Pelvic inflammatory disease

Extracts from "Clinical Evidence"

Interventions

Unknown effectiveness:

Empirical antibiotic treatment

Different durations of antibiotic treatment

Oral versus parenteral antibiotics

Background

Definition Pelvic inflammatory disease (PID) is inflammation and infection of the upper genital tract in women, typically involving the fallopian tubes, ovaries, and surrounding structures.

Incidence/prevalence The exact incidence of PID is unknown because the disease cannot be diagnosed reliably from clinical symptoms and signs.[1-3] Direct visualisation of the fallopian tubes by laparoscopy is the best single diagnostic test, but it is invasive and not used routinely in clinical practice. PID is the most common gynaecological reason for admission to hospital in the United States, accounting for 49 per 10 000 recorded hospital discharges. However, since most PID is asymptomatic, this figure almost certainly underestimates true prevalence.[1 4]

Aetiology/risk factors Factors associated with PID mirror those for sexually transmitted infections: young age, reduced socioeconomic circumstances, African or Afro-Caribbean ethnic origin, lower educational attainment, and recent new sexual partner.[2 5 6] Most cases seem to result from ascending infection from the cervix. Initial epithelial damage caused by bacteria (especially Chlamydia trachomatis and Neisseria gonorrhoeae) allows the opportunistic entry of other organisms. Isolates from the upper genital tract are polymicrobial, including Mycoplasma hominis and anaerobes.[7] The spread of infection to the upper genital tract may be influenced by vaginal douching, instrumentation of the cervix, and use of contraceptives.[8-11]

Prognosis PID has high morbidity; about 20% of affected women become infertile, 20% develop chronic pelvic pain, and 10% of those who conceive have an ectopic pregnancy? We found no placebo controlled trials of antibiotic treatment. Uncontrolled observations suggest that clinical symptoms and signs resolve in an appreciable number of untreated women)[12] Repeated episodes of PID are associated with a fourfold to sixfold increase in the risk of permanent tubal damage).[13]

Aims To alleviate the pain and systemic malaise associated with infection; to achieve microbiological cure; to prevent development of permanent tubal damage with associated sequelae, such as chronic pelvic pain, ectopic pregnancy, and infertility; and to prevent the spread of infection to others.

Outcomes Incidence and severity of acute symptoms and signs; microbiological cure of the upper genital tract; incidence of chronic pelvic pain, ectopic pregnancy, and infertility; rate of transmission to others.

Methods

Clinical Evidence update search and appraisal May 2000.

Question: Should suspected PID be treated Empirically or should treatment be delayed Until results of microbiological Investigations are known?

Option: Empirical treatment with antibiotics

Summary We found no evidence to support or refute empirical treatment for suspected PID.

Benefits

We found no systematic review or randomised controlled trials (RCTs) comparing empirical treatment with delayed treatment.

Harms

We found no reliable evidence on harms of empirical treatment.

Comment

Because there are no reliable clinical diagnostic criteria for PID, early empirical treatment is common.[3] The positive predictive value of a clinical diagnosis is 65-90% compared with laparoscopy.[1-3] The absence of infection from the lower genital tract, where samples are usually taken, does not exclude PID[2] and so may not influence the decision to treat.

Question: How do different antimicrobial regimens compare?

Summary One systematic review has found that several regimens of parenteral followed by oral antibiotic treatment are effective in resolving the acute symptoms and signs associated with PID (table). We found no good evidence on the optimal duration of treatment, or comparing oral versus parenteral treatment.

Cure rates for antibiotic treatment of acute pelvic inflammatory disease. Aggregated data from systematic reviews of randomised controlled trials and case series[14, 15]

Benefits

We found one systematic review (search dates 1966 to 1992),[14] which was subsequently updated (search date 1992 to 1997).[15] These reviews identified 26 studies of 16 antimicrobial regimens in 1925 women with PID. The identified studies included case series, and it is not possible from the aggregated data published in the reviews to ascertain how many studies were RCTs. Inclusion criteria were a diagnosis of PID (clinical, microbiological, laparoscopic, or by endometrial biopsy) and microbiological testing for C trachomatis and N gonorrhoeae. The reviews found antibiotics to be effective in relieving the symptoms associated with PID, with clinical and microbiological cure rates of 90-100% (table). Duration of treatment: The duration of treatment was not addressed, although the most common treatment period was 14 days. Oral versus parenteral treatment: The reviews did not analyse outcomes by oral or parenteral route of administration. Most regimens started with parenteral treatment and continued with oral treatment at different points. Two RCTs (n = 249, n = 72) compared oral ofloxacin against parenteral cefoxitin and doxycycline. The trials found no significant difference in cure rates among groups (clinical cure rates about 95% for all treatments)?[16, 17]

Harms

The harms associated with treatment were not specifically addressed by the systematic reviews?[14, 15] In two RCTs reporting adverse effects, withdrawal from treatment was uncommon (2/20 for doxycycline/metronidazole; 0/20 for perfloxacin/metronidazole; 0/16 for ciprofloxacin).[18, 19]

Comment

We found little evidence about long term sequelae of PID, adverse effects of treatment, treatment of PID of differing severity, the effect of ethnic origin, or the relevance of tracing sexual contacts. The risks of tubal occlusion and subsequent infertility relate to the severity of PID before the start of treatment,[20] and clinical improvement may not translate into preserved fertility?[21, 22] Competing interests: None declared.

