and P.K. have nothing to disclose.
The results of this study were presented, in part, as oral presentation no. 9 at
the 2019 Annual Meeting of the Infectious Diseases Society of
Gynecology in Big Sky, Montana, from August 8 to 10, 2019. The
findings and conclusions in this study are those of the authors and do
not necessarily represent the views of the National Institutes of Health
or National Institute of Allergy and Infectious Diseases.
Correspondence: Christina A. Muzny, MD, MSPH, Division of Infectious
Diseases, University of Alabama at Birmingham, ZRB 240, 703 19th
Street South, Birmingham, AL 35233. E-mail: cmuzny@uabmc.edu.
Received for publication May 31, 2021, and accepted October 14, 2021.
DOI: 10.1097/OLQ.0000000000001574
Copyright © 2021 American Sexually Transmitted Diseases Association.
All rights reserved.
231
 Muzny et al.

interval [CI], 1.23–2.82; P < 0.01). When the one study of HIV-
infected women was excluded from the analysis, the findings were
similar, with a pooled risk ratio of 1.80 (95% CI, 1.07–3.02;
P < 0.03).9 The second is a recent RCT of 623 HIV-negative
women, which found that those receiving multidose MTZ had
45% fewer positive T. vaginalis TOC results than those receiving
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until 24 hours after treatment. Exclusion criteria were HIV infection,
pregnancy or breastfeeding, incarceration, contraindication to MTZ
use, history of alcoholism or liver damage, treatment of BVor T. va-
ginalis within the past 14 days, unwillingness to be randomized, and
inability or unwillingness to return to clinic for a TOC visit (4 weeks
after completion of treatment). The study was approved by the insti-

single-dose (11% vs. 19%; risk ratio, 0.55; 95% CI, 0.34–0.70; tutional review boards at the University of Alabama at Birmingham,
P = 0.0008).10 Taken together, these results provide evidence that University of Mississippi Medical Center, Tulane University, and the
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multidose MTZ should be used for T. vaginalis treatment in
all women.
Prior studies have found that oral MTZ is not consistently
effective for the treatment of T. vaginalis–infected women with a
history of this infection.11,12 Moreover, most MTZ treatment trials
among T. vaginalis–infected women have been performed in
symptomatic women9; little is known if there are differences in re-
sponse to MTZ treatment regimen in asymptomatic women. In ad-
dition, a concurrent diagnosis of bacterial vaginosis (BV) at the
time of T. vaginalis treatment has been associated with single-
dose MTZ treatment failure in HIV-infected women13 but not fully
evaluated in HIV-negative women.10 With this in mind, we performed
a secondary analysis of the recent RCT data of HIV-negative women
with T. vaginalis to determine if the effect found regarding multidose
MTZ was similar by select clinical factors. We were particularly
interested in learning if the use of multidose MTZ was especially
important for women with a T. vaginalis history, symptomatic
women, and those with a concurrent BV diagnosis.
METHODS
This study was a secondary analysis of a randomized, par-
allel, multisite, open-label trial of single-dose versus multidose
MTZ for the treatment of T. vaginalis in HIV-negative women.10
Women were enrolled at STD clinics in Birmingham, AL; Jackson,
MS; and New Orleans, LA. Inclusion criteria were female sex,
English speaking, ≥18 years of age, positive for T. vaginalis
(i.e., by wet mount at the time of enrollment or recent positive
nucleic acid amplification test [NAAT]), confirmed by a second
test (NAAT or culture), and willingness to refrain from alcohol use
Louisiana State University Health Sciences Center. It was also ap-
proved by the Jefferson County Health Department Research Review
Committee and the Mississippi State Department of Health.
Audio computer-assisted self-administered (ACASI) soft-
ware was used at the enrollment and TOC visits to collect socio-
demographic data from participants in addition to data on sub-
stance use, contraception use, sexual behavior, and genital symp-
toms (i.e., vaginal discharge, odor, itch, irritation, painful
urination, pelvic pain, etc.), and history of T. vaginalis (“Before to-
day, has anyone ever told you that you had Trichomonas vaginalis,
also called trichomonas, trichomoniasis, or trich?”). The TOC
ACASI survey also asked questions on MTZ medication adher-
ence (“did you take all your medication as prescribed”) and inter-
val sexual exposure (condomless sex with any baseline partner).
Self-collected vaginal swabs were also obtained at both enrollment
and TOC visits for T. vaginalis NAAT (Aptima T. vaginalis Assay;
Hologic, Bedford, MA), InPouch® culture (Biomed Diagnostics,
White City, OR), and vaginal Gram stain for Nugent score determi-
nation.14 Other STI diagnoses including Chlamydia trachomatis
and Neisseria gonorrhoeae at the time of T. vaginalis NAAT testing
were abstracted from medical records. At the enrollment visit, par-
ticipants were randomly assigned (1:1) to single-dose or multidose
MTZ for T. vaginalis treatment. They were asked to notify sexual
partner(s) within the past 60 days of their diagnosis to encourage
them to seek treatment. Because of legal and/or institutional re-
strictions, none of the clinics provided expedited partner treatment
of T. vaginalis. In addition, all participants received standardized
counseling to refrain from unprotected sex until completion of
treatment, their genital symptoms resolved (if applicable), and
partner(s) were treated. A TOC appointment was scheduled for

