Definitions of the levels of evidence (I-IV) and grades of recommendation (A-C) are repeated at the end of the "Major Recommendations" field.
What is New in the June 2011 Update?
- The dose of ceftriaxone has been increased to 500mg stat to reflect the reduced sensitivity of Neisseria gonorrhoeae to cephalosporins and the current United Kingdom (UK) treatment guidelines for uncomplicated gonorrhoea.
- Pelvic inflammatory disease (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% to 90% compared with laparoscopic diagnosis).
- Testing for gonorrhoea and chlamydia in the lower genital tract is recommended since a positive result supports the diagnosis of PID. The absence of infection at this site does not exclude PID however.
- An elevated erythrocyte sedimentation rate (ESR) or C reactive protein also supports the diagnosis but is non-specific.
- 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%).
The differential diagnosis of lower abdominal pain in a young woman includes:
- Ectopic pregnancy - pregnancy should be excluded in all women suspected of having PID.
- Acute appendicitis - nausea and vomiting occur in most patients with appendicitis but only 50% of those with PID. Cervical movement pain will occur in about a quarter of women with appendicitis.
- Endometriosis - the relationship between symptoms and the menstrual cycle may be helpful in establishing a diagnosis.
- Complications of an ovarian cyst (e.g., torsion or rupture) often of sudden onset
- Urinary tract infection – often associated with dysuria and/or urinary frequency
- Functional pain - may be associated with longstanding symptoms
It is likely that delaying treatment increases the risk of long-term sequelae such as ectopic pregnancy, infertility and pelvic pain. Because of this, and the lack of definitive diagnostic criteria, a low threshold for empirical treatment of PID is recommended. Broad spectrum antibiotic therapy is required to cover N. gonorrhoeae, C. trachomatis, and a variety of aerobic and anaerobic bacteria commonly isolated from the upper genital tract in women with PID.
Some of the best evidence for the effectiveness of antibiotic treatment in preventing the long term complications of PID comes from the PEACH study where women were treated with cefoxitin followed by doxycycline – pregnancy rates after 3 years were similar or higher than those in the general population.
The choice of an appropriate treatment regimen may be influenced by:
- Robust evidence on local antimicrobial sensitivity patterns
- Robust evidence on the local epidemiology of specific infections in this setting
- Patient preference and compliance
- Severity of disease
- Rest is advised for those with severe disease (Grade C [IV]).
- Appropriate analgesia should be provided (Grade C [IV]).
- Intravenous therapy is recommended for patients with more severe clinical disease (Grade C [IV]) (e.g., pyrexia >38ºC, clinical signs of tubo-ovarian abscess, signs of pelvic peritonitis)
- Patients should be advised to avoid unprotected intercourse until they and their partner(s) have completed treatment and follow up (Grade C [IV]).
- 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 (Grade C [IV]).
- When giving information to patients, the clinician should consider the following:
- An explanation of what treatment is being given and its possible adverse effects
- Following treatment fertility is usually maintained but there remains a risk of future infertility, chronic pelvic pain or ectopic pregnancy.
- Clinically more severe disease is associated with a greater risk of sequelae.
- Repeat episodes of PID are associated with an exponential increase in the risk of infertility.
- The earlier treatment is given the lower the risk of future fertility problems.
- Future use of barrier contraception will significantly reduce the risk of PID.
- The need to screen her sexual contacts for infection to prevent her becoming reinfected
Outpatient therapy is as effective as inpatient treatment for patients with clinically mild to moderate PID. Admission for parenteral therapy, observation, further investigation and/or possible surgical intervention should be considered in the following situations:
- A surgical emergency cannot be excluded
- Lack of response to oral therapy
- Clinically severe disease
- Presence of a tubo-ovarian abscess
- Intolerance to oral therapy
All sexually active patients should be offered:
- A pregnancy test
- Screening for sexually transmitted infections including human immunodeficiency virus (HIV)
The following antibiotic regimens are evidence based.
All the recommended regimens are of similar efficacy.
Metronidazole is included in some regimens to improve coverage for anaerobic bacteria. Anaerobes are of relatively greater importance in patients with severe PID and metronidazole may be discontinued in those patients with mild or moderate PID who are unable to tolerate it.
Ofloxacin and moxifloxacin should be avoided in patients who are at high risk of gonococcal PID because of increasing quinolone resistance in the UK (e.g., when the patient's partner has gonorrhoea, in clinically severe disease, following sexual contact abroad). Quinolones should also be avoided as first line empirical treatment for PID in areas where >5% of PID is caused by quinolone resistant Neisseria gonorrhoeae.
Levofloxacin is the L isomer of ofloxacin and has the advantage of once daily dosing (500 mg once daily [OD] for 14 days). It may be used as a more convenient alternative to ofloxacin.
Replacing intramuscular ceftriaxone with an oral cephalosporin (e.g., cefixime) is not recommended because there is no clinical trial evidence to support its use, and tissue levels are likely to be lower which might impact on efficacy. Reports of decreasing susceptibility of Neisseria gonorrhoeae to cephalosporins also support the use of parenteral based regimens when gonococcal PID is suspected (to maximise tissue levels and overcome low level resistance).
