European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 116121

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Single daily dose of moxioxacin versus ooxacin plus metronidazole

as a new treatment approach to uncomplicated pelvic inammatory
disease: a multicentre prospective randomized trial
Osman Asicioglu a,*, Kemal Gungorduk b,1, Aykut Ozdemir b,2, Ibrahim Egemen Ertas b,3,
Gokhan Yildirim c,4, Muzaffer Sanci b,5, Cemal Ark c,6
Sisli Etfal Training and Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey
Tepecik Training and Research Hospital, Department of Gynecologic Oncology, Izmir, Turkey
c
Kanuni Sultan Suleyman Training and Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey
a

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 5 May 2013
Received in revised form 15 July 2013
Accepted 4 August 2013

Objectives: To evaluate the efcacy and safety of moxioxacin versus ooxacin plus metronidazole in
patients with uncomplicated pelvic inammatory disease (uPID; dened as PID symptoms and signs, but
no complications such as septicemia, perihepatitis, and tubo-ovarian abscess) in Turkey.
Study design: This was a multicenter, prospective, randomized, parallel-group study conducted between
June 2010 and March 2013 in four hospitals in Turkey. Women received a 14-day course of either oral
moxioxacin at 400 mg once daily (n = 560) or oral ooxacin at 400 mg twice daily plus oral
metronidazole at 500 mg twice daily (n = 543).
Results: A total of 1156 women were randomized to the study. Total compliance was achieved in 1103
patients. For the primary measure of efcacy (clinical cure), moxioxacin showed no difference
compared with ooxacin plus metronidazole (445/560 [79.5%] vs. 449/543 [82.7%]; p = 0.172).
Bacteriological cure rates were high and comparable between treatment arms (99/119 [83.2%] vs. 93/110
[84.5%]; p = 0.781). Drug-related adverse events occurred less frequently with moxioxacin than with
ooxacin plus metronidazole (210/560 [37.5%] vs. 252/543 [46.4%]; p = 0.003). Furthermore,
moxioxacin treatment was lower in cost and achieved higher patient compliance compared with
ooxacin plus metronidazole (31.4 Euros vs. 23.4 Euros and 7/578 (1.2%) vs. 22/578 (3.8%), respectively;
p = 0.005).
Conclusions: In patients with uPID, once-daily moxioxacin monotherapy was clinically and
microbiologically as efcacious as twice-daily ooxacin plus metronidazole therapy and was associated
with fewer drug-related adverse events, lower patient non-compliance, and a lower treatment cost.
2013 Elsevier Ireland Ltd. All rights reserved.

Keywords:
Randomized trial
Moxioxacin
Pelvic inammatory disease

1. Introduction
Uncomplicated pelvic inammatory disease (uPID) is a common
disorder that affects women of reproductive age. It is estimated that

* Corresponding author. Tel.: +90 0507 140 32 44.

E-mail addresses: oasicioglu@yahoo.com.tr (O. Asicioglu),
maidenkemal@yahoo.com (K. Gungorduk), isaaykutozdemir@hotmail.com
(A. Ozdemir), drertas@gmail.com (I.E. Ertas), gokhan73yildirim@gmail.com
(G. Yildirim), drsanci@yahoo.com (M. Sanci), cark@yahoo.com (C. Ark).
1
Tel.: +90 0505 492 17 66.
2
Tel.: +90 0505 270 35 50.
3
Tel.: +90 0505 405 33 42.
4
Tel.: +90 0532 476 67 30.
5
Tel.: +90 0535 823 09 92.
6
Tel.: +90 0532 424 19 79.
0301-2115/$ see front matter 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejogrb.2013.08.012

in the UK, uPID affects 1.7% of women 1646 years old annually [1].
In the US, 5.1% of women aged 1544 years will develop PID at least
once during their lifetimes [2]. Risk associations for PID include
young age, multiple sexual partners, a previous history of sexually
transmitted disease, insertion of an intrauterine device within the
previous 6 weeks, vaginal douching, smoking, reduced socioeconomic circumstances, and recent new sexual partners [1,3,4]. These
risk associations, especially vaginal douching (vd), also apply in our
country [5,6]. In one study, vd was reportedly performed by 91.6% of
women living in rural areas [6]. In the long term, untreated or
incompletely treated PID can have serious clinical consequences,
including increased risk of infertility, ectopic pregnancy, chronic
pelvic pain, and recurrence of acute episodes of the disease,
particularly for women with chlamydia infections [3].
uPID is thought to occur when microorganisms, frequently
Chlamydia trachomatis or Neisseria gonorrhoeae, ascend from the