TABLE 1. Baseline Sociodemographic, Sexual History, Sexual Behavior, Genital Symptoms, and BV/STI Diagnosis Data, Stratified by Treatment
Arm (n = 540)*
Single-Dose MTZ (n = 270) Multidose MTZ (n = 270) Total P
Age, mean (SD), y 30.9 (9.6) 30.4 (10.2) 30.6 (9.9) 0.55
African American race 258/270 (95.6) 259/269 (96.3) 517/539 (95.6) 0.67
Current cigarette smoking 122/269 (45.4) 125/270 (46.3) 247/539 (45.8) 0.83
Current alcohol use (binge drinking)† 52/270 (19.3) 51/269 (19.0) 103/539 (19.1) 0.93
Vaginal douching (usually) 70/270 (25.9) 69/268 (25.7) 139/538 (25.8) 0.96
STI history
Trichomoniasis 158/270 (58.5) 127/268 (47.4) 285/538 (52.9) 0.01
Chlamydia 148/270 (54.8) 142/268 (53.0) 290/538 (53.9) 0.67
Gonorrhea 95/268 (35.4) 85/268 (31.0) 180/536 (33.6) 0.36
Multiple male sexual partners, past 60 d 104/270 (38.5) 104/269 (38.7) 208/539 (38.6) 0.97
Multiple female sexual partners, past 60 d 5/270 (1.9) 4/270 (1.5) 9/540 (1.7) 0.74
Baseline genital symptoms‡ 215/270 (79.6) 213/269 (79.2) 428/539 (79.3) 0.90
Baseline BV diagnosis (by Nugent score) 124/262 (47.3) 124/260 (47.7) 248/522 (47.5) 0.93
Baseline STI diagnosis
Chlamydia 19/236 (8.1) 28/244 (11.5) 47/480 (9.8) 0.21
Gonorrhea 6/236 (2.5) 18/244 (7.8) 25/480 (5.8) 0.01
Took all MTZ for T. vaginalis as instructed 267/289 (99.3) 256/268 (95.5) 523/237 (97.4) 0.007
Condomless sex during follow-up 88/270 (32.6) 98/269 (36.4) 186/539 (34.5) 0.35

*Data shown as n (%) unless otherwise noted.

†
Binge drinking defined as 4 or more drinks within a 2-hour period.
‡
Genital symptoms including vaginal discharge, odor, itch, and/or pelvic pain.
BV indicates bacterial vaginosis; MTZ, metronidazole; STI, sexually transmitted infection.

232 Sexually Transmitted Diseases • Volume 49, Number 3, March 2022

Copyright © 2022 by the American Sexually Transmitted Diseases Association. Unauthorized reproduction of this article is prohibited.
 Treatment of T. vaginalis by Clinical Factors

