Clinical Infectious Diseases

MAJOR ARTICLE

Long Duration of Asymptomatic Mycoplasma genitalium

Infection After Syndromic Treatment for Nongonococcal
Urethritis
Sarah S. Romano,1,2, Jørgen S. Jensen,3 M. Sylvan Lowens,4 Jennifer L. Morgan,4 Laura C. Chambers,1,2 Tashina S. Robinson,1,2 Patricia A. Totten,2,5,6
Olusegun O. Soge,2,5,6 Matthew R. Golden,1,2,4,6 and Lisa E. Manhart1,2,5
1
Department of Epidemiology and 2Center for AIDS and STD, University of Washington, Seattle; 3Statens Serum Institut, Copenhagen, Denmark; and 4Public Health–Seattle & King County, and
Departments of 5Global Health and 6Medicine, University of Washington, Seattle

Background. Although Mycoplasma genitalium (MG) is an acknowledged cause of nongonococcal urethritis (NGU), access to

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diagnostic testing is limited. Syndromic management is common, yet little is known about natural history.
Methods. Between August 2014 and April 2016, 13 heterosexual men aged ≥16 years with MG were identified within a cohort
study of men with and without NGU attending an urban sexually transmitted diseases clinic. Men had 6–7 monthly visits. NGU
was defined as ≥5 polymorphonuclear leukocytes per high-power field on urethral Gram stain plus either visible urethral discharge
or urethral symptoms. Men with NGU received 1 g of azithromycin. Men with persistent NGU received moxifloxacin 400 mg for
14 days. First-void urine was retrospectively tested for MG using transcription-mediated amplification. Resistance-associated muta-
tions were detected by polymerase chain reaction (PCR) and sequencing. Organism load was determined by quantitative PCR.
Results. Sixty-two percent of MG-positive men had macrolide resistance–mediating mutations (MRMM) at enrollment; 31%
had parC mutations (all outside the quinolone resistance–determining region). MG persisted after azithromycin in 7 men, 6 of
whom had MRMM. The median duration of persistence in the absence of curative therapy was 143 days (range, 21–228). Five men
experienced symptom resolution after azithromycin, but MG persisted for another 89–186 days before moxifloxacin. Organism load
was somewhat lower in MRMM than wild-type infections (P = .16)
Conclusions. The high prevalence of macrolide resistance and long duration of infection after symptom resolution highlights
the need for diagnostic MG testing of men with NGU to direct therapy.
Keywords. Mycoplasma genitalium; antibiotic resistance; urethritis; heterosexual men.

Mycoplasma genitalium (MG) is a sexually transmitted bacte-
rium associated with reproductive tract syndromes in men and
women. Increasing evidence suggests that it is associated with
cervicitis, pelvic inflammatory disease, preterm birth, sponta-
neous abortion, and infertility in women [1], although some
debate remains regarding the causal nature of these associations
[2]. In contrast, MG is an acknowledged cause of male urethritis
[3] and is increasingly considered in the clinical management of
nongonococcal urethritis (NGU). However, effective manage-
ment of MG is complicated by the limited availability of diag-
nostic testing in many settings and increasing antimicrobial
resistance.
Although several diagnostic tests for MG are approved for use
in the European Union, no assay has received Food and Drug
Received 14 May 2018; editorial decision 22 September 2018; accepted 28 September 2018;
published online October 3, 2018.
Correspondence: L. E. Manhart, Department of Epidemiology and Center for AIDS and STD, University
of Washington, 325 Ninth Ave, Box 359931, Seattle, WA 98104 (lmanhart@u.washington.edu).
Clinical Infectious Diseases®  2019;69(1):113–20
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/ciy843
Administration (FDA) approval in the United States. European,
Australian, and British guidelines for managing MG infections
include recommendations for diagnostic testing, partner man-
agement, and tests of cure [4–6]. In contrast, the 2015 Centers
for Disease Control and Prevention sexually transmitted disease
(STD) treatment guidelines focus on syndromic management,
recommending azithromycin for NGU when MG is suspected
and moxifloxacin for persistent NGU. Given the absence of an
FDA-approved assay, there are no testing guidelines and partner
management recommendations are limited [7].
In addition to limited diagnostic testing, antimicrobial resis-
tance is rising rapidly. In a 2015 meta-analysis, azithromycin
efficacy was 85% prior to 2009, but only 67% after 2009 [8].
Similarly, a 2017 meta-analysis of moxifloxacin efficacy found
100% cure rates prior to 2010, but these declined to 89% after
2010 [9]. Coupled with increasing antimicrobial resistance are
anecdotal reports of symptom resolution without concomitant
eradication of MG, which could facilitate sustained transmis-
sion. However, the frequency of persistent asymptomatic infec-
tion is poorly understood and the contribution of antimicrobial
resistance to persistence is unknown. A delay in initiating MG
testing and treatment within a cohort study of heterosexual

