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Canadian Guidelines on Sexually Transmitted Infections

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In 2013, revisions were made to the Gonococcal Infections chapter in response to emerging antimicrobial resistance. As such, this chapter also requires updates. A Supplementary Statement has been developed to highlight key changes in the diagnosis, management and follow-up for Pelvic Inflammatory Disease until such time as the full chapter revision is available. This Supplementary Statement should be used in conjunction with the 2010 chapter to ensure that the most current recommendations are being implemented in your practice.

Supplementary Statement

Section 4 - Management and Treatment of Specific Syndromes

Pelvic Inflammatory Disease (PID)

Definition

  • PID is an infection of the female upper genital tract involving any combination of the endometrium, fallopian tubes, pelvic peritoneum and contiguous structures.

Etiology

  • There are multiple causes of lower abdominal pain in women, including gynecologic disease or dysfunction (complications of pregnancy, acute infections, endometriosis, adnexal disorders, menstrual disorders), as well as gastrointestinal (appendicitis, gastroenteritis, inflammatory bowel disease), genitourinary (cystitis, pyelonephritis, nephrolithiasis), musculoskeletal and neurologic causes.
  • The most common infectious cause of lower abdominal pain in women is pelvic inflammatory disease (PID).Footnote 1
  • PID is a polymicrobial infection with multiple microbial etiologies.
  • Most cases of PID are associated with more than one organism.
  • Pathogens can be categorized as sexually transmitted or endogenous organisms.

Table 1. Microbial causes

Sexually transmitted organisms

  • Chlamydia trachomatis
  • Neisseria gonorrhoeae
  • Viruses and protozoa (rare)
    • Herpes simplex virus
    • Trichomonas vaginalis

Endogenous organisms

  • Genital-tract mycoplasmas
    • Mycoplasma genitalium
    • Mycoplasma hominis
    • Ureaplasma urealyticum

Anaerobic bacteria

  • Bacteroides spp.
  • Peptostreptococcus spp.
  • Prevotella spp.

Facultative (aerobic) bacteria

  • Escherichia coli
  • Gardnerella vaginalis
  • Haemophilus influenzae
  • Streptococcus spp.

Epidemiology

  • PID is a very significant public health problem.
  • Up to two-thirds of cases go unrecognized, and underreporting is common.
  • There are approximately 100,000 cases of symptomatic PID annually in Canada, although PID is not nationally reportable, so exact numbers are unknown.
  • It is estimated that 10–15% of women of reproductive age have had one episode of PID.Footnote 2
  • In recent years, hospitalization rates for PID have declined (118/100,000 women in 1995 and 55/100,000 women in 2001, data from Health Canada) because increasing numbers of patients are treated as outpatients, but the number of patient visits to physician offices for PID has remained stable.
  • The incidence of long-term sequelae of PID (tubal factor infertility, ectopic pregnancy, chronic pelvic pain) is directly related to the number of episodes of PID.Footnote 3
  • In jurisdictions with long-standing chlamydia control programs, PID rates and ectopic pregnancy rates have declined.

Prevention

  • At the community level, health-promotion and education programs are essential to promote screening for sexually transmitted infections (STIs).
  • Health care providers should assume responsibility for primary prevention activities, such as risk-reduction counselling and patient education.
  • At the time of diagnosis of infection, health care providers should reinforce prevention and safer sex practices. They should also identify barriers to prevention practices and ways to overcome them.
  • Patients and contacts should be counselled to abstain from unprotected sexual contact until treatment of both partners is complete.