4 weeks after completion of treatment, with a window of 3 to multivariable analysis (Table 3). All analyses were conducted
12 weeks. Participants were compensated $20 at enrollment and using SPSS v24 (IBM Corporation, Armonk, NY).
$50 at TOC.
All study data were managed with Research Electronic
Data Capture v7.4.15 The primary outcome analysis was a repeat RESULTS
positive T. vaginalis test result at TOC. For the purposes of this Between October 2014 and June 2017, 623 HIV-negative T.
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secondary analysis, complete case analyses were used. Demo- vaginalis–positive women were enrolled in the parent trial. Of
graphics and clinical factors were examined by arm (Table 1). these 623 women, 540 (86.7%) presented for their TOC visit; 83
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The association of arm by TOC results was examined by self-
reported T. vaginalis history, genital symptoms at baseline, and
BV diagnosis at baseline (Figs. 1A–C). Factors found to be asso-
ciated with arm as well as the 3 select clinical factors were exam-
ined by TOC results in unadjusted analyses (Table 2). Factors
found to be associated in unadjusted analyses were included in a
were lost to follow-up. For the purposes of this secondary analysis,
only the 540 women presenting to their TOC visit (270 who re-
ceived single-dose MTZ and 270 who received multidose) were
included. A large majority of participants in both treatment arms
(>95%) were African American women with a mean (SD) age of
30.6 (9.9) years. At baseline, 52.9% had a self-reported history

Figure 1. Trichomonas vaginalis positivity by selected characteristics. A, T. vaginalis positivity at TOC, stratified by presence or absence of
baseline genital symptoms. B, T. vaginalis positivity at TOC by history of T. vaginalis infection. C, T. vaginalis positivity stratified by baseline BV
status, determined by Nugent score.