O. Asicioglu et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 116121

lower genital tract and infect the uterus, fallopian tubes, and
ovaries [7]. The most frequently isolated bacteria in our country
are Chlamydia trachomatis, Neisseria gonorrhoeae, and Group B
streptococcus [5]. Anaerobic Gram-negative rods, Mycoplasma
genitalium, and bacterial vaginosis are also associated with uPID
[8,9]. Because of its polymicrobial nature, PID is treated with
antibiotics covering a broad spectrum of pathogens. Guidelines
from the US Centers for Disease Control and Prevention
recommend outpatient treatment of PID with ooxacin, levooxacin, ceftriaxone plus doxycycline, or cefoxitin and probenecid plus doxycycline, all with optional metronidazole for full
coverage against anaerobes and bacterial vaginosis [10]. Compliance with antibiotic therapy for PID is poor, however,
particularly in adolescents and in patients undergoing complex,
prolonged treatment regimens [11,12]. Many studies have found
that among monotherapies used to improve patient compliance,
ooxacin monotherapy has better patient compliance than
cefoxitin plus doxycycline combination therapy in eradicating
C. trachomatis, although the overall rates of clinical cure or
improvement are reportedly similar [13]. Because anaerobic
coverage provided by ooxacin monotherapy is reportedly poor,
the addition of metronidazole has been advised [14]. Moxioxacin provides improved activity against C. trachomatis over
existing uoroquinolones and greater coverage of anaerobic
bacteria [15]. A comparative clinical study showed moxioxacin
to have a good efcacy and safety prole [16]. It is likely that
these features may facilitate increased compliance among
women.
We compared the efcacy and safety of combination therapy
comprising oral ooxacin at 400 mg twice daily plus oral
metronidazole at 500 mg twice daily for 14 days with the efcacy
and safety of moxioxacin monotherapy at 400 mg once daily for
14 days.
2. Materials and methods
This was a prospective, randomized, parallel-group study
conducted between 1 June 2010 and 1 March 2013 in four
hospitals in Turkey (Sisli Etfal Teaching Hospital, Istanbul Teaching
Hospital, Kanuni Sultan Suleyman Teaching Hospital, and Izmir
Tepecik Teaching Hospital). The study protocol was approved in
accordance with the Declaration of Helsinki, and all clinical work
was subject to the rules of good clinical practice. Ethical approval
was granted by the Bakirkoy Womens and Childrens Teaching
Hospital Ethics Committee (2010-199). The study was registered at
clinicaltrials.gov (NCT01799356). This study did not receive
pharmaceutical company support.
Traditionally, the diagnosis of uPID is based on a triad of
symptoms and signs, including pelvic pain, cervical motion and
adnexal tenderness, and the presence of fever without complications (such as perihepatitis, septicemia, and tubo-ovarian
abscess). It is recognized that there is wide variation in many
symptoms and signs among women with this condition, which
makes the diagnosis of acute PID difcult [17]. The study enrolled
women from 14 to 45 years of age with uPID. A diagnosis of uPID in
our study was based on the presence of all of the following
symptoms and signs: pelvic discomfort, direct lower abdominal
tenderness, adnexal and cervical motion tenderness on bimanual
vaginal examination, and pelvic pain for <30 days, as well as at
least one of the following signs: pyrexia (rectal, tympanic, or oral
temperature of >38 8C or axillary temperature of >37.5 8C),
elevated C-reactive protein (CRP) level >6 mg/l, white blood cell
count (WBC) 10 500 m3, and a normal ultrasonographic scan.
Women who had undergone recent removal of an IUD were
eligible for inclusion in the study because the presence of an IUD is
a risk factor. A visual analog scale (VAS) was used to assess the