Long Duration of M. genitalium in Men • CID 2019:69 (1 July) • 113

men with and without NGU enabled us to observe the natural withdrew, or were lost to follow-up (time from last visit to test-
history of MG infections and address these questions. ing was 15 days–16.7 months). The exception was participant 4,
whose MG-positive test result from month 4 was available prior
METHODS to month 5. Any man with MG detected at his final study visit
was asked to return for retesting. Men with MG-positive tests
Men in this case series were recruited from the Public Health–
were prescribed moxifloxacin.
Seattle & King County (PHSKC) STD Clinic in Seattle, Washington,
and had at least 1 MG-positive test during the retrospective test-
Duration of Infection
ing period. Eligible men were ≥16 years of age, had valid contact
Duration of MG infection was calculated as the number of
information, were English speaking, had vaginal sex at least once
days from the first MG-positive visit to either the midpoint
in their lifetime, and had insertive oral and/or vaginal and/or anal
(~14 days) between the last MG-positive and first MG-negative
sex with a female partner within 60 days before enrollment. Men
visit, or to 14 days after the final study visit if no test of cure
reporting any male sex partners in the last year, receipt of antibiot-
was available. Duration of infection after clinical cure was cal-
ics in the month before enrollment, known human immunodefi-
culated in a similar manner, beginning 14 days after the last

