Academic Writing Do's & Don'ts

Academic Writing Do's & Don'ts

More PowerPoint presentations from april

Leprosy

leprocy

More PowerPoint presentations from deepak talreja

‎70th Annual Meeting -American Academy of Dermatology - March 16-20, 2012

Annual Meeting Program Book 2012

http://onlinedigitalpublishing.com/publication/?i=84683

Single-blind, randomized controlled trial evaluating the treatment of facial seborrheic dermatitis with hydrocortisone 1% ointment compared with tacrolimus 0.1% ointment in adults

Papp KA, Papp A, Dahmer B, Clark CS; Journal of the American Academy of Dermatology (Nov 2011)

BACKGROUND: Tacrolimus is a topical calcineurin inhibitor with immunomodulatory, anti-inflammatory, and fungicidal properties that may be beneficial in the treatment of facial seborrheic dermatitis. OBJECTIVES: We sought to compare the efficacy and safety of tacrolimus with standard corticosteroid treatment in adults with facial seborrheic dermatitis in a phase II, single-blind, randomized controlled trial. METHODS: Adult patients were enrolled in a 12-week study. Subjects were randomized to tacrolimus 0.1% ointment (n = 16) or hydrocortisone 1% ointment (n = 14) applied twice daily to symptomatic regions of the face. The primary efficacy measure was the severity of facial seborrhea at the end of treatment (day 84) as measured by the Seborrhea Area and Severity Index-Face. Secondary efficacy measures included physician and patient assessment of seborrhea, the frequency of medication application, and adverse events. RESULTS: The severity of facial seborrhea was similarly improved in both treatment groups (P = .86). Tacrolimus 0.1% ointment was used on significantly fewer days than 1% hydrocortisone ointment (mean missed doses per patient at first visit: 15.6 vs 7.6, P<.05; at last visit: 13.5 vs 7.7, P = .08). The majority of doses were missed because of lack of symptoms. The adverse event profile for both agents was similar; however, there was a numerically higher incidence of adverse events in the hydrocortisone group. LIMITATIONS: This was a small, open-label study. CONCLUSION: Tacrolimus 0.1% ointment required significantly fewer applications compared with hydrocortisone 1% ointment to achieve a comparable clinical response in adults with facial seborrheic dermatitis. Tacrolimus was generally well tolerated.

Cutaneous Manifestations of Systemic Diseases

Cutaneous Manifestations of Systemic Diseases ppt

Found at ebookbrowse.com

New HIV CME Activity: SCALE Virtual Clinic- MKT

Dear Colleague, On behalf of The Johns Hopkins University School of Medicine and The Institute for Johns Hopkins Nursing, we are pleased to invite you to visit our latest online program: The SCALE (Screening, Counseling, and Linkage to Care Education) HIV- Virtual Clinic. The SCALE HIV Virtual Clinic features two virtual patients presenting to your practice. You’ll use your clinical skills to ensure that these patients are properly screened, counseled, and linked to proper care. The Virtual Clinic also offers goal tracking and the ability to network with your colleagues. Each activity offers 1.0 AMA PRA Category 1 credits™. We will soon be launching our SCALE HIV iPhone/iPod Touch application! The application includes the following tools: 1) Guidance on HIV Counseling and Testing 2) A database of HIV experts 3) Practitioner FAQs For more information or to register for the SCALE HIV Virtual Clinic, please visitwww.SCALEHIV.org. With best regards, Gail V. Berkenblit, MD, PhD Assistant Professor of Medicine Johns Hopkins University School of Medicine Baltimore, MD         Joseph Cofrancesco, MD, MPH, FACP Associate Professor of Medicine Director, Institute for Excellence in Education Johns Hopkins University School of Medicine Baltimore, MD

ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Johns Hopkins University School of Medicine and the Institute for Johns Hopkins Nursing. The Johns Hopkins University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians. The Institute for Johns Hopkins Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. The Institute for Johns Hopkins Nursing and the American Nurses Credentialing Center do not endorse the use of any commercial products discussed or displayed in conjunction with this educational activity. CREDIT DESIGNATIONS Physicians The Johns Hopkins University School of Medicine designates this enduring material for a maximum of 2.0 AMA PRA Category1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurses This 2.0 contact hour Educational Activity is provided by the Institute for Johns Hopkins Nursing. Each patient carries a maximum of 1.0 contact hours or a total of 2.0 contact hours for the two patient in this program. Release date: 7/21/11 This activity expires two years from the date of publication. There are no prerequisites and no fee. CONFIDENTIALITY DISCLAIMER FOR CME CONFERENCE ATTENDEES I certify that I am attending a Johns Hopkins University School of Medicine CME activity for accredited training and/or educational purposes. I understand that while I am attending in this capacity, I may be exposed to "protected health information," as that term is defined and used in Hopkins policies and in the federal HIPAA privacy regulations (the "Privacy Regulations"). Protected health information is information about a person’s health or treatment that identifies the person. I pledge and agree to use and disclose any of this protected health information only for the training and/or educational purposes of my visit and to keep the information confidential. I understand that I may direct to the Johns Hopkins Privacy Officer any questions I have about my obligations under this Confidentiality Pledge or under any of the Hopkins policies and procedures and applicable laws and regulations related to confidentiality. The contact information is: Johns Hopkins Privacy Officer, telephone: 410-735-6509, e-mail:HIPAA@jhmi.edu. “The Office of Continuing Medical Education at the Johns Hopkins University School of Medicine, as provider of this activity, has relayed information with the CME attendees/participants and certifies that the visitor is attending for training, education and/or observation purposes only.” For CME Questions, please contact the CME Office at (410) 955-2959 or e-mailcmenet@jhmi.edu. For CME Certificates, please call (410) 502-9634. Johns Hopkins University School of Medicine Office of Continuing Medical Education Turner 20/720 Rutland Avenue Baltimore, Maryland 21205-2195 Reviewed & Approved by: General Counsel, Johns Hopkins Medicine (4/1/03) Updated 4/09

Leprosy and the natural selection for psoriasis

Leprosy and the natural selection for psoriasis

Ioannis D. Bassukas^a, , , Georgios Gaitanis^a, Max Hundeiker^b

a	Department of Skin and Venereal Diseases, University of Ioannina Medical School, Ioannina, Greece

b	Department of Dermatology, Fachklinik Hornheide, University of Münster, Münster, Germany

Received 19 July 2011; Accepted 21 October 2011. Available online 12 November 2011.

Abstract

Psoriasis is a genetically determined, almost worldwide-distributed inflammatory skin disease with overall higher prevalence among people of northern European ancestry. Since enhanced innate immunity is an important feature of the pathophysiology of this disease, it has been proposed that differences in the prevalence of psoriasis in different populations mainly result from differences in natural selection for gene polymorphisms associated with more vigorous immunity against infectious agents. However the infectious agent(s) that could have acted upon human population as selection pressure for psoriasis is still obscure. Based on the remarkable clinical observation that psoriasis and leprosy are almost mutually exclusive, a fact that is further supported by divergent HLA patterns in patients with psoriasis and leprosy we propose that “resisting leprosy” may have been the evolutionary advantage that favoured the expansion of some psoriasis-associated genotypes especially in the progenitors of modern Europeans. Moreover, we suggest that the spreading out of a certain genetic resistance trait may offer a supplementary explanation for the better understanding of the relatively rapid decline of leprosy in the late medieval epoch in Europe. Both genetic and paleoepidemiologic methods could be employed in order to challenge the present hypothesis.

Article Outline

• Introduction
• Hypothesis
• Evidence that psoriasis was selected to resist leprosy
• Leprosy affects fecundity and can act as selection pressure for a relatively frequent phenotype
• Mechanisms of leprosy resistance in psoriasis
• • Psoriasis is an immunological state of increased resistance against mycobacterial infections
  • Molecular mechanisms of leprosy resistance in psoriasis
  • • Toll-like receptors (TLRs) in leprosy and psoriasis
    • Type 1 cytokine axis in leprosy and psoriasis
    • ERBB2 - ERK1/2 pathway in leprosy and psoriasis
• A paleoepidemiologic consequences of the present hypothesis: did psoriasis contribute to the decline of leprosy in medieval Europe?
• Evaluation of the hypothesis
• Conflict of interest
• Funding source
• References

Bụi Phấn

Khi thầy viết bảng bụi phấn rơi rơi
Có hạt bụi nào rơi trên bục giảng, có hạt bụi nào rơi trên tóc thầy.
Em yêu phút giây này thầy em tóc như bạc thêm bạc thêm vì bụi phấn để cho em bài học hay

Mai sau lớn lên người làm sao có thể nào quên
Ngày xưa thầy dạy dỗ khi em tuổi còn thơ...


Khi thầy viết bảng bụi phấn rơi rơi
Có hạt bụi nào rơi trên bục giảng, có hạt bụi nào rơi trên tóc thầy.
Em yêu phút giây này thầy em tóc như bạc thêm bạc thêm vì bụi phấn để cho em bài học hay

Mai sau lớn lên người làm sao có thể nào quên
Ngày xưa thầy dạy dỗ khi em tuổi còn thơ.

Em yêu phút giây này thầy em tóc như bạc thêm bạc thêm vì bụi phấn để cho em bài học hay
Mai sau lớn lên người làm sao có thể nào quên
Ngày xưa thầy dạy dỗ khi em tuổi còn thơ.

Pelvic inflammatory disease

In the right clinical topic?

Age from 13 years onwards

This PRODIGY topic is based on guidelines on the management of acute pelvic inflammatory disease from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], and the European guideline for the management of pelvic inflammatory disease [Ross et al, 2008].

This PRODIGY topic covers the management of acute pelvic inflammatory disease (PID).

This PRODIGY topic does not cover chronic PID, chronic pelvic pain, postpartum endometritis, or PID following childbirth.

There are separate PRODIGY topics on Bacterial vaginosis, Candida - female genital, Chlamydia - uncomplicated genital, and Trichomoniasis.

The target audience for this PRODIGY topic is healthcare professionals working within the NHS in England, and providing first contact or primary health care. Patient information from NHS Choices is intended to be printed and given to people with this condition or their carers.

How up-to-date is this topic?

Changes

Version 1.4, revision planned in 2013.

Last revised in August 2009

October 2011 — minor update. The dose of intramuscular ceftriaxone has been increased from 250 mg to 500 mg to reflect the reduced sensitivity of Neisseria gonorrhoeae to cephalosporins and the current UK treatment guidelines for uncomplicated gonorrhoea [BASHH, 2011b]. Issued in November 2011.

May 2011 — minor update. Expanded on the advice and management of sexual partner nodes to include new recommendations from the British Association for Sexual Health and HIV [BASHH, 2011a]. Also included two new randomized controlled trials that suggest that moxifloxacin monotherapy is therapeutically equivalent to other regimens in the treatment of uncomplicated pelvic inflammatory disease [Heystek and Ross, 2009;Judlin et al, 2010]. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.

February 2011 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that moxifloxacin should be restricted to second-line use for the management of pelvic inflammatory disease, because of the increased risk of liver reactions and QT prolongation [MHRA, 2011]. Issued in February 2011.

August 2010 — updated to include oral cefixime 400 mg as a single dose as an alternative to the intramuscular ceftriaxone component of the recommended antibiotic regimens [HPA and Association of Medical Microbiologists, 2010]. The lower age limit for quinolone prescriptions has also been raised from 16 to 18 years. Issued in September 2010.

March to August 2009 — converted from PRODIGY guidance to PRODIGY topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

There are no major changes to the recommendations.

Previous changes

September 2008 — minor correction to the Changes section. Issued September 2008.

January to March 2006 — reviewed. Validated in June 2006 and issued in July 2006.

October 2005 — minor technical update. Issued in November 2005.

December 2002 — reviewed. Validated in March 2003 and issued in April 2003.

December 1999 — written. Validated in March 2000 and issued in May 2000.

Knowledge update

New evidence

Evidence-based guidelines

Evidence-based guidelines published since the last revision of this topic:

• BASHH (2011) UK national guideline for the management of pelvic inflammatory disease 2011. British Association for Sexual Health and HIV.www.bashh.org [Free Full-text]

HTAs (Health Technology Assessments)

No new HTAs since 1 January 2009.

Economic appraisals

No new economic appraisals relevant to England since 1 January 2009.

Systematic reviews and meta-analyses

No new systematic review or meta-analysis since 1 January 2009.

Primary evidence

Randomized controlled trials published since the last revision of this topic:

• Oaskeshott, P., Kerry, S., Aghaizu, A., et al. (2010) Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial. BMJ 340(Apr 8), c1642. [Abstract] [Free Full-text]

Observational studies published since the last revision of this topic:

• Nicholson, A., Rait, G., Murray-Thomas, T., et al. (2010) Management of first-episode pelvic inflammatory disease in primary care: results from a large UK primary care database. British Journal of General Practice 60(579), e395-e406. [Abstract]

New policies

No new national policies or guidelines since 1 January 2009.

New safety alerts

No new safety alerts since 1 January 2009.

Changes in product availability

No changes in product availability since 1 January 2009.