117

degree of pain at all visits. Exclusion criteria included urinary tract

infection; complicated PID (such as tubo-ovarian abscess);
endometriosis; pelvic pain for >30 days; history of antibiotic
therapy within the last week; previous failure to adhere to
antibiotic treatment; other causes of abdominopelvic pain such as
appendicitis, diverticulitis, or ovarian cysts; oral intolerance,
dened as one episode of vomiting after the rst oral medication
administration; and delivery, abortion, or surgery within the last
month.
The initial physical examinations and the follow-up visits
were performed by the same researcher. Patients with intrauterine devices had them removed before the initial treatment.
Sexual intercourse was prohibited during the treatment period.
Initial physical examination (day 0) included bimanual vaginal
examination; evaluation of the vagina and cervix with a
speculum; oral, rectal, or axillary temperature measurement;
ultrasound examination; and laboratory assessment for CRP and
WBC levels. Cervical culture was evaluated on the rst day in all
patients. Neisseria gonorrhoeae was identied by ThayerMartin
culture, and Chlamydia antigen testing by polymerase chain
reaction (Cobas Amplicor Detection Kit) was performed in all
samples [18]. The degree of pain was assessed with a VAS of 010
(with 0 representing no pain and 10 representing unbearable
pain).
Women diagnosed with uPID according to clinical and
laboratory test results were randomized to either Group A
(moxioxacin group) or Group B (ooxacin group) before the
initial treatment. Assignment to one of the two treatment groups
was determined using a random-numbers table. The assigned
treatments were written on cards and sealed in secure opaque
envelopes numbered in sequence. The investigators were not
blinded to the procedure allocation. The allocated envelope was
opened by the clinician just before treatment, and the procedure
allocation was recorded on each womans chart.
Treatment in Group A comprised moxioxacin (Avelox
400 mg (Bayer), once daily p.o. for 14 days), and treatment in
Group B comprised ooxacin (Tarivid 400 mg (Sanovi Aventis),
twice daily p.o. for 14 days) plus metronidazole (Flagyl 500 mg
(Eczacibasi), twice daily p.o. for 14 days). Seven days after drug
treatment at secondary visits (day 21), all patients underwent a
secondary evaluation by the same physician. The secondary
evaluation included bimanual vaginal examination, speculum
examination, ultrasound, laboratory testing, and assessment of
the degree of abdominopelvic pain with the VAS. We asked about
drug-induced gastrointestinal, nervous and infectious complaints and assessed biochemistry and blood count parameters.
Furthermore, patient compliance was investigated according to
reports by the patients and patients relatives; the pill count was
also evaluated. A nal repeat cervical culture and Chlamydia
antigen PCR assay were also performed, and all data were
collected. If patients did not attend secondary visits, we excluded
them from the study.
We calculated the cost of treatment in both groups and
investigated patient compliance. The initial treatment group (ITG)
included women diagnosed with uPID and assigned to a drug
therapy group. The completion of protocol treatment group (CPTG)
included patients who complied with the appropriate medication
dose and duration protocol.
The primary outcome measure of this study was clinical cure,
dened as a 60% reduction in the total pain score at day 21
compared with baseline and the absence of pelvic discomfort and
tenderness, temperature <37 8C, and WBC level < 10,000/mm3 on
day 21 [19]. The secondary outcome measures were microbiological cure and the rate of adverse effects to drugs. Microbiological
cure was dened as a negative result on the second cervical
culture [20].

