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Pelvic Inflammatory Disease - UpToDate Reviews 2014
(Actualizado a Abril 2014)

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  • 1. Pelvic Inflammatory Disease Pathogenesis of and risk factors for pelvic inflammatory disease Author Charles H Livengood, III, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2014. | This topic last updated: ago 17, 2012. INTRODUCTION — Pelvic inflammatory disease (PID) refers to acute infection of the upper genital tract structures in women, involving any or all of the uterus, oviducts, and ovaries; this is often accompanied by involvement of the neighboring pelvic organs. By definition, PID is a community-acquired infection initiated by a sexually transmitted agent, distinguishing it from pelvic infections caused by medical procedures, pregnancy, and other primary abdominal processes. Pelvic inflammatory disease in the United States annually accounts for about 2.5 million outpatient visits, 200,000 hospitalizations, and 100,000 surgical procedures [1]. It is the most frequent gynecologic cause for emergency department visits (350,000/year) and incurs an annual total expense of almost $2 billion [1,2]. However, costs of PID in the US have decreased in the last decade [3]. The pathogenesis of and risk factors for PID will be reviewed here. The clinical features, diagnosis, treatment, and sequelae of this disorder are discussed separately. (See"Clinical features and diagnosis of pelvic inflammatory disease" and "Treatment of pelvic inflammatory disease".) PATHOGENESIS — The vaginal flora of most normal, healthy women includes a variety of potentially pathogenic bacteria [4]. Among these are species of streptococci, staphylococci, Enterobacteriaceae (most commonly Klebsiella spp, Escherichia coli, and Proteus spp), and a variety of anaerobes. Compared with the dominant hydrogen peroxide-producing Lactobacillus acidophilus, these organisms are present in low numbers, and ebb and flow under the influence of hormonal changes (pregnancy, degree of estrogenization), contraceptive method, sexual activity, and other as yet unknown forces. Complete disruption of the vaginal ecosystem can occur, in which anaerobic bacteria assume predominance over the desirable strains of lactobacilli. This condition is known as bacterial vaginosis, which is not associated with an inflammatory response [5]. Bacterial vaginosis affects 15 to 30 percent of American women, one-half of whom are asymptomatic [6]. Its significance is not clearly understood but when found in pregnancy, bacterial vaginosis was an independent risk factor for preterm delivery of a low birthweight infant in a study of 10,397 women of whom 16 percent had the diagnosis [7]. An intermediate situation in which H202-producing lactobacilli and anaerobes coexist in roughly equal numbers is called a transitional flora. The endocervical canal functions as a barrier protecting the normally sterile upper genital tract from the organisms of the dynamic vaginal ecosystem. Disturbance of this barrier provides vaginal bacteria with access to the upper genital organs via canalicular routes, infecting the endometrium, then endosalpinx, ovarian cortex, pelvic peritoneum, and their underlying stroma. This is the clinical entity of PID. Patients with PID can present with clinical disease at any point along the continuum (eg, endometritis with normal tubes, ovaries, and peritoneum) [8]. This observation has required reevaluation of many time-honored concepts of PID, which relied upon the presence of gross salpingitis by direct visualization to establish the diagnosis. (See"Clinical features and diagnosis of pelvic inflammatory disease".) Up to 75 percent of cases occur within seven days of menses, during which time the quality of the cervical mucus favors the ascension of vaginal organisms [9]. Epidemiologic data suggest that all community-acquired agents causing disturbance of the endocervical barrier are sexually transmitted (see below).
  • 2. MICROBIOLOGY — Initiating pathogens in PID include Neisseria gonorrhoeae and Chlamydia trachomatis, although in many cases the etiology of PID is unknown. Neisseria gonorrhoeae — N. gonorrhoeae was the first identified cause of PID. Following a dramatic decline after the advent of penicillin, the incidence of gonorrhea in the United States rebounded to about one million reported cases annually by the mid-1970s, and the Centers for Disease Control and Prevention (CDC) estimated that only about one-third of cases were reported [10]. (See "Epidemiology, pathogenesis, and clinical manifestations of Neisseria gonorrhoeae infection".) The incidence of gonorrhea in the United States has steadily declined since that time despite the simultaneous arrival of beta-lactamase-producing gonococci from West Africa and East Asia in 1978, the evolution of chromosomally mediated multidrug resistant strains in the early 1980s, and reports that more than one-third of United States isolates currently carry some form of drug resistance [11]. In light of rising rates of drug resistance, fluoroquinolone use is no longer recommended for the treatment of gonococcal infections [12]. (See "Treatment of uncomplicated gonococcal infections".) Approximately 15 percent of women acquiring endocervical gonorrhea go on to develop PID [13,14]. Factors differentiating these cases from those with a more benign course are undefined. However, it is common for endocervical gonorrhea to be asymptomatic, which often leads to no treatment or delay in treatment. N. gonorrhoeae accounts for approximately one-third of cases of PID overall: somewhat more in the southeastern United States, less in the western United States, and much less in western Europe [13,15,16]. Chlamydia trachomatis — Chlamydia trachomatis serovars D-K began to be recognized as an initiator of PID in the mid-1970s. Genital chlamydia infections are now the most common bacterial sexually transmissible disease and the most common reportable infectious disease, with about four million new cases occurring annually in the United States [17,18]. They account for about one-third of cases of PID overall, more in the western United States and much more in Western Europe [19]. The geographic distribution of Chlamydia is the converse of that for the gonococcus. As with the gonococcus, about 15 percent of endocervical chlamydia infections produce PID, with the remaining infections being asymptomatic [20]. At our institution, for example, 50 percent of positive chlamydia tests derive from cervices described as normal on examination. Screening in young women — Paradigms to identify whom to test for chlamydia have proven to lack universality, with the exception that women aged 16 to 24 years account for most cases. In one report of 150,000 such women, those at lowest risk still had a 6 percent prevalence of genital chlamydia infection, which accounted for 17 percent of infections in this sample [21]. Furthermore, if only those with one or more identified risk factors had been tested, 60 percent of cases would have been missed. Annual screening more than five years decreased the prevalence of genital chlamydia infection by 42 percent. Similar findings were noted in a large HMO population [22]. Annual screening and treatment of at risk 18 to 34 year-old women reduced the prevalence of PID by 56 percent (8 versus 18 per 10,000) woman-months in those managed traditionally by risk and symptomatic assessment [22]. (See "Screening for Chlamydia trachomatis".) Annual screening of sexually active adolescent girls and young women for chlamydia is recommended by the United States Preventive Services Task force and other professional organizations [23-26]. However, only 20 percent of eligible young women who receive health care through health maintenance organizations are screened [27,28]. Screening rates can be increased through clinical practice improvement interventions (eg, involvement of practice leaders, team building, and monitoring of progress) [27]. In one study, pediatric clinics that were randomly assigned to receive such interventions for 16 to 18 months had a greater increase in screening rates than those that were assigned to provide usual care (5 to 65 percent versus 14 to 21 percent) [27]. The USPSTF clinical practice guideline for screening for chlamydial infection, as well as other USPSTF guidelines, can be accessed through the website for the Agency for Healthcare Research and Quality at www.ahrq.gov/clinic/uspstfix.htm.
  • 3. Other initiating pathogens — Other agents that initiate PID, while almost certainly sexually transmitted and probably infectious, remain obscure. Bacterial vaginosis (BV) is more common among women with PID but, in the most comprehensive pathogenetic study to date, was shown not to be responsible alone for PID [29]. Another study of 1179 women found that BV did not increase risk of PID during three years of prospective follow-up [30]. However, in another study, PID risk was increased two-fold among those with the highest colony counts of BV- associated organisms [31]. Investigations of various mycoplasma species, such as Mycoplasma hominis, have been fueled by the ability of these organisms to cause urethritis in the male. (See"Mycoplasma hominis and Ureaplasma urealyticum infections".) M. genitalium has been identified by nucleic acid amplification in clinical cases of non-chlamydial, non- gonococcal PID, and infection with this pathogen has been associated with tubal infertility [32]. However, in a large community-based prospective cohort study of 2378 female college students, the prevalence of M. genitalium at baseline (3.3 percent) and the incidence of this infection (0.9 percent) over 12 months of follow-up was low, despite testing via polymerase chain reaction assays [33]. Since the incidence and prevalence of M. genitalium was less than half that of chlamydia, the researchers concluded that M. genitalium was unlikely to be a major risk factor for PID. Mixed infection — Regardless of the initiating event, the microbiology of PID, especially for clinical purposes, should be viewed and treated as a mixed (facultative and anaerobic) polymicrobial infection. Older studies isolated groups A and B streptococci (rarely enterococci), E. coli, Klebsiella spp, Proteus mirabilis, Haemophilus spp,Bacteroides/Prevotella spp, Peptococcus, and Peptostreptococcus spp [15,34,35]. A more recent study with comprehensive microbiologic methodology in 102 patients confirmed the older findings and emphasized the association of H. influenzae and Streptococcus pyogenes with clinically severe disease [29]. These studies found that, among cases of PID initiated by the gonococcus, a mixed polymicrobial infection was seen in approximately 35 percent. Another study, which employed particularly stringent microbiologic techniques, identified other organisms in more than 50 percent of patients with gonococcal PID [36]. Microbiologic findings at different levels of the genital tract of a given patient with PID often show poor correlation [15,29,35-37]. RISK FACTORS — Celibate women are not at risk for PID [38], and women with longstanding monogamous relationships rarely develop PID. On the other hand, women with multiple partners are at greatest risk. The clinical status of the partner, age, previous PID, and race are other important risk factors for PID. The frequency is also affected by the method of contraceptive used. In one case control study among sexually active, inner city adolescents with and without PID, younger age at first intercourse, older sex partners, prior involvement with a child protection agency, prior suicide attempt, alcohol use before intercourse, and current C. trachomatis infection were all significant risk factors for the development of PID [39]. The number of total sexual partners, history of rape, prior PID, or other STD (eg, syphilis, hepatitis B, or HIV) were not different between the girls with PID and the sexually active controls in this report. Multiple partners — The importance of multiple partners was illustrated in a report that compared 712 women hospitalized for PID to 2719 controls [40]. The risk for PID was increased 3.4 times by four or more sexual partners during the last six months, and 3.2 times by intercourse with a single partner six or more times per week [40]. Other studies have confirmed the importance of multiple partners with an increase in frequency of PID ranging from 4.6- to 20-fold [41,42]. One report, however, did not confirm a role for coital frequency [41]. Status of the partner — Approximately one-half of men with gonococcal or chlamydial urethritis are asymptomatic. Having a symptomatic (dysuria, urethral discharge) male partner greatly increases a woman's risk of PID [15]. Age — PID occurs in highest frequency among those 15 to 25 years of age [14,43]; the incidence in women older than the age of 35 is only one-seventh that in younger women [44]. The initiators of PID in both the United States and Europe, particularly Chlamydia, are densely concentrated among adolescent and young adult women, with a prevalence around 10 percent [45-47].