[1] Morcos R, Frost N, Hnat M, Petrunak A, Caldito G. Laparoscopic versus clinical diagnosis of acute pelvic inflammatory disease. J Reprod Med 1993;38:53-6.

[2] Metters JS, Catchpole M, Smith C, et al. Chlamydia trachomatis: summary and conclusions of CMO's expert advisory group. London: Department of Health, 1998.

[3] Centers for Disease Control. 1998 guidelines for treatment of sexually transmitted diseases. MMWR 1998;47:1-118. www.cdc.gov/epo/mmwr/ preview/mmwrhtml/00050909.htm (accessed 9 Feb 2001).

[4] Velebil P, Wingo PA, Xia Z, Wilcox LS, Peterson HB. Rate of hospitalization for gynecologic disorders among reproductive-age women in the United States. Obstet Gynecol 1995;86:764-9.

[5] Simms I, Catchpole M, Brugha R, Rogers P, Mallinson H, Nicoll A. Epidemiology of genital Chlamydia trachomatis in England and Wales. Genitourin Med 1997;73:122-6.

[6] Grodstein F, Rothman KJ. Epidemiology of pelvic inflammatory disease. Epidemiology 1994;5:234-42.

[7] Bevan CD, Johal BJ, Mumtaz G, Ridgway GL, Siddle NC. Clinical, laparoscopic and microbiological findings in acute salpingitis: report on a United Kingdom cohort. Br J Obstet Gynaecol 1995;102:407-14.

[8] Wolner-Hanssen P, Eschenbach DA, Paavonen J, et al. Association between vaginal douching and acute pelvic inflammatory disease. JAMA 1990;263:1936-41.

[9] Jacobson L, Westrom L. Objectivized diagnosis of acute pelvic inflammatory disease. Diagnostic and prognostic value of routine laparoscopy. Am J Obstet Gynecol 1969;105:1088-98.

[10] Kelaghan J, Rubin GL, Ory HW, Layde PM. Barrier-method contraceptives and pelvic inflammatory disease. JAMA 1982;248:184-7.

[11] Wolner-Hanssen P, Eschenbach DA, Paavonen J, et al. Decreased risk of symptomatic chlamydial pelvic inflammatory disease associated with oral contraceptive use. JAMA 1990;263:54-9.

[12] Curtis AH. Bacteriology and pathology of fallopian tubes removed at operation. Surg Gynecol Obstet 1921;33:621.

[13] Hillis SD, Owens LM, Marchbanks PA, Amsterdam LF, MacKenzie WR. Recurrent chlamydial infections increase the risks of hospitalization for ectopic pregnancy and pelvic inflammatory disease. Am J Obstet Gynecol 1997;176:103-7.

[14] Walker CK, Kahn JG, Washington AE, Peterson HB, Sweet RL. Pelvic inflammatory disease: metaanalysis of antimicrobial regimen efficacy. J Infect Dis 1993;168:969-78.

[15] Walker CK, Workowski KA, Washington AE, Soper DE, 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:S29-36.

[16] 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 1993; 86:604-10.

[17] Wendel GD, Cox SM, Bawdon RE, Theriot SK, Heard MC, Nobles BJ. A randomized trial of ofloxacin versus cefoxitin and doxycycline in the outpatient treatment of acute salpingitis. Am J Obstet Gynecol 1991;164:1390-6.

[18] Witte EH, Peters AA, Smit IB, et al. A comparison of pefloxacin/ metronidazole and doxycycline/metronidazole in the treatment of laparoscopically confirmed acute pelvic inflammatory disease. Eur J Obstet Gynecol Peprod Biol 1993;50:153-8.

[19] Heinonen PK, Teisala K, Miettinen A, Aine R, Punnonen R, Gronroos P. A comparison of ciprofloxacin with doxycycline plus metronidazole in the treatment of acute pelvic inflammatory disease. Scand J Infect Dis Suppl 1989;60:66-73.

[20] Soper DE, Brockwell NJ, Dalton HP. Microbial etiology of urban emergency department acute salpingitis: treatment with ofloxacin. Am J Obstet Gynecol 1992;167:653-60.

[21] Buchan H, Vessey M, Goldacre M, Fairweather J. Morbidity following pelvic inflammatory disease. Br J Obstet Gynaecol 1993;100:558-62.

[22] Brunham RC, Binns B, Guijon F, et al. Etiology and outcome of acute pelvic inflammatory disease. J Infect DIS 1988; 158:510-7.

Birmingham Specialist Community Health NHS Trust, Whittall Street Clinic, Birmingham B4 6DH

Jonathan Ross consultant in genitourinary medicine

j.d.c.ross @bham.ac.uk

BMJ 2001;322:658-9

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