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O. Asicioglu et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 116121

The MONALISA trial sample size model was used to calculate

the power of the study. This was not a non-inferiority study. We
used the MED-Calc sample size calculation method. The power
calculation was based on a previous study of uPID treatment
(moxioxacin vs. ooxacin plus metronidazole), which showed
clinical response rates of 75.7% and 82.6%, respectively, for the
intention-to-treat analyses [21]. After setting the signicance at 5%
and power at 80% and establishing a one-to-one recruitment ratio,
541 women were required in each arm.
The SPSS for Windows 17 software (Chicago, IL) was used for
statistical analysis. The analysis was performed on an intention-totreat basis. The normal distribution of continuous variables was
assessed by the KolmogorovSmirnov test. Chi-square analysis was
used for categorical variables, Students t-test was used for normally
distributed continuous variables, and the MannWhitney U-test
was used for non-normally distributed variables. Relative risk (RR)
with 95% condence intervals (CIs) was also calculated. A pvalue < 0.05 was considered statistically signicant.
3. Results
The numbers of patients who were recruited and randomized
into the study and eligible for the analyses are summarized in
Fig. 1. A total of 1156 patients with mild PID were randomized in
this investigation. Eighteen patients in the moxioxacin group
were lost to follow-up, and 35 in the ooxacin plus metronidazole
group were analyzed as failures (Fig. 1). Total compliance was
achieved in 1103 patients (560 and 543 in the moxioxacin
(Group A) and ooxacin plus metronidazole (Group B) groups,
respectively).
Overall, the demographic and baseline characteristics, mean
VAS scores, and proportion of patients with conrmed C.
trachomatis or N. gonorrhoeae infection were similar between
the treatment groups (Table 1). The average age of participants was
30.3  3.7 years in Group A and 29.3  3.5 years in Group B. The
median VAS scores were 5.1 in Group A and 5.2 in Group B. A
microorganism (N. gonorrhoeae or C. trachomatis) was identied at
cervical culture in 119 patients in Group A and in 110 patients in
Group B (Table 1).
Table 2 shows the clinical and microbiological cure results of
the study groups. The rate of clinical cure was higher in Group B,
but the difference was not signicant (79.5% in Group A vs. 82.7%
in Group B; p = 0.172). The rate of microbiological cure was similar
between the two groups (83.2% in Group A vs. 84.5% in Group B;
p = 0.781). A remarkable nding was that the microbiological cure
rate was more favorable in patients with identied chlamydia
(Table 2). Furthermore, the median VAS score was similar
between the two groups (0.7 in Group A vs. 0.5 in Group B;
p = 0.654) at 21 days.
Table 3 shows the drug-related adverse effects in the study
groups. The overall adverse event rate was signicantly lower in
Group A than in Group B (37.5% vs. 46.4%; p = 0.003). The most
common drug-related adverse events affected the gastrointestinal
system (including nausea, vomiting and dyspepsia) (Table 3). The
rate of gastrointestinal adverse effects was signicantly higher in
Group B (37.2% vs. 25.5%; p = 0.001). The rates of infectious and
nervous system adverse effects were similar between the two
groups (Table 3).
The number of patients who were non-compliant with the
medication in terms of use and oral intolerance in the ITG
population was signicantly higher in Group B (3.8% vs. 1.2%;
p = 0.005) (Table 4). Furthermore, the cost of treatment per patient
was higher in Group B than in Group A31.4 Euros (Flagyl 500 mg/
20 pills, two boxes at 2.5 Euros  2 + Tarivid 400 mg/5 pills, six
boxes at 4.4 Euros  6) vs. 23.4 Euros (Avelox 400 mg/7 pills, two
boxes at 11.7 Euros  2).