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ciency virus–infected status, recent sexual contact with someone
NGU-positive visit. Among men without NGU at enrollment,
with gonorrhea, or who had evidence of gonorrhea, were excluded.
duration of asymptomatic MG infection prior to therapy was
calculated as the number of days from the first MG-positive visit
Enrollment
to 14 days after receipt of curative therapy. In sensitivity anal-
After providing written informed consent, men underwent
yses, we assumed that infection persisted through the retesting
a genital examination and provided urethral swab and urine
timepoint for the 2 men who returned for a nonstudy test.
specimens. NGU was defined as ≥5 polymorphonuclear leu-
kocytes (PMNs) per high-power field on a Gram-stained slide
Markers of Antimicrobial Resistance and Organism Load
of urethral exudates plus either urethral symptoms (dysuria,
Aptima-positive specimens underwent testing for macrolide resis-
pruritus, or tingling; reported urethral discharge) or visible
tance–mediating mutations (MRMM) in the 23S ribosomal RNA
urethral discharge on examination. Men also completed a com-
gene, all of which correlate well with treatment failure [11] and muta-
puter-assisted self-interview reporting sociodemographic char-
tions in the parC gene, some of which correlate with treatment failure
acteristics and sexual behavior. Those with NGU at enrollment
(eg, mutations at positions S83 and D87) [12]. DNA extraction was
were treated syndromically with 1 g of azithromycin.
performed using a MagnaPure96 (Roche, Pleasanton, California)
Urine was tested for Chlamydia trachomatis and Neisseria
with large volume (1 mL) universal pathogen extraction protocol
gonorrhoeae using the Aptima Combo 2 assay (Hologic, Inc,
and elution in 50 µL. Samples were subsequently tested by poly-
San Diego, California). An additional 2 mL of urine was stored
merase chain reaction (PCR) [13, 14], and MRMMs were detected
in Aptima transport medium, designed to stabilize RNA, at
with PyroMark96 sequencing [13]. The parC gene was amplified
–80°C for future MG testing. From December 2015 to April
and sequenced by conventional Sanger sequencing [15]. Organism
2016, transcription-mediated amplification (TMA) testing
load was determined by quantitative PCR with a limit of detection
was conducted with the direct tube sampling system using
of <5 geq per reaction [14]. We performed a Wilcoxon rank-sum
analyte-specific reagents (ASR) on the SB100 instrument [10].
test to test for differences in duration of infection by MRMM status.
Subsequently, testing was conducted on the Panther instru-
We performed a correlated t test to evaluate differences in organism
ment, using ASR. The 95% limit of detection for this assay is
load, plus a regression model of log10 organism load vs resistance
0.02 genome equivalents (geq) per reaction (Damon Getman,
mutations, including a random-person effect.
personal communication).
All study procedures were approved by the University of
Washington Institutional Review Board.
Follow-up
Men without NGU at enrollment returned for 6 monthly visits.
RESULTS
Men with NGU at enrollment had an additional visit 1 month
after enrollment so that all began the 6-month follow-up period Among 138 enrolled men, 16 had 1 or more MG-positive spec-
without NGU. Men with urethral symptoms between visits were imens between 8 August 2014 and 15 April 2016 (Figure 1).
asked to return for evaluation. At each visit, clinical examina- Of these, 3 had only 1 visit with a retrospective test and were
tion and sexually transmitted infection (STI) testing employed excluded, leaving 13 men in this case series. Twelve of these
the same procedures described for enrollment. New cases of 13 men had MG at enrollment, of whom 10 also had NGU.
NGU received 1 g of azithromycin. Persistent NGU was treated One man had a single asymptomatic infection at his final visit
syndromically with 400 mg of moxifloxacin daily for 14 days. (Figure 2; Supplementary Table).
With one exception, all MG testing was performed on stored The mean age at enrollment was 28.1 years (range, 22–34 years).
specimens after men completed their study participation, Eight (62%) participants were white, 3 (23%) were black, 1 (8%)

114 • CID 2019:69 (1 July) • Romano et al

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Figure 1. Flowchart of enrollment and characteristics of men in the case series. Abbreviations: MG, Mycoplasma genitalium; MRMM, macrolide resistance–mediating
mutation; NGU, nongonococcal urethritis; WT, wild-type. *Macrolide resistance mutation status could not be determined for the enrollment visit specimen but was deter-
mined to be wild-type at the subsequent visit.

was Asian, and 1 (8%) was multiracial (Table 1). Eleven participants
(85%) were circumcised. Nine men reported an exact number of
lifetime sexual partners (mean, 34 partners [range, 6–70]), whereas
4 men reported a range of 10–99. Nine men reported inconsistent
condom use and multiple partners throughout the study, while 2
men reported no condom use and a single partner. Two men re-
ported no sexual activity during follow-up (participants 3 and 10).
Resistance-associated Mutations
Testing for MRMM was successful in 37 of 48 (77%) MG-positive
specimens. Eight men (62%) had MRMM at enrollment (partici-
pants 1–7 and 12), and 5 (participants 8–11 and 13) were infected
with wild-type (WT) organisms (eg, no resistance mutations).
All but 1 (participant 8) had the same mutation in all typeable
specimens. The A2058C mutation was detected in 1 man (partic-
ipant 5), 3 had A2058G (participants 4, 7, and 8), 1 had A2059C
(participant 1), and 4 had A2059G (participants 2, 3, 6, and 12).
The parC gene was successfully amplified and sequenced in 36
of 48 (75%) MG-positive specimens. Four men had parC muta-
tions (participants 2, 4, 5, and 13). All had the same mutation in
all typeable specimens (Table 2), but none was in the quinolone
resistance–determining region. Two men had a silent C234T
mutation (participants 2 and 5), 1 had a P62S mutation (partici-
pant 13), and 1 had silent C234T/P62S mutations (participant 4).
Duration of Infection After Azithromycin for NGU
Ten men with MG at enrollment had NGU and received 1 g
of azithromycin (participants 1–10). MG was eradicated in 3