Manifestations and Diagnosis

  • Abdominal pain may be a clinical feature of many disorders, and the symptoms of PID may overlap with other gynecologic disorders or disorders of the gastrointestinal, urinary and musculoskeletal systems.
  • There is no single historical, physical or laboratory finding that is both sensitive and specific for the diagnosis of PID.Footnote 4
  • Only one-third of women with acute PID have a temperature above 38°C.Footnote 5
  • Common findings on physical examination of patients with acute PID include bilateral lower abdominal, uterine, adnexal and cervical motion tenderness, but these findings may be present with a variety of other conditions as well.
  • The clinical diagnosis of PID is imprecise, and clinicians should have a high index of suspicion.
Table 2. Criteria for diagnosis
Minimum diagnostic criteria Additional diagnostic criteria Definitive diagnostic criteria
PID
pelvic inflammatory disease
  • Lower abdominal tenderness
  • Adnexal tenderness
  • Cervical motion tenderness
  • Oral temperature >38.3°C.
  • Presence of white blood cells on saline microscopy of vaginal secretions/wet mount
  • Elevated erythrocyte sedimentation rate
  • Elevated C-reactive protein
  • Laboratory documentation of cervical infection with Neisseria gonorrhoeae or Chlamydia trachomatis
  • Endometrial biopsy with histopathologic evidence of endometritis (at least 1 plasma cell per x120 field and at least 5 neutrophils per x400 field)
  • Transvaginal sonography or other imaging techniques showing thickened fluid-filled tubes, with or without free pelvic fluid or tubo-ovarian complex
  • Gold standard: Laparoscopy demonstrating abnormalities consistent with PID, such as fallopian tube erythema and/or mucopurulent exudates
Physical examination and specimen collection
  • A complete abdominal and pelvic examination should be performed in any patient with lower abdominal pain.
  • Pelvic examination should include speculum and bimanual examinations.
  • The external genital area, vagina and cervix should all be inspected.
  • Stat serum beta HCG to rule out ectopic pregnancy.
  • With the aid of a speculum, endocervical swabs should be obtained for diagnostic tests for Neisseria gonorrhoeae and Chlamydia trachomatis.
  • Cervical lesions should be sampled with swabs for diagnostic tests for herpes simplex virus, if suspected.
  • Vaginal swabs should be obtained for culture; pH testing; amine odour whiff testing; normal saline and potassium hydroxide wet preparations; and Gram stain. Clinical assessment for bacterial vaginosis includes three of four Amsel criteria (vaginal discharge, elevated pH, amine odour whiff test and clue cellsFootnote * on microscopy).Footnote 6 An aerobic and anaerobic culture may assist with the detection of unusual vaginal pathogens, such as Group A streptococcus.
Footnote *
Clue cells are vaginal epithelial cells covered with numerous coccobacilli
Laboratory diagnosis
  • Negative laboratory results do not rule out a diagnosis of PID.
  • A normal ultrasound study does not rule out a diagnosis of PID.
  • Ultrasound may aid in the diagnosis, especially if tubo-ovarian abscess is suspected.
  • A STAT beta HCG pregnancy test should be done to exclude ectopic pregnancy from the differential diagnosis.
  • Detection of Gram-negative intracellular diplococci on a stained smear of endocervical secretions; positive results of a diagnostic test for N. gonorrhoeae or C. trachomatis; or both.
  • Detection of N. gonorrhoeae or C. trachomatis may be enhanced by using nucleic acid amplification tests (NAAT).
  • Other tests that may be helpful in the diagnosis of acute PID include complete blood count, erythrocyte sedimentation rate, C-reactive protein and endometrial biopsy.

Management

  • Early diagnosis and treatment are crucial to the maintenance of fertility.
  • Antibiotic therapy can be administered orally or parenterally, and in inpatient or outpatient settings.
  • Data suggest that efficacy and long-term complication rates are not significantly different between parenteral and oral therapy or inpatient and outpatient treatment.Footnote 7
  • Individuals treated as outpatients need careful follow-up and should be re-evaluated 2 to 3 days after therapy is initiated.
  • If no clinical improvement has occurred, hospital admission for parenteral therapy, observation and consideration for laparoscopy is required; consultation with colleagues experienced in the care of these patients should be considered.

Table 3. Criteria for hospitalization

  • Surgical emergencies such as appendicitis cannot be excluded.
  • The patient is pregnant.
  • The patient does not respond clinically to oral antimicrobial therapy.
  • The patient is unable to follow or tolerate an outpatient oral regimen.
  • The patient has severe illness, nausea and vomiting, or high fever.
  • The patient has a tubo-ovarian abscess.
  • Consider hospitalization for observed oral or parenteral therapy in the following cases:
  • HIV infection
  • Youth/adolescents (particularly if compliance is an issue)