Sexually Transmitted Diseases • Volume 49, Number 3, March 2022 233

Copyright © 2022 by the American Sexually Transmitted Diseases Association. Unauthorized reproduction of this article is prohibited.
 Muzny et al.
TABLE 2. Unadjusted Logistic Regression Analysis Examining the
Influence of Select Clinical Factors on Repeat T. vaginalis Infection
Rates at Test of Cure (n = 519)*
Unadjusted
Odds Ratio 95% CI P treatment of trichomoniasis in women has changed from a 2 g dose
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History of trichomoniasis 2.04 1.24–3.37 0.005
Genital symptoms at baseline 1.75 0.89–3.43 0.10
Gonorrhea at baseline 0.68 0.25–1.87 0.45
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BV diagnosis at baseline 1.31 0.81–2.11 0.28
(by Nugent score)
Multidose versus 0.52 0.32–0.85 0.008
single-dose MTZ
Took all MTZ for T. vaginalis, 0.62 0.17–2.29 0.47
as instructed
*n = 519 due to missing data.
BV indicates bacterial vaginosis; CI, confidence interval; MTZ, metro-
nidazole.
of T. vaginalis; 79.3%, genital symptoms; 5.2%, gonorrhea; and
47.5%, BV.
There were no significant differences between treatment
arms with regard to age, race, current tobacco use, current alcohol
use (binge drinking), vaginal douching, history of chlamydia or
gonorrhea, history of multiple male and/or female sexual partners
during the past 60 days, baseline genital symptoms (vaginal dis-
charge, odor, itch, and/or pelvic pain), or baseline diagnosis of
BV or chlamydial infection. However, women randomized to the
single-dose MTZ arm were more likely than women in the
multidose arm to report a history of T. vaginalis (58.5% vs.
47.4%; P = 0.01), adhere to their MTZ medication (99.3% vs.
95.5%; P = 0.007), and less likely to have gonorrhea at baseline
(2.5% vs. 7.8%; P = 0.01; Table 1).
Of the women who returned for TOC, 97.4% took all MTZ
as instructed and 34.7% had interval condomless sex with at least
one baseline partner. At TOC, 14.8% had a repeat positive test re-
sult for T. vaginalis. In stratified analysis, women randomized to
single-dose MTZ had a higher rate of TOC T. vaginalis positivity
compared with those randomized to multidose if they were symp-
tomatic at baseline (21.4% vs. 10.8%, P = 0.003; Fig. 1A). The
same was true for women who reported a history of T. vaginalis
compared with those without (24.1% vs. 12.6%, P = 0.01;
Fig. 1B). Test-of-cure T. vaginalis positivity was higher for women
receiving single-dose MTZ compared with those receiving
multidose (18.9% vs. 10.8%, P = 0.008), which was similar for
women with baseline BV (Fig. 1C). There was no difference
among women who did not have these factors.
Table 2 demonstrates results from unadjusted analysis ex-
amining the influence of select factors on a repeat positive T. vagi-
nalis test result at TOC. In this analysis, women with a history of T.
vaginalis had greater odds of being repeat positive at TOC than
women without this history (odds ratio [OR], 2.04; 95% CI,
1.24–3.37; P = 0.009). Women receiving multidose MTZ had a
48% reduction in the odds of being repeat positive at TOC (OR,
0.52; 95% CI, 0.32–0.85; P = 0.008) compared with women re-
ceiving a single dose. There was a trend for women with baseline
genital symptoms to have greater odds of being repeat positive at
TOC (OR, 1.75; 95% CI, 0.89–3.43; P = 0.10). There was no sig-
nificant difference in the odds of being repeat positive at TOC
among women with a baseline diagnosis of BVor a baseline diag-
nosis of gonorrhea compared with those without these diagnoses.
In adjusted analyses (Table 3), only arm and history of T. vaginalis
were associated with TOC positivity.
234
Copyright © 2022 by the American Sexually Transmitted Diseases Association. Unauthorized reproduction of this article is prohibited.
DISCUSSION
In the 2021 CDC STI Treatment Guidelines and the 2020
American College of Obstetricians and Gynecologists Practice
Bulletin on vaginitis in nonpregnant women, the recommended
of oral MTZ to 500 mg twice daily for 7 days (multidose), with a
single oral dose of TDZ 2 g remaining an alternative regimen.7,8
Some clinicians may choose the alternative single 2 g oral dose
of TDZ (or even the single 2 g oral dose of MTZ) because they
are concerned about patient adherence to a multidose MTZ regi-
men.16 Although medication adherence was high in both groups
of HIV-negative T. vaginalis–infected women in the parent RCT
(96% in the multidose MTZ group vs. 99% in the single-dose
group, P = 0.006),10 Keizur and Klausner,16 in their accompany-
ing editorial, state that adherence measured in a research setting
with monetary compensation for participation might not be repre-
sentative of real world adherence. This point is exemplified in a
study of women with suspected pelvic inflammatory disease,
which found an adherence rate of only 70% among women pre-
scribed 14 days of oral doxycycline (in addition to a parenteral
dose of cefoxitin 2 g); participants in this study were not provided
compensation.17 The data presented here indicate that it is espe-
cially important that T. vaginalis–positive women with a history
of T. vaginalis be given multidose oral MTZ.
Although the mechanism by which a history of T. vaginalis
increases the chance of treatment failure was not studied here, sev-
eral studies have reported treatment failure after single-dose MTZ
in circumstances where reinfection from untreated sexual partners
was very unlikely. In these cases, the organism may be relatively
resistant to MTZ or there may be nonvaginal reservoirs of infec-
tion (i.e., urethra and perivaginal glands) that require higher and/
or longer dosing (i.e., MTZ 2 g orally daily for 7 days) for effective
treatment.11,12 Reported rates of in vitro MTZ resistance among
mainly HIV-uninfected women range from 2.2% to 9.6%.18–22 Al-
though these infections can occasionally be resolved with a repeat
single dose of 2 g oral MTZ,20 retreatment with multidose oral
MTZ (500 mg twice daily for 7 days if initially treated with
single-dose oral MTZ; 2 g daily for 7 days if initially treated with
the 500 mg multidose MTZ regimen) is preferable in an attempt to
overcome suspected drug resistance.5,18 Tinidazole resistance in T.
vaginalis is less well studied than MTZ resistance, although one
study of 178 T. vaginalis isolates found TDZ resistance in only 1
case (0.56%).18 A second study of 538 T. vaginalis isolates from
women at 6 STD clinics across the United States found no TDZ
resistance.21 Thus, a single oral dose of TDZ 2 g is an additional
treatment option for patients with suspected MTZ-resistant T. va-
ginalis infection.5 Tinidazole 2 g orally daily for 7 days could
also be considered if patients do not respond to the single 2 g oral
TDZ dose.5
TABLE 3. Stratified Logistic Regression Analysis Examining Single-
Dose vs. Multidose MTZ and Infection at Test of Cure by History of
T. vaginalis and Baseline Genital Symptoms
Adjusted
Odds Ratio 95% CI P
Single-dose vs. Multidose MTZ 1.87 1.10–3.0 0.02
History of T. vaginalis vs. no 1.87 1.13–3.11 0.02
history of T. vaginalis
Genital symptoms at baseline 1.66 0.84–3.28 0.15
vs. no symptoms
CI indicates confidence interval; MTZ, metronidazole.
Sexually Transmitted Diseases • Volume 49, Number 3, March 2022