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Figure 2. Clinical characteristics of heterosexual men and detection of urethral Mycoplasma genitalium infection, presence of macrolide resistance–mediating mutations,
and organism load at monthly visits (no parC mutations previously associated with quinolone resistance were detected). Abbreviations: AZM, azithromycin; Enroll, enrollment;
MG, Mycoplasma genitalium; MOX, moxifloxacin; MRM, macrolide resistance mutation; ND, not done; NGU, nongonococcal urethritis; Rx, treatment received. *Received
azithromycin for Chlamydia trachomatis infection. †Patient declined antibiotic treatment. ‡Received moxifloxacin for lower urinary tract symptoms. §Received azithromycin
due to high polymorphonuclear leukocyte count, but did not meet criteria for nongonococcal urethritis diagnosis.

of these by month 1 (participants 7, 9, and 10). Two men had MG persisted after initial azithromycin therapy in 7 (70%) of the
macrolide-sensitive infections (participants 9 and 10) and no men with NGU (participants 1–6 and 8), of whom 6 had MRMM.
subsequent positive tests. One had MRMM at enrollment (par- The seventh man had a WT infection at enrollment but MRMM
ticipant 7) and asymptomatic MG at month 3. at month 1 (participant 8). One man with persistent infection had

116 • CID 2019:69 (1 July) • Romano et al

Table 1. Sociobehavioral and Clinical Characteristics of Heterosexual Men With Urethral Mycoplasma genitalium Infection in Retrospectively Tested
Urine Specimens From a Cohort Study

Lifetime No. of No. of Sex Partners Condom Use Circumcision

Participant No. Age at Enrollment Race Sex Partners Throughout Follow-up Throughout Follow-up Status

1 29 White 15 1 None Yes

2 27 Black 50–99 ≥2 Inconsistent No
3 22 White 9 0 NA Yes
4 26 White 70 ≥2 Inconsistent Yes
5 23 Black 10–24 ≥2 Inconsistent Yes
6 34 White 60 ≥2 Inconsistent Yes
7 32 Asian 10–24 ≥2 Inconsistent Yes
8 29 White 50–99 ≥2 Inconsistent Yes
9 28 White 20 ≥2 Inconsistent No
10 30 White 6 0 NA Yes
11 23 Asian & black 6 1 None Yes

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12 29 White 50 ≥2 Inconsistent Yes
13 33 Black 70 ≥2 Inconsistent Yes

Abbreviation: NA, not applicable - participant remained abstinent.

a negative test at month 5 but was MG positive again at month 6
(participant 2). All others remained persistently infected through
their last positive test. Five of the 7 (71%) men in whom MG was
detected after azithromycin had persistent NGU (participants
1–3, 6, and 8): 2 received moxifloxacin (participants 6 and 8), 2
received azithromycin again because they were considered reex-
posed (participants 1 and 2), and 1 was not treated (participant
3). Of the 4 men who received additional therapy at month 2, MG
was only eradicated in the 2 who received moxifloxacin.
The median duration of MG infection after azithromy-
cin among the 2 men with macrolide-sensitive infections
(participants 9 and 10) was 14.75 days (range, 12.5–17 days). In
contrast, the median duration of infection in the absence of cur-
ative therapy among the 7 men with MRMM (participants 1–6
and 8) was 143 days (range, 21–228 days) (P = .04).
Five of the 6 men with persistent infections experienced clin-
ical cure after 1–2 doses of azithromycin but remained infected
for another 89–186 days (participants 1–5). One man received
moxifloxacin at month 1 for persistent NGU (participant 6) and
3 received moxifloxacin at month 5 for recurrent NGU (partic-
ipants 3–5). All experienced clinical and microbiological cure
after moxifloxacin.

