Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: una revisión sistemática
Autor: Viveros Carreño, David Andrés
Asesor: Grillo Ardila, Carlos Fernando (Thesis advisor)
Fecha: 2016-10-01
Programa: Bogotá - Medicina - Especialidad en Anestesiología y Reanimación
Facultad: Facultad de Medicina

Resumen: La vaginosis bacteriana es una infección muy frecuente, con una prevalencia que varía  entre el 10% y el 50%. Los microorganismos asociados con la VB han sido aislados de la  flora normal del tracto masculino y su presencia podría estar relacionada con la  recurrencia de la infección luego del tratamiento. De esta manera, el tratamiento a la  pareja sexual podría ofrecer las ventajas de disminuir la recurrencia de la infección,  romper la cadena de infección y posiblemente disminuir la carga de la enfermedad. El  objetivo de la revisión fue Determinar la efectividad y seguridad del tratamiento  antibiótico concurrente a la pareja sexual de mujeres tratadas para VB.  Siete Ensayos clínicos controlados (1026 participantes) cumplieron los criterios de  inclusión, cuatro de ellos fueron patrocinados por la industria. Encontramos con evidencia  de alta calidad que el tratamiento antibiótico no incrementa la tase de mejora clínica o  sintomática durante la primera semana (RR 0.9, IC 95% 0.96 a 1.03; RR 1.06, IC 95%  1.00 a 1.12 respectivamente), entre la primer y cuarta semana (RR 1.02, IC 95% 0.94 a  1.11; RR 0.93, IC 95% 0.84 a 1.03 respectivamente) o después de la cuarta semana (RR  0.98, IC 95% 0.90 a 1.07; RR 1.03 con IC 95% 0.90 a 1.17 respectivamente). Con calidad  de evidencia baja el tratamiento antibiótico no llevó a una menor tasa de recurrencia  durante la primer y cuarta semana (RR 1.28, IC 95% 0.68 a 2.43) o después de la cuarta  semana de tratamiento (RR 1.00, IC 95% 0.67 a 1.52) pero incrementó la frecuencia de  eventos adversos reportados por los compañeros sexuales (RR 2.55, IC 1.55 a 4.18).

Tratamiento antibiótico para la pareja
sexual de mujeres con vaginosis
bacteriana: Una revisión sistemática
Eloisa Mercedes Sierra Barrios
David Andrés Viveros Carreño
Universidad Nacional de Colombia
Facultad de Medicina, Departamento de Obstetricia y Ginecología
Bogotá DC, Colombia
2016Tratamiento antibiótico para la pareja
sexual de mujeres con vaginosis
bacteriana: Una revisión sistemática
Eloisa Mercedes Sierra Barrios
David Andrés Viveros Carreño
Trabajo de investigación presentado como requisito parcial para optar al título de:
Especialista en Obstetricia y ginecología
Director:
Jairo Amaya Guio, MD, MSc
Codirector:
Carlos Fernando Grillo Ardila, MD, MSc
Grupo de Investigación:
Enfermedades infecciosas Departamento Obstetricia y Ginecología
Universidad Nacional de Colombia
Facultad de Medicina, Departamento Obstetricia y Ginecología
Bogotá DC, Colombia
2016A nuestras familias por apoyarnos en todo momento,
A nuestros tutores por tantas enseñanzas, risas y
experiencias.
A nuestra Universidad por brindárnoslo todo.Resumen y Abstract VII
Resumen
La vaginosis bacteriana es una infección muy frecuente, con una prevalencia que varía
entre el 10% y el 50%. Los microorganismos asociados con la VB han sido aislados de la
flora normal del tracto masculino y su presencia podría estar relacionada con la
recurrencia de la infección luego del tratamiento. De esta manera, el tratamiento a la
pareja sexual podría ofrecer las ventajas de disminuir la recurrencia de la infección,
romper la cadena de infección y posiblemente disminuir la carga de la enfermedad. El
objetivo de la revisión fue Determinar la efectividad y seguridad del tratamiento
antibiótico concurrente a la pareja sexual de mujeres tratadas para VB.
Siete Ensayos clínicos controlados (1026 participantes) cumplieron los criterios de
inclusión, cuatro de ellos fueron patrocinados por la industria. Encontramos con evidencia
de alta calidad que el tratamiento antibiótico no incrementa la tase de mejora clínica o
sintomática durante la primera semana (RR 0.9, IC 95% 0.96 a 1.03; RR 1.06, IC 95%
1.00 a 1.12 respectivamente), entre la primer y cuarta semana (RR 1.02, IC 95% 0.94 a
1.11; RR 0.93, IC 95% 0.84 a 1.03 respectivamente) o después de la cuarta semana (RR
0.98, IC 95% 0.90 a 1.07; RR 1.03 con IC 95% 0.90 a 1.17 respectivamente). Con calidad
de evidencia baja el tratamiento antibiótico no llevó a una menor tasa de recurrencia
durante la primer y cuarta semana (RR 1.28, IC 95% 0.68 a 2.43) o después de la cuarta
semana de tratamiento (RR 1.00, IC 95% 0.67 a 1.52) pero incrementó la frecuencia de
eventos adversos reportados por los compañeros sexuales (RR 2.55, IC 1.55 a 4.18).
Palabras clave: Compañeros sexuales, Vaginosis bacteriana, Tratamiento
Abstract
Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50%
worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms
associated with BV have been isolated from the normal flora of the male genital tract, and
their presence could be related to the recurrence of BV after antibiotic treatment.
Therefore, the treatment of sexual partners could decrease the recurrence of infection and
possibly the burden of the disease. The objective of the revision was to assess the
effectiveness in women and the safety in men of concurrent antibiotic treatment for the
sexual partners of women treated for BV.VIII
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry
funded four of these trials. Based on high quality evidence, antibiotic treatment does not
increase the rate of clinical or symptomatic improvement in women during the first week
(risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; RR 1.06, 95% CI 1.00 to
1.12, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; RR
0.93, 95% CI 0.84 to 1.03, respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to
1.07; RR 1.03, 95% CI 0.90 to 1.17, respectively). With low quality evidence antibiotic
treatment does not led to a lower recurrence during the first and fourth week (RR 1.28,
95% CI 0.68 to 2.43) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52)
in women, but increases the frequency of adverse events reported by sexual partners (RR
2.55, 95% CI 1.55 to 4.18).
Key words: sexual partners, bacterial vaginosis, treatment.IX
TABLE OF CONTENTS
ABSTRACT VII
SUMMARY 10
PLAIN LANGUAGE SUMMARY 12
BACKGROUND 13
OBJECTIVES 20
METHODS 20
RESULTS 29
DISCUSSION 37
AUTHORS’CONCLUSIONS 39
ACKNOWLEDGEMENTS 39
REFERENCES 41
CHARACTERISTICS OF STUDIES 46
DATA AND ANALYSES 66
SUMMARY OF FINDINGS FOR THE MAIN COMPARISON 72
ADDITIONAL SUMMARY OF FINDINGS 7310
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Summary
Background
Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50%
worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms
associated with BV have been isolated from the normal flora of the male genital tract, and
their presence could be related to the recurrence of BV after antibiotic treatment. Therefore,
the treatment of sexual partners could decrease the recurrence of infection and possibly the
burden of the disease.
Objectives
To assess the effectiveness in women and the safety in men of concurrent antibiotic
treatment for the sexual partners of women treated for BV.
Search methods
We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23
July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase
(1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization
(WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016),
ClinicalTrials.gov (23 July 2016) and the Web of ScienceTM (2001 to 23 July 2016). We
also handsearched conference proceedings, contacted trial authors and reviewed the
reference lists of retrieved studies.
Selection criteria
Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic
treatment with placebo, no intervention or any other intervention by the sexual partners of
women treated for BV.
Data collection and analysis
Three review authors independently assessed trials for inclusion, extracted data and
assessed the risk of bias in the included studies. We resolved any disagreements through
consensus. We assessed the quality of the evidence using the GRADE approach.
Main results
Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry
funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of
sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not
increase the rate of clinical or symptomatic improvement in women during the first week
(risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, fourTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 11
studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between
the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR
0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth
week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90
to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a
lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218
participants, one study; low quality evidence) or after the fourth week of treatment (RR
1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women,
but increases the frequency of adverse events (most frequently gastrointestinal symptoms)
reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies;
low quality evidence).
Two trials (172 participants) compared any antibiotic treatment for sexual partners with no
intervention. When we compared it with no intervention, the effects of antibiotic treatment
on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one
study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to
1.25; 152 participants, two studies) and symptomatic improvement after the fourth week
(RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were
no differences between groups. We downgraded the quality of the evidence to low or very
low.
Authors’ conclusions
High quality evidence shows that antibiotic treatment for sexual partners of women with
BV, compared with placebo, does not increase the rate of clinical or symptomatic
improvement during the first, between the first and fourth or after the fourth week into the
women. Low quality evidence suggests that antibiotic treatment does not led to a lower
recurrence rate during the first and fourth or after the fourth week of treatment into the
women, but increases the frequency of adverse events reported by sexual partners. Finally,
compared with no intervention, antibiotic treatment does not decrease the recurrence rate
after the fourth week and does not increase the frequency of clinical or symptomatic
improvement between the first and fourth or after the fourth week into the women,
respectively.12
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
PLAIN LANGUAGE SUMMARY
Antibiotic treatment for the sexual partners of women with bacterial vaginosis
Review question
We assessed the effectiveness in women and the safety in men of concurrent antibiotic
treatment for the sexual partners of women treated for bacterial vaginosis (BV).
Background
Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50%
worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms
associated with BV have been isolated from the normal flora of the male genital tract, and
their presence could be related to the recurrence of infection after antibiotic treatment.
Therefore, the treatment of sexual partners could offer the advantages of decreasing the
recurrence of infection and possibly reducing the burden of the disease.
Trial characteristics
Cochrane researchers searched the available literature up to the 23 July 2016 and included
seven trials with 1026 participants. The trials included sexually-active non-pregnant women
between 17 and 56 years of age, either single or married, with symptomatic BV. Four
studies only included women involved into a monogamous heterosexual relationship and
there was no information about this for the remaining trials. Six trials used 5-
nitroimidazoles to treat the sexual partner, four trials used metronidazole and two trials
used tinidazole; only one study used a lincosamide for treatment. Five trials compared
antibiotic versus placebo (854 participants) and two trials compared antibiotic treatment
with no intervention (172 participants). Pharmaceutical companies funded four of the
included trials.
Key results
Compared with placebo, antibiotic treatment for the sexual partners of women treated for
BV had no effects on clinical or symptomatic improvement in women, regardless of the
time period over which the trials assessed these outcomes (during the first, between the first
and fourth, or after the fourth week). Furthermore, antibiotic treatment of the sexual partner
may have no effect on the recurrence of BV up to 12 weeks after treatment, but may
increase the frequency of minor adverse events reported by sexual partners. Compared with
no intervention, treatment of sexual partners of women with BV may have no effect on
decreasing the recurrence rate or over the frequency of clinical or symptomatic
improvement between the first and fourth or after the fourth week, respectively.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 13
Quality of evidence
The quality of evidence was high for the outcomes of clinical and symptomatic
improvement. The quality of evidence was very low for recurrence due to some limitations
regarding risk of bias and imprecision.
BACKGROUND
Description of the condition
Secretions from the vagina (known as vaginal discharge) are a nor- mal occurrence and
result from cervical secretion and other com- ponents derived from micro-organisms that
colonize the vaginal flora, mostly lactobacilli (Mylonas 2011). Lactobacilli play a pre-
dominant role in vaginal homeostasis through the production of lactic acid, hydrogen
peroxide and bacteriocins, which are com- pounds that control the overgrowth of
pathogenic micro-organ- isms (Taylor 2013). An increase in the amount of vaginal dis-
charge is usually associated with the presence of a genital tract infection (Mylonas 2011).