4. Comments
The aims of this study were to compare the efcacy and safety
of monotherapy with moxioxacin, a new uoroquinolone, with a
rst-line dual combination of ooxacin plus metronidazole. In this
study, we showed that moxioxacin was non-inferior to ooxacin
plus metronidazole in patients with uPID.
Many previous studies of oral moxioxacin in patients with
uPID have been performed. In one of these studies, moxioxacin at
400 mg once daily was compared with doxycycline at 100 mg
twice daily plus metronidazole at 400 mg three times daily plus a
single 500 mg ciprooxacin dose for 14 days [16]. Here, too, the
clinical and bacteriological success rates for moxioxacin were
high: 96.6% (224/232 patients) and 92.5% (37/40 patients) at 2 and
14 days post-therapy, respectively. In comparison, the clinical and
bacteriological success rates in the combination group were 98.0%
(198/202 patients) and 88.2% (30/34 patients), respectively [16].
Hence, moxioxacin appears to provide efcacy that is at least
comparable to that of the regimens in current use [3].
Moxioxacin and ooxacin plus metronidazole were found to
have comparable clinical efcacy. The clinical resolution rates
were 79.5% for moxioxacin and 82.7% for ooxacin plus
metronidazole. These values are lower than those found by Ross
et al. [21] and Heystek et al. [16] (published clinical cure rates of
90% and 92.5%, respectively). Nevertheless, our ndings were at
acceptable levels. Furthermore, the clinical cure rates in our study
were comparable to those reported for other uoroquinolones as
well as for other antimicrobials in previous investigations (72
97%) [2224].
Many previous studies have found that C. trachomatis and N.
gonorrhoeae were the most frequently isolated causative organisms and that a regimen comprising both moxioxacin and
ooxacin plus metronidazole was highly effective against both of
these pathogens. Ross et al. reported a bacteriological success rate
of 87.5% (49/56 patients) for moxioxacin and 82.1% (46/56
patients) for ooxacin plus metronidazole (95% CI: 28.318.8%)
[21]. Later, Judlin et al. reported a success rate of 90.0% for
moxioxacin and 84.6% for levooxacin plus metronidazole [30].
In our study, the bacteriological success rates in the CPTG were
83.2% for moxioxacin and 84.5% for ooxacin plus metronidazole, respectively. Our ndings are similar to those of previous
studies. The proportion of women in the present study infected
with chlamydia or gonorrhea was 20%, which is lower than that in
many previous studies (Heinonen et al. [25] reported 30%, and
Bevon et al. [26] reported 39%). We attribute these lower rates of
isolation of C. trachomatis and N. gonorrhoeae to the fact that those
studies were typically undertaken on populations with a higher
proportion of patients at risk for sexually transmitted infections
than in our ethnic group (individuals in the Turkish population
generally do not have multiple sexual partners and prefer married
life) [27]. The proportion of women with identied chlamydia was
higher than that with identied gonorrhea. This nding is similar
to those of Bevan et al. [26] and Kisa et al. [5]. The reason for this
difference is that gonorrhea was identied using culture, which
has limitations compared with nucleic-acid-based methods.
Furthermore, in our study, no patients were co-infected with
chlamydia and gonorrhea. We attribute these ndings to the
difculty of diagnosis by culture. Our study showed that a regimen
comprising both medications (moxioxacin and ooxacin) is
more effective in patients with identied chlamydia than in those
with identied gonorrhea. This nding differs from that of Ross
et al. [21], who reported a uoroquinolone treatment regimen
that was more effective in patients with identied chlamydia
(100% vs. 88.5%). The reason for this may be the increase in the
number of quinolone-resistant gonococci worldwide. Increasing
reports of quinolone-resistant gonococcal infection throughout

O. Asicioglu et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 116121

119

Assessed for eligibility (n = 1303)

Excluded (n = 147)
Refused to participite (n = 13)
Did not meet inclusion criteria
(n = 121)
Other (n = 13)

Randomised (n = 1156)

Allocated to intervention (n = 578)

Allocated to intervention (n = 578)

Received intervention

Received intervention

(moxifloxacin)

(ofloxacin + metronidazole)

ITG

ITG

Lost to follow-up (n = 18)

Lost to follow-up (n = 35)

Oral intolerance (n = 2)

Oral intolerance (n = 4)

Noncompliant with medication (n = 5)

Noncompliant with medication (n = 18)

Worsening pain (n = 3)

Worsening pain (n = 2)

Tubo-ovarian abscess (n = 2)
Urinary tract infection (n = 2)

Tubo-ovarian abscess (n = 2)
Urinary tract infection (n = 4)
Other reason (n =5)

Other reason (n = 4)

Analysed (n = 560) CPTG

Analysed (n = 543) CPTG

Fig. 1. Flow diagram of this study. ITG: initiation treatment group; CPTG: completion of protocol treatment group.

