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Pelvic Inflammatory Disease
Pelvic Inflammatory Disease Mary Duff University of Kansas Medical Center, Kansas City, USA ã 2007 Elsevier Inc. All rights reserved.
Introduction Pelvic inflammatory disease (PID) is a broad term referring to a spectrum of inflammatory disorders and infections involving the upper female genital tract. The upper genital tract includes the uterine endometrium, the fallopian tubes (sometimes referred to as the oviducts), ovaries, and surrounding pelvic peritoneum. The most common cause of PID is a sexually-transmitted disease. While the most frequent causative organisms are Neisseria gonorrhoeae and Chlamydia trachomatis, other microorganisms have been implicated. PID, which is common in young, sexually active women, can have long-term sequelae affecting reproductive health.
Definition Pelvic inflammatory disease (PID) is inflammation and infection of the normally sterile environment of the upper genital tract including any combination of the endometrium, fallopian tubes, ovaries, and pelvic peritoneum.
Classification Pelvic inflammatory disease is usually classified as an infectious disease, although it can be considered a genitourinary disorder as well.
Consequences Severe infection associated with pelvic inflammatory disease requires hospitalization and intravenous antibiotics. Inflammation of the fallopian tube can be seen as a hydrosalpinx or pyosalpinx. Abscesses, usually involving the tubes and ovaries, or surrounding pelvic peritoneum, can occur. Abscesses frequently require surgery in addition to antibiotic therapy for resolution. Infection can ascend from the pelvis to the abdomen. Ascending infection can result in perihepatitis or inflammation of the liver capsule, which is referred to as Fitz-HughCurtis syndrome. The characteristic finding of Fitz-Hugh-Curtis syndrome is violinstring adhesions between the liver capsule and the abdominal wall Pickhardt et al (2003) Long-term consequences of pelvic inflammatory disease (PID) include scarring and adhesions in the pelvis and abdomen. Scarring and adhesions of the adnexa can result in infertility, or chronic pelvic pain. A history of PID is a risk factor for recurrent infection, pain, infertility, and ectopic pregnancy. 1
2
Pelvic Inflammatory Disease
Associated Disorders Inflammation and infection of the pelvic organs comprise pelvic inflammatory disease. This can include endometritis, salpingitis, peritonitis, and tubo-ovarian abscess Sequelae of scarring can result in pain and tubal factor infertility.
Etiology Pelvic inflammatory disease (PID) is usually attributed to a sexually transmitted disease ascending from the vagina and cervix to the upper genital organs, i.e., the uterus, tubes and ovaries. The most common organisms are Neisseria gonorrhoeae and Chlamydia trachomatis. Other organisms that have been implicated include vaginal flora such as aerobic and anaerobic bacteria. Many organisms have been identified including streptococcus species, staphylococci, enteric gram negative rods, peptostreptococci, bacteroides, Gardnerella vaginalis, trichomonads, Mycoplasma hominis, Ureaplasma urealyticum, Haemophilus influenzae and cytomegalovirus. Pelvic tuberculosis caused by Mycobacterium tuberculosis is less common. The most common path of infection begins in the vagina and cervix. Endometritis can occur if bacteria gain access to the normally sterile environment of the upper genital tract. Infection of the uterus can then disseminate to the pelvis. This dissemination can occur with retrograde menstruation, or after instrumentation of the uterus for an intrauterine device, an abortion, an invasive diagnostic procedure such as hysterosalpingogram, or childbirth. Other mechanisms for infection of the upper genital tract include spread from adjacent infected organs such as appendicitis or inflammation and infection of the bowel. Less common is metastasis through the blood stream from a distant organ such as might occur with tuberculosis Pastorek (1989).
Epidemiology Pelvic inflammatory disease (PID) is common condition. Approximately 1 in 7 women will be treated for PID during their life. About one million women are treated for this condition each year. Approximately 1% of women aged between 15-25 years old are diagnosed with PID annually. PID is a major cause of morbidity, precipitating approximately 342,000 emergency department visits Curtis et al (1998) and over 1 million clinic visits each year. Close to 200,000 women require hospitalization and more than 100,000 surgical procedures are performed annually in the United States for a diagnosis of PID.