Goals and outcome measures

Goals

• To recognize the condition promptly
• To make an accurate assessment (for example of the severity of the illness)
• To begin appropriate treatment in the primary care setting
• To refer to secondary care or other specialist service as required
• To provide appropriate advice to the woman

QIPP - options for local implementation

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Review the appropriateness of NSAID prescribing widely and on a routine basis. Older patients are at higher risk of both gastrointestinal and cardiovascular morbidity and mortality.
• Co-prescribing NSAIDs with angiotensin converting enzyme inhibitors (ACE inhibitors) may pose particular risks to renal function; this combination should be especially carefully considered and regularly monitored if continued.
• If initiating an NSAID is obligatory, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day).
• Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day).
• Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA and NICE guidance.
• Co-prescribe a proton pump inhibitor with NSAIDs in accordance with NICE [NICE, 2008; NICE, 2009] .

[NPC, 2011]

Background information

What is it?

• Pelvic inflammatory disease (PID) is a general term for infection of the upper genital tract. Infection spreads upwards from the endocervix causing one or more of the following [CDC, 2006; RCOG, 2009; BASHH, 2011a]:
• Endometritis.
• Salpingitis.
• Parametritis.
• Oophoritis.
• Tubo-ovarian abscess.
• Pelvic peritonitis.

What causes it?

• Pelvic inflammatory disease (PID) is almost always a sexually transmitted disease.
• PID develops in 10–45% of women with endocervical Neisseria gonorrhoeae infection and in 10–30% of women with endocervical Chlamydia trachomatisinfection [Utah Department of Health, 2008].
• Very rarely, PID follows instrumentation of the uterus.
• The commonest sexually transmitted organisms detected in PID are C trachomatis and N gonorrhoeae.
• Organisms in normal vaginal flora (such as anaerobes, Gardnerella vaginalis, Haemophilus influenzae, enteric Gram-negative rods, and Streptococcus agalactiae) have also been implicated.
• Other organisms associated with PID include cytomegalovirus, Mycoplasma hominis, Ureaplasma urealyticum, and Mycoplasma genitalium [Barrett and Taylor, 2005; CDC, 2006; RCOG, 2009; BASHH, 2011a].

How common is it?

• The incidence of PID is unknown because of the difficulty in making a clinical diagnosis, and because pelvic inflammatory disease (PID) is often unrecognized if it presents atypically or is asymptomatic [Simms et al, 1999].
• An Office of Population Censuses Survey (1991–1992) of 60 general practices in England and Wales showed that PID was diagnosed in 1.7% of GP attendances by women 16–46 years of age [Simms et al, 1999].

What are the complications?

• Tubal infertility, ectopic pregnancy, and chronic pelvic pain are the main complications of pelvic inflammatory disease [Drife and Magowan, 2004].

Management

Which scenario?

• Scenario: Diagnosis: covers the diagnosis of pelvic inflammatory disease (PID).
• Scenario: Management: covers the management of acute PID.

Scenario: Diagnosis of pelvic inflammatory disease

How should I diagnose pelvic inflammatory disease?

• A diagnosis of pelvic inflammatory disease (PID) should be made on clinical grounds.
• Negative swab results do not rule out a diagnosis of PID.
• Do not delay making a diagnosis and initiating treatment whilst waiting for the results of laboratory tests.
• Ectopic pregnancy should be ruled out.
• Suspect PID if any of the following symptoms are present:
• Pelvic or lower abdominal pain (usually bilateral).
• Deep dyspareunia particularly of recent onset.
• Abnormal vaginal bleeding (intermenstrual, postcoital, or 'breakthrough') which may be secondary to associated cervicitis and endometritis.
• Abnormal vaginal or cervical discharge as a result of associated cervicitis, endometritis, or bacterial vaginosis. This is often very slight and may be transient, especially with chlamydial infection.
• Right upper quadrant pain due to peri-hepatitis (Fitz–Hugh–Curtis syndrome).
• Peri-hepatitis occurs in 10–20% of women with PID.
• It is characterized by the development of adhesions between the liver and the peritoneum, causing right upper quadrant pain.
• On examination look for:
• Lower abdominal tenderness — usually bilateral.
• Adnexal tenderness (with or without a palpable mass), cervical motion tenderness, uterine tenderness (on bimanual vaginal examination).
• Abnormal cervical or vaginal mucopurulent discharge (on speculum examination).
• A fever of greater than 38°C, although the temperature is often normal.
• Take endocervical swabs for gonorrhoea and chlamydia and a high vaginal swab. Consider taking blood for a white cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein.
• For more information see Investigations.

Basis for recommendation

Making a diagnosis of PID on history and examination alone

• These recommendation are based on expert opinion in guidelines on the management of acute pelvic inflammatory disease (PID) from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], and guidelines from the Department of Health and Human Services Centres for Disease Control and Prevention [CDC, 2006].
• Making an accurate clinical diagnosis of PID from the symptoms and signs has been described as 'little better than tossing a coin' [Ross, 2002] and clinicians should have a low threshold for initiating treatment.
• Symptoms and signs for suspected PID lack sensitivity and specificity [RCOG, 2009]. The positive predictive value of making a clinical diagnosis of PID compared with a laparoscopic diagnosis (using laparoscopic diagnosis as the gold standard) is 65–90% [RCOG, 2009]. However, although used as the gold standard, laparoscopy may have a low sensitivity, as 15–30% of women with suspected PID have no signs of acute infection on laparoscopy even when organisms have been found in their fallopian tubes [RCOG, 2009].
• The positive predictive value of a clinical diagnosis of PID also depends on epidemiological factors, including [CDC, 2006]:
• The age of the woman (PID is more common in adolescents).
• Whether the woman is attending a genito-urinary medicine clinic.
• Whether the woman is in a setting where the rates of chlamydia, gonorrhoea, and bacterial vaginosis are high [BASHH, 2011a].
• There is evidence from a large cross-sectional analysis that:
• Adnexal tenderness has a high sensitivity for PID.
• The finding most strongly associated with endometritis was a positive test result for Chlamydia trachomatis or Neisseria gonorrhoeae.

Endocervical and high vaginal swabs

• The recommendation that all women with suspected PID should be tested for C. trachomatis and N. gonorrhoeae (in general by taking endocervical swabs) is based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], the European guideline for the management of pelvic inflammatory disease[Ross et al, 2008], and guidelines from the Department of Health and Human Services Centres for Disease Control and Prevention [CDC, 2006]. These are the most common sexually transmitted organisms detected in PID.
• PRODIGY recommends taking a high vaginal swab to look for other vaginal infections such as bacterial vaginosis and candidiasis.

Erythrocyte sedimentation rate (ESR), C-reactive protein, and leucocyte count

• Increased ESR, C-reactive protein, and leucocyte count supports the diagnosis of PID and can provide useful measures of disease severity[RCOG, 2009].
• However, the ESR or C-reactive protein and white cell count may be normal in mild or moderate PID [Ross et al, 2008].

Who is at risk of developing pelvic inflammatory disease?

• Risk factors for developing pelvic inflammatory disease include:
• Factors related to sexual behaviour:
• Young age (less than 25 years).
• Early age of first coitus.
• Multiple sexual partners.
• Recent new partner (within the previous 3 months).
• History of sexually transmitted infection in the woman or her partner.
• Recent instrumentation of the uterus or interruption of the cervical barrier:
• Termination of pregnancy.
• Insertion of an intrauterine device (within the past 6 weeks).
• Hysterosalpingography.
• In vitro fertilization and intrauterine insemination.

Basis for recommendation

These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], the European guideline for the management of pelvic inflammatory disease[Ross et al, 2008], and a non-systematic review [Barrett and Taylor, 2005].

What else might it be?

• Lower abdominal pain in a young woman may also be due to:
• An ectopic pregnancy.
• Threatened abortion.
• Ruptured corpus luteal cyst.
• Acute appendicitis:
• Nausea and vomiting occur in most women with appendicitis, but in only 50% of women with pelvic inflammatory disease.
• Cervical motion pain occurs in about 25% of women with acute appendicitis.
• Endometriosis.
• Gastrointestinal disorders (most commonly irritable bowel syndrome).
• Complications of an ovarian cyst, such as rupture, torsion, or haemorrhage.
• Urinary tract infection.
• Functional pain (that is of unknown physical origin). There may be longstanding symptoms.
• Mittelschmerz pain.

Basis for recommendation

These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], the European guideline for the management of pelvic inflammatory disease[Ross et al, 2008], and a guideline that was adapted for use in the Department of Pediatrics at the University of Texas — Houston Health Science Center [Eissa and Cromwell, 2003].

What investigations should I do?

• Do a pregnancy test if pregnancy is a possibility.
• Take endocervical swabs for Chlamydia trachomatis and Neisseria gonorrhoeae.
• If uncertain, confirm with the local laboratory which testing methods are available, the samples required, and how soon these should reach the laboratory.
• In general, chlamydia should be tested for by taking endocervical samples, using nucleic acid amplification tests (NAATs). First-catch urine samples or vulvovaginal swabs may be accepted for NAAT testing by some laboratories.
• Endocervical swabs for N. gonorrhoeae should be sent in transport medium to arrive at the laboratory for culture within 24 hours. NAATs may be used, but a positive NAAT should be confirmed using a second NAAT test with a different primer sequence, or with culture.
• Adequate sample collection is important. When taking an endocervical swab, the swab should be inserted inside the cervical os and firmly rotated against the endocervix. Swabbing a collection of discharge will result in an inadequate specimen, so it is generally recommended that excess cervical secretions are cleaned away prior to taking the swab.
• There is no need to take a urethral swab unless local guidelines suggest this.
• If possible, look for endocervical or vaginal pus cells under a microscope on a wet-mount vaginal smear:
• If absent, a diagnosis of pelvic inflammatory disease (PID) is unlikely.
• Excess leucocytes are associated with PID but they are also found in women with lower genital tract infection.
• Consider performing the following tests. If elevated they support the diagnosis of PID but are non-specific:
• Erythrocyte sedimentation rate (ESR).
• C-reactive protein.
• Leucocyte count.

Basis for recommendation

Taking swabs for Chlamydia trachomatis and Neisseria gonorrhoeae

• The recommendation that all women with suspected PID should be tested for C. trachomatis and N. gonorrhoeae is based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV[BASHH, 2011a], the European guideline for the management of pelvic inflammatory disease [Ross et al, 2008], and guidelines from the Department of Health and Human Services — Centres for Disease Control and Prevention [CDC, 2006].
• A positive result supports a diagnosis of PID and reinforces the need to treat sexual partners.
• However, a negative result does not exclude PID [BASHH, 2011a].

Interpreting the results of a wet-mount smear

• The absence of endocervical or vaginal pus cells suggests that the diagnosis is not PID. The negative predictive value for a diagnosis of PID is 95% (that is, 19/20 people who have a negative test result will not have the disease) [BASHH, 2011a; RCOG, 2009].
• The presence of pus cells is a non-specific finding. The positive predictive value is low (that is, the proportion of people who have a positive test result and who have PID is only 17%) [RCOG, 2009; BASHH, 2011a].

Erythrocyte sedimentation rate (ESR), C-reactive protein, and leucocyte count

• Increased ESR or C-reactive protein, and leucocytosis, all support the diagnosis of PID and can provide a useful measure of disease severity[RCOG, 2009].
• However, the ESR, C-reactive protein, or white cell count may be normal in mild or moderate PID [Ross et al, 2008].

Scenario: Management of pelvic inflammatory disease

How should I manage someone with suspected PID?

• Women with suspected mild or moderate pelvic inflammatory disease (PID) may be treated in primary care if an ectopic pregnancy can be ruled out.
• Test for other sexually transmitted infections and other genital infections.
• Refer the woman and her sexual partner(s) to a genito-urinary medicine or sexual health clinic to facilitate screening for infections (and contact tracing). Ideally the woman should be screened for other sexually transmitted diseases before commencing antibiotics so that a diagnosis can be made and is not compromised. However starting antibiotics is a priority if PID is suspected and should not be delayed whilst awaiting an appointment.
• Provide pain relief with ibuprofen or paracetamol. If the response to either drug is insufficient consider:
• Combining/alternating paracetamol and ibuprofen, or
• Adding codeine to paracetamol or ibuprofen.
• Start empirical antibiotics as soon as a presumptive diagnosis of PID is made clinically. Do not wait for swab results.
• If the risk of gonococcal infection is low prescribe any of the following:
• Ofloxacin 400 mg orally twice daily plus oral metronidazole 400 mg twice daily, both for 14 days. (Levofloxacin may be used as a more convenient alternative to ofloxacin).
• Ceftriaxone 500 mg as a single intramuscular dose, followed by oral doxycycline 100 mg twice daily plus oral metronidazole 400 mg twice daily, both for 14 days.
• Ceftriaxone 500 mg as a single intramuscular dose, followed by oral azithromycin 1 g per week for 2 weeks (there is less evidence to support this regimen).
• Oral cefixime 400 mg as a single dose (off-label use) can be used as an alternative to ceftriaxone 500 mg in the above regimens.
• If the risk of gonococcal infection is high (the woman's partner has gonorrhoea, her symptoms and signs are clinically severe, or she has had sexual contact whilst abroad) prescribe either of the following:
• Ceftriaxone 500 mg as a single intramuscular dose, followed by oral doxycycline 100 mg twice daily plus oral metronidazole 400 mg twice daily, both for 14 days.
• Cefixime 400 mg as a single oral dose (off-label use), plus oral doxycycline 100 mg twice daily and oral metronidazole 400 mg twice daily, both for 14 days.
• Regimens containing ofloxacin or azithromycin are not recommended in people at high risk of gonococcal PID.
• A regimen of metronidazole and doxycycline (without intramuscular ceftriaxone) is not recommended.
• See Prescribing information for more information on the recommended antibiotics.
• If there is a risk of a very early pregnancy (too early for a pregnancy test to be positive):
• Offer paracetamol first line for analgesia. Ibuprofen is an alternative if paracetamol is ineffective but should only be used before 30 weeks gestation.
• The risk of giving any of the recommended antibiotic regimens at this stage of pregnancy is low. If drug toxicity did occur at this stage of pregnancy, it would result in failed implantation. For a more detailed discussion of potential risks, see Basis for recommendation.
• Admit women with a positive pregnancy test urgently.
• Treat women who are infected with HIV the same treatment as women who are not infected. PID should be managed in conjunction with their HIV physician.