  • 4. Recurrence of genital chlamydia infection is also a function of age. In one series, for example, the risk of recurrence was eightfold (at 54 percent) and fivefold (at 30 percent) greater among women whose first infection occurred at <15 years and 15 to 19 years, respectively, compared to those whose first infection occurred older than age 30 [48]. Previous PID — Previous PID increased the risk for subsequent episodes by a factor of 2.3 in one report [41], and approximately one in four women with PID will suffer recurrence [49]. However, these data must be used cautiously in practice. Every episode of abdominal pain in a woman whose medical record indicates that she has had PID is not PID. Contraceptive method — Although earlier data suggested that the choice of contraceptive method may affect risk of PID, this was not supported by a large cross-sectional study in 563 women with PID; in this study, no hormonal or barrier contraceptive method was related to a reduction in upper genital tract disease among women with clinical PID [50]. However, other data (see below) support a role for barrier contraception in the prevention of PID. Barrier contraception — Barrier contraception protects against PID [51]. Condoms are the most effective, preventing 50 percent of endocervical gonococcal and chlamydial infections; the addition of nonoxynol-9 confers 25 percent more protection [52]. One large study suggested that inconsistent condom use is associated with greater risk for PID than both consistent condom use and no condom use [53]. Unfortunately, according to survey data reported by the Centers for Disease Control and Prevention from 2002 to 2007, only 31 percent of never- married women aged 20 to 24 years consistently use condoms [54]. Oral contraceptives — Oral contraceptives (OCs) have a complex interaction with PID. Several studies have shown that OC use nearly doubles the prevalence of both chlamydial and gonococcal infection of the cervix [55]. However, OC use has traditionally been associated with a 50 percent reduction in PID risk [56]. Resolution of this apparent quandary is emerging. Among OC users with cervical infection, asymptomatic endometritis is fourfold more common than among their counterparts not using OCs [57], although gross salpingitis is reduced fivefold [58]. Thus, women using OCs appear to develop PID in response to cervical initiating agents about as frequently as other women, but the severity of the infection — with respect to both symptoms and tissue damage — is substantially diminished. Intrauterine device and tubal ligation — Modern intrauterine devices cause little, if any, increased risk for PID [45,59,60]. The risk of PID is primarily limited to the first three weeks after IUD insertion and is uncommon thereafter [60]. No evidence suggests that IUDs should be removed in women diagnosed with acute PID [45]. However, long-term indwelling IUDs have been associated with pelvic actinomycosis, a rare disease that can present as a pelvic mass with weight loss and constitutional symptoms [61]. In a study of 475 isolates of actinomyces species, 30 percent of the clinical specimens originated in association with IUDs [62]. The decision to treat a patient for possible pelvic actinomycosis is influenced by the presence or absence of clinical symptoms, since actinomyces are part of normal vaginal flora. Thus, the identification of this organism on any cervical smears should not prompt antibiotic therapy or IUD removal, unless there are associated symptoms, such as fever, abdominal pain, abnormal vaginal bleeding [63], or abnormal rectovaginal exam. Antibiotics that are commonly used in the treatment of PID (doxycycline, clindamycin, beta-lactams, fluoroquinolones) also have activity against actinomyces, although the treatment duration is longer (three to six months). (See "Treatment of pelvic inflammatory disease".) Tubal ligation may protect the distal oviducts from involvement, but the clinical syndrome of PID is otherwise unaffected. Other — PID occurs significantly more commonly among African-Americans [41]. It may be more common among women who use vaginal douching [64]. However, there is a higher frequency of other risk factors for PID among women who employ this practice, and a causative relationship has not been established [65].
  • 5. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 th to 6 th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)  Basics topic (see "Patient information: Pelvic inflammatory disease (The Basics)") SUMMARY AND RECOMMENDATIONS  Pelvic inflammatory disease (PID) is a community-acquired infection initiated by a sexually transmitted agent, distinguishing it from pelvic infections caused by medical procedures, pregnancy, and other primary abdominal processes. (See 'Introduction' above.)  Anatomically, PID refers to acute infection of the upper genital tract structures in women, involving any or all of the uterus, oviducts, and ovaries and sometimes other surrounding pelvic organs. (See 'Introduction' above.)  Initiating pathogens in pelvic inflammatory disease include Neisseria gonorrhoeae and Chlamydia trachomatis account for an estimated one-third of all cases of pelvic inflammatory disease, although in the majority of cases the etiology of PID is unknown. Regardless of the initiating event, the microbiology of PID should be viewed and treated as a mixed (facultative and anaerobic) polymicrobial infection. (See 'Microbiology' above.)  The main risk factor for pelvic inflammatory disease is having intercourse with multiple sex partners. The choice of contraceptive method does not clearly affect the risk of pelvic infection, though consistent use of condoms may offer significant reduction of risk. (See 'Risk factors' above.) REFERENCES 1. Washington AE, Katz P. Cost of and payment source for pelvic inflammatory disease. Trends and projections, 1983 through 2000. JAMA 1991; 266:2565. 2. Curtis KM, Hillis SD, Kieke BA Jr, et al. Visits to emergency departments for gynecologic disorders in the United States, 1992-1994. Obstet Gynecol 1998; 91:1007. 3. Rein DB, Kassler WJ, Irwin KL, Rabiee L. Direct medical cost of pelvic inflammatory disease and its sequelae: decreasing, but still substantial. Obstet Gynecol 2000; 95:397. 4. Galask RP, Larsen B, Ohm MJ. Vaginal flora and its role in disease entities. Clin Obstet Gynecol 1976; 19:61. 5. Platz-Christensen JJ, Mattsby-Baltzer I, Thomsen P, Wiqvist N. Endotoxin and interleukin-1 alpha in the cervical mucus and vaginal fluid of pregnant women with bacterial vaginosis. Am J Obstet Gynecol 1993; 169:1161. 6. Fleury FJ. Adult vaginitis. Clin Obstet Gynecol 1981; 24:407. 7. Hillier SL, Nugent RP, Eschenbach DA, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 1995; 333:1737. 8. Paavonen J, Aine R, Teisala K, et al. Comparison of endometrial biopsy and peritoneal fluid cytologic testing with laparoscopy in the diagnosis of acute pelvic inflammatory disease. Am J Obstet Gynecol 1985; 151:645. 9. Eschenbach DA. Acute pelvic inflammatory disease: etiology, risk factors and pathogenesis. Clin Obstet Gynecol 1976; 19:147. 10. U.S. Public Health Service. V.D. fact sheet, 1976. Publication No. (CDC) 77-8195, USPHS; 1976. 11. Morse SA, Trees DL. Prevalence and treatment of multi-drug resistant Neisseria gonorrhoeae. Infect Med 1995; 12:609. 12. Centers for Disease Control and Prevention (CDC). Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 2007; 56:332. 13. Rendtroff RC, Curran JW, Chandler RW, et al. Economic consequences of gonorrhea in women: experience from an Urban hospital. J Am Vener Dis Assoc 1974; 1:40. 14. Forslin L, Falk V, Danielsson D. Changes in the incidence of acute gonococcal and nongonococcal salpingitis. A five-year study from an urban area of central Sweden. Br J Vener Dis 1978; 54:247. 15. Eschenbach DA, Buchanan TM, Pollock HM, et al. Polymicrobial etiology of acute pelvic inflammatory disease. N Engl J Med 1975; 293:166. 16. Treharne JD, Ripa KT, Mårdh PA, et al. Antibodies to Chlamydia trachomatis in acute salpingitis. Br J Vener Dis 1979; 55:26. 17. Recommendations of the International Task Force for Disease Eradication. MMWR Recomm Rep 1993; 42:1. 18. Centers for Disease Control and Prevention (CDC). Ten leading nationally notifiable infectious diseases--United States, 1995. MMWR Morb Mortal Wkly Rep 1996; 45:883. 19. Bowie WR, Jones H. Acute pelvic inflammatory disease in outpatients: association with Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med 1981; 95:685. 20. Arya OP, Mallinson H, Goddard AD. Epidemiological and clinical correlates of chlamydial infection of the cervix. Br J Vener Dis 1981; 57:118.