A single oral 2 g dose of secnidazole (SEC), a new next-
generation 5-nitroimidazole with a longer half-life (17–18 hours)
than both MTZ (7–8 hours) and TDZ (11–12 hours),23 currently
Food and Drug Administration approved for the treatment of BV, has
been studied for the treatment of uncomplicated T. vaginalis infection
in women24 and is now Food and Drug Administration approved for
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this additional indication. Given its longer half-life, it is possible that
SEC may be an additional treatment option for MTZ-resistant T.
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vaginalis infections, although this will require additional clinical
studies. In an in vitro study of the susceptibility of 100 T. vaginalis iso-
lates to MTZ and SEC, 96% of the isolates demonstrated a lower min-
imum lethal concentration for SEC than MTZ, suggesting that SEC
could have better in vivo activity than MTZ, although this has not
yet been studied in clinical trials of T. vaginalis–infected women.25
Although unadjusted analysis found a trend of T. vaginalis–
infected women randomized to single-dose MTZ having a greater
odds of being repeat test positive at TOC than women randomized
to multidose if they had baseline genital symptoms, this finding
was not significant in multivariable analysis. We had originally
thought that this may be due to this secondary analysis not being
adequately powered to determine a significant effect. However, a
post hoc power analysis using SAS v9.0 revealed that this study
had 0.89 power to detect this difference. It may be that this finding
was due to a sampling issue as the majority of women in both arms
of the study (>79%) were symptomatic at baseline. It is possible
that genital symptoms are a proxy for T. vaginalis parasite load,
and more parasites require longer treatment with MTZ beyond a
2 g single dose. This should be further investigated in future stud-
ies that include a sufficient number of asymptomatic women.
In contrast to the RCT of HIV-infected women with T. vagi-
nalis reported several years ago,6 this secondary analysis did not
find a relationship between T. vaginalis treatment success and
baseline BV status. One possible explanation could be differences
in host immunity between HIV-uninfected and HIV-infected
women.26 Another possibility could be that there are subtle differ-
ences in the vaginal microbiota between HIV-infected and HIV-
uninfected women that may change the relationship between vag-
inal bacterial communities and T. vaginalis.27–29
The CDC recommends all sexually active women with T.
vaginalis be retested again at 3 months.7 In the parent RCT,
women who received multidose MTZ and had a T. vaginalis his-
tory had a TOC rate of 11.3%, which is still unacceptably high.
Thus, a TOC (preferably a T. vaginalis NAAT at 4 weeks after
completion of treatment) should be considered for infected women
with a T. vaginalis history rather than waiting for 3 months.
This secondary analysis has several limitations. It is possi-
ble that multiple comparisons could have resulted in α error. How-
ever, the robust and consistent findings suggest otherwise. In addi-
tion, the majority of the study sample was symptomatic African
American women from the southern United States with high rates
of co-occurring BV, which may not be generalizable to all popula-
tions of women. History of T. vaginalis infection was also obtained
by self-report, and more than half (76%) of the women in the parent
RCT (data not shown) did not know the date of their prior infection.
Thus, nuanced treatment recommendations based on the timing of a
history of T. vaginalis infection cannot be provided as a result of this
analysis. In addition, we were not able to include EPT to sexual part-
ners of women infected with T. vaginalis in the parent trial because
of state laws and other issues at the time that the parent study was
conducted. Because of this, we are unable to comment on recom-
mendations for TOC based on whether or not successful partner
management occurred. Despite these limitations, there are many
strengths in this study including a randomized, multicentered de-
sign, laboratory blinding using objective measures, and the use
of ACASI, which can minimize social desirability bias.30
Sexually Transmitted Diseases • Volume 49, Number 3, March 2022
Copyright © 2022 by the American Sexually Transmitted Diseases Association. Unauthorized reproduction of this article is prohibited.
Treatment of T. vaginalis by Clinical Factors
In conclusion, multidose MTZ should be recommended
over a single dose for all women with T. vaginalis infection, along
with counseling messages stressing the need for strict adherence to
medication. It is particularly imperative that women who report a
T. vaginalis history receive the multidose MTZ regimen and have
a follow-up TOC.
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• Volume 49, Number 3, March 2022