Basis for recommendation

Women with mild or moderate PID can be treated in primary care

• There is evidence from a large randomized trial that women with mild-to-moderate PID can be safely treated at home. Outpatient and inpatient treatments are equally effective for women with clinically mild-to-moderate PID, and there is evidence that long-term reproductive outcomes are also similar.

Importance of excluding pregnancy

• National guidance from the Royal College of Obstetrics and Gynaecology stresses the importance of excluding an ectopic pregnancy in all women suspected of having PID [RCOG, 2009].

Referral for contact tracing and screening

• These recommendations are based on guidance from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009] and the British Association for Sexual Health and HIV [BASHH, 2011a].

Analgesia

• This recommendation is based on expert advice in the European guideline for the management of pelvic inflammatory disease [Ross et al, 2008]and the British Association for Sexual Health and HIV [BASHH, 2011a].

Importance of prompt treatment

• It is likely that delaying treatment increases the risk of the PID becoming worse, and increases the risk of complications such as ectopic pregnancy, subfertility, or chronic pelvic pain occurring in the future [CDC, 2006; Ross, 2008; RCOG, 2009; BASHH, 2011a].
• A low threshold for commencing an empirical antibiotic (that is, before the results of tests are available) is recommended because of the risk of serious complications if treatment is delayed. This is particularly important in women younger than 25 years of age because there is a higher incidence of PID in this age group.
• Negative swabs do not exclude PID and should not necessarily influence the decision to treat.
• There is limited evidence from a case-controlled study that fertility may be impaired and ectopic pregnancy may be more likely if treatment for acute pelvic inflammatory disease is delayed for 3 days or more after the onset of symptoms.

Recommended antibiotic regimens

• The antibiotic regimens included are those which are practical for use in primary care (that is, they do not require intravenous antibiotics) and are recommended in guidelines produced by the Royal College of Obstetricians and Gynaecologists (RCOG) and the British Association for Sexual Health and HIV (BASHH) [RCOG, 2009; BASHH, 2011a].
• These guidelines recognize that there is uncertainty about the optimum treatment regimen [RCOG, 2009] due to limited evidence from clinical trials. However, the recommended regimens are likely to be effective against the most likely pathogens involved (Chlamydia trachomatis, Neisseria gonorrhoeae,anaerobes).
• There is a better evidence base for the use of cefoxitin than ceftriaxone but, as it is not easily available in the UK, intramuscular ceftriaxone is recommended in its place [RCOG, 2009; BASHH, 2011a]. The dose of ceftriaxone has been increased to 500 mg to reflect the reduced sensitivity of N gonorrhoeae to cephalosporins and the current UK treatment guidelines for uncomplicated gonorrhoea [BASHH, 2011b].
• Metronidazole is included in the intramuscular ceftriaxone plus oral doxycycline regimen to improve coverage for anaerobic bacteria. However, anaerobic bacteria are of more importance in women with severe PID so metronidazole may be stopped in women with mild or moderate PID who cannot tolerate it [BASHH, 2011a].
• Ofloxacin, moxifloxacin and azithromycin should be avoided in women at high risk of gonorrhoea because of increasing resistance in the UK [BASHH, 2005; BASHH, 2011a].
• Levofloxacin is the L isomer of ofloxacin and may be used as a more convenient alternative to ofloxacin (500 mg once daily for 14 days) [BASHH, 2011a].
• Although PID presenting in primary care may be less severe than in other settings, there is no published evidence to support the use of less intensive regimens.
• Recent guidance from the RCOG and BASHH recommends the combination of intramuscular ceftriaxone and oral azithromycin but states that since clinical trial evidence for this regimen is limited, it should be reserved for when other regimens are not appropriate [RCOG, 2009; BASHH, 2011a]. There is limited evidence from two randomized controlled trials that azithromycin used alone or in combination with ceftriaxone is effective in the treatment of PID.

Oral cefixime as alternative to intramuscular ceftriaxone

• Ceftriaxone is included in the regimen primarily to cover gonorrhoea but it is not always practical to administer ceftriaxone in primary care. A single dose of oral cefixime 400 mg (off-label use) is recommended by the Health Protection Agency, as an alternative to the intramuscular ceftriaxone component of the regimens for practical issues of administration in primary care [HPA and Association of Medical Microbiologists, 2010].
• However, BASHH does not recommend replacing intramuscular ceftriaxone with an oral cephalosporin (such as cefixime) due to the lack of clinical trial evidence to support their use. There are reports of increased resistance of Neisseria gonorrhoeae to cephalosporins and a parenteral based regimen (when gonococcal PID is suspected) is thought to maximize tissue levels of the cephalosporin and overcome low level resistance [BASHH, 2011a].

Antibiotic regimens not recommended

• A combination of metronidazole and doxycyline (without intramuscular ceftriaxone). Although this regimen has been recommended in the past and is still used in primary care it is not recommended in the guidelines produced by the British Association for Sexual Health and HIV or the Royal College of Obstetricians and Gynaecologists [RCOG, 2009; BASHH, 2011a]. Guidelines from the Royal College of Obstetricians and Gynaecologists state that there are no clinical trials adequately assessing the effectiveness of this regimen, and its use in isolation (that is, without intramuscular ceftriaxone) is not recommended [RCOG, 2009]. There is evidence from a retrospective study and a systematic review that metronidazole combined with doxycycline is not suitable for the treatment of acute PID in the UK. The addition of intramuscular ceftriaxone as an initial dose significantly improved the clinical cure rate in the one retrospective study [Piyadigamage and Wilson, 2005].
• Azithromycin used alone (that is, without intramuscular ceftriaxone). Data supporting its use alone are limited and it is not recommended [RCOG, 2009].
• BASHH recommend that oral moxifloxacin can be used alone in the treatment of PID as there is evidence from three randomized controlled trials that it has similar efficacy to a combination of ofloxacin and metronidazole. However, due to the increased risk of liver reactions and other serious adverse effects with moxifloxacin, it should only be used when other appropriate regimens are unsuitable or have failed [BASHH, 2011a].
• PRODIGY does not recommend the use of oral moxifloxacin as it is a black triangle drug (under intensive surveillance by the Medicines and Healthcare products Regulatory Agency [MHRA]), and there are concerns that it may have similar issues with gonococcal resistance to ofloxacin. In addition, although moxifloxacin is now licensed for the treatment of PID, the MHRA has restricted its indications to second-line use when other medicines cannot be prescribed or have failed. This is because of an increased risk of life-threatening liver reactions and other serious risks associated with its use (such as prolongation of QT interval) [MHRA, 2008; MHRA, 2011 ].

Drug choice during very early pregnancy (before a positive pregnancy test)

• Experience suggests that paracetamol can be used at any time during pregnancy or breastfeeding [NTIS, 2004; Schaefer et al, 2007].
• The UK Teratology Information Service (UKTIS, formerly the National Teratology Information Service [NTIS]), reviewed safety data of NSAIDs from published research and postmarketing surveillance systems. They concluded that 'the available data do not indicate that exposure to ibuprofen before 30 weeks of pregnancy is associated with an increased risk of congenital defects or spontaneous abortions' [NTIS, 2004].
• The Royal College of Obstetricians and Gynaecologists recommends that the risk of giving any of their recommended antibiotic regimens in very early pregnancy (before a positive pregnancy test) is low, since significant drug toxicity results in failed implantation [RCOG, 2009].
• Ceftriaxone has not specifically been studied during pregnancy. However, the risk associated with use of cephalosporins during pregnancy is thought to be low and, although data are limited for individual agents such as ceftriaxone, the cephalosporins as a class are considered to be an appropriate choice during pregnancy [NTIS, 2008b]. Although ceftriaxone crosses the placental barrier, it has not been associated with adverse events on fetal development in laboratory animals [ABPI Medicines Compendium, 2009].
• Doxycycline is contraindicated beyond the 15th week of gestation because, from the 16th week of pregnancy it causes tooth and bone discolouration and inhibits bone growth. However, it can be used in the first trimester. Inadvertent first-trimester use of tetracyclines occurs frequently and has not been associated with an increased risk of congenital malformations [Schaefer et al, 2007].
• Metronidazole has been in clinical use for a long time, and experience suggests that it is not teratogenic in humans [Schaefer et al, 2007]. A recent prospective controlled study in 228 women exposed to metronidazole in pregnancy, 86% of whom had first trimester exposure, confirms these findings[Schaefer et al, 2007].
• Ofloxacin has only limited pregnancy-exposure data. Quinolones have caused arthropathy in animal studies. However, a recent study (most of the data are on ciprofloxacin and norfloxacin, but some are on ofloxacin) did not find that quinolone use in the first trimester of pregnancy was associated with an increased risk of malformations or other adverse effects on pregnancy outcome [Schaefer et al, 2007].
• There are fewer published data on the use of azithromycin rather than erythromycin during pregnancy and breastfeeding. The limited published data and follow-up data collected by the UK Teratology Information Service (UKTIS, formerly the National Teratology Information Service [NTIS]), do not demonstrate an increased risk of congenital malformations following exposure to azithromycin in human pregnancy [NTIS, 2008a].

Management of women with HIV

• Women with HIV may experience more severe symptoms of PID, but will usually respond to the standard antibiotic regimens. No change in treatment from that recommended for women without HIV infection is required [BASHH, 2011a]. There is no evidence to suggest that HIV-positive women benefit from hospitalization or parenteral treatment [Sweet, 2009].

When should I seek specialist advice or admit urgently?

• Admit urgently if:
• Ectopic pregnancy cannot be ruled out.
• Symptoms and signs are severe (such as nausea, vomiting, and a fever greater than 38°C).
• There are signs of pelvic peritonitis.
• A surgical emergency such as acute appendicitis cannot be ruled out.
• The woman is pregnant.
• A tubo-ovarian abscess is suspected.
• The woman is unwell and there is diagnostic doubt.
• The woman is unable to follow or tolerate an outpatient regimen.
• Consider seeking specialist advice:
• If the woman is immunocompromised (such as HIV, taking immunosuppressants).
• Admission is required for women who have HIV only if they have clinically severe pelvic inflammatory disease (PID).
• Discussion with a genito-urinary specialist or gynaecologist is advised if there is doubt regarding whether admission is necessary.
• If peri-hepatitis (Fitz–Hugh–Curtis syndrome) is suspected.

Basis for recommendation

Urgent admission

• These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], the European guideline for the management of pelvic inflammatory disease [Ross et al, 2008], and guidelines from the Department of Health and Human Services Centres for Disease Control and Prevention [CDC, 2006].

Pregnant women

• If the pregnancy is intrauterine, then pelvic inflammatory disease (PID) is rare except in the case of septic abortion [RCOG, 2009].
• The recommendation that pregnant women with PID should be admitted to hospital under the care of an obstetrician is based on expert opinion, as intravenous antibiotics are required because of the increased risk of maternal and fetal morbidity and pre-term delivery [CDC, 2006; Ross et al, 2008; RCOG, 2009; BASHH, 2011a].
• Neonatal complications can occur as a result of perinatal transmission of infection, such as ophthalmia neonatorum (due to Chlamydia trachomatisor Neisseria gonorrhoeae infection) and chlamydial pneumonitis [Brocklehurst and Rooney, 1998].

Women with HIV

• Women with HIV may experience more severe symptoms of PID. Expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists and the British Association for Sexual Health and HIV [RCOG, 2009; BASHH, 2011a] recommend that only women with severe disease should be admitted.

Suspected peri-hepatitis

• Guidelines from the Royal College of Obstetricians and Gynaecologists and the British Association for Sexual Health and HIV [RCOG, 2009; BASHH, 2011a] state that although laparoscopic division of adhesions is sometimes performed, there is insufficient trial evidence to make any recommendations other than giving the usual treatment for PID. PRODIGY therefore recommends seeking specialist advice if peri-hepatitis is suspected.

What advice should I give?