Treatment

  • Goals of treatment are to control the acute infection and to prevent long-term sequelae such as infertility, ectopic pregnancy and chronic pelvic pain.
  • Treatment regimens should provide empiric broad-spectrum coverage of likely etiologic pathogens and take into account the polymicrobial nature of PID.
  • Treatment regimens should provide coverage for N. gonorrhoeae, C. trachomatis, Gram-negative facultative bacteria and streptococci.Footnote 8 Anaerobic coverage should be considered, but whether elimination of anaerobes from the upper tract is necessary remains to be answered even though anaerobes are detected in the majority of PID cases.
  • Although quinolones are no longer recommended for the treatment of gonococcal infections in Canada, due to the polymicrobial nature of PID, they still can be useful in the treatment of acute infection that does not involve quinolone resistant N. gonorrhoeae. Recent clinical trials have shown that quinolones are very effective at producing cure of acute PID.Footnote 9-Footnote 11
  • For patients with contraindications to treatment with cephalosporins or quinolones, recent evidence suggests that short course azithromycin at a dose of either 250 mg PO daily for one week or 1 gram PO weekly for two weeks combined with oral metronidazole is effective in producing a clinical cure for acute PID.Footnote 12
  • Discontinuation of parenteral therapy may be considered 24 hours after a patient improves clinically.Footnote 8
  • Oral step-down therapy should then begin and continue for a total of 14 days of treatment.Footnote 8
  • If recovery does not occur, other differential diagnoses and a laparoscopy need to be considered.

Table 4. Recommended parenteral treatment regimens

Regimen AFootnote 13 [A-l]

  • Cefoxitin 2 g IV every 6 hours PLUS doxycycline 100 mg IV or PO every 12 hours
    • Parenteral therapy may be discontinued 24 hours after a patient improves clinically, and oral therapy with doxycycline (100 mg bid) should continue for a total of 14 days
    • Most authorities recommend administering doxycycline in oral form even in hospitalized patients, because IV administration is painful and more costly, and because oral and IV administration provide similar bioavailability

Regimen B [A-l]

  • Clindamycin 900 mg IV every 8 hours PLUS gentamicinTable 4 - Footnote * loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Once-daily dosing may be substituted (5mg/kg of body weight IV every 24h)
    • Parenteral therapy may be discontinued 24 hours after a patient improves clinically, and oral therapy with doxycycline (100 mg bid) or clindamycin (450 mg PO qid) should continue for a total of 14 days

Alternative regimensFootnote 14 [A-ll]

  • Ofloxacin 400 mg IV every 12 hoursTable 4 - Footnote PLUS/MINUS metronidazole 500 mg IV every 8 hoursTable 4 - Footnote

    OR
  • Levofloxacin 500 mg IV once dailyTable 4 - Footnote PLUS/MINUS metronidazole 500 mg IV every 8 hoursTable 4 - Footnote

    OR
  • Ampicillin/sulbactam 3 g IV every 6 hours PLUS doxycycline 100 mg IV or PO every 12 hours
    OR
  • Ciprofloxacin 200 mg IV every 12 hoursTable 4 - Footnote PLUS doxycycline 100 mg IV or PO every 12 hours PLUS/MINUS metronidazole 500 mg IV every 8 hoursTable 4 - Footnote
    • Because ciprofloxacin has poor coverage against C trachomatis, it is recommended that doxycycline be added routinely
    • Because of concerns regarding the anaerobic coverage of both quinolones, metronidazole should be included with each regimenTable 4 - Footnote

Notes:

  • Patients should not drink alcohol during and for 24 hours following treatment with metronidazole because of a possible disulfiram (antabuse) reaction.
  • The use of ofloxacin, ciprofloxacin, levofloxacin, and doxycycline is contraindicated for pregnant and lactating women. Pregnant women should not be treated with quinolones or tetracyclines.
Table 4 - Footnote *
These recommendations apply for those patients with normal renal function; gentamicin dosage to be adjusted for renal impairment. Renal function and gentamicin levels should be monitored during treatment.
Table 4 - Footnote
Due to the rapid increase in quinolone resistant Neisseria gonorrhoeae, quinolones such as ciprofloxacin and ofloxacin are no longer preferred drugs for the treatment of gonococcal infections in Canada.
  • Quinolones may be considered as an alternative treatment option ONLY IF :
    • antimicrobial susceptibility testing is available and quinolone susceptibility is demonstrated;

      OR
    • where antimicrobial testing is not available, a test of cure is essential.
Table 4 - Footnote
Anaerobic coverage should be considered, but whether elimination of anaerobes from the upper tract is necessary remains to be answered even though anaerobes are detected in the majority of PID cases.

Table 5. Recommended outpatient treatment regimens

Regimen AFootnote 15 [A-ll]

For each of three treatment options listed below, many experts recommend the addition of metronidazole 500 mg PO bid for 14 days to this regimen for additional anaerobic coverage and the treatment of bacterial vaginosis Table 5 - Footnote [B-lll].