Pathophysiology Pelvic inflammatory disease (PID) occurs when an organism infects some or all of the following: the endometrium, fallopian tubes, ovaries and surrounding peritoneum. An inflammatory reaction occurs. Histologic changes include endometritis, salpingitis, oophoritis, and peritonitis. How and why upper genital tract infection occurs is not yet completely understood. The upper genital tract is thought to be a sterile environment, while the cervix and vagina are polymicrobial. Not all episodes of gonococcal or chlamydial cervicitis cause an ascending infection. Conversely, it is rare to recover Chlamydia trachomatis or Neisseria gonorrhoeae from a tubo-ovarian abscess. A break in the usual protective mechanisms of the cervix probably occurs, allowing ascent of an organism with subsequent infection of the
Pelvic Inflammatory Disease
uterine endometrium. There is a frequent observed correlation of gonococcal PID immediately following menses, while this correlation is not seen with chlamydia. The mechanisms involved in the inflammatory response to infection probably vary with the infecting agent. Factors involved in the virulence of infectious organisms are under investigation. For N. gonorrhoeae these include opacity-associated proteins, lipooligosaccharides, and outer-membrane proteins Gorby et al (2001). Infection with chlamydia probably involves different mechanisms that determine whether acute infection is resolved or progresses into a chronic inflammation with tubal scarring. Multiple determinants are under investigation, including immune pathways, cytokine profiles, heat shock proteins, infectious load, and endocrinology Debattista et al (2003). The other pathogens could all have different mechanisms for attachment to the epithelium and for causing cellular damage. Regardless of the mechanism, an inoculum accesses the upper genital structures, with the resulting infection and inflammation subsequently involving the fallopian tube or ovary. A pyosalpingo-oophoritis or purulent inflammation of the tube or ovary develops. The inflamed and infected tube can adhere to the ovary, resulting in a closed space that becomes a tubo-ovarian abscess. Spillage of pus into the pelvis can result in additional pockets of inflammation and abscesses in the abdomen.
Signs and Symptoms The symptoms of pelvic inflammatory disease (PID) can vary widely, making diagnosis and clinical investigation difficult. Patients report symptoms include foul-smelling or excessive vaginal discharge, abnormal vaginal bleeding, pain and cramping in the lower abdomen and pelvis, fever and chills, nausea, vomiting or diarrhea. Signs noted on physical examination may include fever with a temperature over 38.3 C, tenderness in the lower abdomen and pelvis, mucopurulent discharge from the cervix, and white blood cells on saline microscopy. Important physical exam findings include cervical motion tenderness or adnexal tenderness. An adnexal mass or fullness in the pouch of Douglas is suggestive of abscess. Cultures for gonorrhea and chlamydia should be performed. Culdocentesis can reveal pus in the pelvic cavity, and provide an additional source to culture. Ultrasound can help identify abscesses. More advanced radiographic studies such as computerized tomography or magnetic resonance imaging are only rarely required. Laboratory tests can reveal leukocytosis, elevated erythrocyte sediment rate, or elevated C-reactive protein. Laparoscopy can help identify salpingitis (inflammation of the fallopian tubes) if the diagnosis is in doubt.
Standard Therapies Traditionally, severe pelvic inflammatory disease (PID) with tuboovarian abscess was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Studies in the 1970s and 1980s found sufficient cure rates to allow a trial of intravenous antibiotics. There appears to be no statistical difference in long-term reproductive outcomes such as time to pregnancy, PID recurrence, chronic pain or ectopic pregnancy in women with mild-to-moderate PID randomized to inpatient or outpatient treatment Ness et al (2002). Treatment of PID is aimed at providing empiric, broad-spectrum antibiotic coverage of likely pathogens, including gonococci, chlamydia, streptococci, gram-negative bacteriae and facultative anaerobic bacteria. Current standard treatment guidelines published by the Centers for Disease Control and Prevention are listed below:
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Pelvic Inflammatory Disease