Women with an abnormal vaginal dis- charge most commonly have bacterial vaginosis
(BV) (39.6%) or, less frequently, vulvovaginal candidiasis (11%) or trichomoniasis (0.8%);
however, the exact etiology of the vaginal discharge can change according to the population
(Ángel-Müller 2012). BV is thought to arise as a result of an imbalance in the normal
vaginal flora when lactobacilli decrease in concentration and are replaced by anaerobic and
facultative aerobic bacteria (Taylor 2013), such as Gardnerella vaginalis (40%) or, less
frequently, by Mycoplasma hominis, Clostridia (Mirmonsef 2012), Peptostreptococcus or
Mobiluncus (Mylonas 2011). Although the precise cause of this dys- bacteriosis is not
completely understood, some factors, such as high sexual activity, a new sexual partner and
risky sexual behavior (Bradshaw 2005; Mirmonsef 2012; Mylonas 2011), could con-
tribute to this condition (Mylonas 2011).
BV is found worldwide with a prevalence between 10% and 50%, and is usually higher
among sex workers, the HIV-positive pop- ulation, black and Hispanic women (Kenyon
2013), and among women with a new or a high number of sexual partners (Marrazzo 2011).
Having three or more male sexual partners in the past 12 months has been identified as a
risk factor for BV (Marrazzo 2011). Also, having a female sexual partner has been reported
to increase the risk of BV by 60% (Smart 2004). The burden of BV is related not only to
the prevalence of the condition, but also to a reduction in quality of life, as well as to
anxiety and self-conscious feelings re- lating to the fear of exclusion due to the foul smell
associated with the infection (Bilardi 2013). The bacteria associated with BV may be
carried by male genitalia, but men are usually asymptomatic (Nelson 2012). The direct cost
of BV care has been evaluated in pregnant women, and is particularly related to the
complications of pregnancy that derive from it: in a study evaluating a popula- tion from
the USA, the Netherlands and the UK it was estimated that the overall cost of BV was
around one thousand million USD a year (Oleen-Burkey 1995). BV has also been
associated with a risk of acquiring a sexually transmitted infection (STI), such as pelvic14
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
inflammatory disease (Mirmonsef 2012; Taylor 2013), and infections caused by Neisseria
gonorrhoeae, Chlamydiia trachoma- tis and HIV (Mirmonsef 2012), and with a higher risk
of devel- oping cervical cancer (Gillet 2012), and even subfertility (Taylor 2013). In
addition, BV may increase the risk of adverse perinatal outcomes, such as low birth weight,
preterm delivery and very low birth weight (Sangkomkamhang 2008), and may result in ap-
proximately 80,000 excess preterm births every year in the USA (Goldenberg 2005).
The Amsel criteria and Gram staining can be used to diagnose BV, and Gram staining is
considered the gold standard for this purpose (Workowski 2015). The Nugent scoring
system is applied to Gram stains of vaginal smears to visually estimate the numbers of
lactobacilli and BV-associated organisms; a Nugent score of zero to three is considered
healthy, four to six is intermediate and a score of seven to ten implies the presence of BV
(Brotman 2011). This method has a number of disadvantages: a trained professional is
required for the interpretation of results and the Gram stain is unable to detect some micro-
organisms, such as Ureaplasma and Mycoplasma (Taylor 2013). When Gram staining is not
possible, the Amsel criteria provide a good clinical tool for the diagnosis of BV, which
requires the presence of at least three of the following four criteria (Taylor 2013).
• Homogeneous, thin, white vaginal discharge. • Presence of clue cells on microscopic
examination. • A pH greater than 4.5. • A positive ‘whiff test’ (a fishy odour after 10%
potassium hydroxide is added).
In vitro cultures for G. vaginalis are of limited utility because al- though cultures in almost
all women with a symptomatic infec- tion are positive, 50% of the cultures from healthy
asymptomatic women are also positive (Mylonas 2011). Finally, in some circum- stances a
diagnosis can be reached through combining the medical history with the clinical
characterization of the discharge during a gynaecological examination (Ministerio de Salud
y Protección Social 2013). This approach, the syndromic approach, is based on the
assumption that genital tract infections share some common symptoms and signs thus
making it possible to assign them a spe- cific etiology without the need for a laboratory test
(Ministerio de Salud y Protección Social 2013).
BV is not currently considered a STI but it is well-recognized that both have many aspects
in common (Morris 2001). Several studies have reported an association between BV and
the coexistence of STIs, risky sexual behaviours, young age at first sexual intercourse,
sharing sexual toys, and a new or multiple male or female partners ( Chavez 2009; Fethers
2008; Fethers 2009; Marrazzo 2005; Morris 2001). Furthermore, BV is unusual in women
without a history of sexual contact (Fethers 2009), and its prevalence is less frequent in
women who report that they regularly use condoms or have a stable sexual partner (Chavez
2009; Fethers 2008); these findings are consistent with a strong association between BV
and sexual activity (Fethers 2009).
Additionally, some studies have proposed that the bacteria associ- ated with BV may be
carried by the male genitalia (Nelson 2012), based on the microbiological isolation of theTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 15
micro-organisms as- sociated with this infection in the flora of the penis and urethra in male
partners of infected females (Mandar 2013; Nelson 2012). This is particularly notable in
uncircumcized males in whom the presence of a major surface of contact could have a
major role as a reservoir, and favour the occurrence of an infection after sexual intercourse
(Bukusi 2011; Mehta 2012). Bacteria associated with BV have been isolated from the
normal flora of the male coronal sulcus and urethra, and could be related to infection in
female partners and to the recurrence of infection after treatment (seen in about 20% of
individuals and defined as three or more proven episodes of BV in 12 months) (Colli 1997;
Cook 1992). Another mechanism for infection could be the mechanical transfer of perneal
enteric bacteria from the flora of the male genitalia through unprotected and protected
intercourse (Mandar 2013).16
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Description of the intervention
As BV is considered to arise from an imbalance in the normal vagi- nal flora (Taylor 2013),
treatment includes the administration of antibiotics, such as nitroimidazoles, lincosamides,
macrolides (e.g. erythromycin) and, in some circumstances, penicillins (Oduyebo 2009;
Workowski 2015), the objective being to eradicate the ab- normal vaginal bacterial flora
(Mylonas 2011). 5-Nitroimidazole derivatives are available for oral and intravaginal
administration (Workowski 2015). These medications are absorbed completely after oral
intake and the volume of distribution of these agents ap- proximates to that of total body
water because they are associated with a low level of protein binding (Lamp 1999). 5-
Nitroimida- zole derivatives penetrate well into body tissues and fluids, with the exception
of the placenta, and are eliminated in the urine af- ter being metabolized in the liver
(Brunton 2011; Trevor 2012). The side effects of 5-nitroimidazoles are usually mild and the
most common are headache, nausea, dry mouth and a metallic taste (Brunton 2011; Trevor
2012). The regimens recommended for the treatment of BV include metronidazole 500 mg
orally twice a day for seven days or metronidazole gel 0.75% one full applicator (5 g)
intravaginally once a day for five days; tinidazole 2 g orally once daily for one or two days
or 1 g orally once daily for five days; or secnidazole 1 g or 2 g orally in single doses
(Oduyebo 2009; Workowski 2015).
Clindamycin, the most representative of the lincosamides, is al- most completely absorbed
following oral administration (Bouazza 2012), with a half-life of about three hours, and is
widely dis- tributed into fluids and tissues (Bouazza 2012; Gatti 1993). More than 80% of
this agent is bound to plasma proteins, primarily α1- acid glycoprotein (Flaherty 1996); it is
metabolized in the liver by cytochrome P450 3A4 and is excreted in the urine and bile
(Trevor 2012; Wynalda 2003, Yasuda 2008). The most common side effects related to the
administration of clindamycin include diarrhoea and, in a small number of individuals,
pseudomembra- nous colitis (Gurwith 1977). Rash can occur in about 10% of in- dividuals;
other reactions, such as Stevens-Johnson syndrome, the reversible elevation of
transaminases, granulocytopenia, thrombocytopenia and anaphylactic reactions, are less
frequent (Brunton 2011). Regimens suggested for the treatment of BV include clin-
damycin cream 2% one full applicator (5 mg) intravaginally at bedtime for seven days;
clindamycin 300 mg orally twice daily for seven days; or clindamycin ovules 100 mg
intravaginally once at bedtime for three days (Workowski 2015).
The serum half-life of erythromycin is approximately two hours (Josefsson 1982;
Zuckerman 2011). The drug is metabolized in the liver by cytochrome P450 3A4 and 2% to
5% is eliminated in an active form in the urine (Trevor 2012; Zuckerman 2011). Cholestatic
hepatitis is the most notable side effect of macrolides and hepatotoxicity has also been
observed (Derby 1993). Large doses have been associated with abdominal cramps, nausea,Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 17
vom- iting and diarrhoea (Zuckerman 2011). Among the recognized allergic reactions are
fever, eosinophilia and skin eruptions, which may occur alone or in combination; all
disappear shortly after therapy is suspended (Brunton 2011). Erythromycin for the treat-
ment of BV is used at a dose of 333 mg oral three times daily for 14 days in combination
with metronidazole (Brocklehurst 2013). Some studies have used the aminopenicillin
amoxicillin for the treatment of BV (Amit 2013; Brocklehurst 2013). This agent is a semi-
synthetic penicillin with a half-life of almost 80 minutes, which binds to proteins in the
plasma and is excreted renally (Brocklehurst 2013). The most important side effects
associated with amoxicillin are nausea, vomiting, rash and antibiotic-associ- ated colitis.
The use of ampicillin is now generally avoided due to the emergence of ampicillin-resistant
bacteria in individuals with BV (Amit 2013).18
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
How the intervention might work
To date, the evidence regarding whether to treat or not the sexual partner of a woman with
BV is inconclusive (Mehta 2013; Potter 1999). As frequently-used antibiotics for treating
BV are widely distributed into the fluids and tissues of the human body (Bouazza 2012;
Brunton 2011; Gatti 1993; Trevor 2012), the treatment of sexual partners could eliminate
the abnormal flora present in the male genital area that may promote relapse in, or
reinfection of, women with BV (Bradshaw 2006).
The 5-nitroimidazole derivatives are agents with antiprotozoal and antibacterial properties
(Amit 2013). When a 5-nitroimidazole enters the cellular environment, it is reduced by the
pyruvate ferre- doxin oxidoreductase system present in bacterial mitochondria, which
modifies its chemical structure (Amit 2013). Pyruvate ferre- doxin oxidoreductase
generates adenosine triphosphate (ATP) via the oxidative decarboxylation of pyruvate; in
the presence of a structurally modified 5-nitroimidazole, the electrons that would be
transferred to hydrogen ions during the generation of ATP are captured by the nitro group
(Amit 2013). This disruption of ATP production promotes the formation of intermediate
compounds and free radicals that are highly toxic to the bacteria (Brunton 2011). The
lincosamides bind to the 50S subunit of bacterial ri- bosomes and consequentially suppress
bacterial protein synthesis (Brunton2011;Trevor2012).Themacrolides(e.g.erythromycin) are
bacteriostatic agents that inhibit protein synthesis by binding reversibly to the 50S
ribosomal subunits of sensitive micro-organ- isms (Brunton 2011; Trevor 2012).
The administration of any effective and safe intervention to the sexual partner of a woman
with BV could offer the advantages of decreasing the recurrence of infection, thus breaking
the chain of infection and possibly decreasing the prevalence of STIs, reducing the burden
associated with the condition and impacting positively on the sexual and reproductive
health of the woman (Mehta 2013).Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 19
Why it is important to do this review
This systematic review is of paramount importance as some stud- ies suggest that BV
exhibits a behaviour similar to that of an STI (Potter 1999). However, there is still some
uncertainty regarding whether recurrence of BV in women could be due to a failure to
eradicate the causative organism(s) or a consequence of reinfec- tion by the sexual partner
(Bradshaw 2006). Currently, the treat- ment of sexual partners of women with BV is not
recommended (Workowski 2015), but this is based on the critical appraisal of in- dividual
clinical trials (none of which provide conclusive evidence regarding the efficacy and safety
of male sex partner treatment for women with BV (Mehta 2013)) rather than a synthesis of
the avail- able clinical evidence (Mehta 2012; Potter 1999). If the treatment of sexual
partners were found to reduce the rate of recurrence of BV then this could reduce costs.
