20172 European Guideline for the Management of Pelvic Inflammatory Disease

Jonathan Ross1, Secondo Guaschino2, Marco Cusini3, Jorgen Jensen3Jensen4

1
University Hospital Birmingham NHS Foundation Trust, UK
2
University of Trieste, Italy
3
Department of Dermatology, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, Italy
4 Statens Serum Institut, Copenhagen, Denmark

keywords: pelvic infection, pelvic inflammatory disease, salpingitis, treatment, antibiotics, guideline

Address for correspondence:

Prof. Jonathan Ross MB ChB MD FRCP
University Hospital Birmingham NHS Foundation Trust
Whittall Street Clinic
Whittall Street
Birmingham B4 6DH
UK
Tel. 0121 237 5721 Fax. 0121 237 5729
email: jonathan.ross@uhb.nhs.uk

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 This guideline was produced by the European region of the International Union against Sexually
Transmitted Infections (IUSTI) and refers to ascending infections in the female genital tract
unrelated to delivery and surgery and does not include actinomyces related infection.

Aetiology and Transmission

 Pelvic inflammatory disease (PID) is usually the result of infection ascending from the

endocervix causing endometritis, salpingitis, parametritis, oophoritis, tuboovarian abcess

and/or pelvic peritonitis.

 Neisseria gonorrhoeae and Chlamydia trachomatis have been identified as causative agents,

[1]1 whilst Mycoplasma genitalium is a likely cause,[2] and anaerobes can are also be

implicated. Micro-organisms from the vaginal flora including streptococci, staphylococci, E.

coli and H. influenzae are also can be associated with upper genital tract inflammation. Mixed

infections are common.

 The relative importance of different pathogens varies in between different countries and regions

within Europe.

A number of factors are associated with PID:

 Factors related to sexual behaviour

 young age

 multiple partners

 recent new partner (within previous 3 months)

 past history of sexually transmitted infections (STIs) in the patient or their partner

 Instrumentation of the uterus / interruption of the cervical barrier

 termination of pregnancy

 insertion of intrauterine device within the past 6 weeks

 hysterosalpingography

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  hysteroscopy

 saline infusion sonography

 in vitro fertilisation

Clinical Features

Symptoms

PID may be symptomatic or asymptomatic. Even when present, clinical symptoms and signs lack

sensitivity and specificity (the positive predictive value of a clinical diagnosis is 65-90% compared

to laparoscopic diagnosis). [1, 3, 4]1-3.

The following symptoms are suggestive of a diagnosis of PID [1, 3, 4] 1-3;4:

 lower abdominal pain – usually bilateral

 deep dyspareunia – particularly of recent onset

 abnormal bleeding – intermenstrual bleeding, post coital bleeding and menorrhagia can occur

secondary to associated cervicitis and endometritis

 abnormal vaginal or cervical discharge – as a result of associated cervicitis, endometritis or

bacterial vaginosis

Physical signs

These signs are associated with PID:

 lower abdominal tenderness

 adnexal tenderness on bimanual vaginal examination

 cervical motion tenderness on bimanual vaginal examination

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 fever (>38°C)

PID should be considered in a patient with the clinical signs and/or symptoms outlined above.

Differential Diagnosis

The differential diagnosis of lower abdominal pain in a young woman includes:

 ectopic pregnancy

 acute appendicitis

 endometriosis

 irritable bowel syndrome

 complications of an ovarian cyst i.e. rupture, torsion

 functional pain (pain of unknown physical origin)

Complications

 Tuboovarian abscesses and pelvic peritonitis account for the main complications. Acute lower

abdominal pain and fever are usually present. Ultrasound scanning may be useful to confirm a

pelvic abscess while computed tomography or magnetic resonance imaging may help rule out

other causes of peritonitis.

 The Fitz-Hugh-Curtis syndrome comprises rRight upper quadrant pain associated with

perihepatitis (Fitz-Hugh Curtis syndrome) can occur and may be the dominant symptom.

Although laparoscopic division of hepatic adhesions has been performed, there is insufficient

clinical trial evidence to make specific recommendations for treatment beyond those for

PIDantibiotic therapy.