In patients requiring hospitalization, parenteral antibiotics are initiated, frequently in combination with oral agents. Parenteral therapy can be discontinued 24 hours after the patient shows clinical improvement. Oral therapy continues to complete a 14-day course of antibiotic therapy. Parenteral Regimen A: Cefotetan 2 g i.v. every 12 hours or cefoxitin 2 g i.v. every 6 hours plus doxycycline 100 mg orally or i.v. every 12 hours. The cephalosporin provides antimicrobial activity against N. gonorrhoeae and aerobic and anaerobic bacteria. Doxycycline provides coverage for C. trachomatis. If an abscess is suspected, clindamycin or metronidazole is often included to improve empiric coverage against the presumed presence of anaerobic bacteria. Parenteral Regimen B: Clindamycin 900 mg i.v. every 8 hours, plus gentamicin loading dose i.v. or i.m. followed by a maintenance dose every 8 hours. Alternative Parenteral Regimens: These include ofloxacin 400 mg i.v. every 12 hours or levofloxacin 500 mg i.v. once daily with or without metronidazole 500 mg i.v. every 8 hours or ampicillin/sulbactam 3 g i.v. every 6 hours plus doxycycline 100 mg every 12 hours. When outpatient management of PID is deemed safe, the following oral regimens provide antibiotic coverage of the usual infectious organisms involved in this condition. Oral Regimen A: Ofloxacin 400 mg twice a day for 14 days or levofloxacin 500 mg once daily for 14 days with or without metronidazole 500 mg twice a day for 14 days. Oral Regimen B: Ceftriaxone 250 mg i.m. or cefoxitin 2 g i.m. and probenecid 1 g p.o. in a single dose or other parenteral third-generation cephalosporin plus doxycycline 100 mg twice a day for 14 days with or without metronidazole 500 mg twice a day for 14 days. The optimal choice of a cephalosporin is not clear. While cefoxitin has better anaerobic coverage, ceftriaxone has better coverage against N. gonorrhoeae. Follow-up includes evaluation by a health-care provider within 3 days to insure clinical improvement. Lack of improvement might require hospitalization, additional tests, or surgical intervention. Agent Name Cefotetan
Discussion
Cefotetan is a second generation cephalosporin antibiotic. Cephalosporins inhibit bacterial cell wall synthesis. The second-generation cephalosporins display enhanced activity against gram-negative organisms and gram-negative diplococci like Neisseria Gonorrhoeae, with some activity against anaerobic bacteria. Cefoxitin Cefoxitin is a second generation cephalosporin antibiotic. It has activity against the anaerobic bacteria Bacteroides fragilis. Doxycycline Doxycycline is a second-generation tetracycline antibiotic. Tetracyclines selectively inhibit protein synthesis by targeting the bacterial ribosome. Tetracyclines exhibit activity against chlamydia species. Clindamycin Clindamycin is effective against anaerobic bacteria. It is an inhibitor of bacterial protein synthesis. Clindamycin is of benefit when treating an abscess that is presumed to contain anaerobic bacteria. Gentamicin Gentamicin is an aminoglycoside antibiotic effective against gram-negative bacilli. Ofloxacin Ofloxacin is a second generation quinolone antibiotic. It is effective against both Chlamydia trachomatis and N. gonorrhoeae. Because ofloxacin lacks anaerobic coverage, the addition of metronidazole is common. Levofloxacin Levofloxacin is a second-generation quinolone. Preliminary information suggests it is equivalent to ofloxacin in terms of efficacy, with the added benefit of once-aday dosing to improve compliance. Metronidazole Metronidazole is an antiprotozoal agent that is toxic to amoebae and anaerobic organisms. The agent of choice for treating Trichomonas vaginalis, metronidazole is an effective treatment for abscesses. Ampicillin/ Ampicillin is an extended-spectrum penicillin. Sulbactam is administered Sulbactam concomitantly to protect the antibiotic from beta-lactamase.
Pelvic Inflammatory Disease
Experimental Therapies Antibiotic therapy aimed at destroying the most common infectious agents has been the mainstay of treatment for pelvic inflammatory disease. Development of vaccines could be especially beneficial for treating those at high risk for this condition. Agent Name Vaccine
Discussion Chlamydia cervicitis and major complications like endometritis, pelvic inflammatory disease and tubal factor infertility exist in addition to other chlamydia-associated chronic syndromes. A prophylactic vaccine could help limit the morbidity of chlamydial infection. A unified approach to vaccines for the genus Chlamydia is validated by common immunogenic proteins among member species, several conserved genes, and similar immune effectors in animals and humans Igietseme et al (2003).
Animal Models While there are no animal models for pelvic inflammatory disease (PID), there is an animal model that simulates intraluminal tubal damage and adhesion formation seen in this condition Roberts et al (2002). Animal models are under development to study chlamydia and its effects. For example, the role of delayed hypersensitivity in the pathogenesis of Chlamydia trachomatis salpingitis has been studied using the monkey "pocket" model. Pigtailed monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat-shock protein (rhsp60) was injected into pockets either previously sensitized with C. trachomatis or not sensitized in the same monkey. Delayedtype hypersensitivity reaction was observed. Injection of rhsp60 into the pockets of a naive animal did not induce inflammation. This study revealed that C. trachomatis infection in monkeys induces delayed hypersensitivity, which is mediated by hsp60. Histologic findings of the salpinx were consistent with delayed hypersensitivity reaction observed in ocular C. trachomatis infection, further suggesting a similar pathogenesis for both salpingitis and trachoma Patton et al (1994).