  • 6. 21. Mosure DJ, Berman S, Fine D, et al. Genital Chlamydia infections in sexually active female adolescents: do we really need to screen everyone? J Adolesc Health 1997; 20:6. 22. Scholes D, Stergachis A, Heidrich FE, et al. Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 1996; 334:1362. 23. United States Preventive Service Task Force. Chlamydial infection: Screening 2001. In: Guide to Clinical Preventive Services, International Medical Publishing Co, Alexandria, VA 2001. p.332. 24. American Academy of Pediatrics. Guidelines for Health Supervision, Third Ed, Stein M (Ed), American Academy of Pediatrics, Elk Grove, IL 1997. 25. American College of Obstetricians and Gynecologists. Guidelines for Women's Health Care. American College of Obstetricians and Gynecologists, Washington, DC 1996. 26. American Medical Association. AMA Guidelines for Adolescent Preventive Services (GAPS), Elster A, Kuznets N (Eds), Williams & Wilkins, Baltimore, MD 1994. 27. Shafer MA, Tebb KP, Pantell RH, et al. Effect of a clinical practice improvement intervention on Chlamydial screening among adolescent girls. JAMA 2002; 288:2846. 28. National Committee on Quality Assurance. State of managed care quality report. National Committee for Quality Assurance, Washington, DC 2001. 29. Soper DE, Brockwell NJ, Dalton HP, Johnson D. Observations concerning the microbial etiology of acute salpingitis. Am J Obstet Gynecol 1994; 170:1008. 30. Ness RB, Hillier SL, Kip KE, et al. Bacterial vaginosis and risk of pelvic inflammatory disease. Obstet Gynecol 2004; 104:761. 31. Ness RB, Kip KE, Hillier SL, et al. A cluster analysis of bacterial vaginosis-associated microflora and pelvic inflammatory disease. Am J Epidemiol 2005; 162:585. 32. Haggerty CL. Evidence for a role of Mycoplasma genitalium in pelvic inflammatory disease. Curr Opin Infect Dis 2008; 21:65. 33. Oakeshott P, Aghaizu A, Hay P, et al. Is Mycoplasma genitalium in women the "New Chlamydia?" A community-based prospective cohort study. Clin Infect Dis 2010; 51:1160. 34. Thompson SE 3rd, Hager WD, Wong KH, et al. The microbiology and therapy of acute pelvic inflammatory disease in hospitalized patients. Am J Obstet Gynecol 1980; 136:179. 35. Chow AW, Malkasian KL, Marshall JR, Guze LB. The bacteriology of acute pelvic inflammatory disease. Am J Obstet Gynecol 1975; 122:876. 36. Sweet RL, Draper DL, Hadley WK. Etiology of acute salpingitis: influence of episode number and duration of symptoms. Obstet Gynecol 1981; 58:62. 37. Sweet RL, Mills J, Hadley KW, et al. Use of laparoscopy to determine the microbiologic etiology of acute salpingitis. Am J Obstet Gynecol 1979; 134:68. 38. Stemmer W. Uber die ursachen von eileiterentzundungen. Gentral fur Gynnak 1941; 65:1062. 39. Suss AL, Homel P, Hammerschlag M, Bromberg K. Risk factors for pelvic inflammatory disease in inner-city adolescents. Sex Transm Dis 2000; 27:289. 40. Lee NC, Rubin GL, Grimes DA. Measures of sexual behavior and the risk of pelvic inflammatory disease. Obstet Gynecol 1991; 77:425. 41. Flesh G, Weiner JM, Corlett RC Jr, et al. The intrauterine contraceptive device and acute salpingitis: a multifactor analysis. Am J Obstet Gynecol 1979; 135:402. 42. Rein MF. Epidemiology of gonococcal infection. In: The Gonococcus, Roberts RB (Ed), Wiley and Sons, New York 1977. p.1. 43. Westrom, L, Mardh PA. Epidemiology, etiology, and prognosis of acute salpingitis: A study of 1,457 laparoscopically verified cases. In: Nongonococcal Urethritis and Related Diseases, Hobson D, Holmes KK (Eds), Am Soc Microbiol, Washington DC 1977. p.84. 44. Weström L. Incidence, prevalence, and trends of acute pelvic inflammatory disease and its consequences in industrialized countries. Am J Obstet Gynecol 1980; 138:880. 45. Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006; 55:1. 46. Biro FM, Rosenthal SL, Kiniyalocts M. Gonococcal and chlamydial genitourinary infections in symptomatic and asymptomatic adolescent women. Clin Pediatr (Phila) 1995; 34:419. 47. Lan J, Melgers I, Meijer CJ, et al. Prevalence and serovar distribution of asymptomatic cervical Chlamydia trachomatis infections as determined by highly sensitive PCR. J Clin Microbiol 1995; 33:3194. 48. Hillis SD, Nakashima A, Marchbanks PA, et al. Risk factors for recurrent Chlamydia trachomatis infections in women. Am J Obstet Gynecol 1994; 170:801. 49. Weström L. Effect of acute pelvic inflammatory disease on fertility. Am J Obstet Gynecol 1975; 121:707. 50. Ness RB, Soper DE, Holley RL, et al. Hormonal and barrier contraception and risk of upper genital tract disease in the PID Evaluation and Clinical Health (PEACH) study. Am J Obstet Gynecol 2001; 185:121. 51. Eschenbach DA, Harnisch JP, Holmes KK. Pathogenesis of acute pelvic inflammatory disease: role of contraception and other risk factors. Am J Obstet Gynecol 1977; 128:838. 52. Niruthisard S, Roddy RE, Chutivongse S. Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections. Lancet 1992; 339:1371. 53. Ness RB, Randall H, Richter HE, et al. Condom use and the risk of recurrent pelvic inflammatory disease, chronic pelvic pain, or infertility following an episode of pelvic inflammatory disease. Am J Public Health 2004; 94:1327. 54. Gavin L, MacKay AP, Brown K, et al. Sexual and reproductive health of persons aged 10-24 years - United States, 2002-2007. MMWR Surveill Summ 2009; 58:1. 55. Louv WC, Austin H, Perlman J, Alexander WJ. Oral contraceptive use and the risk of chlamydial and gonococcal infections. Am J Obstet Gynecol 1989; 160:396. 56. Rubin GL, Ory HW, Layde PM. Oral contraceptives and pelvic inflammatory disease. Am J Obstet Gynecol 1982; 144:630. 57. Ness RB, Keder LM, Soper DE, et al. Oral contraception and the recognition of endometritis. Am J Obstet Gynecol 1997; 176:580. 58. Wølner-Hanssen P, Svensson L, Mårdh PA, Weström L. Laparoscopic findings and contraceptive use in women with signs and symptoms suggestive of acute salpingitis. Obstet Gynecol 1985; 66:233. 59. Lee NC, Rubin GL, Borucki R. The intrauterine device and pelvic inflammatory disease revisited: new results from the Women's Health Study. Obstet Gynecol 1988; 72:1. 60. Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet 2000; 356:1013. 61. Lee YC, Min D, Holcomb K, et al. Computed tomography guided core needle biopsy diagnosis of pelvic actinomycosis. Gynecol Oncol 2000; 79:318. 62. Hall V, Talbot PR, Stubbs SL, Duerden BI. Identification of clinical isolates of actinomyces species by amplified 16S ribosomal DNA restriction analysis. J Clin Microbiol 2001; 39:3555. 63. Lippes J. Pelvic actinomycosis: a review and preliminary look at prevalence. Am J Obstet Gynecol 1999; 180:265. 64. Wølner-Hanssen P, Eschenbach DA, Paavonen J, et al. Association between vaginal douching and acute pelvic inflammatory disease. JAMA 1990; 263:1936. 65. Rosenberg MJ, Phillips RS. Does douching promote ascending infection? J Reprod Med 1992; 37:930.
  • 7. Clinical features and diagnosis of pelvic inflammatory disease Authors Charles H Livengood, III, MD Mariam R Chacko, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2014. | This topic last updated: sep 18, 2012. INTRODUCTION — Pelvic inflammatory disease (PID) refers to acute infection of the upper genital tract structures in women, involving any or all of the uterus, oviducts, and ovaries; this is often accompanied by involvement of the neighboring pelvic organs. Involvement of these structures results in endometritis, salpingitis, oophoritis, peritonitis, perihepatitis and tubo-ovarian abscess. Sexually transmitted agents, such as Neisseria gonorrhoeae and Chlamydia trachomatis are often implicated, although vaginal flora may also play an important role [1]. Post-operative pelvic cellulitis and abscess, pregnancy-related pelvic infection, and pelvic infection secondary to spread of another infection (appendicitis, diverticulitis, tumor, tuberculous peritonitis, actinomycosis, others) produce a very similar clinical picture, and indeed are referred to as PID by some. However, the etiologic differences among these processes have significant implications for treatment and prevention. According to a National Ambulatory Medical Care Survey, the estimated number of cases of PID in women 15 to 44 years of age in the United States decreased from 189,662 in 2002 to 168,837 in 2003. The number of hospitalizations for acute PID steadily declined from approximately 70,000 cases/year in 1998 to 45,000 cases/year in 2007 [2]. Visits to physicians’ offices for PID also have declined, primarily due to aggressive population-based chlamydia screening and treatment programs nationwide [2,3]. The last 30 years have witnessed an interesting, if circular, evolution of the clinical approach to the diagnosis of PID. Diagnostic procedures to document PID at one time replaced a primary clinical diagnosis. It is now appreciated that PID represents a spectrum of infection, that there is no single diagnostic gold standard, and that the practical value of clinical diagnosis retains central importance. The clinical features and diagnosis of PID will be reviewed here. The pathogenesis, risk factors for acquisition, treatment, and sequelae associated with this disorder are discussed separately. (See "Pathogenesis of and risk factors for pelvic inflammatory disease" and "Treatment of pelvic inflammatory disease".) CLINICAL FEATURES — The clinical diagnosis of PID is imprecise [1]. Lower abdominal pain is the cardinal presenting symptom in women with PID although the character of the pain may be quite subtle. The recent onset of pain that worsens during coitus or with jarring movement may be the only presenting symptom of PID; the onset of pain during or shortly after menses is particularly suggestive [4]. The abdominal pain is usually bilateral and rarely of more than two weeks' duration [5]. Abnormal uterine bleeding occurs in one-third or more of patients with PID [6]. New vaginal discharge, urethritis, proctitis, fever, and chills can be associated signs but are neither sensitive nor specific for the diagnosis. The presence of PID is less likely if symptoms referable to the bowel or urinary tract predominate. While it is rare to have PID during pregnancy, the infection can occur in the first 12 weeks of gestation before the mucus plug and decidua seal off the uterus from ascending bacteria [7]. Evaluation of the patient for risk factors for sexually transmitted disease and those that increase the probability of PID can be quite helpful. (See "Pathogenesis of and risk factors for pelvic inflammatory disease".) Risk factors for STD include:  Age less than 25 years  Young age at first sex  Nonbarrier contraception  New, multiple, or symptomatic sexual partners
  • 8.  Oral contraception  Cervical ectopy Factors that potentially facilitate PID include:  Previous episode of PID  Sex during menses  Vaginal douching  Bacterial vaginosis  Intrauterine device On physical examination, only about one-half of patients with PID have fever. Abdominal examination reveals diffuse tenderness greatest in the lower quadrants, which may or may not be symmetrical. Rebound tenderness and decreased bowel sounds are common. Marked tenderness in the right upper quadrant does not exclude PID, since approximately 10 percent of these patients have perihepatitis (Fitz-Hugh Curtis syndrome). (See 'Perihepatitis' below.) On pelvic examination, the finding of a purulent endocervical discharge and/or acute cervical motion and adnexal tenderness with bimanual examination is strongly suggestive of PID. Rectovaginal examination should reveal the uterus and adnexae to be the focus of tenderness. Other diagnoses should be considered if uterine and adnexal tenderness are not prominent. One study found that adnexal tenderness was the sign that correlated best with the finding of endometritis on endometrial biopsy [8]. However, significant lateralization of adnexal tenderness is uncommon in PID. The presence of a palpable adnexal mass is equally likely to represent tuboovarian abscess complicating PID and other diseases processes in the differential diagnosis. (See "Approach to the patient with an adnexal mass" and "Differential diagnosis of the adnexal mass" and "Epidemiology, clinical manifestations, and diagnosis of tuboovarian abscess".) Subclinical PID — Lower genital tract infection with gonorrhea, chlamydia, or bacterial vaginosis is a risk factor for subclinical PID, defined histologically by the presence of neutrophils and plasma cells in endometrial tissue [9]. Women with tubal factor infertility apparently induced by past episodes of PID often give no history of PID [10-12]. As an example, in one study of 112 infertile women, 36 had adhesions or distal tube occlusion suggestive of PID by laparoscopy but only 11 had a history of this diagnosis [12]. In addition, up to one-third of women without a history of PID harbor persistent Chlamydia trachomatis in the upper genital tract despite the absence of clinical findings except infertility [13,14]. Based upon these observations, it seems clear that subclinical PID severe enough to produce significant sequelae is common. Subclinical episodes are particularly common among oral contraceptive users [15,16]. This was illustrated in a study in which 43 women with endometritis but no clinical signs of PID were four times more likely to have used oral contraceptives than 111 control patients with clinical PID and endometritis [16]. An indolent presentation of PID with low-grade fever, weight loss, and abdominal pain, has also been reported with actinomycosis. An association between an indwelling IUD and risk of actinomycosis has been suggested, although this relationship remains unclear. The diagnosis of this pathogen is discussed elsewhere. (See "Abdominal actinomycosis".) Perihepatitis — Perihepatitis (Fitz-Hugh Curtis Syndrome) was first associated with gonococcal salpingitis in 1920 [17] and subsequently with Chlamydia [18-22]. It consists of infection of the liver capsule and peritoneal surfaces of the anterior right upper quadrant, with minimal stromal hepatic involvement. It manifests as a patchy purulent and fibrinous exudate in the acute phase ("violin string" adhesions), most prominently affecting the anterior surfaces of the liver (not the liver parenchyma). Thus, aminotransferases are also usually normal [23]. Symptoms are typically the sudden onset of severe right upper quadrant abdominal pain with a distinct pleuritic component, sometimes referred to the right shoulder. The severity of the pain in this location may mask the diagnosis of PID and lead to concerns regarding cholecystitis [22]. Aminotransferases are abnormal in approximately one-half of patients with perihepatitis [24,25]. DIAGNOSTIC CONSIDERATIONS — There are several important concepts about PID that must be appreciated:
