Guidelines International Journal of STD & AIDS 2018, Vol. 29(2) 108–114 2017 European guideline for the ! The Author(s) 2017 Reprints and permissions: management of pelvic inflammatory sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462417744099 disease journals.sagepub.com/home/std Jonathan Ross1, Secondo Guaschino2, Marco Cusini3 and Jorgen Jensen4 Abstract The European guideline for the management of pelvic inflammatory disease includes evidence-based advice on the investigation and treatment of pelvic inflammatory disease (PID). It has been updated to acknowledge the role of Mycoplasma genitalium as an important cause of PID with testing now recommended for women presenting with possible PID and for the male partners of women with confirmed M. genitalium infection. Recent evidence suggests that serious adverse events are uncommon when using moxifloxacin and its use is now recommended as a first-line therapy, espe- cially in those women with M. genitalium PID. The potential utility of MRI scanning of the pelvis in excluding differential diagnoses has been highlighted. The use of doxycycline is now suggested as empirical treatment for male partners of women with PID to reduce exposure to macrolide antibiotics, which has been associated with increased resistance in M. genitalium. Keywords Pelvic infection, pelvic inflammatory disease, salpingitis, treatment, antibiotics, guideline Date received: 16 October 2017; accepted: 1 September 2017 Aetiology and transmission • instrumentation of the uterus/interruption of the • Pelvic inflammatory disease (PID) is usually the result cervical barrier of infection ascending from the endocervix causing • termination of pregnancy endometritis, salpingitis, parametritis, oophoritis, • insertion of intrauterine device within the past six tuboovarian abscess and/or pelvic peritonitis. weeks • Neisseria gonorrhoeae and Chlamydia trachomatis • hysterosalpingography have been identified as causative agents,1 • hysteroscopy Mycoplasma genitalium is a likely cause2 and anae- • saline infusion sonography robes are also implicated. Microorganisms from the • in vitro fertilisation vaginal flora including streptococci, staphylococci, Escherichia coli and Haemophilus influenzae can be associated with upper genital tract inflammation. Mixed infections are common. • The relative importance of different pathogens varies between different countries and regions within Europe. A number of factors are associated with PID: 1University Hospital Birmingham NHS Foundation Trust, Birmingham, UK 2University of Trieste, Trieste, Italy 3 • Factors related to sexual behaviour Department of Dermatology, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, Milano, Italy ᭺ young age 4Statens Serum Institut, Copenhagen, Denmark ᭺ multiple partners ᭺ recent new partner (within previous three months) Corresponding author: Jonathan Ross, University Hospital Birmingham NHS Foundation Trust, ᭺ past history of sexually transmitted infections Whittall Street Clinic, Whittall Street, Birmingham B4 6DH, UK. (STIs) in the patient or their partner Email: [email protected] Ross et al. 109 Clinical features • Right upper quadrant pain associated with perihe- patitis (Fitz-Hugh–Curtis syndrome) can occur and Symptoms may be the dominant symptom. • In pregnancy, PID is uncommon but has been asso- PID may be symptomatic or asymptomatic. Even when ciated with an increase in both maternal and fetal present, clinical symptoms and signs lack sensitivity morbidity, therefore parenteral therapy is advised and specificity (the positive predictive value of a clinical although none of the suggested evidence-based regi- diagnosis is 65–90% compared to laparoscopic mens are of proven safety in this situation. There are diagnosis).1,3,4 insufficient data from clinical trials to recommend a The following symptoms are suggestive of a diagno- specific regimen for pregnant women with PID and sis of PID1,3,4: empirical therapy with agents effective against gon- orrhoea, Chlamydia and anaerobic infections should • lower abdominal pain – usually bilateral be considered taking into account local antibiotic • deep dyspareunia – particularly of recent onset sensitivity patterns (e.g. i.v. ceftriaxone 2 g once • abnormal bleeding – intermenstrual bleeding, post- daily plus i.v. erythromycin 50 mg/kg once daily, coital bleeding and menorrhagia can occur second- with the addition of metronidazole given orally ary to associated cervicitis and endometritis [500 mg twice daily], per rectum [1 g three times • abnormal vaginal or cervical discharge – as a result daily] or i.v. [500 mg three times daily]) of associated cervicitis, endometritis or bacterial (Evidence level III, B) vaginosis • Women with HIV may have more severe symptoms associated with