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 In pregnancy, PID is uncommon but has been associated with an increase in both maternal and

foetal morbidity, therefore parenteral therapy is advised although none of the suggested

evidence based regimens are of proven safety in this situation. There is insufficient data from

clinical trials to recommend a specific regimen for pregnant women with PID and empirical

therapy with agents effective against gonorrhoea, chlamydia and anaerobic infections should be

considered taking into account local antibiotic sensitivity patterns (e.g. i.v. cefoxitin ceftriaxone

2g three timesonce daily plus i.v. erythromycin 50mg/kg continuous infusiononce daily, with

the possible addition of i.v. metronidazole 500mg three times dailygiven orally [400mg twice

daily], per rectum [1g three times daily] or i.v. [500mg three times daily])

(Evidence level III, B)

 Women with HIV may have more severe symptoms associated with PID but respond well to

antibiotic therapy, although parenteral regimens may be required [5-8] 5-8.

 There is no evidence of the superiority of any one of the recommended regimens over the

others. Therefore patients known to be allergic to one of the recommended regimens should be

treated with an alternative.

 In women with an intrauterine contraceptive device (IUD) in situ, consider removing the IUD

since a single randomised controlled trial suggests that this may be associated with better short

term improvement in symptoms and signs [9]. However a subsequent systematic review

concluded that there is little difference in outcomes for women with mild to moderate PID who

retain their IUD in situ during treatment [10]9.

(Evidence level Ib, A)

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 Diagnosis

 Testing for gonorrhoea, and chlamydia and M. genitalium in the lower genital tract is

recommended since a positive result supports the diagnosis of PID. However the absence of

infection from the endocervix or urethra does not exclude PID [1-4].

 1-3
.

 The absence of endocervical or vaginal pus cells has a good negative predictive value (95%)

for a diagnosis of PID but their presence is non-specific (poor positive predictive value – 17%)

[11].10.

 An elevated ESR or C reactive protein supports the diagnosis [12] 11 but is non-specific and

often normal in mild/moderate PID

 Elevation of the white cell count (WBC) supports the diagnosis but can beis usually normal in

mild cases.

 Laparoscopy may strongly support a diagnosis of PID but is not justified routinely on the basis

of associated morbidity, cost and the potential difficulty in identifying mild intra-tubal

inflammation or endometritis [1, 3, 4, 13] 1-3

 Endometrial biopsy and ultrasound scanning may also be helpful when there is diagnostic

difficulty but there is insufficient evidence to support their routine use

 A pregnancy test should be performed to help exclude an ectopic pregnancy

Management

Information, explanation and advice for the patient

 Patients should be advised to avoid unprotected intercourse until they, and their partner(s),

have completed treatment and follow-upsymptoms have resolved (Evidence level IV, C)

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 A detailed explanation of their condition with particular emphasis on the long-term implications

for the health of themselves and their partner(s) should be provided, reinforced with clear and

accurate written information. Appropriate information should include:

o fertility is usually well preserved in women with first episode PID who receive prompt

appropriate anti-microbial therapy

o the risk of impaired fertility increases significantly with each subsequent episode of PID

(approximately doubling with each new presentation [14]12)

o the risk of impaired fertility is increased in clinically more severe PID

o chronic pelvic pain of varying severity affects around 30% of women following PID

o PID increases the relative risk of a subsequent pregnancy being an ectopic, but the absolute

risk of ectopic pregnancy remains low at around 1%

A patient information leaflet is available at

http://www.iusti.org/regions/europe/PatientInformation.htmhttp://www.iusti.org/regions/europ

e/euroguidelines.htm#Current.

(Evidence level IV, C)

Therapy

Broad spectrum antibiotic therapy is required to cover N. gonorrhoeae, C. trachomatis and

anaerobic infection [1, 3][1, 3]1, 2. It is also desirable to include microbiological cover for

other possible pathogens (e.g. Mycoplasma genitalium, anaerobes, streptococci,

staphylococci, E. coli, H. influenzae) [15]13. Recent data suggest that few antibiotics

(azithromycin and moxifloxacin, mainly) are effective against Mycoplasma genitalium14.