  • 9.  PID represents a spectrum of clinical disease, from endometritis to fatal intraabdominal sepsis.  There are multiple gold standards in use to establish the diagnosis, because no one among them is adequate alone. Older studies defining PID by a single standard, such as laparoscopic visualization of gross salpingitis, are now felt to lack sensitivity [6,26]. The following discussion will review the tests that have been used to confirm the diagnosis of PID and diagnostic criteria that have been proposed. As will be seen, none of these tests is highly specific and sensitive. Thus, in many cases, clinicians must have a low threshold for considering the diagnosis and be prepared to initiate empiric antibiotic therapy. Plasma cell endometritis — Plasma cell endometritis (PCE) has been identified as an important component of PID [27]. In one study of 45 women admitted for acute PID, PCE was documented in 26 (87 percent) of 30 women with gross salpingitis; four of five women with PCE and no salpingitis had positive tests for chlamydia and/or gonorrhea in the genital tract and were also felt to have PID. In addition, the density of the plasma cell infiltrate correlated with the clinical severity of disease. Several other studies have confirmed these findings [28,29]. In one report, endometritis was present in one-third of 44 patients with confirmed PID, four of whom had negative laparoscopic findings for salpingitis; the specificity of endometritis for the diagnosis of PID was 92 percent with a positive predictive value of 77 percent [29]. PCE correlates closely with the follicular/proliferative phase of the menstrual cycle, the interval during which most cases of PID arise [4]. Other evidence, however, tempers enthusiasm for linking the finding of PCE with the diagnosis of PID. PCE occurs among asymptomatic women with no other evidence of PID (eg, in 42 percent of women with isolated bacterial vaginosis and 13 percent with no genital tract infection) [4]. Furthermore, one study found a poor correlation between PCE and the clinical findings classically associated with PID [30]. Whether PCE when found alone is representative of the subclinical cases of PID discussed above or is, in some cases, a benign finding remains to be elucidated. Laparoscopy — The diagnosis of PID had been almost exclusively a clinical one until a pivotal 1969 study in which laparoscopy was performed in 814 women with a clinical diagnosis of PID [6]. The presence of PID was verified by laparoscopy in 532 patients and other disorders were diagnosed in 98; 184 patients were classified as normal because of a negative laparoscopy. Almost a generation of physicians were trained to diagnose PID based upon clinical correlates derived from this study since laparoscopy was difficult to justify in all suspected cases of acute PID and was not always available [6,31]. Subsequent studies from the 1990s found the sensitivity of laparoscopy to be as low as 50 percent with a specificity approaching 100 percent [28,29,32]. Thus, laparoscopy has substantial value in confirming the diagnosis of PID but is not sensitive enough to be considered a diagnostic gold standard. We recommend laparoscopy for the following:  A sick patient with high suspicion of a competing diagnosis (usually appendicitis, etc.)  An acutely ill patient who has failed outpatient treatment for PID  Any patient not clearly improving after approximately 72 hours of inpatient treatment for PID Consent for laparotomy at the same procedure should be obtained in advance for these patients. We do not recommend endometrial biopsy for PCE at present unless the procedure is part of a protocol. Diagnostic criteria and guidelines — The index of suspicion for the clinical diagnosis of PID should be high, especially in adolescent women, even if they deny sexual activity. The current favored approach to the diagnosis of PID is multifaceted [28-30,33]. A minimal set of clinical criteria has been recommended by the CDC for empirical treatment of PID, including cervical motion tenderness or uterine or adnexal tenderness in the presence of lower abdominal or pelvic pain. The following additional criteria can also be used to support a clinical diagnosis of PID [1]:  Oral temperature >101° F (>38.3°C)  Abnormal cervical or vaginal mucopurulent discharge
  • 10.  Presence of abundant numbers of white blood cells (WBCs) on saline microscopy of vaginal secretions  Elevated erythrocyte sedimentation rate  Elevated C-reactive protein Patients with pelvic pain and tenderness and any one or more of the following are currently considered "confirmed" cases:  Acute or chronic (plasma cell) endometritis or acute salpingitis on histologic evaluation of a biopsy  Demonstration of N. gonorrhoeae or C. trachomatis in the genital tract  Gross salpingitis visualized at laparoscopy or laparotomy  Isolation of pathogenic bacteria from a clean specimen from the upper genital tract  Inflammatory/purulent pelvic peritoneal fluid without another source The Centers for Disease Control and Prevention (CDC) also has issued guidelines for the "definitive" diagnosis of PID in symptomatic patients [1]. One or more of the following three findings are required:  Histologic evidence of endometritis in a biopsy  An imaging technique revealing thickened fluid-filled tubes/oviducts with or without free pelvic fluid or tuboovarian complex  Laparoscopic abnormalities consistent with PID (eg, tubal erythema, edema, adhesions; purulent exudate or cul-de-sac fluid; abnormal fimbriae) Standards for the diagnosis of subclinical PID, assuming that it exists, remain to be established. DIFFERENTIAL DIAGNOSIS — In addition to PID, the differential diagnosis of lower abdominal pain in a young woman includes the following conditions:  Gastrointestinal: Appendicitis, cholecystitis, constipation, gastroenteritis, inflammatory bowel disease  Renal: Cystitis, pyelonephritis, nephrolithiasis, urethritis  Obstetric/Gynecologic: Dysmenorrhea, ectopic pregnancy, intrauterine pregnancy complication, ovarian cyst, ovarian torsion, ovarian tumor In a woman with right upper quadrant pain related to Fitz-Hugh Curtis syndrome, aminotransferases are usually normal; in contrast, a patient with acute viral hepatitis would be expected to have significant abnormalities of aminotransferases [23]. DIAGNOSTIC TESTING — Noninvasive diagnostic tests for PID include general laboratory studies looking for signs of inflammation, culture testing and microscopy of cervical or vaginal secretions, and imaging studies. All patients who are diagnosed with acute PID should also be tested for HIV infection [1]. Laboratory tests — Laboratory testing for patients suspected of PID always begins with a pregnancy test to rule out ectopic pregnancy and complications of an intrauterine pregnancy. Blood counts have limited value. Although PID is usually an acute process, less than half of PID patients exhibit leukocytosis [34]. A hematocrit of less than 0.30 makes PID less likely, relative to hemorrhagic conditions such as ovulatory ovarian bleeding and ectopic pregnancy [34]. Gram stain and microscopic examination of vaginal discharge may provide useful information. If a cervical Gram stain is positive for Gram negative intracellular diplococci when interpreted by an experienced microscopist, the probability of PID greatly increases; if negative, it is of little use [34]. One study of 120 women showed that increased white blood cells (WBC) in vaginal fluid was the most sensitive single laboratory test for PID (78 percent for ≥3 WBC per high power field (hpf) compared with 57, 70, and 71 percent
  • 11. respectively for serum WBC, erythrocyte sedimentation rate (ESR), and C reactive protein) [33]. However, the specificity was only 39 percent. A meta-analysis also concluded that there was no single test or combination that was both sensitive and specific for the diagnosis of PID [35]. However, certain combinations may have a high negative predictive value. In the series of 120 women described above, the probability of PID was only 11 percent in women with the combination of a normal peripheral WBC and ≤3 WBC/hpf from vaginal fluid; no patient had PID if the ESR also was normal [33]. The ovarian tumor marker CA-125 is apparently elevated in all cases of PID [36]. We recommend the following laboratory tests:  Pregnancy test  Microscopic exam of vaginal discharge in saline  Complete blood counts  Nucleic acid amplification tests for chlamydia and gonococcus  Urinalysis  C-reactive protein (optional)  HIV testing  Hepatitis B surface antigen and surface antibody  Testing for syphilis Imaging techniques — Several studies have evaluated sonographic findings in PID with mixed results; a transvaginal rather than transabdominal approach is required [37].  One study of 51 outpatients compared transvaginal ultrasound with endometrial biopsy [38]. For the 13 patients with PCE, 11 had thickened, fluid-filled oviducts on ultrasound with or without free pelvic fluid (sensitivity 85 percent and specificity of 100 percent).  Another report evaluated 84 patients who met accepted clinical criteria for diagnosis of acute PID; 31 had normal sonograms including 26 with positive endocervical cultures [37].  In a third series, 55 women with clinical PID confirmed histologically or by laparoscopy underwent transvaginal sonography looking for abnormal oviducts, multicystic ovaries, and increased cul-de-sac fluid [39]. The respective sensitivities for these parameters were poor at 32 percent, 42 percent, and 37 percent, respectively; the specificities were 97 percent, 86 percent, and 58 percent. It was concluded that sonography has limited value in the diagnosis of PID. Sonographic findings consistent with PID, especially thickened, fluid-filled oviducts, are useful to support a clinical diagnosis of PID. However, the absence of findings does not diminish the probability of PID and should not be used as a reason to delay treatment. We reserve ultrasounds for acutely ill patients with PID in whom a pelvic abscess is a consideration. One study compared pelvic ultrasonography in 60 adolescents with a clinical diagnosis of PID and 40 age-matched controls [40]. The presence of fluid in the cul-de-sac was not helpful in distinguishing patients with PID from those without, but 19 percent of adolescents with PID in this series had a tubo-ovarian abscess demonstrated by ultrasound before clinically suspected. Given the major contribution of tubo-ovarian abscess to failure of medical therapy for PID, this information is of considerable importance. Recommendations — Despite this reservation about the CDC criteria for the diagnosis of PID, we strongly agree with their recommendation that "health care providers should maintain a low threshold for the diagnosis of PID" and that sexually active young women with the combination of lower abdominal, adnexal, and cervical motion tenderness should receive empiric treatment [1]. The specificity of these clinical criteria can be enhanced by the presence of fever, abnormal cervical/vaginal discharge, elevated ESR and/or serum C-reactive protein, and the demonstration of cervical gonorrhea or chlamydia infection. However, if PCE is used to define PID among women with genital symptoms, even the CDC minimum criteria lack sensitivity (65 percent [32] and 33 percent [30] in two studies).