Other Information – Web Sites The American College of Obstetricians and Gynecologists maintains a web site to facilitate patient education: http://www.ACOG.org Clinical Evidence evaluates questions relevant to the practice of clinical medicine. The current medical literature is then summarized, and the contributions undergo peerreview: http://www.clinicalevidence.com The Centers for Disease Control and Prevention (CDC) maintains a website that includes recommendations for treatment of sexually transmitted diseases: http://www.cdc.gov/ std/treatment/5-2002TG.htm#PelvicInflammatoryDisease
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Journal Citations Pastorek, J.G., 1989. Pelvic inflammatory disease and tubo-ovarian abscess. Obstet. Gynecol. Clin. North Amer., 16(2), 347–361. Ness, R.B., Soper, D.E., Holley, R.L., Peipert, J., Randall, H., Sweet, R.L., Sondheimer, S.J., Hendrix, S.L., Amortegui, A., Trucco, G., Songer, T., Lave, J.R., Hillier, S.L., Bass, D.C., Kelsey, S.F., 2002. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Amer. J. Obstet. Gynecol., 186(5), 929–937. Pickhardt, P.J., Fleishman, M.J., Fisher, A.J., 2003. Fitz-Hugh-Curtis syndrome: multidetector CT findings of transient hepatic attenuation difference and gallbladder wall thickening. Amer. J. Roentgenol., 180(6), 1605–1606. Curtis, K.M., Hillis, S.D., Kieke, B.A. Jr, Brett, K.M., Marchbanks, P.A., Peterson, H.B., 1998. Visits to emergency departments for gynecologic disorders in the United States, 1992-1994. Obstet. Gynecol., 91, 1007–1012. Patton, D.L., Sweeney, Y.T., Kuo, C.C., 1994. Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in moneys: a pathogenic mechanism of tubal damage. J. Infect. Dis., 169, 680–683. Igietseme, J.U., Eko, F.O., Black, C.M., 2003. Contemporary approaches to designing and evaluating vaccines against Chlamydia. Expert Rev. Vaccines, 2(1), 129–146. Roberts, L.M., Sanfilippo, J.S., Raab, S., 2002. Effects of laparoscopic lavage on adhesion formation and peritoneum in an animal model of pelvic inflammatory disease. J. Amer. Assoc. Gynecol. Laparoscopists, 9(4), 503–507. Gorby, G.L., Ehrhardt, A.F., Apicella, M.A., Elkins, C., 2001. Invasion of human fallopian tube epithelium by Escherichia coli expressing combinations of a gonococcal porin, opacity-associated protein, and chimeric lipo-oligosaccharide. J. Infect. Dis., 184(4), 460–472. Debattista, J., Timms, P., Allan, J., Allan, J., 2003. Immunopathogenesis of chlamydia trachomatis infections in women. Fertility and Sterility, 79(6), 1273–1287.
Further Reading Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR 51 (No. RR-6) 2002 pp. 48–53. Peipert, Ness, Blume, Soper, Holley, Randall, Sweet, Sondheimer, Hendrix, Amortegui, Trucco, Bass, Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease, Amer. J. Obstet. Gynecol., 184(5) (2001) 856–863. Ross, Pelvicinflammatorydisease: how should it be managed?, Curr. Opinion Infect. Dis., 16(1) (2003) 37–41. Kamwendo, Forslin, Bodin, Danielsson, Decreasing incidences of gonorrhea- and chlamydia-associated acute pelvicinflammatorydisease. A 25-year study from an urban area of central Sweden, Sexually Transm. Dis. 23(5) (1996) 384–391. Jossens, Eskenazi, Schachter, Sweet, Risk factors for pelvicinflammatorydisease. A case control study, Sexually Transm. Dis., 23(3) (1996) 239–247. Eschenbach D.A., Pelvic Infections and Sexually Transmitted Diseases. In J. R. Scott MD, P. J. DiSaia MD, C. B. Hammond MD and W. N. Spellacy (Eds.) MD Danforth’s Obstetrics and Gynecology, Vol. 8, Lippincottt William and Wilkins, Philadelphia, PA, 1999, pp. 579–600.