Table 2. Detection of Mutations in the Quinolone Resistance–determining Region of parC at Monthly Visits Among Heterosexual Men With Urethral
Mycoplasma genitalium Infection

Participant Poststudy
No. Enrollment Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7 MG Test

1 WT WT WT NT WT WT WT WT WT
2 Silent C234T NT NT NT Silent C234T – Silent C234T Silent C234T NT
3 NT WT NT WT ND WT – – NA
a
4 P62S, Silent C234T NT NT P62S, Silent C234T P62S, Silent C234T – – NA
5 Silent C234T Silent C234T Silent C234T Silent C234T Silent C234T NDb – – – NA
6 WT WT – – – – – – NA
7 WT – – NT – – – – NA
8 WT WTc – a
– – d d d
NA
d d d d d
9 WT – – NA
d d d d d d
10 WT – NA
11 NT WT NT WT WT – – – NA
d d d d d
12 WT WT WT NA
13 – – – – – – – P62S NA

Abbreviations: –, participant was M. genitalium negative at this visit; MG, Mycoplasma genitalium; NA, not applicable (participant was not recalled for a poststudy test); ND, not done; NT,
not typeable; WT, wild-type.
a
Participant missed this visit.
b
Participant had a symptom visit preceding month 5.
c
Participant had a symptom visit preceding month 1.
d
Participant withdrew or was lost to follow-up.