Table 1
Demographic and clinical characteristics in CPTG.
Characteristics

Group A (n = 560)

Group B (n = 543)

p-Value

RR (CI 95%)

Turkish ethnicity, n (%)

Mean age  SD (years)
Previously diagnosed PID, n (%)
Use of contraceptive pills, n (%)
Mean BMI  SD (kg/m2)
Previous uterine curettage, n (%)
Use of barrier contraceptive method (condom)
Organism identied, n (%)
C. trachomatis, n (%)
N. gonorrhoeae, n (%)
Regular vaginal douching, n (%)
Median VAS at day 0 (minmax)
Mean WBC count at day 0  SD (mm3)
Mean CRP level at day 0  SD (mg/l)

560 (100)
30.3  3.7
45 (8.0)
141 (25.2)
26.9  3.4
178 (31.8)
145 (25.9)
119 (21.2)
69 (12.3)
50 (8.9)
31 (5.5)
5.1 (410)
18,114  5610
21.6  5.2

543 (100)
29.3  3.5
42 (7.7)
156 (28.7)
26.4  3.6
167 (30.8)
128 (23.6)
110 (20.3)
56 (10.3)
54 (9.9)
28 (5.2)
5.2 (310)
17,835  6150
23.8  4.9

0.094
0.853
0.184
0.094
0.712
0.372
0.685
0.293
0.564
0.780
0.866
0.416
0.369

1.0
0.8

1.0
1.0
1.0
1.1
0.8
1.0

(0.61.5)
(0.71.0)
(0.81.2)
(0.81.3)
(0.81.3)
(0.81.6)
(0.61.2)
(0.61.7)

SD: standard deviation; BMI: body mass index; VAS: visual analog scale; WBC: white blood cell count; CRP: C-reactive protein; CPTG: completion of protocol treatment group.

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O. Asicioglu et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 116121

Table 2
Clinical and microbiological cure results in CPTG.
Parameter

Group A (n = 560)

Group B (n = 543)

p-Value

RR (CI 95%)

Clinical cure rate, n (%)

Total microbiological cure rate, n (%)
C. trachomatis, n (%)
N. gonorrhoeae, n (%)
Median VAS at day 21 (minmax)
Mean WBC count at day 21  SD (mm3)
Mean CRP level at day 21  SD (mg/l)

445 (79.5)
99/119 (83.2)
60/69 (87.0)
39/50 (78.0)
0.7 (07)
9810  1620
9.6  5.6

449 (82.7)
93/110 (84.5)
54/56 (94.6)
39/54 (72.2)
0.5 (06)
9940  1850
9.8  5.7

0.172
0.781
0.063
0.497
0.654
0.321
0.498

0.9
0.9
0.9
1.0

(0.81.0)
(0.81.1)
(0.81.0)
(0.81.3)

SD: standard deviation; WBC: white blood cell count; CRP: C-reactive protein; CPTG: completion of protocol treatment group.

Table 3
Drug-related adverse effects in CPTG.
Parameter

Group A (n = 560)

Group B (n = 543)

p-Value

RR (95% CI)

Total drug-related adverse effects, n (%)

GIS, n (%)
Infections, n (%)
Nervous system, n (%)
Other, n (%)

210
143
34
18
15

252
202
20
20
10

0.003*
<0.001*
0.066
0.669
0.350

0.8
0.6
1.6
0.8
1.4

(37.5)
(25.5)
(6.1)
(3.2)
(2.7)

(46.4)
(37.2)
(3.7)
(3.7)
(1.8)

(0.70.9)
(0.50.8)
(0.92.8)
(0.41.6)
(0.63.2)

GIS: gastrointestinal system; CPTG: completion of protocol treatment group

*
Statistically signicant.