However, it would need to be weighed against the possible risk of antibiotic resistance that
could arise from the additional multiple treatments such a policy would involve. There is
therefore a need for high-quality systematic re- views to improve the clinical management
of BV (Madhivanan 2013). This systematic review will facilitate the synthesis of the
current evidence, and recognize its strengths and weakness, address the uncertainty of the
current knowledge and make it possible to assess the effectiveness and safety of this
intervention.20
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
OBJECTIVES
To assess the effectiveness in women and the safety in men of concurrent antibiotic
treatment for the sexual partners of women treated for BV.
METHODS
Criteria for considering studies for this review
Types of studies
Randomized controlled clinical trials, published and unpublished, that compared the
concurrent use of any antibiotic treatment (any concentration, frequency, duration and
route) with placebo, no intervention or any other intervention (any concentration, fre-
quency, duration and route) by the sexual partners of women treated for bacterial vaginosis
(BV). We excluded quasi-random- ized trials because this approach produces effect
estimates that in- dicate more extreme benefits compared with those generated by
randomized controlled clinical trials (Higgins 2011). We also ex- cluded cross-over trials
and cluster-randomized trials because of the nature of the condition (Higgins 2011).
Types of participants
The sexual partners (either male or female) of women treated for non-recurrent BV.
Types of interventions
Any antibiotic treatment (at any concentration, frequency, dura- tion and route) versus one
of the following.
• Placebo. • No intervention. • Any other intervention different to antibiotic treatment
(any concentration, frequency, duration and route).
Types of outcome measures Primary outcomes
• Recurrence of BV in women treated for BV (proportion of participants who were
previously healthy following treatment for BV that developed a new episode of BV,
according to Amsel’s criteria or any other clinical criteria).
• Clinical improvement (according to Amsel’s criteria or any other clinical criteria) in
women treated for BV.
• Symptomatic improvement defined as the (self-reported) improvement or disappearance
of symptoms in women treated for BV.
• Serious adverse events of the intervention (hypersensitivity, pseudomembranous colitis orTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 21
Stevens-Johnson syndrome) in sexual partners of women treated for BV.
Secondary outcomes
• Minor adverse events of the intervention during therapy (metallic taste, nausea, vomiting,
diarrhoea or headache) in sexual partners of women treated for BV.
• Cost-effectiveness of the intervention. The primary outcomes (recurrence, clinical and
symptomatic improvement) were assessed during the first week, between the first and
fourth week and after the fourth week. We assessed adverse events of the intervention
during therapy.
Search methods for identification of studies
We identified as many relevant randomized controlled trials (RCTs) of “antibiotic
treatment” for the “sexual partner of the woman being treated for bacterial vaginosis” as
possible, irrespec- tive of language of publication, publication date and publication status
(published, unpublished, in press or in progress). We used both the electronic searching of
bibliographic databases and hand- searching, as described in the Cochrane Handbook for
Systematic Reviews of Interventions (Higgins 2011).
Electronic searches
We contacted the Information specialist of the Cochrane Sexu- ally Transmitted Infections
Group in order to implement a com- prehensive search strategy to identify as many relevant
RCTs as possible in the electronic databases. We used a combination of controlled
vocabulary (MeSH, Emtree terms, Health Sciences Descriptors -DeCS for its acronym in
Spanish-, including ex- ploded terms) and free-text terms (considering spelling variants,
synonyms, acronyms and truncation) for “sexual partner of the woman being treated for
bacterial vaginosis” and “antibiotic treat- ment”, with field labels, proximity operators and
boolean opera- tors. We have listed our search strategies in the ’Appendices’ section
(Appendix 1; Appendix 2; Appendix 3; Appendix 4; Appendix 5; Appendix 6; Appendix
7).
We searched the following electronic databases. • Cochrane Sexually Transmitted
Infections Group
Specialized Register (searched 23 July 2016). • Cochrane Central Register of Controlled
Trials
(CENTRAL), Ovid platform (searched from Cochrane Library Issue 1, 1991 to 23 July
2016).
• MEDLINE, Ovid platform (searched from 1946 to 23 July 2016).
• MEDLINE In-Process & Other Non-Indexed Citations, Ovid platform (searched from
1966 to 23 July 2016).22
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
• MEDLINE Daily Update, Ovid platform (searched from 1966 to 23 July 2016).
• Embase (searched from 1974 to 23 July 2016).
• LILACS (Latin American and Caribbean Health Sciences Literature, IAHx interface;
searched from 1982 to 23 July 2016).
For MEDLINE, we used the Cochrane highly sensitive search strategy for identifying
RCTs: sensitivity and precision maximizing version (2008 revision), Ovid format (Higgins
2011). We com- bined the LILACS search strategy with the RCT filter of the IAHx
interface.
Searching other resources
We searched the following resources for additional trials. • Trial registers:
◦ World Health Organization (WHO) International Clinical Trials Registry Platform
(ICTRP) portal (apps.who.int/ trialsearch/): searched 23 Jul 2016;
◦ ClinicalTrials.gov (clinicaltrials.gov/): searched 23 July 2016.
• Web of ScienceTM: searched from 2001 to 23 July 2016.
We contacted the trial authors of all RCTs we identified by other methods and
handsearched the conference proceeding abstracts of the following events.
• International Society for Sexually Transmitted Diseases Research (ISSTDR)
(www.isstdr.org/) scientific meetings: 2007, 2009 and 2011.
• British Association for Sexual Health and HIV (BASHH) ( www.bashh.org/) scientific
meetings: 2004, 2006, 2007 and 2009.
• The International Congress on Infectious Diseases (ICID) ( www.isid.org/): 2010 and
2012.
• International Union against Sexually Transmitted Infections (IUSTI) (www.iusti.org/)
conferences and meetings: 2011 and 2012.
• International Society for Infectious Diseases (ISID) ( www.isid.org/): 2011.
• International Meeting on Emerging Diseases and Surveillance (IMED) (www.isid.org/):
2007, 2009 and 2011.
• Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
(www.icaac.org/): 2011 and 2012.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 23
• International Federation of Gynecology and Obstetrics (FIGO) (www.figo.org/) World
Congress: 2012.
We also handsearched previous systematic reviews and other rel- evant publications on the
same topic and the reference lists of all RCTs identified by other methods.
Data collection and analysis Selection of studies
Three review authors (JA-G, DAV-C and EMS-B) independently assessed the titles and
abstracts of the records we retrieved from the search strategy for inclusion. Three review
authors indepen- dently performed the final selection of trials for inclusion and we resolved
any disagreements through discussion. We listed all ex- cluded studies and the reasons for
exclusion in a “Characteristics of excluded studies” table and we constructed a PRISMA
diagram to illustrated the study selection process (Figure 1).
Data extraction and management
We designed a data extraction form, which we pilot tested with one of the included studies.
Three review authors (CFG-A, DAV-C and EMS-B) independently extracted the data from
the included studies using the finalized data extraction form. We resolved any
disagreements regarding the extracted data through discussion un- til we reached a
consensus.
We extracted data on the following items.
• Location of the trial and setting.
• Trial design.
• Power calculation performed.
• Inclusion and exclusion criteria.
• Baseline information of the participants in order to have comparable intervention groups
at entry (age, marital status, contraceptive habits, sexual intercourse during treatment,
history of sexually transmitted infections (STIs), sexual behavioral history).
• Total number of intervention groups.
• Types of interventions: antibiotic type (any concentration, frequency, duration and route).
• Types of comparison: placebo, no intervention or any other intervention (any
concentration, frequency, duration and route). • Number of participants enrolled,
randomized and excluded after randomization and analysed. • Number of participants lost
to follow-up in the groups. • Outcomes stated in the methods versus outcomes reported
in the results. • How the trial authors defined the secondary outcomes. • Differences24
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
between groups for outcome assessment. • Time of follow-up in participants for specific
outcomes. • How the trial authors validated adverse event reports. • Funding sources
reported. • Ethical issues: use of signed informed consent and ethics approval.
For eligible studies, two review authors (CFG-A and MYM-V) entered the data into
Review Manager (RevMan) (RevMan 2014), and checked them for accuracy. When
information regarding any of the above was unclear, we contacted authors of the original
re- ports to ask for further details. For a single RCT report, we ex- tracted data directly into
a data collection form; in cases of mul- tiple reports, we extracted data from each report
separately and then combined information across data collection forms.
Assessment of risk of bias in included studies
Two review authors (CFG-A and JA-G) independently assessed the risk of bias for each
included study using the criteria outlined in the Cochrane Handbook for Systematic
Reviews of Interventions (Higgins 2011). We resolved any disagreement by consensus or
we consulted a third review author (MYM-V). The review authors that assessed the risk of
bias in the included studies were theme and methodology experts. In order to collect
missing information, we planned to contact the study investigators using open-ended
questions.
1. Random sequence generation (checking for possible selection bias)
We described, for each included study, the method used to generate the allocation sequence
in sufficient detail to allow an assessment of whether it should produce comparable groups.
We assessed the method as follows.
• Low risk of bias (any truly random process, e.g. random number table; computer random
number generator).
• High risk of bias (any non-random process, e.g. odd or even date of birth; hospital or
clinic record number).
• Unclear risk of bias.
2. Allocation concealment (checking for possible selection bias)
For each included study we reported the method used to conceal allocation to interventions
prior to assignment and we assessed whether intervention allocation could have been
foreseen in ad- vance of, or during, recruitment or changed after assignment. We assessed
the methods as follows.
• Low risk of bias (e.g. telephone or central randomization; consecutively numbered sealed
opaque envelopes).Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 25
• High risk of bias (open random allocation; unsealed or non opaque envelopes, alternation;
date of birth).
• Unclear risk of bias.
3a. Blinding of participants and personnel (checking for possible performance bias)
We described, for each included study, the methods used, if any, to blind study participants
and personnel from the knowledge of which intervention a participant received. We
considered that studies were at low risk of bias if they were blinded, or if we judged that the
lack of blinding would have been unlikely to affect results. We assessed blinding separately
for different outcomes or classes of outcomes. We assessed the methods as follows.
• Low, high or unclear risk of bias for participants. • Low, high or unclear risk of bias for
personnel.
3b. Blinding of outcome assessment (checking for possible detection bias)
We described the methods used, if any, to blind outcome assessors from the knowledge of
which intervention a participant received for each included study. We assessed blinding
separately for dif- ferent outcomes or classes of outcomes. We also assessed methods used
to blind outcome assessment as at either low, high or unclear risk of bias.
4. Incomplete outcome data (checking for possible attrition bias due to the amount,
nature and handling of incomplete outcome data)
We described, for each included study, and for each outcome or class of outcomes, the
completeness of the data including attrition and exclusions from the analysis. We stated
whether the trial au- thors reported attrition and exclusions and the number of partic- ipants
included in the analysis at each stage (compared with the total number of randomized
participants), reasons for attrition or exclusion where reported, and whether missing data
were balanced across groups or were related to outcomes. Where an included study
reported sufficient information, we re-included missing data in the analyses we undertook.
We assessed methods as follows.
• Low risk of bias (e.g. no missing outcome data; missing outcome data balanced across
groups).
• High risk of bias (e.g. numbers or reasons for missing data imbalance across groups; ‘as
treated’ analysis done with substantial departure of intervention received from that assigned
at randomization).
• Unclear risk of bias. We used a cut-off point of 20% to determine whether a study was at
low or high risk of bias according to the level of missing data.