Introduction Pelvic inflammatory disease (PID) is a broad term referring to a spectrum of inflammatory disorders and infections involving the upper female genital tract. The upper genital tract includes the uterine endometrium, the fallopian tubes (sometimes referred to as the oviducts), ovaries, and surrounding pelvic peritoneum. The most common cause of PID is a sexually-transmitted disease. While the most frequent causative organisms are Neisseria gonorrhoeae and Chlamydia trachomatis, other microorganisms have been implicated. PID, which is common in young, sexually active women, can have long-term sequelae affecting reproductive health.
Definition Pelvic inflammatory disease (PID) is inflammation and infection of the normally sterile environment of the upper genital tract including any combination of the endometrium, fallopian tubes, ovaries, and pelvic peritoneum.
Classification Pelvic inflammatory disease is usually classified as an infectious disease, although it can be considered a genitourinary disorder as well.
Consequences Severe infection associated with pelvic inflammatory disease requires hospitalization and intravenous antibiotics. Inflammation of the fallopian tube can be seen as a hydrosalpinx or pyosalpinx. Abscesses, usually involving the tubes and ovaries, or surrounding pelvic peritoneum, can occur. Abscesses frequently require surgery in addition to antibiotic therapy for resolution. Infection can ascend from the pelvis to the abdomen. Ascending infection can result in perihepatitis or inflammation of the liver capsule, which is referred to as Fitz-HughCurtis syndrome. The characteristic finding of Fitz-Hugh-Curtis syndrome is violinstring adhesions between the liver capsule and the abdominal wall Pickhardt et al (2003) Long-term consequences of pelvic inflammatory disease (PID) include scarring and adhesions in the pelvis and abdomen. Scarring and adhesions of the adnexa can result in infertility, or chronic pelvic pain. A history of PID is a risk factor for recurrent infection, pain, infertility, and ectopic pregnancy. 1
2
Pelvic Inflammatory Disease
Associated Disorders Inflammation and infection of the pelvic organs comprise pelvic inflammatory disease. This can include endometritis, salpingitis, peritonitis, and tubo-ovarian abscess Sequelae of scarring can result in pain and tubal factor infertility.
Etiology Pelvic inflammatory disease (PID) is usually attributed to a sexually transmitted disease ascending from the vagina and cervix to the upper genital organs, i.e., the uterus, tubes and ovaries. The most common organisms are Neisseria gonorrhoeae and Chlamydia trachomatis. Other organisms that have been implicated include vaginal flora such as aerobic and anaerobic bacteria. Many organisms have been identified including streptococcus species, staphylococci, enteric gram negative rods, peptostreptococci, bacteroides, Gardnerella vaginalis, trichomonads, Mycoplasma hominis, Ureaplasma urealyticum, Haemophilus influenzae and cytomegalovirus. Pelvic tuberculosis caused by Mycobacterium tuberculosis is less common. The most common path of infection begins in the vagina and cervix. Endometritis can occur if bacteria gain access to the normally sterile environment of the upper genital tract. Infection of the uterus can then disseminate to the pelvis. This dissemination can occur with retrograde menstruation, or after instrumentation of the uterus for an intrauterine device, an abortion, an invasive diagnostic procedure such as hysterosalpingogram, or childbirth. Other mechanisms for infection of the upper genital tract include spread from adjacent infected organs such as appendicitis or inflammation and infection of the bowel. Less common is metastasis through the blood stream from a distant organ such as might occur with tuberculosis Pastorek (1989).
Epidemiology Pelvic inflammatory disease (PID) is common condition. Approximately 1 in 7 women will be treated for PID during their life. About one million women are treated for this condition each year. Approximately 1% of women aged between 15-25 years old are diagnosed with PID annually. PID is a major cause of morbidity, precipitating approximately 342,000 emergency department visits Curtis et al (1998) and over 1 million clinic visits each year. Close to 200,000 women require hospitalization and more than 100,000 surgical procedures are performed annually in the United States for a diagnosis of PID.