• Explain:
• The importance of completing the course of antibiotics (even if swabs are negative) in order to reduce the risk of long-term complications such as infertility, ectopic pregnancy, and chronic pelvic pain.
• The exception to this is if the woman has mild or moderate pelvic inflammatory disease (PID) and is unable to tolerate metronidazole. She may stop taking the metronidazole but must continue with the other antibiotics in the regimen.
• That after treatment fertility is usually maintained but there is still a risk of future long-term complications such as infertility, ectopic pregnancy, and chronic pelvic pain. Severe cases of PID are associated with a greater risk of these complications.
• The importance of screening for sexually transmitted infections.
• The need for contact tracing, and screening and treatment of sexual partners to prevent reinfection.
• The need to use a barrier method of contraception (such as a condom) until both the woman and her partner(s) have completed treatment.
• That future use of a barrier method of contraception will greatly reduce the risk of reinfection.
• That repeated episodes of PID are associated with an exponential increase in the risk of infertility.

Basis for recommendation

These recommendations are based on expert advice in guidelines from the Royal College of Obstetricians and Gynaecologists, the British Association for Sexual Health and HIV [BASHH, 2011a], and the European guideline for the management of pelvic inflammatory disease [Ross et al, 2008].

Complications of pelvic inflammatory disease (PID)

• Tubal infertility:
• There is evidence from prospective cohort studies that the risk of infertility is related to the number of episodes of pelvic inflammatory disease (PID) and their severity: 0.6% of women had tubal-factor infertility after an episode of mild PID, and 21.4% of women had tubal-factor infertility after an episode of severe PID.
• The risk of ectopic pregnancy is increased ten-fold after one episode of PID [Oakeshott, 2003].
• Estimates vary but chronic pelvic or abdominal pain (lasting for more than 6 months) develops in 18% of women who have had PID [Drife and Magowan, 2004]. There is evidence from a large randomized trial of 831 women who have had an episode of mild-to-moderate PID that chronic pelvic pain may be present in 34% of women at a mean follow up of 35 months [Ness et al, 2002].
• About a third of women have repeated infections [Drife and Magowan, 2004].

Discontinuation of metronidazole if it is not tolerated

• Although anaerobes may have a role in the pathogenesis of PID, they are probably of more importance in women who have severe PID. Expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV[BASHH, 2011a], and the European guideline for the management of pelvic inflammatory disease [Ross et al, 2008], based on studies which have not included metronidazole but have had good outcomes, is that if the PID is not severe and metronidazole is not tolerated then it may be stopped.

Referral for contact tracing and screening

• These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009] and the British Association for Sexual Health and HIV [BASHH, 2011a].

Avoiding unprotected sexual intercourse

• These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009] and the British Association for Sexual Health and HIV [BASHH, 2011a].

How should I manage sexual partners?

• Ideally, current partners and recent partners (within the last 6 months) should be seen in a genito-urinary medicine (GUM) clinic, or primary care facility with equivalent expertise, for screening, treatment, and contact tracing.
• Partners may need to be managed in primary care if they refuse or are unable to attend a GUM clinic, or if there is likely to be an unacceptable delay in accessing specialist services.
• Screen for chlamydia and gonorrhoea. Whilst awaiting the results, offer the woman and her partner(s) empirical treatment with a broad spectrum antibiotic such azithromycin (1 gram, single dose).
• If chlamydia or gonorrhoea is diagnosed in the partner(s), treat both the partner(s) and the woman appropriately.
• If it is not possible to adequately screen the partner(s) for gonorrhoea, additional treatment with a specific antibiotic effective against Neisseria gonorrhoeae (such as a single intramuscular dose of ceftriaxone 250 mg) should be given.
• For more information, see the PRODIGY topics on Chlamydia - uncomplicated genital and Gonorrhoea.
• Advise sexual abstinence until both the woman with pelvic inflammatory disease and her partner(s) have completed the course of treatment. A barrier method is recommended if sexual intercourse cannot be avoided.

Basis for recommendation

These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009] and the British Association for Sexual Health and HIV (BASHH)[BASHH, 2011a].

• Broad spectrum empirical treatment whilst awaiting results for gonorrhoea and chlamydia testing.
• BASHH recommend that broad spectrum empirical treatment should also be offered to male partners because many cases of pelvic inflammatory disease (PID) are not associated with gonorrhoea or chlamydia.

What follow up should I arrange?

• Review within 72 hours.
• There should be demonstrable clinical improvement (such as a reduction in abdominal tenderness, and a reduction in uterine, adnexal, and cervical motion tenderness).
• If there has been little or no improvement, consider admitting to hospital or review the diagnosis.
• Check the antibiotic sensitivities from swab results. Even if swabs are negative, treatment should be continued.
• If metronidazole is not tolerated it may be discontinued in women with mild or moderate pelvic inflammatory disease (PID) as it has uncertain efficacy in this group.
• Consider further review at about 4 weeks in order to:
• Check compliance with, and response to, treatment.
• Confirm that sexual contacts have been screened and treated.
• Discuss the potential sequelae of PID.
• Tests of cure are only necessary if:
• Symptoms persist after treatment.
• Antibiotic resistance is likely (particularly in cases of gonorrhoea).
• Poor compliance with treatment is suspected, or the treatment has not been tolerated.
• There is a possibility of reinfection (that is, further contact with untreated partners).
• Sensitivity testing has not been undertaken or has indicated resistance.

Basis for recommendation

These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], and the Department of Health and Human Services — Centres for Disease Control and Prevention [CDC, 2006].

Admission, if the woman is failing to improve

• Failure to improve substantially after 72 hours suggests a need for further investigation, intravenous therapy, or surgical intervention [BASHH, 2011a].

Discontinuation of metronidazole if it is not tolerated

• Although anaerobes may have a role in the pathogenesis of pelvic inflammatory disease (PID), they are probably of more importance in women who have severe PID. Expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009], the British Association for Sexual Health and HIV [BASHH, 2011a], and the European guideline for the management of pelvic inflammatory disease [Ross et al, 2008], based on studies which have not included metronidazole but have had good outcomes, suggests that if the PID is not severe and metronidazole is not tolerated then it may be stopped.

How should I manage a woman who has an intrauterine device in situ?

• Consider removing any contraceptive intrauterine device (IUD) in women presenting with pelvic inflammatory disease (PID), after discussion with the woman.
• Experts agree that the device should be removed if the woman wishes removal or if symptoms have not resolved within 72 hours.
• Evidence is limited and expert opinion is divided over whether it is necessary to remove the IUD at the initial presentation.
• If a decision is made to remove the IUD, ask if the woman has had sexual intercourse within the last 7 days and consider offering emergency hormonal contraception. For more information see the PRODIGY topic on Contraception - emergency.
• If the woman develops pelvic pain and has had actinomyces-like organisms (ALOs) identified on a smear in the past:
• Take endocervical swabs, and
• Urgently seek specialist advice regarding treatment.
• Consider removal of the IUD.

Basis for recommendation

Removal of an intrauterine device (IUD)

• Evidence on whether or not to remove an intrauterine device in a woman who has pelvic inflammatory disease is limited and conflicting. There are no long term data on the effects on fertility.
• Expert opinion differs regarding women with pelvic inflammatory disease (PID) who have an IUD:
• Expert advice in the Faculty of Sexual and Reproductive Healthcare clinical guideline on intrauterine contraception does not routinely recommend the removal of an IUD. The Faculty's Clinical Effectiveness Unit supports the continued use of intrauterine contraception and appropriate antibiotic treatment if PID is suspected; there is no need to remove the IUD unless symptoms fail to resolve within 72 hours or the woman wants it removed [FFPRHC, 2006;FSRH, 2007].
• Expert opinion in guidelines on the management of acute PID from the Royal College of Obstetricians and Gynaecologists [RCOG, 2009] advises that consideration be given to removing the IUD especially if symptoms have not resolved within 72 hours.
• The British Association for Sexual Health and HIV recommend considering removing the IUD if the woman develops PID. They advise balancing the decision to remove the IUD against the risk of pregnancy if the woman has had sexual intercourse in the preceding 7 days [BASHH, 2011a].
• Selected practice recommendations for contraceptive use from the World Health Organization state that [WHO, 2004]:
• There is no need for removal of the IUD if the woman wishes to continue its use.
• If the woman wishes removal, remove it after antibiotic treatment has been started.
• If the infection does not improve then generally the course would be to remove the IUD and continue antibiotics. If the IUD is not removed then the antibiotic should be continued and the woman should be monitored closely.

Presence of actinomyces-like organisms (ALOs)

• Expert opinion in guidelines from the Faculty of Sexual and Reproductive Healthcare is that [FSRH, 2007]:
• The role of ALOs in infection in women using intrauterine contraception is unclear. Actinomyces israelii is a commensal organism in the female genital tract and although these organisms may be found on cervical smears or swabs, their presence is not diagnostic or predictive of disease. Therefore, there is no need to remove an IUD if the woman does not have symptoms.
• If PID is suspected in a woman who has a history of ALOs on a cervical smear, it is important to consider that the infection may be due to other organisms.
• It may be appropriate to remove the IUD.

What contraceptive advice should I give?

• Women who have a history of, or currently have, pelvic inflammatory disease (PID) may use the following contraceptive methods (UK Medical Eligibility Criteria [UKMEC] category 1, that is, a condition for which there is no restriction for the use of the contraceptive method):
• Combined oral contraceptive (COC) pill.
• Progestogen-only pill.
• Depot progestogen injection.
• Progesterone-only contraceptive implant.
• For women with a history of PID who wish to have an intrauterine device (IUD) fitted:
• Explain that the relative risk of PID is increased six-fold in the 20 days following insertion, but that the absolute risk remains low (approximately 1%). After this time, the risk is the same as the population without an IUD and remains low unless there is exposure to sexually transmitted infection (STI).
• If the woman has had a subsequent pregnancy, there are no restrictions on the use of both the copper IUD and the levonorgestrel intrauterine system (LNG-IUS) (UKMEC category 1).
• If the woman has not had a subsequent pregnancy, the benefit of using either the copper IUD or the LNG-IUS generally outweighs the theoretical or proven risks (UKMEC category 2, that is, a condition where the advantages of using the method generally outweigh the theoretical or proven risks).
• Test for the following infections a few days before IUD insertion to allow infection to be treated before or at the time of insertion:
• Chlamydia trachomatis in women at risk of STIs.
• Neisseria gonorrhoeae in women at risk or STIs from areas where gonorrhoea is prevalent.
• All STIs, if this is requested by the woman.
• Consider taking a high vaginal swab to test for other vaginal infections.
• Give prophylactic antibiotics before IUD insertion if testing for STIs is not possible or has not been completed.
• There is no consensus about which antibiotic regimen to use. Choose a regimen (seeking specialist advice where appropriate) that will treat chlamydia infection and that will also treat gonorrhoea if local prevalence is high.
• If the woman currently has PID, an IUD should not be inserted as there is an unacceptable health risk (UKMEC category 4, that is, a condition which represents an unacceptable health risk if the contraceptive method is used).
• If the woman requires sterilization:
• A pelvic examination should be done to rule out recurrent or persistent PID and to determine the mobility of the uterus.
• Provided there is no current PID, and if the woman has had a subsequent pregnancy, there are no medical reasons to deny sterilization.
• If the woman has not had a subsequent pregnancy or has current PID, provide an alternative form of contraception until she can be fully assessed. At operation, it may be difficult to localize the tubes due to pelvic adhesions.
• Women should be advised to use a barrier method of contraception to protect against STIs.

Basis for recommendation

Choice of contraception

• These recommendations are based on the UK Medical Eligibility Criteria (UKMEC) for contraceptive use [FFPRHC, 2006] and a guideline from the Faculty of Sexual and Reproductive Healthcare [FSRH, 2007].

Intrauterine device (IUD)

• A review of the World Health Organization's experience of pelvic inflammatory disease (PID) associated with IUD use from around the world included 12 randomized studies and one non-randomized study, and found that [FSRH, 2007]:
• Amongst 22,908 IUD insertions and during 51,399 woman-years of follow up, the overall rate of PID was 1.6 cases per 1000 years of use.
• The risk of PID was six-fold higher during the 20 days after IUD insertion than during later times.

Testing for bacterial vaginosis

• PRODIGY recommends taking a high vaginal swab to look for other vaginal infections such as bacterial vaginosis.

Recommendation on antibiotic prophylaxis

• The recommendation to test for sexually transmitted infections (STIs), or prescribe prophylactic antibiotics if testing for STIs is not possible or has not been completed, before IUD insertion is based on expert opinion in guidelines from the National Institute for Health and Clinical Excellence[NICE, 2005] and the Faculty of Sexual and Reproductive Healthcare [FSRH, 2007] as the risk of PID following insertion of an IUD where infection is present is unknown.
• Both guidelines recommend testing for STIs and prescribing prophylactic antibiotics if testing for STIs is not possible or has not been completed before an IUD is inserted in women at increased risk of STIs. Woman who have a history of PID are at increased risk of STIs.
• However, there is good evidence from a Cochrane systematic review that the use of doxycycline or azithromycin orally before IUD confers little benefit even in populations with a high prevalence of STIs.