5. Selective reporting (checking for reporting bias)
For each included study, we described how we investigated the possibility of selective
outcome reporting bias and what we found. We assessed the methods as follows.26
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
• Low risk of bias (where it was clear that the study authors reported all of the study’s
prespecified outcomes and all expected outcomes of interest).
• High risk of bias (where the study authors did not report all of the study’s prespecified
outcomes; the study authors did not prespecify one or more reported primary outcomes; the
study authors incompletely reported the outcomes of interest and so we could not used
them; the study failed to include the results of a key outcome that we would expected them
to have reported).
• Unclear risk of bias.
6. Other bias (checking for bias due to problems not covered by (1) to (5) above)
We described, for each included study, any important concerns we had about other possible
sources of bias. We assessed whether each included study was free of other problems that
could put it at risk of bias. We assessed methods as follows.
• Low risk of other bias. • High risk of other bias. • Unclear risk of other bias.
Overall risk of bias
We made explicit judgments about whether studies were at high risk of bias, according to
the criteria given in the Cochrane Hand- book for Systematic Reviews of Interventions
(Higgins 2011). With reference to (1) to (6) above, we assessed the likely magnitude and
direction of the bias and whether we considered it was likely to impact on the findings. We
explored the impact of the level of bias by undertaking sensitivity analyses (see the
’Sensitivity analysis’ section).
Measures of treatment effect Dichotomous data
For dichotomous data, we reported the results as risk ratios (RRs) with 95% confidence
intervals (CIs). The RR is used as a relative effect measure, which works well with a low or
high rate of events, and is easy to interpret and use in clinical practice.
Continuous data
For continuous data, we used the mean difference if outcomes were measured in the same
way between trials. We used the standardized mean difference to combine trials that
measured the same outcome but used different methods.
Unit of analysis issues
The units of analysis were individuals instead of couples. We as- sessed the effect of the
intervention independently in the partner and the woman that constitute the couple. The
sexual partner of the woman was randomized to the intervention or comparison group, but
all the women included in the study received treatment forBV.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 27
Where we identified a clinical trial that randomized participants to several intervention
groups, we determined which interven- tion groups were relevant. To avoid confusion for
the reader, we included all the intervention groups of the study in the ’Characteristics of
included studies’ table (in the notes cell), and provided a detailed description only of the
intervention groups that were relevant to this review, and we only used these groups in our
analyses. Finally, in order to overcome a unit-of-analysis error for a study that could
contribute multiple correlated comparisons, we combined all relevant experimental
intervention groups of the studies into a single group and also combined all relevant control
intervention groups into a single control group, in order to create a single pairwise
comparison (Higgins 2011).
Dealing with missing data
We identified the levels of attrition in the included trials and we performed analyses for all
outcomes, as far as possible, on an in- tention-to-treat basis, i.e. we attempted to include all
participants randomized to each group in the analyses, and we analysed all participants in
the group to which they were allocated, regardless of whether or not they received the
allocated intervention. The denominator for each outcome in each trial was the number
randomized minus any participants whose outcomes were known to be missing. We
explored the impact of including trials with high levels of missing data in the overall
assessment of treatment effects by using sensitivity analysis (see the ’Sensitivity analysis’
section).
Assessment of heterogeneity
We assessed statistical heterogeneity in each meta-analysis using the Tau2, I2 statistic and
Chi2 test values (Higgins 2011). We regarded heterogeneity as substantial if the I2 statistic
value was greater than 40% and if either the Tau2 value was greater than zero or there was
a low P value (less than 0.10) in the Chi2 test for heterogeneity.
Assessment of reporting biases
We planned to explored publication bias through assessment of funnel plot asymmetry and
formal tests. For continuous outcomes, we planned to use the test proposed by Egger 1997,
and for dichotomous outcomes we planned to use the test proposed by Harbord 2006.
However, we included fewer than 10 trials in the meta-analysis so we did not perform these
analyses.
Data synthesis
We performed statistical analyses using RevMan (RevMan 2014). We used a fixed-effect
model to combine data when it was reason- able to assume that studies estimated the same
underlying treat- ment effect i.e. where trials examined the same intervention, and we
judged the trials’ populations and methods to be sufficiently similar. We used a random-
effects model if there were clinical het- erogeneity sufficient to expect that the underlying
treatment ef- fects differed between trials or, if we detected substantial statistical
heterogeneity, to produce an overall summary if an average treat- ment effect across trials28
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
was considered clinically meaningful. We treated the random-effects summary as the
average range of possi- ble treatment effects and we discussed the clinical implications of
treatment effects differing between trials. If the average treatment effect was not clinically
meaningful, we did not combine trials.
’Summary of findings’ table
We used the GRADE approach in order to produce a ’Summary of findings’ table for the
outcomes recurrence after treatment, clini- cal and symptomatic improvement and minor or
serious adverse events (Higgins 2011). We downgraded the quality of evidence depending
on the presence of the following factors.
• Study limitations. • Inconsistency of results. • Indirectness of evidence. • Imprecision. •
Publication bias.
Subgroup analysis and investigation of heterogeneity
We planned explore the following potential sources of heterogene- ity using subgroup
analyses.
• Comparison of different antibiotic types (5-nitroimidazole, lincosamides or any other
antibiotic type).
• Comparison of different durations of antibiotic therapy (single versus multiple doses).
• Comparison of women with monogamous relationships and women with multiple sexual
partners.
We restricted subgroup analyses to the primary outcomes: • Recurrence after treatment into
the women. • Clinical improvement. • Symptomatic improvement.
Given that the safety and effectiveness of health interventions can differ within and
between populations, we proposed a subgroup analysis according to low- versus high-
income countries. For fixed- effect inverse variance meta-analyses we assessed differences
between subgroups by interaction tests. For fixed-effect meta-anal- yses using methods
other than inverse variance, we assessed dif- ferences between subgroups by inspection of
the CIs of the sub- groups: non-overlapping CIs indicate a statistically significant dif-
ference in treatment effect between the subgroups.
Sensitivity analysis
We performed sensitivity analyses based on aspects of the review that may have affected
the results; for example, the impact of in- cluding trials at high or unclear risk of bias forTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 29
incomplete out- come data domain. We also carried out a sensitivity analysis to ex- plore
the inclusion of the effects of fixed-effect or random-effects analysis for outcomes with
statistical heterogeneity.
RESULTS
Description of studies
Results of the search
We searched the available literature up to 23 July 2016 and re- trieved a total of 110
references, of which we screened 80 after we removed duplicates. Of these, we initially
screened the full-text articles of 20 references. Seven published trials met our inclusion
criteria (Colli 1997; Heikkinen 1989; Mengel 1989; Moi 1989; Swedberg 1985; Vejtorp
1988; Vutyavanich 1993). We excluded 12 studies (see the ’Characteristics of excluded
studies’ table) and one trial is currently recruiting participants (see the ’Characteristics of
ongoing studies’ table). We have presented a PRISMA diagram in Figure 1 to illustrate the
study selection process.
Included studies
The seven included trials had a total of 1026 participants and sample sizes ranged from 82
to 250 participants. These trials were from Denmark (Vejtorp 1988), Finland (Heikkinen
1989), Italy (Colli 1997), Thailand (Vutyavanich 1993), the USA (Mengel 1989; Swedberg
1985), and one trial involved the participation of institutions located in four Nordic
countries namely Denmark, Finland, Norway and Sweden (Moi 1989). Three trials were
mul- ticentric (Colli 1997; Mengel 1989; Moi 1989), only one trial im- plemented a valid
method for sample size calculation (Colli 1997), and all trials included outpatients and were
published in English.
Population
The included studies recruited sexually-active non-pregnant women between 17 and 56
years of age, either single or married, with symptomatic BV. Four studies only included
women who were involved into a monogamous heterosexual relationship (Colli 1997;
Mengel 1989; Moi 1989; Vutyavanich 1993), and there was no information about this for
the remaining trials (Heikkinen 1989; Swedberg 1985; Vejtorp 1988). All included trials
used the Amsel’s criteria to diagnose the presence of the condition and re- quired the
discovery of at least three of these four criteria, in the absence of clinical evidence of
mucopurulent cervicitis, trichomo- niasis, genital herpes, papilloma virus or candidiasis.
The included studies excluded participants with a recent history of systemic or topical
antibiotic treatment for other condition different to bac- terial vaginosis (BV). There were
no restrictions regarding the concurrent use of con- traceptive methods during the treatment
period, except for Colli 1997, which excluded barrier method users. Four studies specified
the contraceptive method at entry (Heikkinen 1989; Moi 1989; Vejtorp 1988; Vutyavanich30
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
1993), and the most frequently used was the birth control pill, followed by intrauterine
device, tubal resection and the condom. Two trials allowed sexual activity dur- ing the
study (Moi 1989; Vutyavanich 1993), while Colli 1997 invited the participants to abstain.
The remaining included trials did not mentioned whether sexual intercourse allowed or
advised against. Finally, most women were treated with 5-nitroimidazoles, namely the most
commonly prescribed metronidazole (Mengel 1989; Moi 1989; Swedberg 1985; Vejtorp
1988), followed by tinidazole (Heikkinen 1989; Vutyavanich 1993). One study used
clindamycin cream at bed time (Colli 1997).
Interventions
All included trials used the oral route to provide the sexual partner’s treatment. The most
frequently reported intervention was the use of 5-nitroimidazoles in six studies (Heikkinen
1989; Mengel 1989; Moi 1989; Swedberg 1985; Vejtorp 1988; Vutyavanich 1993). Four of
these trials used metronidazole as treatment (Mengel 1989; Moi 1989; Swedberg 1985;
Vejtorp 1988), while two trials used tinidazole (Heikkinen 1989; Vutyavanich 1993). Only
one study used a lincosamide for treatment (Colli 1997).
The schemes used for metronidazole included 2 g as a single dose (Mengel 1989; Swedberg
1985), 2 g on day one and day three (Moi 1989; Vejtorp 1988), and 500 mg twice daily for
seven days (Swedberg 1985). The included studies that used tinidazole gave a 2 g single
dose (Vutyavanich 1993), or 1 g for four days (Heikkinen 1989). One study provided
clindamycin 150 mg four times daily for seven consecutive days (Colli 1997). None of the
included trials assessed the effectiveness of other antibiotic treatments occasionally
prescribed in clinical practice, such as aminopenicillins and macrolides.
Comparisons
Five trials used placebo (Colli 1997; Mengel 1989; Moi 1989; Vejtorp 1988; Vutyavanich
1993). Two trials compared the effec- tiveness of concurrent antibiotic treatment for the
sexual partners with no intervention (Heikkinen 1989; Swedberg 1985).
Outcomes
None of the primary or secondary outcomes were reported by the totality of the retrieved
clinical trials and there were some differ- ences in reporting and definition of the outcomes
between trials. Four included studies reported recurrence (Colli 1997; Heikkinen 1989; Moi
1989; Vejtorp 1988), and their presence was estab- lished based on the application of
Amsel criteria on healthy par- ticipants following treatment for BV, with the exception of
Moi 1989, which also required the reappearance of symptoms. Only one study assessed this
outcome between the first and fourth week (Moi 1989), and the other three studies assessed
for this outcome posterior to the fourth week.
Seven studies reported clinical improvement after treatment (Colli 1997; Heikkinen 1989;
Mengel 1989; Moi 1989; Swedberg 1985; Vejtorp 1988; Vutyavanich 1993), and used the
definition of the absence of Amsel’s criteria through physical exam plus wet mount. FourTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 31
trials assessed clinical improvement at the first week (Colli 1997; Moi 1989; Vejtorp 1988;
Vutyavanich 1993), five trials assessed this outcome between the first and fourth week
(Colli 1997; Heikkinen 1989; Moi 1989; Swedberg 1985; Vutyavanich 1993), and four
trials assessed it after the fourth week (Colli 1997; Mengel 1989; Moi 1989; Vejtorp 1988).