  • Ceftriaxone 250 mg IM in a single dose Table 5 - Footnote § PLUS doxycycline 100 mg PO bid for 14 days
    OR
  • Cefoxitin 2 g IM PLUS probenecid 1 g PO in a single dose concurrently once PLUS doxycycline 100 mg PO bid for 14 days
    OR
  • Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) PLUS doxycycline 100 mg PO bid for 14 days

Regimen BFootnote 16 [A-ll]

Notes:

  • Patients should not drink alcohol during and for 24 hours following treatment with oral metronidazole because of a possible disulfiram (antabuse) reaction.
  • The use of ofloxacin, ciprofloxacin, levofloxacin, and doxycycline is contraindicated for pregnant and lactating women. Pregnant women should not be treated with quinolones or tetracyclines.
Table 5 - Footnote
Due to the rapid increase in quinolone resistant Neisseria gonorrhoea, quinolones such as ciprofloxacin and ofloxacin are no longer preferred drugs for the treatment of gonococcal infections in Canada.
  • Quinolones may be considered as an alternative treatment option ONLY IF :
    • antimicrobial susceptibility testing is available and quinolone susceptibility is demonstrated;

      OR
    • where antimicrobial testing is not available, a test of cure is essential.
Table 5 - Footnote §
Ceftriaxone should not be given to persons with a cephalosporin allergy or a history of immediate and/or anaphylactic reactions to penicillins.
  • The preferred diluent for ceftriaxone is 1% lidocaine without epinephrine (0.9 mL/250 mg, 0.45 mL/125 mg) to reduce discomfort.
Table 5 - Footnote
Anaerobic coverage should be considered, but whether or not elimination of anaerobes from the upper tract is necessary remains to be answered even though anaerobes are detected in the majority of PID cases.

Consideration for Other STIs

  • Individuals infected with one STI are at risk of concurrent infection with one or more other STIs.
  • Following a diagnosis of PID, testing and counselling should be performed for other infections, including HIV and syphilis.
  • Immunization against hepatitis B is recommended if not already immune.
  • Discuss HPV vaccine as per the recommendations outlined in the Canada Communicable Disease Report, Volume 33 ACS-2, (2007) National Advisory Committee on Immunization (NACI) Statement on Human papillomavirus vaccine.

Reporting and Partner Notification

  • Patients with conditions that are notifiable according to provincial and territorial laws and regulations should be reported to local public health authorities.
  • The management of women with PID is considered inadequate unless their sexual partners are also evaluated and treated.
  • Sexual partners should be traced 60 days prior to symptom onset or date of specimen collection (if asymptomatic).
  • The length of time for the trace-back period should be extended:
    1. to include additional time up to the date of treatment
    2. if the index case states that there were no partners during the recommended trace-back period, then the last partner should be notified
    3. if all partners traced (according to recommended trace-back period) test negative, then the partner prior to the trace-back period should be notified.
  • After evaluation, sexual partners should be empirically treated with regimens effective against both gonorrhea and chlamydia regardless of clinical findings and without waiting for test results.
  • Local public health authorities are available to assist with partner notification and appropriate referral for clinical evaluation, testing, treatment and health education when the causative organism is identified as a reportable STI.

Follow-up

  • Pain and tenderness resulting from acute PID should begin to resolve within 48 to 72 hours of initiating antibiotics.Footnote 17
  • If no improvement is observed, further work-up is essential.
  • Individuals treated as outpatients need careful follow-up and should be re-evaluated 2 to 3 days after treatment is initiated.
  • If no clinical improvement has occurred, hospital admission for parenteral therapy and observation is required.
  • Following a diagnosis of PID, patients should be informed that they are at risk of both short-term consequences such as Fitz-Hugh-Curtis syndrome (perihepatitis) and tubo-ovarian abscess, and long-term sequelae, including infertility, ectopic pregnancy and chronic pelvic pain.

Special Considerations

Pregnancy
  • PID is uncommon in pregnancy, especially after the first trimester.
  • Pregnant patients with suspected PID should be hospitalized for evaluation and treatment with parenteral therapy because of an increased risk of adverse outcomes for both the mother and the pregnancy.
  • There is a large differential diagnosis of acute abdominal pain in pregnancy, and consultation with an expert should be sought.
HIV infection
  • HIV-positive women with PID may represent a subgroup of patients with a more difficult clinical course.
  • Some studies have suggested that HIV-positive women with PID have longer hospital stays and are at higher risk for the development of tubo-ovarian abscesses and are more likely to require surgical intervention.Footnote 18,Footnote 19
  • These women should be followed closely and managed aggressively, and consideration should be given to hospitalization.
  • Consultation with a colleague experienced in HIV care is recommended.
Adolescents
  • Consideration should be given to hospitalization for adolescents with suspected PID if compliance is expected to be an issue.
Patients with an intrauterine contraceptive device in situ
  • In patients with an intrauterine device (IUD) in situ, the device should not be removed until after therapy has been initiated and at least two doses of antibiotics have been given.