Sterilization

• These recommendations are based on the UKMEC for contraceptive use [FFPRHC, 2006].

Protection against STIs

• Evidence supports the use of male or female condoms to reduce the risk of several sexually transmitted infections (STIs). For more information see the PRODIGY topics on Contraception - assessment and Contraception - barrier methods and spermicides. However, even with consistent and correct use, infections may still (rarely) be transmitted [FFPRHC, 2007].

What investigations and treatments are available in secondary care?

• In secondary care, investigations that might be considered to help make a diagnosis of pelvic inflammatory disease (PID) include:
• Transvaginal ultrasound scanning supported by power Doppler. This can identify inflamed and dilated tubes and tubo-ovarian masses, especially when there is diagnostic difficulty. However, similar changes may occur in endometriosis or early ectopic pregnancy.
• Magnetic resonance imaging and computerized tomography.
• Laparoscopy with direct visualization of the fallopian tubes. This is an invasive procedure and is not routinely used in clinical practice.
• Endometrial biopsy.
• Surgical management may include:
• Laparoscopy: division of adhesions and drainage of pelvic abscesses may help early resolution.
• Ultrasound-guided aspiration of pelvic fluid collections.
• Adhesiolysis if there is peri-hepatitis.

Basis for recommendation

Other investigations in secondary care

• Transvaginal ultrasound is most useful in detecting large tubal swellings or fluid collections which only occur in women with severe pelvic inflammatory disease (PID) in whom irreversible tubal damage may already have occurred [Ross, 2003]. Power Doppler ultrasound is able to detect changes in blood flow associated with the hyperaemia that occurs with tubal inflammation [Ross, 2003].
• The recommendation that transvaginal ultrasound scanning supported by power Doppler may be helpful is based on expert opinion in a guideline from the Royal College of Obstetricians and Gynaecologists who also commented that there is limited evidence that magnetic resonance imaging and computerized tomography can assist in making a diagnosis [RCOG, 2009].
• Laparoscopy may provide information on the severity of the condition. However there is potential difficulty in identifying mild intra-tubal inflammation or endometritis and there is diagnostic variability between clinicians [Ross, 2003; RCOG, 2009; BASHH, 2011a].
• Endometrial biopsy may be helpful, but there is insufficient evidence to support its routine use [Ross et al, 2008].

Surgical treatment

• These recommendations are based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists and the British Association for Sexual Health and HIV [RCOG, 2009; BASHH, 2011a].
• The British Association for Sexual Health and HIV [BASHH, 2011a] comment that although it is possible to perform adhesiolysis in women with peri-hepatitis there is no evidence that this is superior to antibiotic treatment alone.

Prescriptions

For information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

Antibiotics

Age from 13 years onwards

Multi-therapy: Ceftriaxone injection + doxycycline + metronidazole

Ceftriaxone injection: 500mg single dose

Ceftriaxone 250mg powder for solution for injection vials

Reconstitute the contents of two vials and give a single dose of 500mg by intramuscular injection.

Supply 2 250mg vial.

Age: from 13 years onwards

NHS cost: £4.80

Licensed use: no - off-label dose

Doxycycline capsules: 100mg twice a day for 14 days

Doxycycline 100mg capsules

Take one capsule twice a day for 14 days.

Supply 28 capsules.

Age: from 13 years onwards

NHS cost: £1.94

Licensed use: off-label duration

Metronidazole tablets: 400mg twice a day for 14 days

Metronidazole 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.

Age: from 13 years onwards

NHS cost: £1.63

Licensed use: yes

Multi-therapy: Ceftriaxone injection + azithromycin

Ceftriaxone injection: 500mg single dose

Ceftriaxone 250mg powder for solution for injection vials

Reconstitute the contents of two vials and give a single dose of 500mg by intramuscular injection.

Supply 2 250mg vial.

Age: from 13 years onwards

NHS cost: £4.80

Licensed use: no - off-label dose

Azithromycin capsules: 1 gram single dose

Azithromycin 250mg capsules

Take four capsules as a single dose.

Supply 4 capsules.

Age: from 13 years onwards

NHS cost: £9.64

Licensed use: no - off-label indication

Multi-therapy: Cefixime + doxycycline + metronidazole

Cefixime tablets: 400mg single dose

Cefixime 200mg tablets

Take two tablets as a single dose.

Supply 2 tablets.

Age: from 13 years onwards

NHS cost: £3.78

Licensed use: no - off-label indication

Doxycycline capsules: 100mg twice a day for 14 days

Doxycycline 100mg capsules

Take one capsule twice a day for 14 days.

Supply 28 capsules.

Age: from 13 years onwards

NHS cost: £1.94

Licensed use: off-label duration

Metronidazole tablets: 400mg twice a day for 14 days

Metronidazole 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.

Age: from 13 years onwards

NHS cost: £1.63

Licensed use: yes

Multi-therapy: Cefixime + azithromycin

Cefixime tablets: 400mg single dose

Cefixime 200mg tablets

Take two tablets as a single dose.

Supply 2 tablets.

Age: from 13 years onwards

NHS cost: £3.78

Licensed use: no - off-label indication

Azithromycin tablets: 1g once a week for 2 weeks

Azithromycin 500mg tablets

Take two tablets as a single dose once a week for 2 weeks.

Supply 4 tablets.

Age: from 13 years onwards

NHS cost: £9.86

Licensed use: no - off-label dose

Age from 18 years onwards

Multi-therapy: Ofloxacin + metronidazole

Ofloxacin tablets: 400mg twice a day for 14 days

Ofloxacin 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.

Age: from 18 years onwards

NHS cost: £15.46

Licensed use: no - off-label dose

Metronidazole tablets: 400mg twice a day for 14 days

Metronidazole 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.

Age: from 18 years onwards

NHS cost: £1.63

Licensed use: yes

Analgesia: use when required

Age from 13 years onwards

Ibuprofen tablets: 200mg to 400mg three to four times a day

Ibuprofen 200mg tablets

Take one or two tablets 3 to 4 times a day when required for pain relief. Do not exceed the stated dose.

Supply 56 tablets.

Age: from 13 years onwards

NHS cost: £1.38

OTC cost: £2.38

Licensed use: yes

Paracetamol tablets: 500mg to 1g up to four times a day

Paracetamol 500mg tablets

Take one or two tablets every 4 to 6 hours when required for pain relief. Maximum of 8 tablets in 24 hours.

Supply 50 tablets.

Age: from 13 years onwards

NHS cost: £0.79

Licensed use: yes

Age from 18 years onwards

Codeine 30mg tablets: add on to paracetamol or NSAID if required

Codeine 30mg tablets

Take one or two tablets every 4 to 6 hours when required for pain relief. Maximum of 8 tablets in 24 hours.

Supply 28 tablets.

Age: from 18 years onwards

NHS cost: £1.22

Licensed use: yes

Prescribing information

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this PRODIGY topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

Antibiotics and oral hormonal contraception

• Additional contraceptive precautions are not required during or after courses of doxycycline [FSRH, 2011].
• However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the section on Antibiotics in the PRODIGY topic on Contraception - assessment.

Metronidazole and alcohol

• Women should be warned that they might experience a reaction if they also take alcohol (such as flushing, nausea, headache, and dizziness). However, this disulfiram-like reaction is unpredictable, and some dispute its existence; the incidence of this reaction has been reported to be between 0% and 100% [Baxter, 2008].

Ofloxacin

• Ofloxacin should be avoided where possible in young women when bone development is still occurring (although this recommendation is based on animal studies and no problems have been reported in humans) [RCOG, 2009].
• Avoid giving ibuprofen to women with epilepsy taking the ofloxacin regimen. The combination of quinolones with nonsteroidal anti-inflammatory drugs (NSAIDs) can lower the seizure threshold.

Doxycycline

• Advise women taking doxycycline to avoid exposure to direct sunlight or to sunlamps, because of the risk of photosensitivity reactions.

Evidence

Supporting evidence

Evidence on clinical findings associated with pelvic inflammatory disease

There is evidence from a large cross-sectional analysis that adnexal tenderness has a high sensitivity for pelvic inflammatory disease (PID) and that the finding most strongly associated with endometritis is a positive test result for Chlamydia trachomatis or Neisseria gonorrhoeae.

• A cross-sectional analysis of 651 women enrolled in the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) study considered the clinical predictors of endometritis in women with PID [Peipert et al, 2001]:
• Adnexal tenderness was found to have a high sensitivity (95%) but a low specificity (4%). This means that if this symptom was used alone then many women would be over-treated although it is unlikely many women with PID would be missed.
• Combining symptoms (lower abdominal tenderness, adnexal tenderness, and cervical motion tenderness) lowers the sensitivity to 83% but improves the specificity (22%).
• The finding most strongly associated with endometritis was a positive test result for Chlamydia trachomatis or Neisseria gonorrhoeae (adjusted odds ratio 4.3, 95% CI 2.89 to 2.63).
• Women who had a high temperature as well as a high white cell count were at a significantly increased risk of endometritis (p < 0.001) but women with an elevated temperature alone at presentation were at significantly less risk of having endometritis, possibly because the elevated temperature was due to another cause (such as viral gastroenteritis) that did not increase the white cell count [Ross, 2002].

Evidence on prompt treatment of pelvic inflammatory disease

There is limited evidence from a case-control study that fertility may be impaired and ectopic pregnancy more likely if treatment for acute pelvic inflammatory disease (PID) is delayed for 3 days or more after the onset of symptoms.

• A case-control study [Hillis et al, 1993] analysed data from a cohort of women who had one known episode of clinically recognizable PID. The study included women with either ectopic pregnancy or infertility (n = 76). The control group were women with intrauterine pregnancy (n = 367).
• After adjustment for confounding factors, women who had sought care 3 days or more after developing lower abdominal pain were three times more likely to experience infertility or ectopic pregnancy than women who had sought care within 2 days of onset (odds ratio 2.6, 95% CI 1.2 to 5.9).

Evidence on treating women with mild or moderate pelvic inflammatory disease in primary care

There is very good evidence from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) randomized controlled trial that outpatient treatment of women with mild or moderate pelvic inflammatory disease (PID) is as effective as inpatient treatment. Short-term clinical outcomes were similar (such as symptom severity, adverse reactions) after 30 days. There was no significant difference in pregnancy rates, time to pregnancy, ectopic pregnancies, chronic pelvic pain, and recurrent pelvic inflammatory disease between the outpatient and inpatient groups at 35 months of follow up.

• One randomized controlled trial (the PEACH study) [Ness et al, 2002] included 831 women with mild-to-moderate PID (excluding those with a tubo-ovarian abscess). Women were randomized to receive either one intramuscular dose of cefoxitin plus oral probenecid, followed by oral doxycycline as outpatients, or to receive inpatient treatment with parenteral antibiotics (intravenous cefoxitin and doxycycline).
• At 30 days' follow up, outpatient and inpatient treatment regimens were not found to be significantly different with regard to:
• Uterine or adnexal tenderness on bimanual pelvic examination (20.6% for outpatient treatment compared with 18.4% with inpatient treatment, p = 0.5).
• Gonorrhoeal or chlamydial infection (gonorrhoeal infection 3.9% for outpatient treatment compared with 2.4% with inpatient treatment, p = 0.44; chlamydial infection 2.7% for outpatient treatment compared with 3.6% with inpatient treatment, p = 0.52).
• Endometritis (45.9% with outpatient treatment compared with 37.6% with inpatient treatment, p = 0.09).
• Adverse drug reactions (1.7% for outpatient treatment compared with 1.5% with inpatient treatment, p = 0.85).
• At 35 months' follow up (n = 808), there was no significant difference between outpatient and inpatient treatment in terms of:
• Pregnancy rates (42% compared with 41.7%, p = 1.0).
• PID recurrence (12.4% compared with 16.6%, p = 0.11).
• Chronic pelvic pain (33.7% compared with 29.8%, p = 0.27).
• Infertility (18.4% compared with 17.9%, p = 0.85).
• Ectopic pregnancy (1% compared with 0.3%, p = 0.37).

Evidence on antibiotic treatment of pelvic inflammatory disease

Only trials for antibiotic regimens that are practical for use in primary care and, at the time of writing, are likely to be effective against Chlamydia trachomatis, Neisseria gonorrhoeae, and anaerobes have been reviewed.

No randomized controlled trials comparing antibiotics with placebo or no treatment were found, probably because there is agreement that antibiotics are effective in women with pelvic inflammatory disease, and that studies would therefore be unethical.

Evidence on oral ofloxacin and metronidazole for pelvic inflammatory disease

There is good evidence from two systematic reviews that antibiotics are effective in the treatment of acute pelvic inflammatory disease (PID). It is not possible to determine the most effective regimen from the evidence but ofloxacin used alone and with metronidazole appears to be effective and has high clinical and microbiological cure rates.