On the other hand, four studies monitored symptomatic improvement (Heikkinen 1989;
Moi 1989; Vejtorp 1988; Vutyavanich 1993). Three trials evaluated symptomatic
improvement at the first week (Moi 1989; Vejtorp 1988; Vutyavanich 1993), two trials
assessed it between the first and fourth week (Moi 1989; Vutyavanich 1993), and three
trials reported it after the fourth week (Heikkinen 1989; Moi 1989; Vejtorp 1988).
Finally, three trials reported the frequency of minor adverse events during treatment. Two
of them captured the information through symptoms reported by participants (Colli 1997;
Vutyavanich 1993), and the other trial used a questionnaire (Mengel 1989). The minor side
effects reported in sexual partners of women treated for BV were the presence of nausea,
stomachache, metallic taste and dizziness. We did not obtain any data on the secondary
outcomes serious adverse events and cost-effectiveness of the intervention.
Length of follow-up
There were some differences in length of follow-up between the included studies, which
followed participants for either three (Swedberg 1985), four (Vutyavanich 1993), five
(Vejtorp 1988), eight (Mengel 1989) or 12 weeks (Moi 1989; Colli 1997; Heikkinen 1989).
Excluded studies
We excluded 13 studies for the following reasons: 10 studies were not RCTs or did not
provide a comparison group (all sexual part- ners were treated) and two studies did not
provide a valid interven- tion (the sexual partners did not received antibiotic treatment or
not all women were treated) (see the ’Characteristics of excluded studies’ table). One trial
is currently recruiting participants (see the ’Characteristics of ongoing studies’ table).
Risk of bias in included studies
We have summarized the ’Risk of bias’ assessment in Figure 2 and Figure 3. Also, we
provided additional details of the included trials in the ’Characteristics of included studies’
tables.
Allocation
Random sequence generation (checking for possible selection bias)
Four trials adequately reported the random sequence generation method by using a
computer-generated randomisation list, so that selection bias at entry was low (Mengel
1989; Swedberg 1985; Vejtorp 1988; Vutyavanich 1993). The remaining included trials did
not report the random sequence generation methods, and the risk of selection bias at entry
was unclear (Colli 1997; Heikkinen 1989; Moi 1989).
Allocation concealment (checking for possible selection bias)32
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Two trials adequately implemented a valid allocation concealment method using
sequentially numbered drugs containers (Mengel 1989), or by pharmacy-controlled
allocation (Swedberg 1985); thus the risk of selection bias at entry in these trials was low.
The five remaining included trials did not report the method used to conceal allocation to
interventions prior to assignment, and the risk of selection bias at entry was unclear (Colli
1997; Heikkinen 1989; Moi 1989; Vejtorp 1988; Vutyavanich 1993).
Blinding
Five trials used placebo for the control group to blind trial par- ticipants and personnel, and
we judged the risk of performance bias as low (Colli 1997; Mengel 1989; Moi 1989;
Vejtorp 1988; Vutyavanich 1993). The trial authors assessed two outcomes, re- currence
and clinical improvement objectively, in contrast with other outcomes, such as
symptomatic improvement and side ef- fects pain, which were subjectively evaluated.
However, we judged that the blinding of the outcome assessors from knowledge of which
intervention each participant received prevented the risk of detection bias.
The remaining two trials compared the concurrent use of antibi- otic treatment with no
intervention (Heikkinen 1989; Swedberg 1985). Swedberg 1985 was unblinded to
personnel and trial par- ticipants and was at high risk of performance bias. However, we
appraised the outcome clinical improvement as at low risk of de- tection bias. This is
because it was objectively assessed with Amsel’s criteria, and lack of blinding of the
outcome assessor was unlikely to affect the results. We considered Heikkinen 1989 as at
high risk of performance and detection bias because was unblinded to per- sonnel and trial
participants. Also, the outcomes recurrence and symptomatic improvement were
subjectively assessed and lack of blinding of the outcome assessor was likely to affect the
results. The trial authors objectively assessed the outcome of clinical cure through Amsel’s
criteria, which made detection bias unlikely for this outcome.
Incomplete outcome data
Three trials appropriately stated the attrition and exclusions at each stage and the reasons
were balanced across groups (Mengel 1989; Vejtorp 1988; Vutyavanich 1993). In addition,
the level of missing data was not over 20% and the attrition or exclusion probably was
unrelated to the outcomes, which made attrition bias unlikely.
We assessed two trials as at unclear risk of bias (Colli 1997; Moi 1989). In Colli 1997, we
judged the outcomes of clinical cure at 1, 4 and 12 weeks and gastrointestinal symptoms as
at low risk of bias (e.g. no missing outcome data; missing outcome data balanced across
groups). However, we assessed the outcome of recurrence as at high risk of bias because
the level of missing data was over 20%. Something similar occurred with Moi 1989, where
we judged the outcomes of symptomatic improvement and clinical cure at the first and
fourth week as at low risk of bias (e.g. no missing outcome data; missing outcome data
balanced across groups). However, for the same outcomes at 12 weeks, the risk of bias was
high according to the level of missing data (greater than 20%).Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 33
Two trials had missing data greater that 20% and did not state the reasons why (Heikkinen
1989; Swedberg 1985); the trial authors conducted the analyses only for those participants
who were com- pletely treated (per protocol analysis). We assessed these trials as at high
risk of bias.
Selective reporting
The trial protocol was unavailable for each of the included trials (Colli 1997; Heikkinen
1989; Mengel 1989; Moi 1989; Swedberg 1985; Vejtorp 1988; Vutyavanich 1993). It is
unclear whether or not the published reports included all the expected outcomes, including
those that were prespecified. The report had insufficient information to permit judgment of
“yes” or “no”, and we rated this factor as at unclear risk of bias in each of the included
trials.
Other potential sources of bias
Pharmaceutical companies funded four trials (Heikkinen 1989; Moi 1989; Swedberg 1985;
Vejtorp 1988), and academic insti- tutions sponsored two trials (Mengel 1989; Vutyavanich
1993). One trial did not mention the funding sources (Colli 1997). We judged one trial,
Mengel 1989, as at high risk of bias because of the nature and direction of their results. The
remaining studies appeared to be free from other sources of bias.
Effects of interventions
See: Summary of findings for the main comparison Any antibiotic treatment versus
placebo; Summary of findings 2 Any antibiotic treatment versus no intervention;
Summary of findings 3 Any antibiotic treatment versus placebo
1. Any antibiotic treatment versus placebo
Five trials ( Colli 1997; Mengel 1989; Moi 1989; Vejtorp 1988; Vutyavanich 1993)
including 854 participants compared any an- tibiotic treatment versus placebo. They did not
all contribute data to each outcome.
1.1. Recurrence of BV between the first and fourth week
Only one trial reported on this outcome (Moi 1989). There was no evidence of significant
difference between antibiotic treatment and placebo in the recurrence between first and
fourth week of treatment (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study;
Analysis 1.1). The quality of evidence was low due to the limitations of imprecision.
1.2. Recurrence of BV after the fourth week
The results correspond to the meta-analysis of three trials (Colli 1997; Moi 1989; Vejtorp
1988). There was no evidence of sig- nificant difference between antibiotic treatment and
placebo in recurrence of BV after the fourth week of treatment (RR 1.00, 95% CI 0.67 to
1.52; 372 participants, three studies; I2 statistic = 17%; Analysis 1.2; Figure 4). The quality
of the evidence was very low due to the limitations of imprecision.34
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
1.3. Clinical improvement during the first week
The results correspond to the meta-analysis of four trials (Colli 1997; Moi 1989; Vejtorp
1988; Vutyavanich 1993). There was no evidence of significant difference in clinical
improvement during the first week (RR 0.99, 95% CI 0.96 to 1.03; 712 participants, four
studies; I2 statistic = 14%; Analysis 1.3; Figure 5). The quality of the evidence was high.
1.4. Clinical improvement between the first and fourth week
The results correspond to the meta-analysis of three trials (Colli 1997; Moi 1989;
Vutyavanich 1993). There was no evidence of significant difference in clinical
improvement between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590
participants, three studies; I2 statistic = 31%; Analysis 1.4; Figure 6). The quality of the
evidence was high.
1.5. Clinical improvement after the fourth week
The results correspond to the meta-analysis of four trials (Colli 1997; Moi 1989; Vejtorp
1988; Mengel 1989). There was no evidence of significant difference in clinical
improvement after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four
studies; I2 statistic = 0%; Analysis 1.5; Figure 7). The quality of the evidence was high.
1.6. Symptomatic improvement during the first week
The results correspond to the meta-analysis of three trials (Moi 1989; Vejtorp 1988;
Vutyavanich 1993). Antibiotic treatment was not associated with a significant symptomatic
improvement during the first week (RR 1.06, 95% CI 1.00 to 1.12; 577 participants, three
studies; I2 statistic = 0%; Analysis 1.6; Figure 8). The quality of the evidence was high.
1.7. Symptomatic improvement between the first and fourth week
Two trials informed this outcome (Moi 1989; Vutyavanich 1993). There was no evidence
of significant difference in this outcome (RR 0.93, 95% CI 0.84 to 1.03; 444 participants,
two studies; I2 statistic = 0%; Analysis 1.7). The quality of the evidence was high.
1.8. Symptomatic improvement after the fourth week
Two trials informed this outcome (Moi 1989; Vejtorp 1988). There was no evidence of
significant difference in this outcome (RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two
studies; I2 statistic = 0%; Analysis 1.8). The quality of the evidence was high.
1.9. Minor adverse events during therapy in the sexual partner
The results correspond to the meta-analysis of three trials (Colli 1997; Mengel 1989;
Vutyavanich 1993). Antibiotic treatment was associated with a significant minor adverse
events report during therapy in sexual partner (RR 2.55, 95% CI 1.55 to 4.18; 477Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 35
participants, three studies; I2 statistic = 0%; Analysis 1.9; Figure 9). The quality of the
evidence was low due to the limitations of imprecision.
2. Any antibiotic treatment versus no intervention
Two trials including 172 participants compared the effectiveness of concurrent antibiotic
treatment for the sexual partners with no intervention.
2.1. Recurrence of BV after the fourth week
One trial informed this outcome (Heikkinen 1989). There was no evidence of statistically
significance difference in recurrence of BV after the fourth week (RR 1.71, 95% CI 0.65 to
4.55; 51 participants, one study; Analysis 2.1). The quality of the evidence was very low
due to the limitations of imprecision, blinding and incomplete outcome data domains.
2.2. Clinical improvement between the first and fourth week
Two trials informed this outcome (Heikkinen 1989; Swedberg 1985) There was no
evidence of statistically significance differ- ence in this outcome (RR 0.93, 95% CI 0.70 to
1.25; 152 partic- ipants, two studies; I2 statistic = 62%; Analysis 2.2). The quality of the
evidence was very low due to the limitations of imprecision, substantial heterogeneity,
blinding and incomplete outcome data domains.
2.3. Symptomatic improvement after the fourth week
One trial informed this outcome (Heikkinen 1989). There was no evidence of statistically
significance difference in symptomatic improvement after the fourth week (RR 0.66, 95%
CI 0.39 to 1.11; 70 participants, one study; Analysis 2.3). The quality of the evidence was
very low due to the limitations of imprecision, blinding and incomplete outcome data
domains.
Subgroup analysis and investigation of heterogeneity
We performed subgroup analyses to explore the heterogeneity sources that we found in the
analyses of “recurrence” for the com- parison antibiotic versus placebo. For this analysis
we explored whether differences by antibiotic type (5-Nitroimidazoles versus
Lincosamides) reduced the heterogeneity in the overall effect size. The tests for subgroup
effect were not significantly different when we explored heterogeneity source by antibiotic
type (assessed after the fourth week, P = 0.16, Analysis 3.1). We did not perform sub-
group analysis by antibiotic doses (single versus multiple), because the included trials did
not provide enough information for this outcome.