Table 4
Noncompliance with medication and oral intolerance in ITG.
Parameter

Group A (n = 578)

Group B (n = 578)

p-Value

RR (CI 95%)

Noncompliance with medication and oral intolerance, n (%)

Necessity of taking multiple drugs, n (%)
Due to side-effects of drugs, n (%)

7 (1.2)
0 (0)
7 (1.2)

22 (3.8)
12 (2.1)
10 (1.7)

0.005*

0.464

0.3 (0.10.7)

0.7 (0.21.8)

ITG: initiation treatment group.

*
Statistically signicant.

the world support this conclusion [28,29]. In addition to WBC

counts and mean VAS scores, we evaluated the C-reactive protein
level and found that it signicantly decreased with this treatment
regimen. This nding is similar to that of the MONALISA study
[30].
From a safety perspective, there was a signicantly lower
incidence of all adverse events and drug-related adverse events in
the moxioxacin group compared with the ooxacin plus metronidazole group (37.5% vs. 46.4%). In particular, there was a trend
toward lower rates of gastrointestinal tract adverse events (25.5% vs.
37.2%). This nding is similar to those of Heystek et al. and Ross et al.
[16,21]. Heystek et al. also found that moxioxacin was well
tolerated and associated with fewer gastrointestinal events than
was ciprooxacin plus doxycycline plus metronidazole. The present
nding, however, differs from that in the MONALISA study. In
that study, Judlin et al. reported that drug-related gastrointestinal
tract adverse events were similar in the moxioxacin group
compared with the ooxacin plus metronidazole group (40.1% vs.
39.7%) [30]. The infectious and nervous system adverse events in
the present study (6.1% vs. 3.7% and 3.2% vs. 3.7%) were similar
between the groups, as in many previous studies [16,21,28]. These
ndings suggest that moxioxacin is safe and well tolerated in
patients with uPID, as reported by Tulkens et al. [31]. Tulkens et al.
reported that moxioxacin is not associated with life-threatening
side effects (such as cardiac arrhythmia, hepatitis, and renal
disorders), contrary to popular belief. They reported a cardiac
disorder incidence of <0.1%, hepatobiliary disorder incidence of
<0.1%, and renal and urinary disorder incidence of 0.1% [31]. In our
study, we identied no life-threatening side effects of moxioxacin,
similar to the report by Tulkens.
Compliance with the recommended regimens for PID is a well
recognized concern in clinical practice [32]. We found that the
number of patients who were non-compliant with the medication
in terms of use of the drugs and oral intolerance in the ITG

population was signicantly lower in the moxioxacin group.

From a compliance perspective, it is possible that the once-daily
dose regimen and good gastrointestinal tolerability of moxioxacin may improve patient adherence to therapy. Furthermore,
moxioxacin treatment seems to be less expensive than ooxacin
plus metronidazole treatment.
The strength of this investigation was that it was a large,
prospective, randomized trial of patients with similar demographics. Additionally, conducting this investigation in four
tertiary institutions with an experienced research team probably
increased the validity of our results because the assessment of
clinical cure was performed by experienced researchers. Our study
had several limitations, however: we investigated only the Turkish
ethnic group, the diagnosis of uPID was not conrmed by
laparoscopy, we did not review some risk factors (such as
socioeconomic status and number of sexual partners), and the
severity of PID was assessed using only a VAS; no clinician-based
measurement was performed (e.g., McCormack score).
In conclusion, this study showed that 14 days of monotherapy
with oral moxioxacin at 400 mg once daily is clinically and
microbiologically comparable to 14 days of combination therapy
with oral ooxacin at 400 mg twice daily plus oral metronidazole
at 500 mg twice daily in women with uPID. Furthermore,
moxioxacin therapy was associated with fewer overall adverse
events and drug-related adverse events, and it was less expensive
than comparable treatments. Because of the similar efcacy, better
safety, better compliance, and relatively low cost, moxioxacin
may be considered a rst-line antibiotic regimen for uPID.
Conict of interest statement
None of the authors has any conict of interest relative to
this work. This study did not receive pharmaceutical company
support.

O. Asicioglu et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 116121

Acknowledgment
We gratefully acknowledge the investigators, coinvestigators,
study coordinators, and patients who participated in this trial.
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