  • 12. To summarize, for all of the new insights into PID and its diagnosis, the practical clinical reality remains that patients will be best served if simple clinical findings (epidemiologic, symptomatic, and physical examination) suggesting PID are followed by prompt empiric treatment. Even patients with minimal findings should be treated since the consequences of withholding therapy are great. (See "Treatment of pelvic inflammatory disease".) The differential diagnosis for PID is extensive (table 1). However, a trial of antibiotics should not be delayed while the other diagnoses are pursued when the clinical suspicion of PID is high. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 th to 6 th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)  Basics topics (see "Patient information: Pelvic inflammatory disease (The Basics)")  Beyond the Basics topics (see "Patient information: Gonorrhea (Beyond the Basics)" and "Patient information: Chlamydia (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS  Pelvic inflammatory disease (PID) refers to acute infection of the upper female genital tract structures, including the uterus, oviducts, and/or ovaries. Neisseria gonorrhoeae and Chlamydia trachomatis are often implicated, although vaginal flora may also play an important role in pathogenesis. (See 'Introduction' above.)  Women with PID may complain of lower abdominal pain in association with new vaginal discharge, dysuria, or painful defecation. Constitutional symptoms may include fever and chills. Perihepatitis can also occur; thus, PID should be considered in women with marked tenderness in the right upper quadrant. (See 'Clinical features' above.)  Acute PID is difficult to diagnose because of the wide variation in symptoms and signs, which may be subtle. A minimal set of clinical criteria has been recommended by the Centers for Disease Control and Prevention (CDC) for a presumptive diagnosis of PID, including cervical motion tenderness or uterine or adnexal tenderness with lower abdominal or pelvic pain. Supportive diagnostic findings include fever and cervical or vaginal discharge. (See 'Diagnostic criteria and guidelines' above.)  Noninvasive diagnostic tests for PID include general laboratory studies looking for signs of inflammation (eg, erythrocyte sedimentation rate, white blood cell count), microscopic examination and cultures of cervical or vaginal secretions, and imaging studies. Laboratory testing for patients suspected of PID should include a pregnancy test to rule out ectopic pregnancy or complications of an intrauterine pregnancy. We perform pelvic ultrasounds for acutely ill patients with PID when there is concern for a pelvic abscess. (See 'Diagnostic testing' above.)  All patients who are diagnosed with acute PID should also be tested for HIV infection. (See 'Laboratory tests' above.)  Because of the adverse consequences of untreated PID, health care providers should maintain a low threshold for the diagnosis of PID and consider presumptive treatment in suspect cases, particularly in sexually active young women with lower abdominal, adnexal, or cervical motion tenderness. (See 'Recommendations'above and "Treatment of pelvic inflammatory disease".) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES
  • 13. 1. http://www.cdc.gov/std/treatment/2010/default.htm (Accessed on January 03, 2011). 2. U.S. Department of Health and Human Services Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2009. Atlanta, GA. U.S. Department of Health and Human Services, 2010. www.cdc.gov/std/stats09/Exordium.htm#copy (Accessed on August 02, 2011). 3. Owusu-Edusei K Jr, Bohm MK, Chesson HW, Kent CK. Chlamydia screening and pelvic inflammatory disease: Insights from exploratory time-series analyses. Am J Prev Med 2010; 38:652. 4. Korn AP, Hessol NA, Padian NS, et al. Risk factors for plasma cell endometritis among women with cervical Neisseria gonorrhoeae, cervical Chlamydia trachomatis, or bacterial vaginosis. Am J Obstet Gynecol 1998; 178:987. 5. Westrom L, Mardh PA. Epidemiology, etiology, and prognosis of acute salpingitis: A study of 1,457 laparoscopically verified cases. In: Nongonococcal Urethritis and Related Diseases, Hobson D, Holmes KK (Eds), Am Soc Microbiol, Washington, DC 1977. p.84. 6. Jacobson L, Weström L. Objectivized diagnosis of acute pelvic inflammatory disease. Diagnostic and prognostic value of routine laparoscopy. Am J Obstet Gynecol 1969; 105:1088. 7. Zeger W, Holt K. Gynecologic infections. Emerg Med Clin North Am 2003; 21:631. 8. Peipert JF, Ness RB, Blume J, et al. Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease. Am J Obstet Gynecol 2001; 184:856. 9. Wiesenfeld HC, Hillier SL, Krohn MA, et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol 2002; 100:456. 10. Moore DE, Spadoni LR, Foy HM, et al. Increased frequency of serum antibodies to Chlamydia trachomatis in infertility due to distal tubal disease. Lancet 1982; 2:574. 11. Punnonen R, Terho P, Nikkanen V, Meurman O. Chlamydial serology in infertile women by immunofluorescence. Fertil Steril 1979; 31:656. 12. Wølner-Hanssen P. Silent pelvic inflammatory disease: is it overstated? Obstet Gynecol 1995; 86:321. 13. Keilani A, Boulieu D, Raudrant D, et al. [Role of Chlamydia trachomatis in tubal pathology (acute salpingitis and tubal sterility). Microbiological study of 175 samples of peritoneal fluid]. J Gynecol Obstet Biol Reprod (Paris) 1989; 18:167. 14. Shepard MK, Jones RB. Recovery of Chlamydia trachomatis from endometrial and fallopian tube biopsies in women with infertility of tubal origin. Fertil Steril 1989; 52:232. 15. Washington AE, Gove S, Schachter J, Sweet RL. Oral contraceptives, Chlamydia trachomatis infection, and pelvic inflammatory disease. A word of caution about protection. JAMA 1985; 253:2246. 16. Ness RB, Keder LM, Soper DE, et al. Oral contraception and the recognition of endometritis. Am J Obstet Gynecol 1997; 176:580. 17. Stajano C. La reaccio'n frenich en ginecologia. Semana Méd 1920; 27:243. 18. Müller-Schoop JW, Wang SP, Munzinger J, et al. Chlamydia trachomatis as possible cause of peritonitis and perihepatitis in young women. Br Med J 1978; 1:1022. 19. Wølner-Hanssen P, Weström L, Mårdh PA. Perihepatitis and chlamydial salpingitis. Lancet 1980; 1:901. 20. Wang SP, Eschenbach DA, Holmes KK, et al. Chlamydia trachomatis infection in Fitz-Hugh-Curtis syndrome. Am J Obstet Gynecol 1980; 138:1034. 21. Paavonen J, Saikku P, von Knorring J, et al. Association of infection with Chlamydia trachomatis with Fitz-Hugh-Curtis syndrome. J Infect Dis 1981; 144:176. 22. Piton S, Marie E, Parmentier JL. [Chlamydia trachomatis perihepatitis (Fitz Hugh-Curtis syndrome). Apropos of 20 cases]. J Gynecol Obstet Biol Reprod (Paris) 1990; 19:447. 23. McCormack WM. Pelvic inflammatory disease. N Engl J Med 1994; 330:115. 24. Semchyshyn S. Fitz-Hugh and Curtis syndrome. J Reprod Med 1979; 22:45. 25. Litt IF, Cohen MI. Perihepatitis associated with salpingitis in adolescents. JAMA 1978; 240:1253. 26. Livengood CH 3rd, Hill GB, Addison WA. Pelvic inflammatory disease: findings during inpatient treatment of clinically severe, laparoscopy- documented disease. Am J Obstet Gynecol 1992; 166:519. 27. Paavonen J, Teisala K, Heinonen PK, et al. Microbiological and histopathological findings in acute pelvic inflammatory disease. Br J Obstet Gynaecol 1987; 94:454. 28. Soper DE, Brockwell NJ, Dalton HP, Johnson D. Observations concerning the microbial etiology of acute salpingitis. Am J Obstet Gynecol 1994; 170:1008. 29. Sellors J, Mahony J, Goldsmith C, et al. The accuracy of clinical findings and laparoscopy in pelvic inflammatory disease. Am J Obstet Gynecol 1991; 164:113. 30. Korn AP, Hessol N, Padian N, et al. Commonly used diagnostic criteria for pelvic inflammatory disease have poor sensitivity for plasma cell endometritis. Sex Transm Dis 1995; 22:335. 31. Hadgu A, Westrom L, Brooks CA, et al. Predicting acute pelvic inflammatory disease: a multivariate analysis. Am J Obstet Gynecol 1986; 155:954. 32. Peipert JF, Boardman LA, Sung CJ. Performance of clinical and laparoscopic criteria for the diagnosis of upper genital tract infection. Infect Dis Obstet Gynecol 1997; 5:291. 33. Peipert JF, Boardman L, Hogan JW, et al. Laboratory evaluation of acute upper genital tract infection. Obstet Gynecol 1996; 87:730. 34. Eschenbach DA, Buchanan TM, Pollock HM, et al. Polymicrobial etiology of acute pelvic inflammatory disease. N Engl J Med 1975; 293:166. 35. Kahn JG, Walker CK, Washington AE, et al. Diagnosing pelvic inflammatory disease. A comprehensive analysis and considerations for developing a new model. JAMA 1991; 266:2594. 36. Moley KH, Massad LS, Mutch DG. Pelvic inflammatory disease. Correlation of severity with CA-125 levels. J Reprod Med 1996; 41:341. 37. Bulas DI, Ahlstrom PA, Sivit CJ, et al. Pelvic inflammatory disease in the adolescent: comparison of transabdominal and transvaginal sonographic evaluation. Radiology 1992; 183:435. 38. Cacciatore B, Leminen A, Ingman-Friberg S, et al. Transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease. Obstet Gynecol 1992; 80:912. 39. Boardman LA, Peipert JF, Brody JM, et al. Endovaginal sonography for the diagnosis of upper genital tract infection. Obstet Gynecol 1997; 90:54. 40. Golden N, Cohen H, Gennari G, Neuhoff S. The use of pelvic ultrasonography in the evaluation of adolescents with pelvic inflammatory disease. Am J Dis Child 1987; 141:1235. Treatment of pelvic inflammatory disease Author Harold C Wiesenfeld, MD, CM All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2014. | This topic last updated: mar 28, 2014.
