Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 6: Disease-Specific Treatment

Pelvic Inflammatory Disease

Background

Pelvic inflammatory disease (PID) is the syndrome resulting from the ascent of microorganisms from the vagina and cervix to the uterine endometrium, fallopian tubes, ovaries, or contiguous abdominal structures. Many episodes of PID go unrecognized, because of lack of symptoms or mild, nonspecific symptoms (eg, dyspareunia, abnormal bleeding, and vaginal discharge). Infecting organisms may include Neisseria gonorrhoeae and Chlamydia trachomatis, which are sexually transmitted, and anaerobic bacteria (Gardnerella vaginalis or Haemophilus influenzae), gram-negative rods (Escherichia coli), Streptococcus agalactiae, gastrointestinal flora, and mycoplasmas (Mycoplasma hominis), which may not be sexually transmitted. PID is coepidemic with HIV among some urban populations of reproductive age. Data on PID outcomes in HIV-infected women are limited. Many studies have documented no difference in length or severity of lower abdominal pain, vaginal discharge, fever, abnormal vaginal bleeding, or low back pain between HIV-positive and HIV-negative women with PID. However, there is a higher rate of tubo-ovarian abscesses and severe salpingitis and pyosalpinx in HIV-positive women.

Clinical presentation may include salpingitis, endometritis, tubal and/or ovarian abscess, and pelvic peritonitis, although PID may present with subtle or mild symptoms even in HIV-infected women. Long-term complications of PID may include infertility, ectopic pregnancy, pelvic adhesions, and chronic pain.

S: Subjective

The patient may complain of mild-to-moderate lower abdominal pain and tenderness, pain with intercourse, vaginal discharge, fever, chills, heavy menstrual bleeding, or other abnormal vaginal bleeding.

Inquire about the following during the history:

• Symptoms listed above, and duration
• New sex partner(s), unprotected sex
• Use of intrauterine device
• Last menstrual period
• Previous diagnosis of gonorrhea or chlamydia
• Previous abdominal or gynecologic surgery

O: Objective

Perform a focused physical examination, documenting fever (temperature may be elevated or normal) and other vital signs. Check abdomen for bowel sounds, distention, rebound, guarding, masses, suprapubic and costovertebral angle (CVA) tenderness; perform complete pelvic examination looking for abnormal bleeding or discharge; uterine, adnexal, or cervical motion tenderness; pelvic masses or adnexal enlargement.

A: Assessment

A partial differential diagnosis includes the following:

• Pregnancy, uterine or ectopic
• Ruptured or hemorrhagic ovarian cyst
• Dysmenorrhea
• Appendicitis
• Pyelonephritis
• Diverticulitis
• Irritable bowel syndrome
• Cystitis
• Uterine fibroids/leiomyomas
• Ovarian torsion
• Mittelschmerz
• Kidney stones
• Pyelonephritis

P: Plan

Diagnostic Evaluation

• Gram stain of endocervical discharge
• Microscopic examination of saline preparation of vaginal secretions
• Endocervical and rectal cultures, urine for N gonorrhoeae
• Endocervical and rectal culture, or nucleic acid amplification test, for endocervical swab or first void urine
• Pregnancy test (if menses is late or pregnancy is possible)

Treatment

Because clinical diagnostic criteria for PID are not always conclusive, presumptive diagnosis and early treatment is common. The positive predictive value of a clinical diagnosis is 65-90%. The absence of infection from the lower genital tract, where samples are usually taken, does not exclude PID and should not influence the decision to treat.

Empiric treatment for PID should be initiated in sexually active women at risk for sexually transmitted infection if the following minimum criteria are met:

• Uterine or adnexal tenderness
• Cervical motion tenderness
• Additional criteria that support the diagnosis of PID include:
• Oral temperature >101°F
• Abnormal cervical or vaginal mucopurulent discharge
• Presence of white blood cells in vaginal secretions
• Elevated erythrocyte sedimentation rate
• Elevated C-reactive protein
• Laboratory documentation of infection with N gonorrhoeae or C trachomatis
• Definitive criteria:
• Endometrial biopsy with histopathologic evidence of endometritis
• Transvaginal sonogram showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex
• Laparoscopic abnormalities consistent with PID

Treatment considerations

Antimicrobial regimens must provide broad-spectrum coverage of likely pathogens (Table 1). HIV-infected women respond equally well to standard antibiotic regimens as HIV-negative women. Whether the management HIV-infected women with advanced immunocompromise requires more aggressive interventions (eg, hospitalization or parenteral antimicrobial regimens) has not been determined. Decisions about whether to use oral or parenteral therapy must be individualized.

In moderate to severe cases of PID, intrauterine devices (IUDs) should be removed, if present.

The goals of treatment are to:

• Alleviate the pain and systemic malaise associated with infection
• Achieve microbiological cure
• Prevent development of permanent tubal damage with associated problems, such as chronic pelvic pain, ectopic pregnancy, and infertility
• Prevent the transmission of infection to others

Indications for hospitalization of patients with PID include:

• Unsure diagnosis; surgical emergency cannot be excluded
• Tubo-ovarian abscess
• Severe illness with nausea and vomiting or high fever
• Pregnancy
• Inability to follow outpatient regimen
• Immunosuppression (low CD4 count or significant comorbidity)

Pregnancy

If the patient is pregnant, aggressive treatment is essential to prevent preterm delivery, fetal loss, and maternal morbidity. Certain medications should be avoided to reduce the risk of fetal toxicity; these include doxycycline, fluoroquinolones, and gentamicin. Hospitalization for parenteral antibiotic therapy is recommended.