References

Footnote 1
Eschenbach DA. Epidemiology and diagnosis of acute pelvic inflammatory disease. Obstet Gynecol 1980; 55(suppl 5):142S–152S.
Footnote 2
Aral SO, Mosher WD, Cates W Jr. Self-reported pelvic inflammatory disease in the United States, 1988. JAMA 1991; 266:2570–2573.
Footnote 3
Westrom L, Joesoef MJ, Reynolds G, Hagdu A, Thompson SE. Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis 1992;19:185–192.
Footnote 4
Kahn JG, Walker CK, Washington AE, Landers DV, Sweet RL. Diagnosing pelvic inflammatory disease: a comprehensive analysis and considerations for developing a new model. JAMA 1991; 266:2594–2604.
Footnote 5
Wolner-Hanssen P. Diagnosis of pelvic inflammatory disease. In: Landers DV, Sweet RL, eds. Pelvic Inflammatory Disease. New York, NY: Springer-Verlag; 1997: 60–75.
Footnote 6
Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14–22.
Footnote 7
Ness RB, Soper DE, Holley RL, et al. 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. Am J Obstet Gynecol 2002; 186:929–937.
Footnote 8
Walker CK, Kahn JG, Washington AE, Peterson HB, Sweet RL. Pelvic inflammatory disease: meta-analysis of antimicrobial regimen efficacy. J Infect Dis 1993;168:969–978.
Footnote 9
Martens MG, Gordon S, Yarborough DR, Faro S, Binder D, Berkeley A. Multicenter randomized trial of ofloxacin versus cefoxitin and doxycycline in outpatient treatment of pelvic inflammatory disease. Ambulatory PID research Group. South Med J 993;86:604-10.
Footnote 10
Arredondo JL, Diaz V, Gatian H, et al. Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease. Clin Infect Dis 1997; 24:170-8.
Footnote 11
Ross JDC, Cronje S, Paskowski T, et al. Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial. Sex Trans Infect 2006; 82:446-51.
Footnote 12
Haggerty CL, Ness RB. Newest approaches to treatment of pelvic inflammatory disease: a review of recent randomized clinical trials. Clin Infect Dis 2007; 44:953-60.
Footnote 13
Sweet RL, Schachter J, Landers DV, Ohm-Smith M, Robbie MO. Treatment of hospitalized patients with acute pelvic inflammatory disease: comparison of cefotetan plus doxycycline and cefoxitin plus doxycycline. Am J Obstet Gynecol 988;158:736–741.
Footnote 14
Matsuda S. Clinical study of levofloxacin (LVFX) on the infectious diseases in the field of obstetrics and gynecology. Chemotherapy 1992;40:311–323.
Footnote 15
Walker CK, Workowski KA, Washington AE, Soper D, Sweet RL. Anaerobes in pelvic inflammatory disease: implications for the Centers for Disease Control and Prevention’s guidelines for treatment of sexually transmitted diseases. Clin Infect Dis 1999; 28(suppl 1):S29–S36.
Footnote 16
Peipert JF, Sweet RL, Walker CK, Kahn J, Reilly-Gauvin K. Evaluation of ofloxacin in the treatment of laparoscopically documented acute pelvic inflammatory disease (salpingitis). Infect Dis Obstet Gynecol 1999; 7:138–144.
Footnote 17
Cunningham FG, Hauth JC, Strong JD, et al. Evaluation of tetracycline or penicillin and ampicillin for treatment of acute pelvic inflammatory disease. N Engl J Med 1977; 296:1380–1383.
Footnote 18
Korn AP, Landers DV, Green JR, Sweet RL. Pelvic inflammatory disease in human immunodeficiency virus-infected women. Obstet Gynecol 1993; 82:765–768.
Footnote 19
Barbosa D, Macasaet M, Brockmann S, Sierra MF, Xia Z, Duerr A. Pelvic inflammatory disease and human immunodeficiency virus infection. Obstet Gynecol 1997;89:65–70.

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