There are comparatively fewer data on oral than parenteral regimens.

The choice of an appropriate treatment regimen may be influenced by:

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 robust evidence on local antimicrobial sensitivity patterns

 robust evidence on the local epidemiology of specific infections in this setting

 cost

 patient preference and compliance

 severity of disease

General measures include:

 Rest is advised for those with severe disease (Evidence level IV, C)

 If there is a possibility that the patient could be pregnant, a pregnancy test should be performed

(Evidence level IV, C)

 Appropriate analgesia should be provided (Evidence level IV, C)

 Intravenous therapy is recommended for patients with more severe clinical disease (Evidence

level IV, C)

Admission for parenteral therapy, observation, further investigation and/or possible surgical

intervention should be considered in the following situations [3] 2 (Evidence level IV, C):

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 diagnostic uncertainty

 clinical failure with oral therapy

 severe symptoms or signs

 presence of a tuboovarian abcessabscess

 inability to tolerate an oral regimen

 pregnancy

In inpatients the treatment response can be monitored by changes in C reactive protein and WBC .

In severe cases and cases with failure of the initial treatment tuboovarian abcessabscess should be

excluded by vaginal ultrasonography, CT or MRI imaging.

All patients should be offered screening testing for sexually transmitted infections

includingchlamydia, gonorrhoea, Mycoplasma genitalium, syphilis and HIV testing (Evidence

level IV, C) .

It is likely that delaying treatment increases the risk of long term sequelae such as ectopic

pregnancy, infertility and pelvic pain [16] 15. Because of this, and the lack of definitive diagnostic

criteria, a low threshold for empiric treatment of PID is recommended (Evidence level IV, C).

In cases with suspected repeat PID, especially if it is of mild severity, other causes should be

sought and treated accordingly, especially functional pain, pain originating in the ileopsoas muscles,

the pelvic floor and urinary tract (Evidence level IV, C).

Recommended Regimens

Choice of treatment regime should be influenced by the following:

 Mild and moderate cases should be treated as outpatients with oral therapy [17]16

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 (Evidence level Ib, A).

 Intravenous therapy, when given, should be continued until 24 hours after clinical

improvement and then switched to oral (Evidence level IV, C).

 Dosage recommendations may need to be adjusted slightly depending on local licensing

regulations and the availability of drug formulations.

 The optimal duration of treatment is not known but most clinical trials report a response to

10-14 days of therapy.

 No difference in efficacy has been demonstrated between the recommended regimens

The following antibiotic regimens are evidence based. It should be noted, however, that the

changing spectrum of antimicrobial resistance over time and in different geographical areas may

overestimate the efficacy of some regimens which were evaluated several years ago.

Outpatient Regimens

 i.m. ceftriaxone 500mg single dose. or [i.m. cefoxitin 2g single dose with oral probenecid 1g]

followed by

oral doxycycline 100mg twice daily plus metronidazole 400mg twice daily for 14 days [18-21]2, 17,
18;16, 19

(Evidence level Ia, A)

 oral ofloxacin* 400mg twice daily plus oral metronidazole 500mg twice daily for 14 days2

[19, 21-23] 18-21

(ofloxacin may be replaced by levofloxacin* 500mg once daily [24]22)

(Evidence level Ib, A)

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 oral moxifloxacin* 400mg once daily for 14 days [24-26]

(Evidence level Ia, A)

* High levels of quinolone resistance in N. gonorrhoeae occur in many areas of Europe. Therefore

in women who are at high risk of gonococcal PID (e.g. when the patient’s partner has gonorrhoea,

in clinically severe disease, following sexual contact abroad) ofloxacin, levofloxacin and

moxifloxacin should be avoided or a single dose of i.m. ceftriaxone 500mg added.