Pathophysiology Pelvic inflammatory disease (PID) occurs when an organism infects some or all of the following: the endometrium, fallopian tubes, ovaries and surrounding peritoneum. An inflammatory reaction occurs. Histologic changes include endometritis, salpingitis, oophoritis, and peritonitis. How and why upper genital tract infection occurs is not yet completely understood. The upper genital tract is thought to be a sterile environment, while the cervix and vagina are polymicrobial. Not all episodes of gonococcal or chlamydial cervicitis cause an ascending infection. Conversely, it is rare to recover Chlamydia trachomatis or Neisseria gonorrhoeae from a tubo-ovarian abscess. A break in the usual protective mechanisms of the cervix probably occurs, allowing ascent of an organism with subsequent infection of the
Pelvic Inflammatory Disease
uterine endometrium. There is a frequent observed correlation of gonococcal PID immediately following menses, while this correlation is not seen with chlamydia. The mechanisms involved in the inflammatory response to infection probably vary with the infecting agent. Factors involved in the virulence of infectious organisms are under investigation. For N. gonorrhoeae these include opacity-associated proteins, lipooligosaccharides, and outer-membrane proteins Gorby et al (2001). Infection with chlamydia probably involves different mechanisms that determine whether acute infection is resolved or progresses into a chronic inflammation with tubal scarring. Multiple determinants are under investigation, including immune pathways, cytokine profiles, heat shock proteins, infectious load, and endocrinology Debattista et al (2003). The other pathogens could all have different mechanisms for attachment to the epithelium and for causing cellular damage. Regardless of the mechanism, an inoculum accesses the upper genital structures, with the resulting infection and inflammation subsequently involving the fallopian tube or ovary. A pyosalpingo-oophoritis or purulent inflammation of the tube or ovary develops. The inflamed and infected tube can adhere to the ovary, resulting in a closed space that becomes a tubo-ovarian abscess. Spillage of pus into the pelvis can result in additional pockets of inflammation and abscesses in the abdomen.
Signs and Symptoms The symptoms of pelvic inflammatory disease (PID) can vary widely, making diagnosis and clinical investigation difficult. Patients report symptoms include foul-smelling or excessive vaginal discharge, abnormal vaginal bleeding, pain and cramping in the lower abdomen and pelvis, fever and chills, nausea, vomiting or diarrhea. Signs noted on physical examination may include fever with a temperature over 38.3 C, tenderness in the lower abdomen and pelvis, mucopurulent discharge from the cervix, and white blood cells on saline microscopy. Important physical exam findings include cervical motion tenderness or adnexal tenderness. An adnexal mass or fullness in the pouch of Douglas is suggestive of abscess. Cultures for gonorrhea and chlamydia should be performed. Culdocentesis can reveal pus in the pelvic cavity, and provide an additional source to culture. Ultrasound can help identify abscesses. More advanced radiographic studies such as computerized tomography or magnetic resonance imaging are only rarely required. Laboratory tests can reveal leukocytosis, elevated erythrocyte sediment rate, or elevated C-reactive protein. Laparoscopy can help identify salpingitis (inflammation of the fallopian tubes) if the diagnosis is in doubt.
Standard Therapies Traditionally, severe pelvic inflammatory disease (PID) with tuboovarian abscess was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Studies in the 1970s and 1980s found sufficient cure rates to allow a trial of intravenous antibiotics. There appears to be no statistical difference in long-term reproductive outcomes such as time to pregnancy, PID recurrence, chronic pain or ectopic pregnancy in women with mild-to-moderate PID randomized to inpatient or outpatient treatment Ness et al (2002). Treatment of PID is aimed at providing empiric, broad-spectrum antibiotic coverage of likely pathogens, including gonococci, chlamydia, streptococci, gram-negative bacteriae and facultative anaerobic bacteria. Current standard treatment guidelines published by the Centers for Disease Control and Prevention are listed below:
3
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Pelvic Inflammatory Disease