In the analyses of “clinical improvement” for the comparison an- tibiotic versus placebo,
neither of the tests for subgroup effect showed evidence of statistically significant
differences, analysing by antibiotic type (assessed during first week, P = 0.53, Analysis
3.2; between the first and fourth week, P = 0.53, Analysis 3.3; and after the fourth week, P
= 0.92, Analysis 3.4) or by antibiotic doses (assessed during first week, P = 0.18, Analysis36
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
4.1; between the first and fourth week, P = 0.12, Analysis 4.2; and after the fourth week, P
= 0.76, Analysis 4.3). The effects of the intervention for these outcomes did not change
according to the intervention char- acteristics.
In the analyses of “symptomatic improvement” for the comparison antibiotic versus
placebo, neither of the tests for subgroup effect showed evidence of statistically significant
differences, analysing by antibiotic doses (assessed during first week, P = 0.29, Analysis
4.4; and between the first and fourth week, P = 0.71, Analysis 4.5). We did not perform
subgroup analysis by antibiotic type because the included trials did not provide the required
information for these analyses. However, for the analyses “minor adverse events during
therapy” for the same comparison, neither of the tests for subgroup effect showed evidence
of statistically significant differ- ences, analysing by antibiotic type (P = 0.49, Analysis 3.5)
or by dose (P = 0.49, Analysis 4.6).
We did not perform the subgroup analysis according to kind of relationship, because not all
of the included trials, provided enough information on these basal conditions. Finally we
neither analysed by income classifications (low- versus high-income) because all retrieved
studies were performed in a high-income country.
Sensitivity analysis
We explored the impact of including trials at high or unclear risk of bias for incomplete
outcome data domain in the overall assess- ment of treatment effects. For the comparison
antibiotic treatment versus placebo, neither of the test effects showed evidence of sta-
tistically significant differences regardless of the outcome assessed (recurrence, clinical or
symptomatic improvement and minor ad- verse events) or the period of time during which
it was measured (during the first, between the first and fourth or after the fourth week).
In this sense, we observed the following results for low risk studies. • Recurrence after the
fourth week (RR 0.96, 95% CI 0.48 to 1.92; 98 participants, one study; Vejtorp 1988) •
Clinical improvement during first week (RR 0.99, 95% CI 0.93 to 1.05; 242 participants,
two studies; I2 statistic = 66%; Vejtorp 1988; Vutyavanich 1993); between the first and
fourth week (RR 1.13, 95% CI 0.95 to 1.35; 233 participants, one study; Vutyavanich
1993); and after the fourth week (RR 1.03, 95% CI 0.90 to 1.17; 243 participants, two
studies; I2 statistic = 0%; Mengel 1989; Vejtorp 1988).
• Symptomatic improvement during first week (RR 1.06, 95% CI 0.98 to 1.14; 348
participants, two studies; I2 statistic = 40%; Vejtorp 1988; Vutyavanich 1993); between the
first and fourth week (RR 0.95, 95% CI 0.83 to 1.08; 232 participants, one study;
Vutyavanich 1993); and after the fourth week (RR 1.03, 95% CI 0.83 to 1.29; 107
participants, one study; Vejtorp 1988 ).
• Minor adverse events of the intervention during therapy (RR 2.76, 95% CI 1.60 to 4.77;
339 participants, two studies; I2 statistic = 0%, Mengel 1989; Vutyavanich 1993).Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 37
We did not perform a sensitivity analysis for the comparison of antibiotic versus no
intervention, because we assessed all of the included trials as at high risk of bias for
incomplete outcome data domain.
DISCUSSION
Summary of main results
Seven RCTs (1026 participants) met our inclusion criteria of this review, and industry
funded four of these trials. Five trials (854 patients) compared any antibiotic treatment for
the treatment of sexual partners with placebo. Based on high quality evidence an- tibiotic
treatment does not increase the rate of clinical or symp- tomatic improvement in women
during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712
partic- ipants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies,
respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590
participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies;
respec- tively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants,
four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively).
Antibiotic treatment does not led to a lower recurrence rate during the first and fourth week
(RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after
the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies;
low quality evidence) in women, but increases the frequency of adverse events (most
frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to
4.18; 477 participants, three studies; low-certainty evidence) see the ’Summary of findings’
ta- bles Summary of findings for the main comparison; Summary of findings 2; Summary
of findings 3.
Two trials (172 participants) compared any antibiotic treatment for the sexual partners with
no intervention. When we compared it with no intervention, the effects of antibiotic
treatment on re- currence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51
participants, one study), clinical improvement between the first and fourth week (RR 0.93,
95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the
fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and
there were no differences between groups. We downgraded the quality of the evidence to
low or very low.
Overall completeness and applicability of evidence
We conducted a comprehensive search to retrieve all published and unpublished RCTs. We
were able to evaluate all primary outcomes except for serious adverse events and the
secondary outcome of cost effectiveness of the intervention that were not reported in any38
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
trial. The applicability of the evidence into the target population (the sexual partners of
women treated for non-recurrent bacte- rial vaginosis (BV)) is broad because the retrieved
trials were con- ducted in different clinical settings. In this sense, the result of this
systematic review can be applied into clinical practice regardless of the marital status, the
form of relationship (monogamous or not), the concurrent use of contraceptive methods or
the frequency of sexual intercourse during the treatment. On the other hand, the
interventions analysed in the review encompass multiple clinical scenarios that are common
in current practice: various antibiotic regimens including 5-nitroimidazoles and
lincosamides with dif- ferent schemes single dose, and treatments from two to seven days.
Finally, because the included studies only assessed the safety and effectiveness of the
intervention for heterosexual relationships, the results should not be extrapolated to a
different population.
Quality of the evidence
We considered five of the seven included trials to be at low risk of bias. These studies
corresponded to the comparison of any antibi- otic treatment versus placebo, and
consequently with high confi- dence on the effect estimate for most outcomes. However,
for the comparison any antibiotic treatment versus non-intervention, the confidence on the
effect estimate was very low due to trial limita- tions (lack of blinding and incomplete
outcome data), inconsis- tency (unexplained variability in some results) and some
imprecise results (few participants and outcome events with wide CIs). We could not
evaluate publication bias, because there were too few in- cluded trials into each comparison
(see the ’Summary of findings’ tables: Summary of findings for the main comparison;
Summary of findings 2; Summary of findings 3).
Potential biases in the review process
This systematic review has many strengths regarding the review process: we adhered to the
predefined objectives and study eligi- bility criteria; our literature search included an
appropriate range of databases and sources, including relevant additional methods to
identify relevant reports and retrieve as many eligible studies as possible; and we assessed
all studies adequately for risk of bias. Two authors performed data extraction
independently. However, we have some concerns about publication bias. Publication bias is
a possibility because the included trials were mostly funded by industry and due to the
limited number of trials for each comparison.
Agreements and disagreements with other studies or reviews
There are two previous systematic reviews published on this topic (Mehta 2012; Potter
1999). Our review includes one study that the previous two reviews did not include
(Heikkinen 1989). The authors of those reviews considered that a meta-analysis could notTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 39
be conducted due to significant risk of bias in the retrieved studies and by some limitations
about heterogeneity; however, these were not a limiting issue for a meta-analysis. Also, as
we have shown, the included studies (particularly for the antibiotic treatment versus
placebo comparison) are of high quality, there is no significant heterogeneity and we have
presented the meta-analyses.
Our conclusions, about the lack of benefit following sexual partner treatment, agree with
the recommendation of some important guidelines where this is not recommended
(Workowski 2015; van Schalkwyk 2015). However, these recommendations were not
based on a systematic and explicit approach.
AUTHORS’ CONCLUSIONS
Implications for practice
Given the high quality evidence for most outcomes we assessed in this Cochrane Review,
there is no benefit of antibiotic treatment compared with placebo for sexual partners of
women with BV. Also, there is no increase in the rate of clinical or symptomatic
improvement during the first, between the first and fourth or after the fourth week of
treatment into the women. There is still some uncertainty due to the low quality of
evidence, which suggests that antibiotic treatment does not led to a lower recurrence rate
during the first and fourth or after the fourth week of treatment into the women, but
increases the frequency of adverse events reported by sexual partners.
Implications for research
Due to the high quality of evidence for most included outcomes in this Cochrane Review,
future studies that evaluate the same outcomes will probably not change our conclusions.
However, there is a need for high-quality RCTs that assess recurrence rate adequately,
treatment of female partners, treatment for pregnant patients, use of other antibiotic
treatments occasionally prescribed in clinical practice such as aminopenicillins and
macrolides, and cost effectiveness of interventions. Therefore, study authors should focus
their investigations on these problems in the future.
ACKNOWLEDGEMENTS
As part of the prepublication editorial process, three peers (an ed- itor and two referees who
were external to the editorial team), a member of the Sexually Transmitted Infection
Group’s interna- tional panel of consumers and the Group’s Statistical Adviser com-
mented on the review draft.
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infections of the genital tract. [Gui a de pra ctica clinica para el manejo sindro mico de los pacientes con
infecciones de transmision sexual y otras infecciones del tracto genital].
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23/07/2015.
Mirmonsef 2012
Mirmonsef P, Krass L, Landay A, Spear GT. The role of bacterial vaginosis and trichomonas in HIV
transmission across the female genital tract. Current HIV Research 2012; 10(3):202–10.
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Morris MC, Rogers PA, Kinghorn GR. Is bacterial vaginosis a sexually transmitted infection?. Sexually
Transmitted Infections 2001;77(1):63–8. [PUBMED: 11158694]
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Mylonas I, Bergauer F. Diagnosis of vaginal discharge by wet mount microscopy: a simple and
underrated method. Obstetrical & Gynecological Survey 2011;66(6):359–68.
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Nelson DE, Dong Q, Van der Pol B, Toh E, Fan B, Katz BP, et al. Bacterial communities of the coronal
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Oduyebo 2009
Oduyebo OO, Anorlu RI, Ogunsola FT. The effects of antimicrobial therapy on bacterial vaginosis in
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Zuckerman JM, Qamar F, Bono BR. Review of macrolides (azithromycin, clarithromycin), ketolids
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Ángel-Müller E, Rodríguez A, Núñez-Forero LM, Moyano LF, González P, Osorio E, et al. TheTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 47
prevalence of and factors associated with C. trachomatis, N. gonorrheae, T. vaginalis, C. albicans
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Characteristics of studies
Characteristics of included studies
Colli 1997
Methods Setting: Italy, outpatient clinic.
Trial design: multicentre randomized clinical trial, parallel, 2 arms.
Funding sources: not mentioned.
Ethical issues: ethical board and signed consent.
Participants Age of participants: from 18 to 45 years.
Inclusion criteria: sexually-active women with 1 current sexual partner.
Clinical diagnosis of bacterial vaginosis (BV and whose partner agreed to
be treated. The study authors defined BV as the presence of clue cells on a
wet mount slide plus at least 2 of the following.
• Vaginal discharge with pH greater than 4.5.
• Increased thin homogeneous vaginal discharge that adheres to
vaginal walls.
• Release of amine odour from a simple of the discharge after
addition of 10% KOH.
Exclusion criteria: patients treated with systemic or topical antibacterial
agents in the 2 weeks before diagnosis of BV; use of intrauterine device or
condom; clinical evidence of mucopurulent cervicitis, candidiasis,
trichomoniasis, herpes genitalis, papilloma virus, Chlamydia
trachomatis, or Neisseria gonorrhoeae infection.
Population48
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Number of participants: 139 women, 139 men.
Baseline characteristics: sexually-active women with 1 current sexual
partner. Women were treated with clindamycin 2% cream, administered
intravaginally at bed time for 7 days. Participants were invited to abstain
from intercourse during the treatment period and for 1 week after the end
of treatment. Most participant couples were married (intervention 66%
versus placebo 75%), did not use contraception method (intervention 66%
versus placebo 63%) and lacked a previous history of pelvic infection
(intervention 79% versus placebo 68%) or male urethritis (intervention
98% versus placebo 95%).