Inpatient Regimens

 i.v. cefoxitin 2g four times daily (or i.v. cefotetan 2g twice daily or i.v./i.m. ceftriaxone 1g once

daily ) plus i.v. doxycycline 100mg twice daily (oral doxycycline may be used if tolerated)

followed by

oral doxycycline 100mg twice daily plus oral metronidazole 400mg twice daily to complete 14

days [18, 19, 21][16, 23]2, 17, 18;19

(Evidence level Ia, A)

 i.v. clindamycin 900mg three times daily plus i.m./i.v. gentamicin (3-62mg/kg loading dose

followed by 1.5mg/kg three times daily [as a single daily dose with renal monitoring may be

substituted])

followed by either

[oral clindamycin 450mg four times daily [oral doxycycline 100mg twice daily

to complete 14 days] plus oral metronidazole 400mg twice daily

to complete 14 days] [18, 21]2, 17;19

(Evidence level Ia, A)

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 Alternative Regimens

The evidence for alternative regimens is either less robust than the regimens above, or they have a

poorer safety profile.

 i.v. ofloxacin 400mg twice daily plus i.v. metronidazole 500mg three times daily for 14 days

[19, 21-23] 2, 18-21

 (Evidence level Ib, B)

 i.v. ciprofloxacin 200mg twice daily plus i.v. (or oral) doxycycline 100mg twice daily plus i.v.

metronidazole 500mg three times daily for 14 days[18, 26]2, 18, 23

 (Evidence level Ia, B)

 i.m. ceftriaxone 500mg single dose plus oral azithromycin 1g single dose followed by a second

dose of oral azithromycin 1g after one week [27] 24

 (Evidence level Iab, AB)

 oral moxifloxacin 400mg once daily for 14 days22, 25, 26

(Evidence level Ia, A)

Where the above regimens are not available antibiotic therapy should be given for 14 days and

attempt to cover:

 Neisseria gonorrhoeae e.g. cephalosporins

 Chlamydia trachomatis e.g. tetracyclines, macrolides

 anaerobic bacteria e.g. metronidazole

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Metronidazole is included in the recommended outpatientsome regimens to improve coverage for

anaerobic bacteria which may have a role in the pathogenesis of PID [3, 28]27. Anaerobes are

probably of relatively greater importance in patients with severe PID and some studies have shown

good outcomes without the use of metronidazole. Metronidazole may therefore be discontinued in

those patients with mild or moderate PID who are unable to tolerate it.

Ceftriaxone may be used when cefoxitin or cefotetan are not available since it offers a similar

spectrum of activity, although with less effective cover for anaerobic infection.

Quinolones, including ofloxacin and moxifloxacin, should be combined with a single dose of

ceftriaxone 500mg i.m. in patients who are at high risk of gonococcal PID because of increasing

reports of quinolone resistance in Neisseria gonorrhoeae. The risk of gonorrhoea is high (e.g.

avoid when the patient’s partner has gonorrhoea [or is from a high prevalence area] or the patient

has clinically severe disease). Moxifloxacin has a strong evidence base for effectiveness in the

treatment of PID but has been associated with severe, although rare, liver and cardiac toxicity.

In women who are positive for M. genitalium treatment with moxifloxacin is recommended.

Partner notification

 Current male partners of women with PID should be contacted and offered health advice and

screening for gonorrhoea and chlamydia (and M. genitalium if the index patient is infected).

Other recent sexual partners may also be offered screening - tracing of contacts within a 6

month period of onset of symptoms is recommended but this time period is not evidence based

and may be influenced by the sexual history, available resources or local practice.

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 Partners should be advised to avoid unprotected intercourse until they and their partner have

completed the treatment course.

 Gonorrhoea, chlamydia and M. genitalium diagnosed in the male partner should be treated

appropriately (see European Guidelines at www.iusti.org) and concurrently with the index

patient.

 Because many cases of PID are not associated with gonorrhoea, chlamydia or M. genitalium,

broad spectrum empirical therapy should also be offered to male partners e.g. doxycycline

100mg twice daily for 1 weekConcurrent empirical treatment for chlamydia is recommended

(see European Guidelines at www.iusti.org) for all sexual contacts due to the variable sensitivity

of currently available diagnostic tests.