In patients requiring hospitalization, parenteral antibiotics are initiated, frequently in combination with oral agents. Parenteral therapy can be discontinued 24 hours after the patient shows clinical improvement. Oral therapy continues to complete a 14-day course of antibiotic therapy. Parenteral Regimen A: Cefotetan 2 g i.v. every 12 hours or cefoxitin 2 g i.v. every 6 hours plus doxycycline 100 mg orally or i.v. every 12 hours. The cephalosporin provides antimicrobial activity against N. gonorrhoeae and aerobic and anaerobic bacteria. Doxycycline provides coverage for C. trachomatis. If an abscess is suspected, clindamycin or metronidazole is often included to improve empiric coverage against the presumed presence of anaerobic bacteria. Parenteral Regimen B: Clindamycin 900 mg i.v. every 8 hours, plus gentamicin loading dose i.v. or i.m. followed by a maintenance dose every 8 hours. Alternative Parenteral Regimens: These include ofloxacin 400 mg i.v. every 12 hours or levofloxacin 500 mg i.v. once daily with or without metronidazole 500 mg i.v. every 8 hours or ampicillin/sulbactam 3 g i.v. every 6 hours plus doxycycline 100 mg every 12 hours. When outpatient management of PID is deemed safe, the following oral regimens provide antibiotic coverage of the usual infectious organisms involved in this condition. Oral Regimen A: Ofloxacin 400 mg twice a day for 14 days or levofloxacin 500 mg once daily for 14 days with or without metronidazole 500 mg twice a day for 14 days. Oral Regimen B: Ceftriaxone 250 mg i.m. or cefoxitin 2 g i.m. and probenecid 1 g p.o. in a single dose or other parenteral third-generation cephalosporin plus doxycycline 100 mg twice a day for 14 days with or without metronidazole 500 mg twice a day for 14 days. The optimal choice of a cephalosporin is not clear. While cefoxitin has better anaerobic coverage, ceftriaxone has better coverage against N. gonorrhoeae. Follow-up includes evaluation by a health-care provider within 3 days to insure clinical improvement. Lack of improvement might require hospitalization, additional tests, or surgical intervention. Agent Name Cefotetan
Discussion
Cefotetan is a second generation cephalosporin antibiotic. Cephalosporins inhibit bacterial cell wall synthesis. The second-generation cephalosporins display enhanced activity against gram-negative organisms and gram-negative diplococci like Neisseria Gonorrhoeae, with some activity against anaerobic bacteria. Cefoxitin Cefoxitin is a second generation cephalosporin antibiotic. It has activity against the anaerobic bacteria Bacteroides fragilis. Doxycycline Doxycycline is a second-generation tetracycline antibiotic. Tetracyclines selectively inhibit protein synthesis by targeting the bacterial ribosome. Tetracyclines exhibit activity against chlamydia species. Clindamycin Clindamycin is effective against anaerobic bacteria. It is an inhibitor of bacterial protein synthesis. Clindamycin is of benefit when treating an abscess that is presumed to contain anaerobic bacteria. Gentamicin Gentamicin is an aminoglycoside antibiotic effective against gram-negative bacilli. Ofloxacin Ofloxacin is a second generation quinolone antibiotic. It is effective against both Chlamydia trachomatis and N. gonorrhoeae. Because ofloxacin lacks anaerobic coverage, the addition of metronidazole is common. Levofloxacin Levofloxacin is a second-generation quinolone. Preliminary information suggests it is equivalent to ofloxacin in terms of efficacy, with the added benefit of once-aday dosing to improve compliance. Metronidazole Metronidazole is an antiprotozoal agent that is toxic to amoebae and anaerobic organisms. The agent of choice for treating Trichomonas vaginalis, metronidazole is an effective treatment for abscesses. Ampicillin/ Ampicillin is an extended-spectrum penicillin. Sulbactam is administered Sulbactam concomitantly to protect the antibiotic from beta-lactamase.
Pelvic Inflammatory Disease
Experimental Therapies Antibiotic therapy aimed at destroying the most common infectious agents has been the mainstay of treatment for pelvic inflammatory disease. Development of vaccines could be especially beneficial for treating those at high risk for this condition. Agent Name Vaccine
Discussion Chlamydia cervicitis and major complications like endometritis, pelvic inflammatory disease and tubal factor infertility exist in addition to other chlamydia-associated chronic syndromes. A prophylactic vaccine could help limit the morbidity of chlamydial infection. A unified approach to vaccines for the genus Chlamydia is validated by common immunogenic proteins among member species, several conserved genes, and similar immune effectors in animals and humans Igietseme et al (2003).
Animal Models While there are no animal models for pelvic inflammatory disease (PID), there is an animal model that simulates intraluminal tubal damage and adhesion formation seen in this condition Roberts et al (2002). Animal models are under development to study chlamydia and its effects. For example, the role of delayed hypersensitivity in the pathogenesis of Chlamydia trachomatis salpingitis has been studied using the monkey "pocket" model. Pigtailed monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat-shock protein (rhsp60) was injected into pockets either previously sensitized with C. trachomatis or not sensitized in the same monkey. Delayedtype hypersensitivity reaction was observed. Injection of rhsp60 into the pockets of a naive animal did not induce inflammation. This study revealed that C. trachomatis infection in monkeys induces delayed hypersensitivity, which is mediated by hsp60. Histologic findings of the salpinx were consistent with delayed hypersensitivity reaction observed in ocular C. trachomatis infection, further suggesting a similar pathogenesis for both salpingitis and trachoma Patton et al (1994).