Table 1. Treatment Regimens for Pelvic Inflammatory Disease

Antibiotic Regimens Oral / Outpatient Treatment (see CDC STD Treatment Guidelines, referenced below) Regimen 1 Ofloxacin* 400 mg orally twice daily for 14 days or Levofloxacin* 500 mg orally once daily for 14 days with or without Metronidazole 500 mg orally twice daily for 14 days (provides activity against anaerobes) Regimen 2 Ceftriaxone 250 mg intramuscular (IM) injection in a single dose or Cefoxitin 2 g IM injection in a single dose, administered concurrently with probenecid 1 g orally in a single dose or Other parenteral third generation cephalosporin (eg, ceftizoxime or cefotaxime) plus Doxycycline 100 mg orally twice daily for 14 days with or without Metronidazole 500 mg orally twice daily for 14 days Parenteral / Inpatient Treatment Regimen 1 Cefotetan 2 g intravenously (IV) every 12 hours or Cefoxitin 2 g IV every 6 hours plus Doxycycline 100 mg orally or IV every 12 hours (oral form is preferable because of the irritant qualities of the IV solution) Regimen 2 Clindamycin 900 mg IV every 8 hours plus Gentamicin loading dose IV or IM injection (2 mg/kg of body weight) followed by maintenance dose (1.5 mg/kg) IV every 8 hours or 5-7 mg/kg IV daily Alternative Parenteral Regimens Regimen 1 Ofloxacin* 400 mg IV every 12 hours or Levofloxacin* 500 mg IV daily with or without Metronidazole 500 mg IV every 8 hours (provides anaerobic activity) Regimen 2 Ampicillin/Sulbactam 3 g IV every 6 hours plus Doxycycline 100 mg orally or IV every 12 hours (oral form is preferable due to the irritant qualities of IV solution)

* Fluoroquinolones should not be used to treat PID in California, Hawaii, Massachusetts, New York City, the Pacific Basin, or Asia, because of high rates of fluoroquinolone-resistant gonorrhea in these areas.

Follow-Up

• Patients should show significant clinical improvement within 3 days of initiation of therapy (eg, improvement in fever, abdominal tenderness, and uterine, adnexal, and cervical motion tenderness). If the patient has not improved, consider hospitalization, additional diagnostic testing, or surgical intervention. Patients who are initially hospitalized for treatment may be switched to an oral regimen and discharged on oral therapy after they have improved clinically.
• Evaluate sexual partners and offer them treatment if they had sexual contact with the patient during the 60 days preceding the patient's onset of symptoms. Treat empirically for both chlamydia and gonorrhea.
• Some specialists recommend rescreening for C trachomatis and N gonorrhoeae after therapy is completed in women with documented infection with these pathogens.
• Provide education about sexual risk reduction. Instruct patients to use condoms with every sexual contact to prevent becoming reinfected with chlamydia or gonorrhea, to prevent other sexually transmitted infections, and to prevent passing HIV to sexual partners.

Patient Education

• Instruct patients to take all of their medications. Advise patients to take medications with food if they are nauseated, and to call or return to clinic right away if they have vomiting or are unable to take their medications.
• Sexual partners from the previous 60 days need to be tested for sexually transmitted pathogens, and treated as soon as possible with a regimen effective against gonorrhea and chlamydia, even if they have no symptoms. Advise patients to inform their partner(s) that they need to be tested and treated. Otherwise, they may be reinfected.
• Advise patients to avoid sexual contact until the infection has been cured.
• Provide education about sexual risk reduction. Instruct patients to use condoms with every sexual contact to prevent becoming reinfected, to prevent other sexually transmitted infections, and to prevent passing HIV to sexual partners.
• Advise patients that PID can recur, and that they should call or return to the clinic if symptoms such as pain or fever develop.
• Patients must not drink beer, wine, or any other alcoholic beverage during treatment while taking metronidazole, and for at least 24-48 hours after the last dose. Metronidazole may cause a disulfiram reaction, resulting in severe nausea and vomiting. Note that patients taking ritonavir may experience symptoms due to the small amount of alcohol in the capsules; advise patients to call if nausea and vomiting occur.

References

• Abularach S, Anderson J. Gynecologic Problems. In: Anderson JR, ed. A Guide to the Clinical Management of Women with HIV. Rockville, MD: Health Resources and Services Administration, HIV/AIDS Bureau; 2005. Available online at hab.hrsa.gov/publications/womencare05/WG05chap6.htm.
• Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep. 2002 May 10;51(RR-6):1-78.
• Cohn SE, Clark RA. Sexually transmitted diseases, HIV, and AIDS in women. In: The Medical Clinics of North America, vol. 87; 2003:971-995.
• Hatcher RA, Stewart FH, Trussell J, et al. Contraceptive Technology, 17th revised ed. New York: Ardent Media; 1998:204-206.
• Minkoff HL, DeHovitz JA. Care of women infected with the human immunodeficiency virus. JAMA. 1991 Oct 23-30;266(16):2253-8.
• Minkoff HL, DeHovitz JA. HIV infection in women. AIDS Clin Care. 1991; 3: 33-5.
• Ross JDC. Pelvic Inflammatory Disease. Birmingham, UK: University of Birmingham; 2004.
• Slaven EM, Lopez F, Weintraub SL, et al. The AIDS patient with abdominal pain: a new challenge for the emergency physician. Emerg Med Clin North Am. 2003 Nov;21(4):987-1015.