• A systematic review (search date: 2004, 34 RCTs, n = 3548) investigated the clinical effectiveness and cost effectiveness of antibiotic treatments for PID. Many of the trials in this review were small, open-label, and of poor methodological quality, and some included women with pelvic infections rather than PID. The review studied, in particular, the seven treatment regimens that were recommended (at the time the review was carried out) in the guideline for the management of PID from the Royal College of Obstetricians and Gynaecologists and by the British National Formulary [Meads et al, 2004].
• One of the regimens relevant to primary care was oral ofloxacin combined with oral metronidazole. One small trial was found, and the review commented that the report on this trial was brief.
• This trial compared intravenous and then oral ofloxacin and metronidazole with clindamycin plus gentamicin.
• The cure rate was 15/15 for ofloxacin and 17/18 for clindamycin plus gentamicin.
• A systematic review [Walker et al, 1993] included 34 trials on the treatment of women with PID. An update of this review (search date: 1997) [Walker et al, 1999] included an additional five studies (total 39 studies, 1925 women). Some of the trials were case-studies and the data were aggregated making it impossible to know how many of the trials were randomized and controlled.
• Three trials were included on ofloxacin alone.
• One inpatient trial (n = 36): clinical cure rate 100% and microbiological cure rate 97%.
• Two outpatient trials (n = 165): clinical cure rate 95% and microbiological cure rate 100%.

Evidence on intramuscular ceftriaxone and oral doxycycline with or without metronidazole for pelvic inflammatory disease

There is evidence from two systematic reviews that intramuscular ceftriaxone or intramuscular cefoxitin (with or without probenecid) followed by oral doxycycline is effective in treating pelvic inflammatory disease (PID).

• A systematic review (search date: 2004, 34 RCTs, n = 3548) investigated the clinical effectiveness and cost effectiveness of antibiotic treatments for PID. Many of the trials in this review were small, open-label, and of poor methodological quality and some included women with pelvic infections rather than just PID. The review studied in particular the seven treatment regimens that were recommended (at the time the review was carried out) in the guideline for the management of PID from the Royal College of Obstetricians and Gynaecologists and by the British National formulary [Meads et al, 2004]. Three of these regimens are suitable for use in primary care; the other four regimens involved intravenous antibiotics. The review looked for trials using:
• Intramuscular ceftriaxone (or intramuscular cefoxitin with oral probenecid) or a third generation cephalosporin plus oral doxycycline.
• Six trials (n = 641) undertaken between 1985 and 1997 were reported. No trials were found that included metronidazole (except for one of the trials in which some women received metronidazole). Intramuscular ceftriaxone (or intramuscular cefoxitin with oral probenecid) or a third generation cephalosporin plus oral doxycycline were compared with non-standard regimens: ciprofloxacin plus clindamycin (one trial); clindamycin plus tobramycin (two trials); clindamycin plus amikacin (one trial), and ofloxacin (two trials).
• All showed no significant difference between cefoxitin, probenecid, and doxycycline compared with the comparative non-standard treatments.
• Cefoxitin plus doxycycline.
• Three trials (n = 216) took place in the 1980s and compared intravenous cefoxitin plus doxycycline (intravenous or oral) followed by oral doxycycline with clindamycin plus gentamicin. Clinical cure rates varied from 46–75% in the cefoxitin plus doxycycline group, and 52–87% in the clindamycin plus gentamicin group, but there was no significant difference between the groups.
• A systematic review [Walker et al, 1993] included 34 trials on the treatment of women with PID. An update of this review (search date: 1997) [Walker et al, 1999] included an additional five studies (total 39 studies, 1925 women). Some of the trials were case studies and the data were aggregated making it impossible to know how many of the trials were randomized controlled trials. Trials that included doxycycline with either cefoxitin or ceftriaxone were categorized as either inpatient or outpatient trials:
• Inpatient trials:
• Cefoxitin plus doxycycline: eight trials (n = 427); clinical cure rate 91% and microbiological cure rate 98%.
• Outpatient trials:
• Cefoxitin, probenecid and doxycycline: three trials (n = 219); clinical cure rate 89% and microbiological cure rate 93%.
• Ceftriaxone plus doxycycline: one trial (n = 64); clinical cure rate 95% and microbiological cure rate 100%.

Evidence on oral azithromycin and intramuscular ceftriaxone for pelvic inflammatory disease

There is limited evidence from two randomized controlled trials (RCTs) that azithromycin used alone or in combination with ceftriaxone is effective in the treatment of pelvic inflammatory disease (PID).

• Two open-label, comparative, multicentre and multinational trials of women with PID confirmed by laparoscopy (n = 310) and requiring hospitalization for treatment, compared azithromycin alone, or azithromycin plus metronidazole, with either cefoxitin (plus probenecid, doxycycline and metronidazole), or co-amoxiclav plus doxycycline [Bevan et al, 2003].
• The intention-to-treat analysis included 300 women and included data from all women who were recruited and who had undergone one pre-dosing, and at least one post-dosing, efficacy test. However the majority of the participants in the trial did not attend the two planned follow-up assessments.
• All regimens had clinical cure rates of over 94%.
• The eradication rate for the key pathogens at the end of treatment (day 13–18) was over 95% and at final follow up (day 35–44) was over 90% for all of the regimens.
• The azithromycin regimens were well tolerated.
• As data from two studies were combined it was not possible to determine the optimum dose of azithromycin.
• These results should be interpreted with caution as the majority of those recruited did not attend all of the planned follow-up appointments, PID was confirmed laparoscopically in only 74.8% of participants, and there was a lack of clear outcome criteria.
• An RCT included women with mild PID (n = 133) who were all given an intramuscular injection of ceftriaxone and then randomized to receive either doxycycline 200 mg daily for 2 weeks or azithromycin 1 g per week for 2 weeks as outpatients [Savaris et al, 2007].
• Clinical cure was assessed on day 14.
• Twenty-seven women were excluded from the analysis (13 were found not to have PID, 11 were lost to follow up, and 3 were intolerant of the antibiotic treatment).
• Clinical cure rates in a modified intention-to-treat analysis were:
• 90.3% for azithromycin (56/62; 95% CI 0.80 to 0.96).
• 72.4% for doxycycline (42/58; 95% CI 0.58 to 0.82, p = 0.01).
• Number needed to treat (NNT): six women had to be treated with azithromycin for one woman to benefit.
• Combined with ceftriaxone, 1 g of azithromycin weekly for 2 weeks is an effective treatment for mild PID.

Evidence on oral metronidazole and doxycycline for pelvic inflammatory disease

There is evidence from a systematic review and a retrospective study that metronidazole combined with doxycycline is not suitable for the treatment of acute pelvic inflammatory disease (PID) in the UK. The addition of intramuscular ceftriaxone as an initial dose significantly improves the clinical cure rate.

• A retrospective review of the case notes of 135 women with PID treated with oral doxycycline and metronidazole in Leeds in 2000 showed that the clinical cure rate was only 55% [Piyadigamage and Wilson, 2005].
• Therefore, all women diagnosed with PID during a 6-month period in 2002 were treated with intramuscular ceftriaxone followed by a 2-week course of doxycycline and metronidazole.
• Using intention-to-treat analysis, there was a significant improvement in cure rate in the group who had received intramuscular ceftriaxone compared with the group who had not (odds ratio 2.03, 95% CI 1.18 to 3.5, p = 0.009).
• A systematic review [Walker et al, 1993] included 34 trials on the treatment of women with PID. An update of this review (search date: 1997) [Walker et al, 1999] included an additional five studies (total 39 studies, 1925 women). Some of the trials were case-studies and the data were aggregated making it impossible to know how many of trials were randomized and controlled.
• Two trials were included on metronidazole and doxycycline.
• Both were inpatient trials (n = 36). The clinical cure rate was 75% and the microbiological cure rate was 71%.
• This review evaluated 10 inpatient and six outpatient treatment regimens. Only the doxycycline plus metronidazole regimen did not perform well. The clinical cure rate for the all of the other regimens was at least 88% and the microbiological cure rate was at least 95%.

Evidence on moxifloxacin for pelvic inflammatory disease

The British Association for Sexual health and HIV (BASHH) identified three randomized controlled trial which suggest that oral moxifloxacin has similar efficacy to other regimens in the treatment of uncomplicated pelvic inflammatory disease (that is, absence of pelvic or tubo-ovarian abscesses).

• One study, a multinational, multicentre, prospective, randomized, double-blinded, parallel group, non-inferiority study, compared moxifloxacin alone with a combination of ofloxacin and metronidazole [Ross et al, 2006]. The women were randomized to receive a 14-day course of either moxifloxacin 400 mg daily (n = 384), or ofloxacin 400 mg twice daily combined with metronidazole 500 mg twice daily (n = 365).
• Clinical resolution rates were similar in both groups for the per protocol population:
• 90.2% (248/275) for moxifloxacin and 90.7% (262/289) for ofloxacin plus metronidazole (95% CI –5.7 to +4.0) at 5–24 days post-therapy.
• 85.8% (236/275) for moxifloxacin and 87.9% (254/289) for ofloxacin plus metronidazole (95% CI –8.0 to +3.1) at 28–42 days post therapy.
• Intention-to-treat analysis (n = 741) found clinical resolution rates:
• At 5–24 days post-therapy of 75.7% (286/378) in the moxifloxacin group and 82.6% (300/363) in the ofloxacin and metronidazole group.
• At 28–42 days post-therapy of 75.1% (284/378) in the moxifloxacin group and 81% (294/363) in the ofloxacin and metronidazole group.
• Moxifloxacin was effective against:
• Neisseria gonorrhoeae (100%, 13/13) compared with ofloxacin and metronidazole (81.2%, 18/22).
• Chlamydia trachomatis (88.5%, 23/26) compared with ofloxacin and metronidazole (85.7%, 18/21).
• Most adverse effects were mild and there were significantly fewer (p = 0.035) in the moxifloxacin group (179/378, 47.4%) compared with the ofloxacin and metronidazole group (200/363, 55.1%).
• Moxifloxacin had similar efficacy to a combination of ofloxacin and metronidazole and had fewer adverse effects.
• The second study, a multicentre, prospective, randomized, double-blinded study, compared moxifloxacin alone with a combination of doxycycline, metronidazole and ciprofloxacin [Heystek and Ross, 2009]. The women were randomized to receive a 14-day course of either moxifloxacin 400 mg daily (n = 343), or doxycyline 100 mg twice daily plus metronidazole 400 mg three times daily plus one single 500 mg ciprofloxacin dose (n = 326).
• The overall clinical success rates (clinical cure and improvement combined) were similar for both the moxifloxacin and the doxycyline, metronidazole, and ciprofloxacin group in the per protocol population:
• 96.6% (224/232) for moxifloxacin and 98.0% (198/202) for doxycyline, metronidazole, and ciprofloxacin (95% CI –4.5 to +1.6) at 2-14 days post therapy.
• 93.8% (166/177) for moxifloxacin and 91.3% (147/161) for doxycyline, metronidazole, and ciprofloxacin (95% CI –3.8 to +7.4) at 21-35 days post therapy.
• Intention-to treat analysis (n=686) found clinical success rates:
• At 2–14 days post-therapy in 77.0% (264/343) of the moxifloxacin group and 76.7% (250/326) of the doxycyline, metronidazole, and ciprofloxacin group.
• At 21–35 days post-therapy in 60.1% (206/343) of the moxifloxacin group and 58.6% (191/326) of the doxycyline, metronidazole, and ciprofloxacin group.
• Moxifloxacin was effective against:
• Neisseria gonorrhoeae (91.7%, 22/24) compared with doxycyline, metronidazole, and ciprofloxacin (90.0%, 18/20).
• Chlamydia trachomatis (95.5%, 21/22) compared with doxycyline, metronidazole, and ciprofloxacin (89.5%, 17/19).
• The adverse effects profile for both groups was very similar (p = 0.14 for any adverse effect). Of the moxifloxacin group, 44.0% (151/343) experienced an adverse effect, compared with 49.7% (162/326) of the doxycyline, metronidazole and ciprofloxacin group.
• Moxifloxacin had similar efficacy to a combination of doxycyline, metronidazole and ciprofloxacin. The once-daily dosing regimen may also enhance patient compliance.
• The final study (a multinational, multicentre, prospective, randomized, double-blinded, parallel group study) compared moxifloxacin alone with a combination of oral levofloxacin and metronidazole [Judlin et al, 2010]. The women were randomized to receive a 14-day course of either moxifloxacin 400 mg daily (n = 228), or levofloxacin 500 mg once daily combined with metronidazole 500 mg twice daily (n = 232). Women who tested positive for Neisseria gonorrhoeae (moxifloxacin group, n=5; levofloxacin and metronidazole group, n=2) were also given a single 250 mg dose of ceftriaxone.
• Clinical cure rates in the levofloxacin plus metronidazole group were no better than those for moxifloxacin alone for the per protocol population (95% confidence interval [CI] -10.7 to +4.9; p = 0.460):
• 78.4% (152/194) for moxifloxacin and 81.6% (155/190) for levofloxacin plus metronidazole at 7–14 days post-therapy.
• Intention-to-treat analysis (n = 460) had similar results:
• 71.5% (163/228) for moxifloxacin and 73.7% (171/232) for levofloxacin plus metronidazole at 7–14 days post-therapy.
• Moxifloxacin was also non-inferior to levofloxacin plus metronidazole during treatment (day 4-7) and at follow up (28-42 days post-therapy), for both the per protocol and the intention-to-treat population.
• Moxifloxacin was effective against:
• Neisseria gonorrhoeae (100%, 4/4) compared with levofloxacin and metronidazole (50%, 1/2).
• Chlamydia trachomatis (100%, 8/8) compared with levofloxacin and metronidazole (83.3%, 10/12).
• Most adverse effects were of mild to moderate intensity, the two most common being nausea and dizziness. One serious drug-related adverse effect (Stevens-Johnson syndrome) was reported in the moxifloxacin group but this improved with treatment.
• 56.6% (129/228) of women in the moxifloxacin group experienced overall adverse effects compared with 56.9% (132/232) in the levofloxacin and metronidazole group.
• 46.5% (106/228) of women in the moxifloxacin group experienced drug-related adverse effects compared with 48.7% (113/232) in the levofloxacin and metronidazole group.
• Moxifloxacin had similar efficacy to a combination of levofloxacin and metronidazole and had slightly fewer adverse effects.