 If adequate screening for gonorrhoea and chlamydia in the sexual partner(s) is not possible,

empirical therapy for gonorrhoea and chlamydia should be given (see European Guidelines at

www.iusti.org).

Follow Up

Review at 72 hours is recommended [3]2, particularly for those with a moderate or severe clinical

presentation, and should show a substantial improvement in clinical symptoms and signs. Failure to

do soimprove suggests the need for further investigation, parenteral therapy and/or surgical

intervention.

(Evidence level IV, C)

Repeat microbiology testing is appropriate in women who are positive for Repeat testing for

gonorrhoea, or chlamydia or M. genitalium at baseline is appropriate:

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 in those with persistent symptoms

 where antibiotic sensitivities are unknown or resistance is present (gonorrhoea or M.

genitalium only)

 history of poor compliance with antibiotics

 inadequate tracing of sexual contacts where there is a possibility of persisting or recurrent

infection.

Prevention/health promotion

Further review 4 weeks after therapy may be useful to ensure:

 adequate clinical response to treatment

 compliance with oral antibiotics

 screening and treatment of sexual contacts

 advice on future use of condoms to prevent recurrent PID

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Appendix 1

Search strategy

This guideline refers to ascending infections in the female genital tract unrelated to delivery and

surgery and does not include actinomyces related infection.

Five Four reference sources were used to provide a comprehensive basis for the guideline:

1. Medline and Embase Search

a.1987 – September 2011November 2016

The search strategy comprised the following terms in the title or abstract: ‘pelvic inflammatory

disease’, ‘adnexitis’, ‘oophoritis’, ‘parametritis’, ‘salpingitis’, ‘endometritis’, ‘PID’ (excluding

‘primary immune deficiency’), ‘adnexal disease’ or ‘adnexal disease’. 10422 citations were

identified.

b.1963 - 1986

The search strategy comprised the following terms in the title or abstract: ‘pelvic inflammatory

disease’, ‘adnexitis’, ‘oophoritis’, ‘parametritis’, ‘salpingitis’ or ‘adnexal disease’. The dataset was

then limited to AIM journals and human subjects, identifying 2321 citations.

2. 20150 CDC STD Treatment Guidelines (www.cdc.gov/std/)

3. 2009 RCOG Green Top Guidelines – Management of Acute Pelvic Inflammatory Disease

(www.rcog.org.uk)

34. Cochrane Collaboration Databases (www.cochrane.org)

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Appendix 2

Levels of evidence and grading of recommendations

Levels of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised controlled trial.
IIa Evidence obtained from at least one well designed study without randomisation.
IIb Evidence obtained from at least one other type of well designed quasi-experimental study.
III Evidence obtained from well designed non-experimental descriptive studies such as
comparative studies, correlation studies, and case control studies.
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of
respected authorities.

Grading of Recommendations
A (Evidence levels Ia, Ib) - Requires at least one randomised control trial as part of the body of
literature of overall good quality and consistency addressing the specific recommendation.
B (Evidence levels IIa, IIb, III) - Requires availability of well conducted clinical studies but no
randomised clinical trials on the topic of recommendation.
C (Evidence IV) - Requires evidence from expert committee reports or opinions and/or clinical
experience of respected authorities. Indicates absence of directly applicable studies of good quality.

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Appendix 3

Declarations of Interest

Jonathan Ross – no interests to declareJR has received speaker fees from Becton Dickinson

Diagnostics and consultancy fees from Glaxo Smith Kline pharma

Secondo GuaschinoPhilippe Judlin - has received speaker fees from Pierre Fabre

Marco Cusini – no interests to declare no interests to declare

Jorgen Jensen – no interests to declare

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Appendix 4

European STI Guidelines Editorial Board and List of contributing organisations

Membership of the European STI Guidelines Editorial Board is available at:

Dr Keith Radcliffe, UK – Editor-in-Chief

Dr Karen Babayan, Armenia (appointed 2009)