Long Duration of M. genitalium in Men • CID 2019:69 (1 July) • 117

Sensitivity Analysis
Participants 1 and 2 remained asymptomatically infected at
their final study visits. When recalled 9–10 months later, both
still had MG. One had MRMM. One had an interim negative
test and nontypeable poststudy MG but MRMM at month
7. Both were treated with moxifloxacin, but neither had a test
of cure. Assuming these 2 men remained infected from enroll-
ment to receipt of moxifloxacin, the maximum duration of
infection was 542 days; the maximum duration of persistence
after clinical cure was 500 days.
Duration of Infection in the Absence of NGU and Associated Antibiotic
Therapy
Two men with MG at enrollment did not have NGU. Participant
11 had an asymptomatic macrolide-sensitive infection through
month 4 when he received azithromycin for urethral inflam-
mation. MG was eradicated. Participant 12 had an asympto-
matic MRMM infection, developed NGU at month 2, received
azithromycin, and was lost to follow-up. The median duration
of asymptomatic infection prior to azithromycin was 100 days
(range, 70–130 days).
Sporadic Asymptomatic Infection
Participant 13 had a new MG infection at his final visit accom-
panied by elevated PMNs but no symptoms and no visible
discharge. He was not treated and could not be reached for
retesting.
Treatment Efficacy
MG was eradicated in 3 of the 4 (75%) men with WT infections
after azithromycin (participants 9–11) and a test of cure, while
MRMM emerged in 1 man (participant 8). In contrast, MG
was undetectable after azithromycin in only 1 of the 7 (14%)
men with MRMM (participant 7). MG was eradicated in all 5
(100%) who received moxifloxacin and had a test of cure (par-
ticipants 3–6 and 8), none of whom had resistance-associated
parC mutations.
Organism Load
The organism load assay yielded results in 38 of 49 (78%) spec-
imens (Figure 2). In WT infections, the median load was 97
geq/5 µL template (range, 4–108 403). In MRMM infections, it
was 39 geq/5 µL template (range, 8–11 829). In the regression
model, men with MRMM had a 0.15-fold lower organism load
than those with WT infections (95% confidence interval, .01–
2.1; P = .16).
DISCUSSION
In this case series of 13 men with urethral MG infection, muta-
tions consistent with macrolide resistance were detected in
62% at enrollment and organism load was somewhat lower in
MRMM than in WT infections. Only 1 man appeared to clear
his infection in the absence of antimicrobial therapy to which
118 • CID 2019:69 (1 July) • Romano et al
MG was susceptible. Six of the 7 men with MRMM experienced
persistent infections following azithromycin, a currently rec-
ommended treatment for NGU in the United States, and over-
all MG infections persisted for a median of 143 days (range,
21–228 days) from initial clinical presentation to receipt of
curative treatment or study end. Five of 6 men with persistent
infections experienced symptom resolution after azithromycin
and would have been considered cured in the absence of testing.
Our estimated median duration of infection was significantly
longer in MRMM than in WT infections. The true duration of
infection was likely longer. We estimated duration conserva-
tively, defining the end of infection as the first negative test. If
an MG-negative test between 2 positive tests represents a drop
below the threshold of detection followed by reemergence rather
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than clearance and reinfection or flare-up, the median dura-
tion of infection would be longer. Additionally, the duration of
infection prior to enrollment was unknown and not included in
our estimates. Although persistence was primarily due to anti-
biotic resistance–associated treatment failure, we also observed
1 man with an asymptomatic WT infection that persisted for
5 months prior to receiving azithromycin, suggesting that long
duration infections can also occur in the absence of treatment
failure or MRMM. While few other data are available on the
duration of MG infection in men, persistence in women from
various settings ranges widely from 1.5 to 21 months [16–21].
As estimates of duration depend on length of follow-up time
and frequency of testing, larger studies with longer follow-up
periods and frequent sampling will be needed to more accu-
rately determine the duration of MG infection.
Syndromic therapy for NGU with 1 g of azithromycin was
associated with clinical cure in many cases but was mostly inef-
fective in eradicating the organism. In contrast, moxifloxacin
was uniformly effective. Prior observations of azithromycin
resistance range from 40% to 100% [13, 22–26] and the 62%
prevalence of MRMM we observed is consistent with increas-
ing rates of treatment failure [22]. The resolution of symptoms
after azithromycin despite persistent infection may be related
to anti-inflammatory properties inherent in azithromycin,
although the long duration of infection in the absence of symp-
toms suggests that this does not entirely explain the disparate
clinical and microbiologic outcomes we observed. Organism
load decreased after initial administration of azithromycin, and
this may have been below the threshold required to promote
clinical symptoms. Alternatively, patients’ NGU may have been
caused by an organism other than MG that was eradicated with
azithromycin.
Given the worldwide emergence of moxifloxacin treatment
failures [27, 28] and parC mutations linked to treatment failure
[29, 30], it was surprising that we observed neither of these. This
may be due to the small number of men in this case series, par-
ticularly since moxifloxacin treatment failures were previously
observed in Seattle men (unpublished data). The PHSKC STD