Other Information – Web Sites The American College of Obstetricians and Gynecologists maintains a web site to facilitate patient education: http://www.ACOG.org Clinical Evidence evaluates questions relevant to the practice of clinical medicine. The current medical literature is then summarized, and the contributions undergo peerreview: http://www.clinicalevidence.com The Centers for Disease Control and Prevention (CDC) maintains a website that includes recommendations for treatment of sexually transmitted diseases: http://www.cdc.gov/ std/treatment/5-2002TG.htm#PelvicInflammatoryDisease
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Pelvic Inflammatory Disease
Journal Citations Pastorek, J.G., 1989. Pelvic inflammatory disease and tubo-ovarian abscess. Obstet. Gynecol. Clin. North Amer., 16(2), 347–361. Ness, R.B., Soper, D.E., Holley, R.L., Peipert, J., Randall, H., Sweet, R.L., Sondheimer, S.J., Hendrix, S.L., Amortegui, A., Trucco, G., Songer, T., Lave, J.R., Hillier, S.L., Bass, D.C., Kelsey, S.F., 2002. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Amer. J. Obstet. Gynecol., 186(5), 929–937. Pickhardt, P.J., Fleishman, M.J., Fisher, A.J., 2003. Fitz-Hugh-Curtis syndrome: multidetector CT findings of transient hepatic attenuation difference and gallbladder wall thickening. Amer. J. Roentgenol., 180(6), 1605–1606. Curtis, K.M., Hillis, S.D., Kieke, B.A. Jr, Brett, K.M., Marchbanks, P.A., Peterson, H.B., 1998. Visits to emergency departments for gynecologic disorders in the United States, 1992-1994. Obstet. Gynecol., 91, 1007–1012. Patton, D.L., Sweeney, Y.T., Kuo, C.C., 1994. Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in moneys: a pathogenic mechanism of tubal damage. J. Infect. Dis., 169, 680–683. Igietseme, J.U., Eko, F.O., Black, C.M., 2003. Contemporary approaches to designing and evaluating vaccines against Chlamydia. Expert Rev. Vaccines, 2(1), 129–146. Roberts, L.M., Sanfilippo, J.S., Raab, S., 2002. Effects of laparoscopic lavage on adhesion formation and peritoneum in an animal model of pelvic inflammatory disease. J. Amer. Assoc. Gynecol. Laparoscopists, 9(4), 503–507. Gorby, G.L., Ehrhardt, A.F., Apicella, M.A., Elkins, C., 2001. Invasion of human fallopian tube epithelium by Escherichia coli expressing combinations of a gonococcal porin, opacity-associated protein, and chimeric lipo-oligosaccharide. J. Infect. Dis., 184(4), 460–472. Debattista, J., Timms, P., Allan, J., Allan, J., 2003. Immunopathogenesis of chlamydia trachomatis infections in women. Fertility and Sterility, 79(6), 1273–1287.
Further Reading Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR 51 (No. RR-6) 2002 pp. 48–53. Peipert, Ness, Blume, Soper, Holley, Randall, Sweet, Sondheimer, Hendrix, Amortegui, Trucco, Bass, Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease, Amer. J. Obstet. Gynecol., 184(5) (2001) 856–863. Ross, Pelvicinflammatorydisease: how should it be managed?, Curr. Opinion Infect. Dis., 16(1) (2003) 37–41. Kamwendo, Forslin, Bodin, Danielsson, Decreasing incidences of gonorrhea- and chlamydia-associated acute pelvicinflammatorydisease. A 25-year study from an urban area of central Sweden, Sexually Transm. Dis. 23(5) (1996) 384–391. Jossens, Eskenazi, Schachter, Sweet, Risk factors for pelvicinflammatorydisease. A case control study, Sexually Transm. Dis., 23(3) (1996) 239–247. Eschenbach D.A., Pelvic Infections and Sexually Transmitted Diseases. In J. R. Scott MD, P. J. DiSaia MD, C. B. Hammond MD and W. N. Spellacy (Eds.) MD Danforth’s Obstetrics and Gynecology, Vol. 8, Lippincottt William and Wilkins, Philadelphia, PA, 1999, pp. 579–600.