Evidence on removal of an intrauterine device in a woman who has pelvic inflammatory disease

Evidence on whether or not to remove an intrauterine device in a woman who has pelvic inflammatory disease (PID) is limited and conflicting. There are no long term data on the effect on fertility.

• A prospective study of 53 hospitalised women with an intrauterine device (IUD) and acute salpingitis investigated whether the IUD should be removed or left in position [Soderberg and Lindgren, 1981]. The diagnosis of acute salpingitis was based on acute pelvic pain, adnexal tenderness, and an increased erythrocyte sedimentation rate (ESR) of at least 40 mm/hour.
• Forty six women completed the study by staying in hospital until their ESR had halved.
• In 23 women the device was removed before treatment with pivampicillin and doxycycline and in the other 23 women the device was left in place and the same treatment was given.
• Early removal of the IUD did not influence the course of the disease, which was monitored by the course of the ESR.
• This study is limited by its small size, and by choosing to use only one outcome measure, the ESR, to monitor progress. It also did not take place in a primary care setting.
• A randomized controlled trial of 126 women with mild-to-moderate PID during IUD usage evaluated the effects of removing the IUD [Altunyurt et al, 2003]. The diagnosis was made by using a variety of clinical symptoms (recent onset of pelvic pain and vaginal discharge, dysuria and frequency, nausea and vomiting, intermenstrual bleeding, and recent onset of dyspareunia); clinical signs (abdominal tenderness, purulent cervical discharge, and cervical tenderness); and ESR and white cell counts.
• All of the participants were given ciprofloxacin, metronidazole, and doxycycline and in 60 women the IUD was removed. Twelve women defaulted from the follow up assessment at 15 days.
• Women in whom the IUD had been removed had significantly less pelvic pain (p = 0.0001), vaginal discharge (p = 0.007), dysuria and frequency (p = 0.0003), dyspareunia (p = 0.0001), cervical tenderness (p = 0.0001), and a lower white cell count (p = 0.001) and ESR (p = 0.001) than the group in whom the device was not removed.
• However this study is limited by its short follow up interval and therefore long term outcomes such as whether the risk of tubal infertility is reduced are unknown.
• A retrospective study of 186 women with acute PID investigated the effect of removing the IUD on the resolution of the disease. The diagnosis of PID was based on a history of acute pelvic pain, uterine and adnexal tenderness, and an increased ESR of above 15 mm/hour [Teisala, 1989].
• The IUD was removed on admission in 81 women and left in place in 105 women. All women received penicillin with or without metronidazole and 17 women received penicillin before admission.
• There was no significant difference between the two groups in the outcome measures: duration of fever, highest ESR during hospitalisation, ESR on discharge, and the mean time in hospital.
• This study is limited by its lack of long term data and that it did not take place in primary care.
• A randomized trial of 928 women with PID who were hospitalised investigated the effect of a copper IUD on the resolution and recurrence of PID. The diagnosis of PID was based on palpable, tender adnexal masses, and/or an ESR above 15 mm/hour in addition to lower abdominal pain and sometimes a fever of over 38°C [Larsson and Wennergren, 1977]. There were three groups of women: 632 with no IUD in situ, 236 women whose IUD was not removed during treatment, and 60 women selected at random on admission who had their IUD removed.
• A significantly higher proportion of women in whom the IUD had been removed spent more than 3 weeks in hospital but there was no difference between the other two groups.
• 184 women (17 women in whom the device had been removed before treatment, 46 women in whom the device had been left in situ and 121 women  who did not have an IUD) were followed up for approximately 18 months. Recurrence rates were 15% in the group who had had the IUD removed and 9% in the other two groups. This difference was not statistically significant.
• The authors concluded that there was no evidence that the copper IUD had an unfavourable effect on either the recurrence or the resolution of PID.
• This study is limited by its lack of detail regarding randomization, the choice of a non-specific outcome measure of a hospital stay of over 3 weeks and the small number of women who were followed up.

Evidence on antibiotic prophylaxis for intrauterine contraceptive device (IUD) insertion

There is good evidence from a Cochrane systematic review that the use of doxycycline or azithromycin orally before intrauterine device (IUD) insertion confers little benefit.

• A Cochrane systematic review [Grimes and Schulz, 1999] investigated whether antibiotic prophylaxis at the time of insertion of an IUD reduces the risk of upper genital tract infection.
• Randomized trials that compared an antibiotic with placebo were included. Four trials were found and two also had pilot study data available (n = 5797). Trials were from Kenya, Nigeria, the USA, and Turkey.
• Use of prophylactic antibiotics (doxycycline 200 mg or azithromycin 500 mg by mouth) before IUD insertion reduced the likelihood of an unplanned visit to the provider by 18%, which was marginally significant (odds ratio [OR] 0.82, 95% CI 0.70 to 0.98).
• There was no significant difference in the number of upper genital tract infections (OR 0.89, 95% CI 0.53 to 1.51) or in IUD continuation rates (OR 1.05, 95% CI 0.68 to 1.63).
• The authors concluded that IUD insertion has a good safety profile with or without the use of prophylactic antibiotics, even in populations with a high prevalence of sexually transmitted disease.

Evidence on the risk of infertility with pelvic inflammatory disease

There is evidence from prospective cohort studies that the risk of infertility is related to the number of episodes of pelvic inflammatory disease (PID) and their severity.

• A prospective cohort study enrolled 2501 women who had undergone laparoscopy for suspected pelvic inflammatory disease. At laparoscopy 1844 had abnormal findings and 657 had normal findings. The time of follow up was related to the time of the index laparoscopy; 136.6 months in those enrolled between 1960–1964 and 45.7 months in those enrolled between 1980–1984. Of the 1309 women with a history of laparoscopically-confirmed PID, and the 451 women who had had a normal laparoscopy (control group) who were attempting to conceive [Westrom et al, 1992]:
• 16% of women with a history of PID were not pregnant within 1 year, compared with 2.7% of controls.
• 10.8% of women with a history of PID had confirmed tubal-factor infertility, compared with none in the control group.
• 0.6% of women had tubal-factor infertility after an episode of mild PID and 21.4% of women had tubal-factor infertility after an episode of severe PID.
• Each repeated episode of PID roughly doubled the rate of tubal-factor infertility: after one episode the rate was 8%, after two episodes the rate was 19.5%, and after three or more episodes the rate was 40%.
• A prospective cohort study followed up 1288 women who had experienced clinical symptoms of PID and who wanted to get pregnant [Lepine et al, 1998]. The cumulative probability of a live birth after 12 years was, for women who had:
• Mild salpingitis (371 women): 90%.
• Moderate salpingitis (580 women): 82%.
• Severe salpingitis (337 women): 57%.

References

All references with links to [Free Full-text] are freely available online to users in the UK. Links to PubMed abstracts are also provided where available. Clarity is not responsible for the content of external sites.

Free Full-text links are to dynamic documents that may have been updated since they were originally cited in the PRODIGY topic. All links are checked regularly by Information Specialists and updated to the latest version. Changes in the content of updated documents will not be reflected in the PRODIGY topic text until the next revision.

The following references were cited in August 2009. References dated after this reflect new evidence incorporated since original publication of this topic.

1. ABPI Medicines Compendium (2009) Summary of product characteristics for Rocephin 250mg, 1g and 2g vials. Electronic Medicines Compendium. Datapharm Communications Ltd. www.emc.medicines.org.uk [Free Full-text]
2. Altunyurt, S., Demir, N. and Posaci, C. (2003) A randomized controlled trial of coil removal prior to treatment of pelvic inflammatory disease.European Journal of Obstetrics, Gynecology, & Reproductive Biology 107(1), 81-84. [Abstract]
3. Barrett, S. and Taylor, C. (2005) A review on pelvic inflammatory disease. International Journal of STD & AIDS 16(11), 715-720. [Abstract]
4. BASHH (2005) National guideline on the diagnosis and treatment of gonorrhoea in adults 2005. British Association for Sexual Health and HIV.www.bashh.org [Free Full-text]
5. BASHH (2011a) UK national guideline on the management of pelvic inflammatory disease 2011. British Association for Sexual Health and HIV.www.bashh.org [Free Full-text]
6. BASHH (2011b) UK national guideline on the management of gonorrhoea in adults 2011. British Association for Sexual Health and HIV.www.bashh.org [Free Full-text]
7. Baxter, K. (Ed.) (2008) Stockley's drug interactions: a source book of interactions, their mechanisms, clinical importance and management.8th edn. London: Pharmaceutical Press.
8. Bevan, C.D., Ridgway, G.L. and Rothermel, C.D. (2003) Efficacy and safety of azithromycin as monotherapy or combined with metronidazole compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease. Journal of International Medical Research 31(1), 45-54. [Abstract] [Free Full-text]
9. Brocklehurst, P. and Rooney, G. (1998) Interventions for treating genital Chlamydia trachomatis infection in pregnancy (Cochrane Review).The Cochrane Library. Issue 4. John Wiley & Sons Ltd. www.thecochranelibrary.com [Free Full-text]
10. CDC (2006) Sexually transmitted diseases treatment guidelines, 2006. Morbidity & Mortality Weekly Report 55(RR11), 1-94. [Abstract] [Free Full-text]
11. Drife, J. and Magowan, B. (Eds.) (2004) Female genital infections. In: Clinical obstetrics and gynaecology. Edinburgh: Saunders. 119
12. Eissa, M.A. and Cromwell, P.F. (2003) Diagnosis and management of pelvic inflammatory disease in adolescents. Journal of Pediatric Health Care 17(3), 145-147.
13. FFPRHC (2006) UK medical eligibility criteria for contraceptive use [Superseded]. Faculty of Family Planning and Reproductive Health Care.www.ffprhc.org.uk
14. FFPRHC (2007) Male and female condoms. Faculty of Family Planning and Reproductive Health Care. www.ffprhc.org.uk [Free Full-text]
15. FSRH (2007) FSRH guidance (November 2007): intrauterine contraception. Faculty of Sexual & Reproductive Healthcare. www.ffprhc.org.uk[Free Full-text]
16. FSRH (2011) Drug interactions with hormonal contraception. Faculty of Sexual and Reproductive Healthcare. www.ffprhc.org.uk [Free Full-text]
17. Grimes, D.A. and Schulz, F.K. (1999) Antibiotic prophylaxis for intrauterine contraceptive device insertion (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
18. Heystek, M. and Ross, J.D.C. (2009) A randomized double-blind comparison of moxifloxacin and doxycycline/metronidazole/ciprofloxacin in the treatment of acute, uncomplicated pelvic inflammatory disease. International Journal of STD and AIDS 20(10), 690-695. [Abstract]
19. Hillis, S.D., Joesoef, R., Marchbanks, P.A. et al. (1993) Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility.American Journal of Obstetrics and Gynecology 168(5), 1503-1509. [Abstract]
20. HPA and Association of Medical Microbiologists (2010) Management of infection guidance for primary care for consultation and local adaptation. Health Protection Agency. www.hpa.org.uk [Free Full-text]
21. Judlin, P., Liao, Q., Liu, Z. et al. (2010) Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study.British Journal of Obstetrics and Gynaecology 117(12), 1475-1484. [Abstract]
22. Larsson, B. and Wennergren, M. (1977) Investigation of a copper-intrauterine device (Cu-IUD) for possible effect on frequency and healing of pelvic inflammatory disease. Contraception 15(2), 143-149.
23. Lepine, L.A., Hillis, S.D., Marchbanks, P.A. et al. (1998) Severity of pelvic inflammatory disease as a predictor of the probability of live birth.American Journal of Obstetrics and Gynecology 178(5), 977-981. [Abstract]
24. Meads, C., Knight, T., Hyde, C. and Wilson, J. (2004) The clinical effectiveness and cost effectiveness of antibiotic regimens for pelvic inflammatory disease. West Midlands Health Technology Assessment Group. www.rep.bham.ac.uk [Free Full-text]
25. MHRA (2008) Moxifloxacin: restricted use. Drug Safety Update 2(1), 8. [Free Full-text]
26. MHRA (2011) Moxifloxacin: use in pelvic inflammatory disease only when other antibacterials are inappropriate or ineffective. Drug Safety Update 4(6), S1. [Free Full-text]
27. Ness, R.B., Soper.D.E., Holley, R.L. et al. (2002) Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) randomized trial. American Journal of Obstetrics and Gynecology 186(5), 929-937. [Abstract]
28. NICE (2005) Long-acting reversible contraception (NICE guideline). National Institute for Health and Clinical Excellence. www.nice.org.uk [Free Full-text]
29. NICE (2008) Osteoarthritis. The care and management of osteoarthritis in adults (NICE guideline). National Institute for Health and Clinical Excellence. www.nice.org.uk [Free Full-text]
30. NICE (2009) Rheumatoid arthritis: the management of rheumatoid arthritis (NICE guideline). National Institute for Health and Clinical Excellence. www.nice.org.uk [Free Full-text]
31. NPC (2011) Key therapeutic topics 2010/11 - Medicines management options for local implementation. National Prescribing Centre.www.npc.nhs.uk [Free Full-text]
32. NTIS (2004) Use of ibuprofen in pregnancy. TOXBASE. National Teratology Information Service, Regional Drug and Therapeutics Centre.www.toxbase.org
33. NTIS (2008a) Use of azithromycin in pregnancy. TOXBASE. National Teratology Information Service. www.toxbase.org
34. NTIS (2008b) Use of cephalosporins in pregnancy. TOXBASE. National Teratology Information Service. www.toxbase.org
35. Oakeshott, P. (2003) Vaginal discharge and sexually transmitted infections. In: Waller, D. and McPherson, A. (Eds.) Women's health. 5th edn. Oxford: Oxford University Press. 363
36. Peipert, J.F., Ness, R.B., Blume, J et al. (2001) Clinical predictors of endometriosis in women with symptoms and signs of pelvic inflammatory disease. American Journal of Obstetrics and Gynecology 184(5), 856-864. [Abstract]
37. Piyadigamage, A. and Wilson, J. (2005) Improvement in the clinical cure rate of outpatient management of pelvic inflammatory disease following a change in therapy. Sexually Transmitted Infections 81(3), 233-235. [Abstract] [Free Full-text]
38. RCOG (2009) Management of acute pelvic inflammatory disease (minor revisions made to this document in March 2009). Royal College of Obstetricians and Gynaecologists. www.rcog.org.uk [Free Full-text]
39. Ross, J.D.C. (2002) An update on pelvic inflammatory disease. Sexually Transmitted Infections 78(1), 18-19. [Abstract] [Free Full-text]
40. Ross, J.D. (2003) Pelvic inflammatory disease: how should it be managed? Current Opinion in Infectious Diseases 16(1), 37-41. [Abstract]
41. Ross, J. (2008) PID. Clinical Evidence. BMJ Publishing Ltd. www.clinicalevidence.com
42. Ross, J.D., Cronje, H.S., Paszkowski, T. et al. (2006) Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial. Sexually Transmitted Infections 82(6), 446-451. [Abstract] [Free Full-text]
43. Ross, J., Judlin, P. and Nilas, L. (2008) European guideline for the management of pelvic inflammatory disease. International Union Against Sexually Transmitted Infections. www.iusti.org [Free Full-text]
44. Savaris, R.F., Teixeira, L.M., Torres, T.G. et al. (2007) Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstetrics & Gynecology 110(1), 53-60. [Abstract]
45. Schaefer, C., Peters, P. and Miller, R.K. (Eds.) (2007) Drugs during pregnancy and lactation: treatment options and risk assessment. 2nd edn. Oxford: Academic Press.
46. Simms, I., Rogers, P. and Charlett, A. (1999) The rate of diagnosis and demography of pelvic inflammatory disease in general practice: England and Wales. International Journal of STD & AIDS 10(7), 448-451. [Abstract]
47. Soderberg, G. and Lindgren, S. (1981) Influence of an intrauterine device on the course of an acute salpingitis. Contraception 24(2), 137-143.
48. Sweet, R.L. (2009) Treatment strategies for pelvic inflammatory disease. Expert Opinion in Pharmacotherapy 10(5), 823-837. [Abstract]
49. Teisala, K. (1989) Removal of an intrauterine device and the treatment of acute pelvic inflammatory disease. Annals of Medicine 21(1), 63-65. [Abstract]
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51. Walker, C.K., Kahn, J.G., Washington, A.E. et al. (1993) Pelvic inflammatory disease: metaanalysis of antimicrobial regimen efficacy. Journal of Infectious Diseases 168(4), 969-978. [Abstract]
52. Walker, C.K., Workowski, K.A., Washington, A.E. et al. (1999) Anaerobes in pelvic inflammatory disease: implications for the Centers for Disease Control and Prevention's guidelines for treatment of sexually transmitted diseases. Clinical Infectious Diseases 28(Suppl 1), S29-S36. [Abstract]
53. Westrom, L.V., Joesoef, R., Reynolds, G. et al. (1992) Pelvic inflammatory disease and fertility: a cohort study of 1844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sexually Transmitted Diseases 19(4), 185-192. [Abstract]
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Search strategy