Clinic does not routinely perform MG testing and only pre-
scribes moxifloxacin for persistent/recurrent NGU. There may
be less selective pressure than in areas with routine MG testing
and more frequent administration of moxifloxacin. While this
suggests that moxifloxacin is still a viable option in this popula-
tion, this may change with the introduction of more widespread
MG testing and should be monitored.
The large proportion of men who experienced asymptomatic
infections that persisted for months after therapy is cause for
concern. These men likely assumed they had been effectively
treated, and nearly all engaged in condomless sex, potentially
infecting their sex partners. Given the high prevalence of
MRMMs and the high frequency of multiple partners among
these heterosexual men, MRMMs are probably also common
among women with MG in the Seattle area, potentially render-
ing treatment of female syndromes equally challenging.
Strengths of this study include the prospective design with
6 months of follow-up and the use of sensitive nucleic acid
amplification tests that captured low organism load infections
[31]. Identification of MRMMs and parC mutations through
sequencing is highly specific. There are also limitations. The
number of men in these analyses was relatively small. We may
have detected residual nucleic acids in some rather than viable
organisms, although the long duration of asymptomatic infec-
tion in many suggests that most were active infections. We were
unable to differentiate persistent infections from new infections
or reinfections, and this likely occurred in some cases. However,
the long duration of infection from the man who reported absti-
nence throughout his study participation (participant 3) and
the stable MRMM and parC mutations, suggest that some
cases truly represented persistence. Finally, some TMA-positive
samples contained insufficient DNA for sequencing to identify
resistance-associated mutations, likely due to the lower limit of
detection of the TMA assay [31].
In conclusion, we found that MG often persists for many
months and that this persistence can occur despite resolution
of signs and symptoms after syndromic therapy for NGU. The
low microbiologic cure rates after azithromycin and the high
prevalence of MRMMs highlights the increasingly diminished
utility of this antibiotic as routine therapy for NGU. Indeed, wide-
spread use of azithromycin to treat STIs has likely contributed to
the development of MG resistance and is one factor prompting
recent changes in European, Australian, and British guidelines
that no longer recommend azithromycin for NGU. While current
data do not support widespread screening for MG, the cases of
persistent MG after resolution of NGU that we describe highlight
the need for MG testing among men with NGU and tests of cure
after azithromycin. Where macrolide resistance is not already
widespread, initial MG testing should ideally include testing for
MRMMs to direct therapy. Beyond this, our findings highlight
the need to better understand the natural history of MG, which
appears to be a chronic and increasingly difficult-to-treat STI.
Supplementary Data
Supplementary materials are available at Clinical Infectious Diseases online.
Consisting of data provided by the authors to benefit the reader, the posted
materials are not copyedited and are the sole responsibility of the authors,
so questions or comments should be addressed to the corresponding author.
Notes
Acknowledgments. We gratefully acknowledge the contributions of the
staff at the Public Health Seattle & King County STD Clinic for facilitating
enrollment; Sean Proll for creation of figures; Sabina Astete for M. geni-
talium testing; and Hologic, Inc, for donated test kits and reagents.
Financial support. This work was supported by the National Institute
of Allergy and Infectious Diseases (grant number R01 AI110666). Study
data were collected and managed using REDCap electronic data capture
tools hosted at the Institute of Translational Health Sciences through a grant
from the National Center for Advancing Translational Sciences (grant num-
ber UL1 TR002319). Partial support for this research (computing software)
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came from a Eunice Kennedy Shriver National Institute of Child Health
and Human Development research infrastructure grant to the Center for
Studies in Demography and Ecology at the University of Washington (grant
number P2C HD042828).
Potential conflicts of interest. L. E. M. has received honoraria,
reagents, and test kits for diagnostic assays from Hologic, Inc; J. S. J. has
received grants, personal fees, and speaker’s fees from Hologic; serves on
the scientific advisory board of Roche Molecular Systems; serves on the
Cepheid scientific advisory board; and has received travel support and
personal fees from Cepheid. The Statens Serum Institut has received remu-
neration for contract work from SpeeDx, Hologic, NYTor, Diagenode,
Nabriva, and GlaxoSmithKline (GSK). P. A. T. has received speaker’s fees
from Hologic and has consulted with SpeeDx for their diagnostic assays.
L. C. C. has received trainee support from the Institute of Translational
Health Sciences (grant number TL1 TR002318). M. G. has received grants
from the National Institutes of Health, Hologic, and GSK. The University
of Washington has received funding for contract work from Hologic,
SpeeDx, Abbott, and Cepheid. All other authors report no potential
conflicts. All authors have submitted the ICMJE Form for Disclosure of
Potential Conflicts of Interest. Conflicts that the editors consider relevant
to the content of the manuscript have been disclosed.
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