  • 14. INTRODUCTION — Pelvic inflammatory disease (PID) refers to acute infection of the upper genital tract structures in women, involving any or all of the uterus, fallopian tubes, and ovaries and may involve the neighboring pelvic organs. Early diagnosis and treatment are believed to be key elements in the prevention of long-term sequelae, such as infertility and ectopic pregnancy. (See "Clinical features and diagnosis of pelvic inflammatory disease".) The treatment of PID will be reviewed here. The pathogenesis of risk factors for acquisition of, and sequelae following this disorder are discussed separately. The management of tubo-ovarian abscess is discussed separately. (See "Pathogenesis of and risk factors for pelvic inflammatory disease" and "Long-term complications of pelvic inflammatory disease" and "Management and complications of tuboovarian abscess".) CANDIDATES FOR TREATMENT — Clinicians should maintain a low threshold of suspicion for the diagnosis of PID since long-term complications are more common if treatment is delayed [1,2]. Acute PID should be considered in sexually active young women with the combination of lower abdominal pain with pelvic tenderness (cervical motion tenderness, uterine tenderness, or adnexal tenderness) [1]. Occasionally, acute PID may be encountered in women without recent sexual activity. Information regarding major and minor diagnostic criteria for PID is found elsewhere. (See "Clinical features and diagnosis of pelvic inflammatory disease".) PATHOGENS OF CONCERN — PID is primarily a disease of sexually active women. The two most important sexually transmitted organisms associated with acute PID, Chlamydia trachomatis and Neisseria gonorrhoeae, should be targeted for treatment; negative endocervical screening for either of these pathogens does not rule out upper tract infection [1]. PID is a polymicrobial infection, which generally requires broad coverage, particularly among those with severe disease requiring hospitalization. Acute PID is an ascending infection caused by cervical microorganisms (including Chlamydia trachomatis and Neisseria gonorrhoeae), as well as the vaginal microflora, including anaerobic organisms, enteric gram- negative rods, streptococci, genital mycoplasmas, and Gardnerella vaginalis, which is associated bacterial vaginosis [2]. Bacterial vaginosis results in complex alterations of the normal vaginal flora, which may alter host defense mechanisms in the cervicovaginal environment [2-5]. In studies utilizing specialized techniques, anaerobic organisms were frequently recovered from the upper genital tract in women with acute PID. However, the importance of effective treatment of anaerobic organisms in women with acute PID is somewhat controversial and is currently under study (Clinical Trials.gov identifier NCT01160640) [5]. Rarely, actinomycetes may be isolated in the patient with an intrauterine device (IUD). AVAILABLE ANTIMICROBIAL AGENTS — Multiple antibacterial agents with activity against the wide variety of implicated pathogens have been studied, including medications within the beta-lactam, fluoroquinolone, aminoglycoside, lincosamide and macrolide classes of drugs [6-8]. Meta-analyses of selected trials have demonstrated overall clinical and microbiological cure rates of greater than 90 percent for most regimens [6,7]. The vast majority of these studies have included dual therapy arms for coverage of N. gonorrhoeae, C. trachomatis, and the wide variety of microbes associated with PID;doxycycline has been the agent of choice for coverage of C. trachomatis in most of these studies, although azithromycin also has activity against this pathogen. The combination of clindamycin and gentamicin has moderate in vitro activity against N. gonorrhoeae and C. trachomatis, while a second generation cephalosporin (eg, cefoxitinor cefotetan) plus doxycycline have excellent in vitro activity against both pathogens [3,9]. Ampicillin-sulbactam is a beta-lactam agent with broad spectrum activity, although there are scant data on its use for the treatment of PID [3]. Fluoroquinolones are no longer recommended in the United States for the treatment of gonorrhea or associated conditions, such as PID, due to increasing rates of resistance [10]. (See 'Gonococcal drug resistance' below.) CLINICAL TRIAL DATA Defining treatment response — Treatment response is based on both short- and long-term outcomes. Clinical cure is defined as "significant" or "complete improvement" in the signs and/or symptoms of PID. Microbiologic cure is defined as eradication of N. gonorrhoeae or C. trachomatis, if present at baseline.
  • 15. Long-term sequelae of PID include infertility, ectopic pregnancy, and chronic pelvic pain. Limitations of current data sets — There are multiple limitations of the clinical trials of PID treatment. Clinical efficacy — Some studies have not used objective criteria to diagnose PID, raising concerns as to the whether the appropriate patient population was included [6]. In addition, others have evaluated subjective improvement in pain scores without blinding of investigators [6]. Few randomized controlled trials have long-term data on reproductive outcomes, such as risk of ectopic pregnancy following treatment. Microbiologic efficacy — Although several studies have demonstrated the presence of anaerobes at initial presentation, there are scant data on their persistence or eradication after therapy. In fact, excellent clinical cure rates among women with mild to moderate PID have been documented for several regimens with modest anaerobic coverage (eg, ceftriaxone plus doxycycline) [5,11]. Assessment of efficacy is also hampered by diagnostic methods that do not distinguish between relapse versus reinfection. The Pelvic Inflammation Disease Evaluation Clinical Health trial (ie, PEACH trial), which carefully assessed patients for N. gonorrhoeae and C. trachomatis infections, demonstrated that 40 percent of the women had evidence of single or dual infections at baseline; by 30 days after therapeutic invention, approximately 3 percent still had evidence of either infection, representing either reinfection or relapse. Management of mild or moderate PID — There has been a persistent trend toward outpatient treatment of PID with only 10 to 25 percent of women now being hospitalized [12]. Clinical trial data support such an approach in patients with mild or moderate PID. The Pelvic Inflammation Disease Evaluation Clinical Health trial (ie, PEACH trial) randomly assigned 831 patients with mild or moderate PID to either [13]: ●Inpatient therapy with intravenous cefoxitin (2 grams every 6 hours) plus doxycycline (100 mg twice daily for 14 days) OR ●Outpatient therapy with a single intramuscular dose of cefoxitin (2 grams) plus a single dose of oral probenecid (1 gram) plus oral doxycycline (100 mg twice daily for 14 days) [13]. Eligible women had a history of lower abdominal pain, uterine or adnexal tenderness on examination, and leukorrhea/mucopurulent cervicitis or documented untreated gonococcal or chlamydial infection. Patients underwent a standardized interview, and cervical swabs were obtained for N. gonorrhoeae and C. trachomatis for polymerase chain reaction (PCR) testing. Vaginal specimens were Gram stained and examined for evidence of bacterial vaginosis by a reference laboratory. Endometrial biopsies were scored for evidence of endometritis by two reference pathologists. Long-term follow-up was conducted through periodic phone calls. Intravenous therapy continued for a minimum of 48 hours; upon clinical improvement, the patient was switched to doxycycline for a 14-day course. This clinical trial showed that short-term clinical and microbiologic outcomes and long-term reproductive outcomes (eg, ectopic pregnancy, chronic pelvic pain) were similar between arms. Intravenous administration of doxycycline was associated with high rates of phlebitis. INDICATIONS FOR HOSPITALIZATION — Recommended indications for hospitalization and parenteral antibiotics include [1]: ●Pregnancy ●Lack of response or tolerance to oral medications ●Nonadherence to therapy ●Inability to take oral medications due to nausea and vomiting ●Severe clinical illness (high fever, nausea, vomiting, severe abdominal pain) ●Complicated PID with pelvic abscess (including tuboovarian abscess) ●Possible need for surgical intervention or diagnostic exploration for alternative etiology (eg, appendicitis)
  • 16. There are no clinical data to suggest that older age or HIV status should be considered criteria for hospitalization [3,14]. RECOMMENDED REGIMENS General approach — The therapeutic regimens for PID, discussed below, provide broad empiric coverage for the wide array of implicated pathogens, although the optimal treatment regimen remains undefined [13]. Antibiotics selected should have activity against Neisseria gonorrhoeae and Chlamydia trachomatis, as both play a significant role in PID. As noted above, meta-analyses have demonstrated that a variety of antibiotics from multiple classes are all associated with clinical and microbiologic cure rates of greater than 90 percent. Cost, convenience of administration, safety, formulary availability and allergy history are all assessed in making antimicrobial selections. The choice of antimicrobial therapy is also guided by whether the patient will be treated as an inpatient or outpatient. Gonococcal drug resistance — As of 2007, the CDC guidelines state that fluoroquinolones are no longer recommended as therapy for PID if N. gonorrhoeae is a proven or suspect pathogen [10]. Role for anaerobic coverage — There is no consensus on the degree of anaerobic coverage that is needed for PID or whether anaerobes need to be targeted at all [3,5]. Anaerobic bacteria are frequently recovered from patients with acute PID; however, there are no studies to demonstrate that inclusion of anaerobic coverage is superior to antibiotic regimens with minimal coverage [3]. Furthermore, experts are concerned that the additional gastrointestinal side effects seen with metronidazole therapy will lead to nonadherence and inadequately treated PID. Some experts have suggested that anaerobes should be treated empirically while others suggest inclusion of anaerobic coverage among select groups of patients, such as those with severe infection requiring hospitalization and tubo- ovarian abscess [5]. The inpatient regimens noted below have excellent anaerobic coverage while the outpatient regimens