Interventions Total number of intervention groups: Two groups.
Intervention: clindamycin hydrochloride capsules, 150 mg by mouth 4
times daily for 7 consecutive days.
Comparison: placebo.
Outcomes The trial included evaluation at 1, 4 and 12 weeks after the start of
treatment. The participants and their partners had a clinical examination,
including the collection of samples of vaginal discharge to check for clue
cells, the determination of vaginal pH, and a KOH test. At both visits,
the participant and her partner were asked about medication side effects.
The study authors defined cure as the absence of clue cells plus at least 2
of the following: vaginal pH less than 4.5; negative 10% KOH sniff test or
grossly normal vaginal discharge (defined as translucent white, flocculent,
low volume). The study authors defined recurrence as participants
previously healthy after treatment that developed a new episode of BV
(Amsel criteria). Participants reported adverse events as symptoms.
Notes
None
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence Unclear risk “…This was a double blind,
generation (selection bias) randomised, controlled trial…”
Comment: there was insufficient
information to enable us to make a
judgement.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 49
Allocation concealment Unclear risk Comment: there was insufficient
(selection bias) information to enable us to make a
judgement.
Blinding of participants Low risk The trial authors did not adequately
and personnel report the method implemented to
(performance bias) blind study participants and
personnel from knowledge of which
intervention a participant received.
"The clinicians were blind to the
study treatment…”
Comment: this was probably done.
Blinding of outcome Unclear risk The trial authors did not adequately
assessment (detection report the method implemented to
bias) blind outcome assessment from
knowledge of which intervention a
participant received. Comment:
there was insufficient information to
enable us to make a judgement.
Incomplete outcome data Unclear risk For the outcomes clinical cure at 1,
(attrition bias) 4 and 12 weeks and gastrointestinal
symptoms the risk of bias was low
(e.g. no missing outcome data;
missing outcome data was balanced
across groups). However, for the
outcome recurrence, the risk of bias
was high according to the level of
missing data (greater than 20%).
Selective reporting Unclear risk The report did not have sufficient
(reporting bias) information to permit a judgment of
“yes” or “no”.
Other bias Low risk This study appeared to be free of
other sources of bias.
Heikkinen 1989
Methods Setting: Finland, outpatient of primary care.
Trial design: single randomized clinical trial, parallel, 2 arms.
Funding sources: Orion pharmaceutical.
Ethical issues: not mentioned.50
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Participants Age of participants: from 19 to 53 years.
Inclusion criteria: women with malodorous vaginal discharge and
anaerobic vaginosis, which was based on the identification of clue cells
in the PAP smear, pH of the vaginal discharge (greater than 4.5) and a
positive amine test.
Screening negative for Neisseria gonorrhoea, Chlamydia trachomatis,
Candida albicans and Trichomonas vaginalis.
Exclusion criteria: presence of N. gonorrhoea, C. trachomatis, C.
albicans or T. vaginalis.
Population
Number of participants: 90 women, 90 men.
Baseline characteristics: the women were treated with oral tinidazole
500 mg twice a day for 4 days or oral tinidazole 150 mg twice a day for
7 days or intravaginal tinidazole 500 mg at bedtime for 14 days. The
trial authors did not provide any more information.
Interventions Total number of intervention groups:Two groups.
Intervention: oral tinidazol 1 g for 4 days.
Control: no treatment.
Outcomes The trial included evaluation at 1 and 3 months after the start of
treatment. Women had a clinical examination, including the collection
of PAP smear to check for clue cells, the determination of vaginal pH,
and a KOH test.
Cure was defined as the absence of symptoms of BV or absence of
clinically verified BV (Amsell criteria)
Relapse was defined as patients who were asymptomatic after treatment
and again developed symptoms of BV. Adverse events were not
reported.
Notes
None
Risk of bias tableTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 51
Bias Authors' judgement Support for judgement
Random sequence Unclear risk "Prospective randomised trial"
generation (selection bias)
Comment: there was
insufficient information to
enable us to make a judgement.
Allocation concealment Unclear risk Comment: there was
(selection bias) insufficient information to
enable us to make a judgement.
Blinding of participants High risk There was no blinding or
and personnel incomplete blinding, and the
(performance bias) outcome or outcome
measurement was likely to be
influenced by a lack of
blinding.
Blinding of outcome High risk There was no blinding or
assessment (detection incomplete blinding, and the
bias) outcome or outcome
measurement was likely to be
influenced by a lack of
blinding. The outcomes
symptomatic of improvement
and relapse were subjectively
assessed and the lack of
blinding could have affected
the results. The outcome of
clinical cure was assessed
objectively and the lack of
blinding could not have
affected the results.
Incomplete outcome data High risk We judged the risk of bias as
(attrition bias) high for all outcomes according
to the level of missing data
(greater than 20%). For Group
A, 7 participants were lost to
follow-up. In Group B 6
participants dropped out and in
Group C 4 participants
discontinued the trial.
Selective reporting Unclear risk The report had insufficient
(reporting bias) information to permit judgment
of “yes” or “no”.52
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Other bias Low risk Industry sponsored this trial.
However, because the result
were not positive, the study
would be free of other sources
of bias.
Mengel 1989
Methods Setting: USA, outpatient of primary care.
Trial design: multicentric randomized clinical trial, parallel, 2 arms.
Funding sources: grants from the research committee, American
Academy of Familiy Physicians; Family Health Foundation of America;
Washington Academy of Family Physicians, and the Washington
Familiy Health Foundation.
Ethical issues: ethical board and signed consent.
Participants Age of participants: from 18 to 40 years.
Inclusion criteria: women with vaginal discharge fulfilled 3 of the 4
Amsel criteria. Participants were required to have a telephone and only
1 current sexual partner.
Exclusion criteria: pregnant or menopausal; had used antibiotics or
vaginal medication in the previous month; clinical evidence of a
mucopurulent cervical discharge or genital herpes, or had T. vaginalis or
C. albicans on wet mounts or KOH preparation of their vaginal
discharge; contraindications to metronidazole; history of seizure
disorder, peripheral neuropathy, cancer or liver disease; prescription
with warfarin, phenytoin or phenobarbital.
Population
Number of participants: 161 women, 98 men
Baseline characteristics: sexually-active women with 1 current sexual
partner. Women were treated with metronidazole 500 mg twice a day
for 7 days or 2 g single doses. Participants were not invited to abstain
from intercourse during the treatment period. The participants included
single and married couples, nulliparous and multiparous women. MostTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 53
participant couples used a contraception method, and lacked a previous
history of pelvic infection and male urethritis.
Interventions Total number of intervention groups: Two groups.
Intervention: 2 g metronidazole oral single dose.
Comparison: placebo.
Outcomes The trial included evaluations at 2 and 8 weeks after the onset of the
treatment. Women had a clinical examination, including the collection
of samples of vaginal discharge to check for clue cells, gram staining
and KOH test; sexual partners were contacted by phone for instructions.
At the follow-up visits participants completed a questionnaire on
symptoms and medication side effects, and underwent a pelvic
examination.
The trial authors defined cure as the absence of at least 3 of the 4 Amsell
criteria. They did not define recurrence. Participants reported adverse
events as symptoms of BV.
Notes
None
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence Low risk "Randomization was
generation (selection bias) accomplished by blocks of
varying sizes (4, 8 or 12) so
that an equal number of women
in each block entered each of
the four treatment groups".
Comment: this was probably
done.
Allocation concealment Low risk "Randomization was
(selection bias) accomplished by blocks of
varying sizes (4, 8 or 12) so
that an equal number of women
in each block entered each of
the four treatment groups"
Comment: this was probably
done. We considered that the
authors implemented a valid54
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
randomized method which
implies that the allocation
concealment was probably
through the use of
consecutively numbered sealed
opaque envelopes.
Blinding of participants Low risk “placebo was used to ensure
and personnel that both subjects and
(performance bias) physicians did not know the
subject's treatment”
"metronidazole was identically
coloured and shaped to
placebo".
Comment: this was probably
done.
Blinding of outcome Low risk “placebo was used to ensure
assessment (detection that both subjects and
bias) physicians did not know the
subject's treatment”
"metronidazole was identically
coloured and shaped to
placebo". The outcomes of cure
rate and side effect were
objectively assessed. Comment:
this was probably done.
Incomplete outcome data Low risk 20% or fewer participants were
(attrition bias) excluded and also intention to
treat analyses was reported.
Selective reporting Unclear risk The report had insufficient
(reporting bias) information to permit a
judgment of “yes” or “no”.
Other bias High risk This trial was supported by
grants from the research
committee, American Academy
of Family Physicians; Family
Health Foundation of America;
Washington Academy of
Family Physicians, and the
Washington Family Health
Foundation.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 55
Moi 1989
Methods Setting: Sweden, Denmark, Finland and Norway. Outpatient clinic.
Trial design: multicentric randomized clinical trial, parallel, 2 arms.
Funding sources: grants from Rhone-Paulenc Pharma Norden AS and
Örebro County Council Research Committee.
Ethical issues: ethical board and signed consent.
Participants Age of participants: from 17 to 56 years.
Inclusion criteria: non-pregnant sexually-active women with 3 of the
4 Amsel criteria. Women had 1 male consort with whom they had
sexual intercourse without using a condom, at least once a week during
the study period.
Exclusion criteria: pregnancy or lactation; haematological or
neurological disease; history of allergy to metronidazole; antibiotic
treatment in the preceding week.
Population
Number of participants: 241 women: 241 men
Baseline characteristics: women were treated with 2 g metronidazole
on days 1 and 3. A few of the men were circumcized. Participants were
not invited to abstain from intercourse during the treatment period.
Women had 1 male consort with whom they had sexual intercourse
without using a condom. The most frequently used contraception
method was oral contraceptives or IUCD.
Interventions Total number of intervention groups: Two groups.
Intervention: oral metronidazole 2 g, that was repeated 2 days later.
Comparison: placebo.
Outcomes The triaI included evaluation at 1, 4, and 12 weeks after starting
treatment. The trial asked participants about symptoms of BV and had a
clinical examination including collection of samples of vaginal
discharge to check for odour of the discharge, vaginal pH, KOH test and
wetness of the vaginal discharge. The trial authors defined cure as the
disappearance of at least 2 previous signs or symptoms reported. The
trial authors defined recurrence as participants who were previously
healthy after treatment but developed a new episode of BV (Amsell
criteria). Adverse events were not reported.56
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Notes
None
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence Unclear risk "They were randomly allocated
generation (selection bias) to one of two groups for a
double blind trial”.
Comment: there was
insufficient information to
make a judgement.
Allocation concealment Unclear risk Comment: there was
(selection bias) insufficient information to
make a judgement
Blinding of participants Low risk “They were randomly allocated
and personnel to one of two groups for a
(performance bias) double blind trial”, “Whose
male consorts were given inert
but identical placebo tablets”.
Comment: this was probably
done.
Blinding of outcome Low risk “They were randomly allocated
assessment (detection to one of two groups for a
bias) double blind trial”, “Whose
male consorts were given inert
but identical placebo tablets”.
Comment: this was probably
done.
Incomplete outcome data Unclear risk For the outcomes of
(attrition bias) symptomatic improvement and
clinical cure at first and fourth
week the risk of bias was lowTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 57
(e.g. no missing outcome data;
missing outcome data balanced
across groups). For the same
outcomes but assessed at 12
weeks, the risk of bias was high
according to the level of
missing data (greater than
20%).
Selective reporting Unclear risk The report had insufficient
(reporting bias) information to permit judgment
of “yes” or “no”.
Other bias Low riesk The trial was sponsored by
industry. However, because the
results were not positives, the
study would be free of other
sources of bias.
Swedberg 1985
Methods Setting: USA, outpatient of family practice clinic.