PID but respond well to antibiotic Physical signs therapy, although parenteral regimens may be required.5–8 The following signs are associated with PID: • There is no evidence of the superiority of any one of the recommended regimens over the others. • lower abdominal tenderness Therefore, patients known to be allergic to one of • adnexal tenderness on bimanual vaginal the recommended regimens should be treated with examination an alternative. • cervical motion tenderness on bimanual vaginal • In women with an intrauterine contraceptive device examination (IUD) in situ, consider removing the IUD since a • fever (>38C) single randomised controlled trial suggests that this may be associated with better short-term improve- PID should be considered in a patient with the clin- ment in symptoms and signs.9 However, a subse- ical signs and/or symptoms outlined above. quent systematic review concluded that there is little difference in outcomes for women with mild- Differential diagnosis to-moderate PID who retain their IUD in situ during treatment.10 The differential diagnosis of lower abdominal pain in a (Evidence level Ib, A) young woman includes: • ectopic pregnancy Diagnosis • acute appendicitis • Testing for gonorrhoea, Chlamydia and M. genita- • endometriosis lium in the lower genital tract is recommended since • irritable bowel syndrome a positive result supports the diagnosis of PID. • complications of an ovarian cyst, i.e. rupture, However, the absence of infection from the endocer- torsion vix or urethra does not exclude PID.1–4 • functional pain (pain of unknown physical origin) • The absence of endocervical or vaginal pus cells has a good negative predictive value (95%) for a diag- nosis of PID but their presence is non-specific (poor Complications positive predictive value – 17%).11 • Tuboovarian abscesses and pelvic peritonitis • An elevated ESR or C-reactive protein supports the account for the main complications. Acute lower diagnosis12 but is non-specific and often normal in abdominal pain and fever are usually present. mild/moderate PID. 110 International Journal of STD & AIDS 29(2) • Elevation of the white cell count can occur in women htm with PID but it is usually normal in mild cases. (Evidence level IV, C) • Laparoscopy may strongly support a diagnosis of PID but is not justified routinely on the basis of Therapy associated morbidity, cost and the potential difficul- Broad spectrum antibiotic therapy is required to cover ty in identifying mild intra-tubal inflammation or N. gonorrhoeae, C. trachomatis and anaerobic infec- endometritis.1,3,4,13 tion.1,3 It is also desirable to include microbiological • Ultrasound scanning may be useful to confirm a cover for other possible pathogens (e.g. M. genitalium, pelvic abscess while computed tomography (CT) or 15 magnetic resonance imaging (MRI) can help rule out streptococci, staphylococci, E. coli, H. influenzae). other causes of peritonitis. However, routine ultra- The choice of an appropriate treatment regimen may sound scanning is not recommended for all women be influenced by: with suspected PID. • • Endometrial biopsy may also be helpful when there local antimicrobial sensitivity patterns • is diagnostic difficulty but there is insufficient evi- local epidemiology of specific infections in this dence to support its routine use. setting • • A pregnancy test should be performed to help cost • exclude an ectopic pregnancy. patient preference and compliance • severity of disease Management General measures include: Information, explanation and advice for the patient • rest is advised for those with severe disease • Patients should be advised to avoid unprotected (Evidence level IV, C) intercourse until they, and their partner(s), have • if there is a possibility that the patient could be preg- completed treatment and symptoms have resolved nant, a pregnancy test should be performed (Evidence level IV, C). (Evidence level IV, C) • A detailed explanation of their condition with par- • appropriate analgesia should be provided (Evidence ticular emphasis on the long-term implications for level IV, C) the health of themselves and their partner(s) should be provided, reinforced with clear and accurate writ- Admission for parenteral therapy, observation, fur- ten information. Appropriate information should ther investigation and/or possible surgical intervention 3 include: should be considered in the following situations ᭺ fertility is usually well preserved in women with (Evidence level IV, C): first-episode PID who receive prompt appropriate antimicrobial therapy • diagnostic uncertainty • ᭺ the risk of impaired fertility increases significant ly clinical failure with oral therapy with each subsequent episode of PID (approxi- • severe symptoms or signs mately doubling