have only modest coverage. The addition of antibiotics with anaerobic activity (eg, metronidazole) may be considered among outpatients with: ●History of gynecological instrumentation within the preceding two to three weeks. (See "Management and complications of tuboovarian abscess".) Inpatient therapy — Patients with severe PID should be hospitalized and treated with parenteral therapy. Indications for hospitalization are discussed above. (See'Indications for hospitalization' above.) First-line therapies — For patients with severe PID, the CDC recommends either of the following parenteral regimens, which result in clinical cure of acute disease in >90 percent of PID cases [1,15-17]: ●Cefoxitin (2 g intravenously every 6 hours) or cefotetan (2 g IV every 12 hours) plus doxycycline (100 mg orally every 12 hours). ●Clindamycin (900 mg intravenously every 8 hours) plus gentamicin loading dose (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily intravenous dosing of gentamicin may be substituted for three times daily dosing [1]. These inpatient regimens provide broad coverage, including streptococci, gram-negative enteric bacilli (Escherichia coli, Klebsiella spp, and Proteus spp), and anaerobic organisms (ie, bacterial vaginosis-associated flora) [7,18-20]. We prefer a second generation cephalosporin plus doxycycline for inpatients with PID due to its overall tolerability. Antiemetic and antipyretic medications should be offered to those patients who are symptomatic. Transitioning from parenteral to oral therapy can usually be started after 24 hours of sustained clinical improvement, such as resolution of fever, nausea, vomiting, and severe abdominal pain, if present [21]. Patients should complete a 14-day course of treatment with doxycycline (100 mg twice daily). Oral administration of doxycycline is generally preferred, as soon as vomiting subsides, because of the pain associated with intravenous drug administration. Importantly, the bioavailability of the oral preparation of doxycycline is equivalent to parenteral administration. Patients with a pelvic abscess should also receive oral clindamycin 450 mg every 6 hours or metronidazole 500 mg every 8 hours for a total of 14 days in addition todoxycycline. Management of the patient with complicated PID with
  • 17. tubo-ovarian abscess is discussed separately. (See "Management and complications of tuboovarian abscess", section on 'Management'.) Alternative regimens — Limited data are available on the following regimens, which are considered "alternative" by the CDC: ●Ampicillin-sulbactam (3 g intravenous every 6 hours) plus doxycycline (100 mg twice daily) led to a similar rate of clinical cure as cefoxitin (2 g every 6 hours) plus doxycycline (100 mg twice daily) among women hospitalized with PID (86 versus 89 percent) [16]. ●One small trial randomly assigned patients with mild or moderate PID to azithromycin monotherapy, azithromycin plus metronidazole, or a combination regimen including a beta-lactam [22]. Clinical and microbiological cure rates were greater than 95 percent in all arms. Outpatient therapy — Patients with mild or moderate PID are suitable candidates for oral therapy since clinical outcomes are equivalent with parenteral or oral therapy. (See 'Management of mild or moderate PID' above.) First-line regimens — The CDC recommends any of the following oral regimens, with or without metronidazole (500 mg twice a day for 14 days) [1]: ●Ceftriaxone (250 mg intramuscularly in a single dose) plus doxycycline (100 mg orally twice a day for 14 days) ●Cefoxitin (2 g intramuscularly in a single dose) concurrently with probenecid (1 g orally in a single dose) plus doxycycline (100 mg orally twice a day for 14 days) ●Other parenteral third-generation cephalosporins, such as cefotaxime (1 gram intramuscularly in a single dose) or ceftizoxime (1 gram intramuscularly in a single dose) plus doxycycline (100 mg orally twice a day for 14 days) Of the cephalosporins listed, ceftriaxone has the overall best activity against gonococcal infection. We prefer ceftriaxone plus doxycycline in patients with mild to moderate PID. Metronidazole should be added for patients with Trichomonas vaginalis or in those women with a recent history of uterine instrumentation. Alternative agents The long half-life of azithromycin, its concentration intracellularly, and its activity against Chlamydia offers the potential for an easier dosing schedule than twice-dailydoxycycline. Small clinical trials suggest clinical efficacy although data on microbiological cures are not available: ●A double-blind randomized controlled trial compared the efficacy of a single intramuscular injection of ceftriaxone followed by either doxycycline (100 mg twice daily for two weeks) or azithromycin (1 gram once per week for two weeks) in 120 women with mild PID [23]. The azithromycin and doxycycline arms were found to be equivalent in clinical cure rates. The study limitations include the subjective nature of the measured outcome, limited microbiologic data and the small sample size. TREATMENT OF THE PENICILLIN-ALLERGIC PATIENT — Treatment considerations must also take into consideration any history of drug allergy and the risk for gonococcal infection. Penicillin-allergic patients who have tolerated cephalosporins may be treated with a cephalosporin-based regimen. Patients at risk for gonorrhea — Patients with PID who require hospitalization can be treated with clindamycin and gentamicin, as outlined above. (See 'Inpatient therapy'above.) However, therapeutic options for outpatient management of the penicillin allergic patient at risk for gonorrhea are limited, particularly among those with a history of severe penicillin allergy. In patients with mild or moderate PID, it is important to obtain a complete history regarding the underlying penicillin allergy so a therapeutic regimen may be constructed, as discussed below. History of mild allergy — A patient with a mild past reaction to a penicillin and who never reacted to a cephalosporin (or never received one) may be a candidate for treatment with intramuscular ceftriaxone. A history of a maculopapular or morbilliform rash, without signs of IgE-mediated allergy (urticaria, angioedema, respiratory symptoms, hypotension) or desquamation, is associated with very low risk for a serious allergic reaction
  • 18. to ceftriaxone. Cross-reactivity between penicillins and third-generation cephalosporins is believed to be uncommon. For such patients, an initial test dose of ceftriaxone (one-tenth of the full dose, intramuscularly) can be administered with patient observation for two hours. If no reaction develops, the remainder of the dose can be given with continued observation for another hour; the patient should be discharged with doxycycline (100 mg twice daily) for 14 days. (See "Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams".) History of severe allergy — Patients with severe or life-threatening penicillin allergies are not candidates for cephalosporin therapy; options for outpatient therapy are limited. We suggest the following possible options: ●Hospitalize the patient and initiate treatment with clindamycin (900 mg intravenously every 8 hours) plus gentamicin loading dose (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily intravenous dosing of gentamicin may be substituted [1]. OR ●Administer a quinolone-based regimen, eg, levofloxacin (500 mg orally once daily for 14 days) AND a single dose of azithromycin (2 grams orally). This dosage of azithromycin is also used for penicillin allergic patients with uncomplicated gonococcal infection; however, this high dose of azithromycin is associated with increased rates of gastrointestinal disturbance. (See "Treatment of uncomplicated gonococcal infections", section on 'Azithromycin monotherapy' and "Treatment of uncomplicated gonococcal infections", section on 'Penicillin allergic patients'.) Following 24 hours of clinical improvement, treatment may be changed to doxycycline (100 mg orally every 12 hours) to complete 14 days of treatment. In the patient with uncomplicated PID, another fluoroquinolone alternative to levofloxacin is moxifloxacin (400 mg) once daily for 14 days [8]. Patients at low risk of gonorrhea — As noted above, fluoroquinolones are not recommended for the treatment of PID because of the risk of gonococcal drug resistance. However, fluoroquinolones, with metronidazole, may be considered for PID therapy in circumstances where N. gonorrhoeae is not likely to be a causative agent (eg, the post-menopausal woman who develops PID following uterine instrumentation) or when the prevalence of fluoroquinolone-resistant N. gonorrhoeae is <5 percent in the locality where the infection was acquired [10]; resistance data can be obtained from the local department of public health. Fluoroquinolone resistance is discussed in detail elsewhere. (See "Treatment of uncomplicated gonococcal infections", section on 'Antibiotic resistance'.) Thus, an alternate treatment regimen in these clinical scenarios may include: ●Levofloxacin (500 mg orally once daily) or ofloxacin (400 mg orally twice daily) with or without metronidazole (500 mg orally twice a day); monotherapy withmoxifloxacin (400 mg once daily), which has good anaerobic coverage, is another option. All regimens are given for 14 days. Prior to quinolone treatment, cervical specimens should be collected for culture for Neisseria gonorrhoeae so that the initial treatment regimen can be altered if fluoroquinolone-resistant N. gonorrhoeae are identified. Nucleic acid amplification testing cannot determine antimicrobial susceptibility. The laboratory should be notified to perform susceptibility testing on N. gonorrhoeae isolates. HIV-INFECTED PATIENTS — HIV-infected women appear to respond to therapy for PID as well as uninfected women [14]. Therefore, recommended antibiotic regimens for HIV-infected women with acute PID are similar to those for HIV- uninfected women. PREGNANT PATIENTS — While it is quite rare to have PID during pregnancy, the infection can occur in the first 12 weeks of gestation before the mucus plug and decidua seal off the uterus from ascending bacteria [24]. As above, pregnancy is an indication for hospitalization and parenteral antibiotics for PID. We typically administer a second generation cephalosporin (eg, intravenous cefoxitin or cefotetan, as in first-line therapies listed above) and azithromycin 1 gram orally (instead of doxycycline).