Dr Marco Cusini, Italy (app. 2010)
Prof Mikhail Gomberg, Russia (app. 2010)
Dr Michel Janier, France (app. 2006)
Dr Jorgen Skov Jensen, Denmark (app. 2006)
Prof. Harald Moi, Norway (app. 2007)
Dr Raj Patel, UK (app. 2006)
Prof Jonathan Ross, UK (app. 2006)
Dr Jackie Sherrard, UK (app. 2009)
Dr Magnus Unemo, Sweden (app. 2009)
Dr Willem van der Meijden, Netherlands (app. 2006)

Dr Simon Barton (UK) – UEMS representative, UK (app. 2010)

Dr Lali Khotenashvili – WHO European Office representative, Georgia (app. 2007)
Dr Marita van de Laar – ECDC representative, Netherlands (app. 2007)
Prof. Martino Neumann – EDF representative, Netherlands (app. 2007)
Dr Angela Robinson, - EADV representative, UK (app. 2009)
http://www.iusti.org/regions/Europe/pdf/2014/Editorial_Board2014.pdf

This guideline has been produced on behalf of the following organisations: the European Branch of
the International Union against Sexually Transmitted Infections (IUSTI Europe); the European
Academy of Dermatology and Venereology (EADV); the European Dermatology Forum (EDF);
the Union of European Medical Specialists (UEMS). The European Centre for Disease Prevention
and Control (ECDC) and the European Office of the World Health Organisation (WHO-Europe)
also contributed to its development.