Further information on the PRODIGY literature searching policy is available in the 'About' section of the PRODIGY website.

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of Pelvic inflammatory disease.

Search dates

July 2006 – January 2009

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

• pelvic inflammatory disease/, pelvic inflammatory disease.tw. PID.tw.

Table 1. Key to search terms.

Search commands	Explanation
/	indicates a MeSH subject heading with all subheadings selected
.tw	indicates a search for a term in the title or abstract
exp	indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$	indicates that the search term was truncated (e.g. wart$ searches for wart and warts)

Sources of guidelines

• National Institute for Health and Clinical Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• National Guidelines Clearinghouse
• New Zealand Guidelines Group
• British Columbia Medical Association
• Canadian Medical Association
• Institute for Clinical Systems Improvement
• Guidelines International Network
• National Library of Guidelines
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• Alberta Medical Association
• University of Michigan Medical School
• Michigan Quality Improvement Consortium
• Royal College of Nursing
• Singapore Ministry of Health
• Health Protection Agency
• National Resource for Infection Control
• CREST
• World Health Organization
• NHS Scotland National Patient Pathways
• Agency for Healthcare Research and Quality
• TRIP database
• Patient UK Guideline links
• UK Ambulance Service Clinical Practice Guidelines
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
• Systematic reviews
• Protocols
• Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
• NHS Economic Evaluations
• Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
• Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug & Therapeutics Bulletin
• MeReC
• NPCi
• DynaMed
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Drugs in this topic

Scenario: Management

Azithromycin 500mg tablets

Age from 13 years onwards

Azithromycin 500mg tablets: Take two tablets as a single dose once a week for 2 weeks.

Azithromycin 500mg tablets

Take two tablets as a single dose once a week for 2 weeks.

Supply 4 tablets.

Age: from 13 years onwards

NHS cost: £9.86

Licensed use: no - off-label dose

Azithromycin 500mg tablets: Take two tablets as a single dose once a week for 2 weeks.

Azithromycin 500mg tablets

Take two tablets as a single dose once a week for 2 weeks.

Supply 4 tablets.

Age: from 13 years onwards

NHS cost: £9.86

Licensed use: no - off-label dose

Age from 13 years onwards

Azithromycin 500mg tablets: Take two tablets as a single dose once a week for 2 weeks.

Azithromycin 500mg tablets

Take two tablets as a single dose once a week for 2 weeks.

Supply 4 tablets.

Age: from 13 years onwards

NHS cost: £9.86

Licensed use: no - off-label dose

Azithromycin 500mg tablets: Take two tablets as a single dose once a week for 2 weeks.

Azithromycin 500mg tablets

Take two tablets as a single dose once a week for 2 weeks.

Supply 4 tablets.

Age: from 13 years onwards

NHS cost: £9.86

Licensed use: no - off-label dose

Cefixime 200mg tablets

Age from 13 years onwards

Cefixime 200mg tablets: Take two tablets as a single dose.

Cefixime 200mg tablets

Take two tablets as a single dose.

Supply 2 tablets.

Age: from 13 years onwards

NHS cost: £3.78

Licensed use: no - off-label indication

Cefixime 200mg tablets: Take two tablets as a single dose.

Cefixime 200mg tablets

Take two tablets as a single dose.

Supply 2 tablets.

Age: from 13 years onwards

NHS cost: £3.78

Licensed use: no - off-label indication

Age from 13 years onwards

Cefixime 200mg tablets: Take two tablets as a single dose.

Cefixime 200mg tablets

Take two tablets as a single dose.

Supply 2 tablets.

Age: from 13 years onwards

NHS cost: £3.78

Licensed use: no - off-label indication

Cefixime 200mg tablets: Take two tablets as a single dose.

Cefixime 200mg tablets

Take two tablets as a single dose.

Supply 2 tablets.

Age: from 13 years onwards

NHS cost: £3.78

Licensed use: no - off-label indication

Ceftriaxone 250mg powder for solution for injection vials

Age from 13 years onwards

Ceftriaxone 250mg powder for solution for injection vials: Reconstitute and give a single dose of 250mg by intramuscular injection.

Ceftriaxone 250mg powder for solution for injection vials

Reconstitute and give a single dose of 250mg by intramuscular injection.

Supply 1 250mg vial.

Age: from 13 years onwards

NHS cost: £2.45

Licensed use: yes

Ceftriaxone 250mg powder for solution for injection vials: Reconstitute and give a single dose of 250mg by intramuscular injection.

Ceftriaxone 250mg powder for solution for injection vials

Reconstitute and give a single dose of 250mg by intramuscular injection.

Supply 1 250mg vial.

Age: from 13 years onwards

NHS cost: £2.45

Licensed use: yes

Age from 13 years onwards

Ceftriaxone 250mg powder for solution for injection vials: Reconstitute and give a single dose of 250mg by intramuscular injection.

Ceftriaxone 250mg powder for solution for injection vials

Reconstitute and give a single dose of 250mg by intramuscular injection.

Supply 1 250mg vial.

Age: from 13 years onwards

NHS cost: £2.45

Licensed use: yes

Ceftriaxone 250mg powder for solution for injection vials: Reconstitute and give a single dose of 250mg by intramuscular injection.

Ceftriaxone 250mg powder for solution for injection vials

Reconstitute and give a single dose of 250mg by intramuscular injection.

Supply 1 250mg vial.

Age: from 13 years onwards

NHS cost: £2.45

Licensed use: yes

Codeine 30mg tablets

Age from 18 years onwards

Codeine 30mg tablets: Take one or two tablets every 4 to 6 hours when required for pain relief. Maximum of 8 tablets in 24 hours.

Codeine 30mg tablets

Take one or two tablets every 4 to 6 hours when required for pain relief. Maximum of 8 tablets in 24 hours.

Supply 28 tablets.

Age: from 18 years onwards

NHS cost: £1.22

Licensed use: yes

Doxycycline 100mg capsules

Age from 13 years onwards

Doxycycline 100mg capsules: Take one capsule twice a day for 14 days.

Doxycycline 100mg capsules

Take one capsule twice a day for 14 days.

Supply 28 capsules.

Age: from 13 years onwards

NHS cost: £1.94

Licensed use: off-label duration

Doxycycline 100mg capsules: Take one capsule twice a day for 14 days.

Doxycycline 100mg capsules

Take one capsule twice a day for 14 days.

Supply 28 capsules.

Age: from 13 years onwards

NHS cost: £1.94

Licensed use: off-label duration

Age from 13 years onwards

Doxycycline 100mg capsules: Take one capsule twice a day for 14 days.

Doxycycline 100mg capsules

Take one capsule twice a day for 14 days.

Supply 28 capsules.

Age: from 13 years onwards

NHS cost: £1.94

Licensed use: off-label duration

Doxycycline 100mg capsules: Take one capsule twice a day for 14 days.

Doxycycline 100mg capsules

Take one capsule twice a day for 14 days.

Supply 28 capsules.

Age: from 13 years onwards

NHS cost: £1.94

Licensed use: off-label duration

Ibuprofen 200mg tablets

Age from 13 years onwards

Ibuprofen 200mg tablets: Take one or two tablets 3 to 4 times a day when required for pain relief. Do not exceed the stated dose. (a)

Ibuprofen 200mg tablets

Take one or two tablets 3 to 4 times a day when required for pain relief. Do not exceed the stated dose.

Supply 56 tablets.

Age: from 13 years onwards

NHS cost: £1.38

OTC cost: £2.38

Licensed use: yes

Metronidazole 400mg tablets

Age from 13 years onwards

Metronidazole 400mg tablets: Take one tablet twice a day for 14 days.

Metronidazole 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.

Age: from 13 years onwards

NHS cost: £1.63

Licensed use: yes

Metronidazole 400mg tablets: Take one tablet twice a day for 14 days.

Metronidazole 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.

Age: from 13 years onwards

NHS cost: £1.63

Licensed use: yes

Age from 18 years onwards

Metronidazole 400mg tablets: Take one tablet twice a day for 14 days.

Metronidazole 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.

Age: from 18 years onwards

NHS cost: £1.63

Licensed use: yes

Age from 13 years onwards

Metronidazole 400mg tablets: Take one tablet twice a day for 14 days.

Metronidazole 400mg tablets

Take one tablet twice a day for 14 days.

Supply 28 tablets.