  • 19. DURATION OF THERAPY — The optimal duration of therapy is unknown. Most studies have used 14 days of therapy and this duration has been maintained in the 2010 STD recommendations from the CDC [1,10]. Shorter courses of therapy have not been explored, mainly related to concerns regarding eradication of C. trachomatis in the setting of upper tract disease [3]. PATIENT RELATED ISSUES — Patient monitoring and counseling are important components of overall management. Patient monitoring — If outpatient therapy is selected, it is important to see the patient within 48 to 72 hours to be certain that clinical improvement has occurred (eg, reduction in abdominal tenderness and reduction in cervical motion tenderness) [25]. If no clinical improvement has occurred within 72 hours, hospitalization, parenteral therapy, and further diagnostic evaluation is recommended [1]. Medication adherence — Compliance with a long course of oral antibiotics can be problematic [26]. Patients should be educated about the importance of medication adherence and clinical outcomes. Counseling and screening — Clinicians should counsel patients regarding the route of acquisition for sexually transmitted infections, the concomitant need for partner treatment, and future safe sex practices. All patients diagnosed with acute PID should be offered HIV testing. (See "Diagnostic assays for HIV infection".) Other important components of the evaluation include: ●Assessment of immunity to Hepatitis B virus (eg, through vaccination history or serologic testing) and vaccination of those who have no evidence of immunity. (See"Hepatitis B virus vaccination".) ●Serologic testing for syphilis (eg, RPR). ●Patients who are 9 through 26 years of age should be offered immunization against human papillomavirus infection, if they have never been vaccinated in the past. (See"Recommendations for the use of human papillomavirus vaccines".) Patients diagnosed with acute PID should undergo counseling for safe sex practices. Drug abuse counseling should be offered to appropriate patients. Sex partners — Male sex partners of women with PID should be examined and treated if they had sexual contact with the patient during the previous 60 days prior to the patient's onset of symptoms, regardless of the woman’s sexually transmitted infection test results. Evaluation and treatment of the sex partner is essential to decrease the risk of reinfection. Regimens should include antibiotics with activity against Neisseria gonorrhoeae and Chlamydia trachomatis, such as ceftriaxone (250 mg) intramuscularly plus either azithromycin (1 gram) orally as a single dose or doxycycline (100 mg) orally twice daily for seven days. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 th to 6 th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) ●Basics topic (see "Patient information: Pelvic inflammatory disease (The Basics)") SUMMARY AND RECOMMENDATIONS ●Pelvic inflammatory disease (PID) refers to acute infection of the upper genital tract structures in women, involving any or all of the uterus, oviducts, and/or ovaries. Up to 10 percent of women with untreated gonorrhea and 20 percent of women with untreated chlamydia infection may go on to develop PID. (See 'Introduction' above.)
  • 20. ●Acute PID is caused by cervical microorganisms (including Chlamydia trachomatis and Neisseria gonorrhoeae) as well as the vaginal microflora, including enteric gram-negative rods, streptococci, genital mycoplasmas, and Gardnerella vaginalis. (See 'Pathogens of concern' above.) ●Multiple broad-spectrum antibacterial agents have been studied for the treatment of PID, including beta-lactams, fluoroquinolones, aminoglycosides, lincosamides and macrolides. Meta-analyses of selected trials have demonstrated overall clinical and microbiological cure rates of greater than 90 percent for most regimens. Cost, convenience of administration, safety, allergy history, and drug resistance patterns are all assessed in making antimicrobial selections. (See 'Available antimicrobial agents' above.) ●Anaerobic coverage is warranted in patients with a history of recent endometrial instrumentation and women with severe or complicated PID (eg, pelvic abscess). (See'Pathogens of concern' above.) ●Due to the rising levels of fluoroquinolone resistance among Neisseria gonorrhoeae isolates, the use of fluoroquinolones is no longer recommended. Cephalosporins still maintain excellent activity against Neisseria gonorrhoeae, although reports of decreasing susceptibility have been reported. (See 'Available antimicrobial agents' above.) ●Indications for hospitalization include: pregnancy, nausea and vomiting, severe clinical illness (fevers, chills, severe abdominal pain), suspected pelvic abscess, or a possible alternative diagnosis (eg, appendicitis). (See 'Indications for hospitalization' above.) ●Treatment of pelvic inflammatory disease requires broad antimicrobial coverage against the likely pathogens, including Neisseria gonorrhoeae, Chlamydia trachomatis, and the gram-negative and gram-positive organisms that comprise the cervical and vaginal flora. Additional anaerobic coverage may be important among patients with severe or complicated PID. There are multiple potential antibiotic regimens that are suitable for such broad spectrum coverage with proven efficacy in the treatment of PID. •For inpatient management of severe or complicated PID, we suggest use of a second generation cephalosporin (eg, cefoxitin 2 g intravenously every 6 hours orcefotetan 2 g IV every 12 hours) combined with doxycycline (100 mg orally every 12 hours) (Grade 2B). Another option is clindamycin (900 mg intravenously every eight hours) plus gentamicin (2 mg/kg loading dose followed by a 1.5 mg/kg maintenance dose every eight hours). Single daily intravenous dosing of gentamicin may be substituted for three times daily dosing. (See 'Inpatient therapy' above.) •Transitioning from parenteral to oral therapy (doxycycline 100 mg twice daily alone) can usually be started after 24 hours of sustained clinical improvement. (See'Inpatient therapy' above.) •For outpatient therapy of mild or moderate PID, we suggest ceftriaxone (250 mg intramuscularly in a single dose) plus doxycycline (100 mg orally twice a day for 14 days) (Grade 2B). We suggest the addition of metronidazole (500 mg orally twice a day for 14 days) for those with a history of gynecological instrumentation in the preceding two to three weeks (Grade 2C). (See 'Outpatient therapy' above.) ●Management of the penicillin allergic patient will depend on the nature of the penicillin allergy and the risk of gonococcal infection. (See 'Treatment of the penicillin-allergic patient' above.) ●The optimal duration of therapy is unknown, although most authorities favor 14 days of treatment. (See 'Duration of therapy' above.) ●Patients receiving outpatient therapy should be carefully evaluated for clinical improvement within 72 hours. (See 'Patient related issues' above.) ●Male sex partners of women with PID should be examined and treated if they had sexual contact with the patient during the previous 60 days prior to the patient's onset of symptoms to decrease the risk of reinfection. (See 'Sex partners' above.) REFERENCES 1. http://www.cdc.gov/std/treatment/2010/default.htm (Accessed on January 03, 2011). 2. Soper DE. Pelvic inflammatory disease. Obstet Gynecol 2010; 116:419. 3. Walker CK, Wiesenfeld HC. Antibiotic therapy for acute pelvic inflammatory disease: the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis 2007; 44 Suppl 3:S111. 4. Short VL, Totten PA, Ness RB, et al. Clinical presentation of Mycoplasma genitalium Infection versus Neisseria gonorrhoeae infection among women with pelvic inflammatory disease. Clin Infect Dis 2009; 48:41.
  • 21. 5. Walker CK, Workowski KA, Washington AE, et al. 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. 6. Walker CK, Kahn JG, Washington AE, et al. Pelvic inflammatory disease: metaanalysis of antimicrobial regimen efficacy. J Infect Dis 1993; 168:969. 7. Dodson MG. Antibiotic regimens for treating acute pelvic inflammatory disease. An evaluation. J Reprod Med 1994; 39:285. 8. Judlin P, Liao Q, Liu Z, et al. Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study. BJOG 2010; 117:1475. 9. Hemsell DL, Little BB, Faro S, et al. Comparison of three regimens recommended by the Centers for Disease Control and Prevention for the treatment of women hospitalized with acute pelvic inflammatory disease. Clin Infect Dis 1994; 19:720. 10. Centers for Disease Control and Prevention (CDC). Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 2007; 56:332. 11. Arredondo JL, Diaz V, Gaitan H, et al. Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease in outpatients. Clin Infect Dis 1997; 24:170. 12. Rein DB, Kassler WJ, Irwin KL, Rabiee L. Direct medical cost of pelvic inflammatory disease and its sequelae: decreasing, but still substantial. Obstet Gynecol 2000; 95:397. 13. 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. 14. Irwin KL, Moorman AC, O'Sullivan MJ, et al. Influence of human immunodeficiency virus infection on pelvic inflammatory disease. Obstet Gynecol 2000; 95:525. 15. Drugs for sexually transmitted infections. Treat Guidel Med Lett 2004; 2:67. 16. McGregor JA, Crombleholme WR, Newton E, et al. Randomized comparison of ampicillin-sulbactam to cefoxitin and doxycycline or clindamycin and gentamicin in the treatment of pelvic inflammatory disease or endometritis. Obstet Gynecol 1994; 83:998. 17. Comparative evaluation of clindamycin/gentamicin and cefoxitin/doxycycline for treatment of pelvic inflammatory disease: a multi-center trial. The European Study Group. Acta Obstet Gynecol Scand 1992; 71:129. 18. Landers DV, Wolner-Hanssen P, Paavonen J, et al. Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease. Am J Obstet Gynecol 1991; 164:849. 19. Wasserheit JN, Bell TA, Kiviat NB, et al. Microbial causes of proven pelvic inflammatory disease and efficacy of clindamycin and tobramycin. Ann Intern Med 1986; 104:187. 20. Brunham RC, Binns B, Guijon F, et al. Etiology and outcome of acute pelvic inflammatory disease. J Infect Dis 1988; 158:510. 21. Livengood CH 3rd, Hill GB, Addison WA. Pelvic inflammatory disease: findings during inpatient treatment of clinically severe, laparoscopy- documented disease. Am J Obstet Gynecol 1992; 166:519. 22. Bevan CD, Ridgway GL, Rothermel CD. 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. J Int Med Res 2003; 31:45. 23. Savaris RF, Teixeira LM, Torres TG, et al. Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol 2007; 110:53. 24. Zeger W, Holt K. Gynecologic infections. Emerg Med Clin North Am 2003; 21:631. 25. Thompson SE, Brooks C, Eschenbach DA, et al. High failure rates in outpatient treatment of salpingitis with either tetracycline alone or penicillin/ampicillin combination. Am J Obstet Gynecol 1985; 152:635. 26. Brookoff D. Compliance with doxycycline therapy for outpatient treatment of pelvic inflammatory disease. South Med J 1994; 87:1088.