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 Reference List

1. Bevan CD, Johal BJ, Mumtaz G, Ridgway GL, Siddle NC. Clinical, laparoscopic and
microbiological findings in acute salpingitis: report on a United Kingdom cohort. British Journal of
Obstetrics & Gynaecology 1995;102(5):407-414.
2. CDC. Sexually Transmitted Diseases Treatment Guidelines 2010.
http://www.cdc.gov/std/treatment/2010/pid.htm (accessed 21.6.12).
3. Morcos R, Frost N, Hnat M, Petrunak A, Caldito G. Laparoscopic versus clinical diagnosis
of acute pelvic inflammatory disease. J Reprod Med 1993;38(1):53-56.
4. Recommendations arising from the 31st Study Group: The Prevention of Pelvic Infection.
In: Templeton A, editor. The Prevention of Pelvic Infection. London: RCOG Press; 1996:267-270.
5. Kamenga MC, De Cock KM, St.Louis ME et al. The impact of human immunodeficiency
virus infection on pelvic inflammatory disease: a case-control study in Abidjan, Ivory Coast. Am J Obstet
Gynecol 1995;172(3):919-925.
6. Mugo NR, Kiehlbauch JA, Nguti R et al. Effect of human immunodeficiency virus-1
infection on treatment outcome of acute salpingitis. Obstet Gynecol 2006;107(4):807-812.
7. Bukusi EA, Cohen CR, Stevens CE et al. Effects of human immunodeficiency virus 1
infection on microbial origins of pelvic inflammatory disease and on efficacy of ambulatory oral therapy.
Am J Obstet Gynecol 1999;181(6):1374-1381.
8. Irwin KL, Moorman AC, O'Sullivan MJ et al. Influence of human immunodeficiency virus
infection on pelvic inflammatory disease. Obstet Gynecol 2000;95(4):525-534.
9. Altunyurt S, Demir N, Posaci C. A randomized controlled trial of coil removal prior to
treatment of pelvic inflammatory disease. European Journal of Obstetrics Gynecology and Reproductive
Biology 2003;107:81-84.
10. Yudin MH, Hillier SL, Wiesenfeld HC, Krohn MA, Amortegui AA, Sweet RL. Vaginal
polymorphonuclear leukocytes and bacterial vaginosis as markers for histologic endometritis among
women without symptoms of pelvic inflammatory disease. American Journal of Obstetrics and
Gynecology 2003;188(2):318-323.
11. Miettinen AK, Heinonen PK, Laippala P, Paavonen J. Test performance of erythrocyte
sedimentation rate and C- reactive protein in assessing the severity of acute pelvic inflammatory disease.
Am J Obstet Gynecol 1993;169(5):1143-1149.
12. Westrom L. Incidence, prevalence, and trends of acute pelvic inflammatory disease and
its consequences in industrialized countries. [Review] [74 refs]. Am J Obstet Gynecol 1980;138(7 Pt
2):880-892.
13. Judlin P. Current concepts in managing pelvic inflammatory disease. Current Opinion in
Infectious Diseases 2010;23(1):83-87.
14. Haggerty CL, Totten PA, Astete SG et al. Failure of cefoxitin and doxycycline to eradicate
endometrial Mycoplasma genitalium and the consequence for clinical cure of pelvic inflammatory disease.
Sex Transm Infect 2008;84(5):338-342.
15. Hillis SD, Joesoef R, Marchbanks PA et al. Delayed care of pelvic inflammatory disease
as a risk factor for impaired fertility. Am J Obstet Gynecol 1993;168(5):1503-1509.
16. Ness RB, Trautmann G, Richter HE et al. Effectiveness of treatment strategies of some
women with pelvic inflammatory disease: A randomized trial. Obstet Gynecol 2005;106(3):573-580.
17. Hemsell DL, Little BB, Faro S et al. Comparison of three regimens recommended by the
Centers for Disease Control and Prevention for the treatment of women hospitalized with acute pelvic
inflammatory disease. Clin Infect Dis 1994;19(4):720-727.
18. Martens MG, Gordon S, Yarborough DR, Faro S, Binder D, Berkeley A. Multicenter
randomized trial of ofloxacin versus cefoxitin and doxycycline in outpatient treatment of pelvic
inflammatory disease. Ambulatory PID Research Group. Southern Medical Journal 1993;86(6):604-610.
19. Walker CK, Kahn JG, Washington AE, Peterson HB, Sweet RL. Pelvic inflammatory
disease: metaanalysis of antimicrobial regimen efficacy. J Infect Dis 1993;168(4):969-978.
20. Wendel GD, Jr., Cox SM, Bawdon RE, Theriot SK, Heard MC, Nobles BJ. A randomized
trial of ofloxacin versus cefoxitin and doxycycline in the outpatient treatment of acute salpingitis. Am J
Obstet Gynecol 1991;164(5 Pt 2):1390-1396.
21. Witte EH, Peters AA, Smit IB et al. A comparison of pefloxacin/metronidazole and
doxycycline/metronidazole in the treatment of laparoscopically confirmed acute pelvic inflammatory
disease. European Journal of Obstetrics, Gynecology, & Reproductive Biology 1993;50(2):153-158.
22. Judlin P, Liao Q, Liu Z, Reimnitz P, Hampel B, Arvis P. Efficacy and safety of moxifloxacin
in uncomplicated pelvic inflammatory disease: the MONALISA study. BJOG: An International Journal of
Obstetrics & Gynaecology 2010;117(12):1475-1484.

430859512.doc page 20
 23. Heinonen PK, Teisala K, Miettinen A, Aine R, Punnonen R, Gronroos P. A comparison of
ciprofloxacin with doxycycline plus metronidazole in the treatment of acute pelvic inflammatory disease.
Scandinavian Journal of Infectious Diseases - Supplementum 1989;60:66-73.
24. Bradshaw CS, Jensen JS, Tabrizi SN et al. Azithromycin failure in Mycoplasma genitalium
urethritis. Emerging Infectious Diseases 12(7):1149-52, 2006.
25. Heystek MJ, Ross JDC, PID Study Group. A randomised double-blind comparison of
moxifloxacin and doxycycline/metronidazole/ciprofloxacin in the treatment of acute, uncomplicated pelvic
inflammatory disease. Int J STD AIDS 2009;20:690-695.
26. Ross JDC, Cronje HS, Paszkowski T et al. Moxifloxacin versus ofloxacin plus
metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind,
randomised trial. Sex Transm Infect 2006;82:446-451.
27. Haggerty CL, Ness RB, Amortegui A et al. Endometritis does not predict reproductive
morbidity after pelvic inflammatory disease. Am J Obstet Gynecol 2003;188(1):141-148.

430859512.doc page 21