Trial design: single randomized clinical trial, parallel, 2 arms.
Funding sources: Searle Pharmaceuticals and School of Human
Medicine, University of Wyoming.
Ethical issues: ethical board and signed consent.
Participants Age of participants: from 18 to 45 years.
Inclusion criteria: non-pregnant women symptomatic for BV; 3 of the
4 Amsel criteria; absence of uterine infection, mucopurulent cervicitis,
trichomoniasis or yeast on microscopic examination.
Exclusion criteria: antibiotics or vaginal cream in the previous 30
days; history of allergy to metronidazole.
Population
Number of participants: 82 women, 82 men.
Number of participants who received the intervention: 14 (single 2-
g dose) and 13 (7-day regimen).58
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Number of participants who received other(s) intervention(s) or
placebo: No treatment was administred to 55 participants, 32 in yhe 2-g
single dose group and 23 in the seven day regimen group.
Baseline characteristics: women were treated with metronidazole 500
mg twice a day for 7 days or 2 g single doses. The trial authors did not
provide more information.
Interventions Total number of intervention groups: Two groups.
Intervention: single oral 2 g or 500 mg of metronidazole twice daily for
7 days.
Comparison: no intervention.
Outcomes The trial included evaluation at 7 to 10 and 21 days after starting
treatment. All participants had a clinical examination, including the
collection of samples of vaginal discharge to check for clue cells, KOH
test, vaginal pH and cultures for gonorrhoea. At both visits, the
participants were evaluated by a Likert-type questionnaire for symptoms
of vaginitis (vulvar itching, vulvar burning, odour and quantity of
discharge).
Cure was defined if G vaginalis was not isolated on culture and if
symptoms had markedly improved or been assent (Likert-type
questionnaire). The participants reported adverse events as symptoms.
Notes
None
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence Low risk "Computer generated random
generation (selection bias) number list".
Comments: this was probably
done.
Allocation concealment Low risk "Regimen dispensed by the
(selection bias) clinic pharmacist"
Comment: this was probably
done. Telephone or central
randomization.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 59
Blinding of participants High risk There was no blinding or
and personnel incomplete blinding, and the
(performance bias) outcome or outcome
measurement is likely to have
been influenced by a lack of
blinding.
Blinding of outcome Low risk "The clinical practitioner and
assessment (detection the laboratory personnel were
bias) "blinded" in that they did not
know to which treatment group
the patient would be assigned".
Comment: this was probably
done.
Incomplete outcome data High risk More than 20% were excluded:
(attrition bias) "18 did no return at 21 days
after treatment, 14 were
excluded because they failed to
return at 7 – 10 day".
Selective reporting Unclear risk The report had insufficient
(reporting bias) information to permit judgment
of “yes” or “no”.
Other bias Low risk Searle Pharmaceuticals
provided the medication, Other
funds for this project were
provided by the School of
Human Medicine, University of
Wyoming.
Comment: sponsored by
industry. However, because the
result were not positives, the
study would be free of other
sources of bias.
Vejtorp 1988
Methods Setting: Denmark, outpatient clinic.
Trial design: single randomized clinical trial, parallel, 2 arms.
Funding sources: Rhone-Poulenc Pharma Norden A/S.
Ethical issues: ethical board and sign consent.60
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Participants Age of participants: from 17 to 50 years.
Inclusion criteria: non-pregnant women with 3 of the 4 Amsel
criteria.
Exclusion criteria: women diagnosed with Candida or trichomonal
infection; mucopurulent cervical discharge; tenderness of the uterus or
adnexa; adnexal masses.
Population
Number of participants: 126 women, 126 men.
Baseline characteristics: women were treated with 2 g metronidazole
on days 1 and 3. Most participant couples used a contraception method
(birth control pill and IUCD). The trial authors did not provide any more
information.
Interventions Total number of intervention groups: Two groups.
Intervention: metronidazole tablets, 2 g on days 1 and 3.
Comparison: placebo.
Outcomes The trial included evaluation at 1 and 5 weeks after the start of
treatment. The women had a clinical examination, including the
collection of samples of vaginal discharge to check for clue cells, the
determination of vaginal pH, and a KOH test. At both visits, the
participant and her partner were asked about medication side effects.
The trial authors defined cure as the absence or symptoms of BV
(increased discharge, malodour, burning sensation or itching) and
without at least 3 of the 4 Amsell criteria.
The trial authors defined recurrence as participants that were clinically
cured after treatment and then developed a new episode of BV (Amsel
criteria).
Adverse events were not reported.
Notes
None.
Risk of bias tableTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 61
Bias Authors' judgement Support for judgement
Random sequence Low risk “The partners were allocated to
generation (selection bias) receive metronidazole or placebo
by random allocation in blocks of
four”
Comment: this was probably
done.
Allocation concealment Unclear risk Comment: there was insufficient
(selection bias) information to make a
judgement.
Blinding of participants Low risk The trial authors did not
and personnel adequately report the method
(performance bias) implemented to blind study
participants and personnel from
knowledge of which intervention
a participant received. "The
women were treated with
metronidazole tablets, 2 g on
days 1 and 3. The partner was
given the same treatment or a
placebo".
Comment: this was probably
done.
Blinding of outcome Low risk The trial authors did not
assessment (detection adequately report the method
bias) implemented to blind study
participants and personnel from
knowledge of which intervention
a participant received. "The
women were treated with
metronidazole tablets, 2 g on
days 1 and 3. The partner was
given the same treatment or a
placebo".
Comment: this was probably
done.
Incomplete outcome data Low risk 20% or fewer participants were
(attrition bias) excluded and also intention to
treat analyses was reported.
Selective reporting Unclear risk The report did not have sufficient
information to permit a judgment62
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
(reporting bias) of “yes” or no”.
Other bias Low risk Rhone-Poulenc Pharma Norden
A/S supported the trial.
Comment: this trial was
sponsored by industry. However,
because the results were not
positive, the study would be free
of other sources of bias.
Vutyavanich 1993
Methods Setting: Thailand, outpatient clinic.
Trial design: single randomized clinical trial, parallel, 2 arms.
Funding sources: Faculty of Medicine, Chiang Mai University.
Ethical issues: ethical board and signed consent.
Participants Age of participants: from 17 to 40 years.
Inclusion criteria: symptomatic patients with 3 of the 4 Amsel
criteria; 1 current sexual partner with whom had regular sexual
intercourse.
Exclusion criteria: pregnant, lactating, or menopausal women;
candidal or trichomonal infection; adnexal masses or mucopurulent
cervical discharge, or tenderness of the uterus or adnexa;
contraindications to nitro imidazole; inability to attend follow-up visits;
antibiotic or other treatment for vaginitis in the previous month.
Population
Number of participants: 250 women, 250 men.
Baseline characteristics: sexually-active women with 1 current sexual
partner whom had regular sexual intercourse. Women were treated with
single dose of tinidazole 2 g. Most participant couples used a
contraception method of tubal resection (intervention 32% versus
placebo 28%), oral pill (intervention 17% versus placebo 26%) or
DMPA (intervention 12% versus placebo 9%) and lacked a previousTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 63
history of STI diseases (intervention 88% versus placebo 81%).
Interventions Total number of intervention groups: Two groups.
Intervention: a single oral dose of 2 g tinidazole.
Comparison: placebo.
Outcomes The trial included evaluation at 1 and 4 weeks after the start of
treatment. The women had a clinical examination, including the
collection of samples of vaginal discharge to check for clue cells, the
determination of vaginal pH and a KOH test. At both visits, the
participant and her partner were asked about of any symptoms after
taking the medication.
The trial authors defined clinical cure as the proportion of women who
remained without at least 2 of the 4 criteria for BV (Amsell criteria).
The trial authors defined symptomatic improvement as participants with
an absence of symptoms of BV (abnormal vaginal discharge or pruritus
vulvae, or both). The participants reported adverse events as symptoms.
Notes
None.
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence Low risk "patients were randomized into
generation (selection bias) two groups using a table of
random numbers”.
Comment: this was probably
done.
Allocation concealment Unclear risk Comment: there was insufficient
(selection bias) information to make a
judgement.
Blinding of participants Low risk “Either 2 g tinidazole or
and personnel identical-looking placebo packed
(performance bias) similarly in packets of four
tablets”. Comment: this was
probably done.
Blinding of outcome Low risk “Either 2 g tinidazole or
assessment (detection identical-looking placebo packed
bias) similarly in packets of four
tablet”. Comment: this was
probably done.64
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Incomplete outcome data Low risk 20% or fewer participants were
(attrition bias) excluded and also intention to
treat analyses was reported.
Selective reporting Unclear risk The report had insufficient
(reporting bias) information to permit a judgment
of “yes” or “no”.
Other bias Low risk The study was supported by
grant from the Faculty of
Medicine Endowment Fund for
Medical Research, Chiang Mai
University. Comment: the
industry probably did not
influence the results.
Footnotes
Abbreviations: BV: bacterial vaginosis. PAP: Papanicolaou ; IUCD:inrauterine divice, USA: United
States of America, DMPA: Depot medroxyprogesterone acetate.
Characteristics of excluded studies
Brenner 1986
Reason for exclusion Randomized controlled trial (RCT), but all
sexual partners were treated.
Bukusi 2011
Reason for exclusion RCT, but sexual partners did not received
antibiotic treatment.
Eschenbach 1983
Reason for exclusion
RCT, but all sexual partners were treated.
Giraldo 2013Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 65
Reason for exclusion
Not a RCT.
Hagström 1983
Reason for exclusion
Not a RCT.
Høvik 1983
Reason for exclusion
RCT, but all sexual partners were treated.
Jerve 1984
Reason for exclusion
Not a RCT.
Koumans 2002
Reason for exclusion
Not a RCT.
Larsson 2011
Reason for exclusion
Not a RCT.
Mehta 2012
Reason for exclusion
Not a RCT.
Potter 1999
Reason for exclusion
Not a RCT.
Sharma 2005
Reason for exclusion
RCT, but all sexual partners were treated.66
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Footnotes
Abbreviations: RCT: randomized controlled trial.
Characteristics of ongoing studies
NCT02209519
Study name Randomized controlled trial of treatment
of male partners of women With BV
Methods
Double-blinded RCT
Participants Male partners of women with recurrent
BV
Interventions Metronidazole 500 mg PO twice a day for
7 days versus placebo capsules PO twice a
day for 7 days.
Outcomes Recurrence of BV in the female,
recurrence/persistence of BV, number of
couples with concordance of
biotypes/strains of Gardnerella vaginalis
and time to recurrence.
Starting date
February 2015
Contact information Jane R Schwebke, MD; e-mail:
schwebke@uab.edu
Notes Study sponsor: University of Alabama at
Birmingham
Abbreviations: BV: bacterial vaginosis. RCT: randomized controlled trial. PO: per os.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 6768
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemáticaTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 6970
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Figure 4. Forest plot of comparison: 1 Any antibiotic treatment versus placebo, outcome: 1.2
Recurrence of BV after the fourth week.
Figure 5. Forest plot of comparison: 1 Any antibiotic treatment versus placebo, outcome: 1.3
Clinical improvement during the first week.Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 71
Figure 6. Forest plot of comparison: 1 Any antibiotic treatment versus placebo, outcome: 1.4
Clinical improvement between the first and fourth week.
Figure 7. Forest plot of comparison: 1 Any antibiotic treatment versus placebo, outcome: 1.5
Clinical improvement after the fourth week.72
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática
Figure 8. Forest plot of comparison: 1 Any antibiotic treatment versus placebo, outcome: 1.6
Symptomatic improvement during the first week.
Figure 9. Forest plot of comparison: 1 Any antibiotic treatment versus placebo, outcome: 1.9
Minor adverse events during therapy in sexual partnerTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 7374
Tratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemáticaTratamiento antibiótico para la pareja sexual de mujeres con vaginosis bacteriana: Una revisión sistemática 75