- Intramuscular ceftriaxone 500 mg immediately, followed by azithromycin 1 g/week for 2 weeks (Grade A [Ib])
Clinical trial evidence for this regimen is limited but it may be used when the treatments above are not appropriate (e.g. allergy, intolerance).
- Oral moxifloxacin 400 mg once daily for 14 days (Grade A [Ib])
Three large randomized controlled trials (RCTs) support the efficacy of moxifloxacin for PID but because of evidence of an increased risk of liver reactions and other serious risks (such as QT interval prolongation), oral moxifloxacin should be used only when it is considered inappropriate to use the other antibacterial agents recommended for PID or when these have failed.
Intravenous (i.v.) therapy should be continued until 24 hours after clinical improvement and then switched to oral. Intravenous doxycycline is not currently licensed in the UK but is available from IDIS World Medicines (01932 824100).
Clinical trial evidence for the following regimens is more limited but they may be used when the treatments above are not appropriate (e.g., allergy, intolerance):
- Intravenous ofloxacin 400 mg twice daily plus i.v. metronidazole 500 mg 3 times daily for 14 days (Grade B [III])
- Intravenous ciprofloxacin 200 mg twice daily plus i.v. (or oral) doxycycline 100 mg twice daily plus i.v. metronidazole 500 mg 3 times daily for 14 days (Grade B [III])
There is no evidence of the superiority of any one of the suggested regimens over the others. Therefore patients known to be allergic to one of the suggested regimens should be treated with an alternative.
Pregnancy and Breastfeeding
- PID in pregnancy is associated with an increase in both maternal and fetal morbidity; therefore, parenteral therapy is advised although none of the suggested evidence based regimens is of proven safety in this situation.
- There are insufficient data from clinical trials to recommend a specific regimen and empirical therapy with agents effective against gonorrhoea, chlamydial and anaerobic infections should be considered, taking into account local antibiotic sensitivity patterns (e.g., intramuscular ceftriaxone plus oral or i.v. erythromycin, with the possible addition of oral or i.v. metronidazole 500 mg 3 times daily in clinically severe disease) (Grade C [IV]).
- The risk of giving any of the recommended antibiotic regimens (listed above for non pregnant women) in very early pregnancy (prior to a pregnancy test becoming positive) is justified by the need to provide effective therapy and the low risk to the foetus.
- Laparoscopy may help early resolution of the disease by dividing adhesions and draining pelvic abscesses, but ultrasound guided aspiration of pelvic fluid collections is less invasive and may be equally effective.
- It is also possible to perform adhesiolysis in cases of perihepatitis although there is no evidence whether this is superior to only using antibiotic therapy.
- Current male partners of women with PID should be contacted and offered health advice and screening for gonorrhoea and chlamydia. 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 may be influenced by the sexual history (Grade C [IV]).
- Gonorrhoea or chlamydia diagnosed in the male partner should be treated appropriately and concurrently with the index patient (Grade C [IV]).
- Because many cases of PID are not associated with gonorrhoea or chlamydia, broad spectrum empirical therapy should also be offered to male partners e.g., azithromycin 1 g single dose (Grade C [IV]).
- If screening for gonorrhoea is not available additional specific antibiotics effective against Neisseria gonorrhoeae should be offered, e.g., i.m. ceftriaxone 500 mg single dose (see also UK National Guidelines for Gonorrhoea) (Grade C [IV]).
- Partners should be advised to avoid intercourse until they and the index patient have completed the treatment course (Grade C [IV]).
Review at 72 hours is recommended, particularly for those with a moderate or severe clinical presentation, and should show a substantial improvement in clinical symptoms and signs (Grade C [IV]). Failure to do so suggests the need for further investigation, parenteral therapy and/or surgical intervention.
Further review 2-4 weeks (Grade C [IV]) after therapy may be useful to ensure:
- Adequate clinical response to treatment
- Compliance with oral antibiotics
- Screening and treatment of sexual contacts
- Awareness of the significance of PID and its sequelae
- Repeat pregnancy test, if clinically indicated
Repeat testing for gonorrhoea or chlamydia after 2 to 4 weeks is appropriate in those in whom persisting symptoms, antibiotic resistance pattern (gonorrhoea only), compliance with antibiotics and/or tracing of sexual contacts indicate the possibility of persisting or recurrent infection.
Levels of Evidence
||Type of Evidence
||Evidence obtained from meta-analysis of randomised controlled trials
||Evidence obtained from at least one randomised controlled trial
||Evidence obtained from at least one well-designed controlled study without randomisation
||Evidence obtained from at least one type of well-designed quasi-experimental study
||Evidence obtained from well-designed, non-experimental descriptive studies, such as comparative studies, correlation studies and case control studies
||Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
Grades of Recommendation
|A (Evidence levels Ia, Ib)
||Requires at least one randomised controlled 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 level 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