Pelvic inflammatory disease medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Treatment depends on the cause and generally involves use of antibiotic therapy. If the patient has not improved within two to three days after beginning treatment with the antibiotics, they should return to the hospital for further treatment. Drugs should also be given orally and/or intravaneously to the patient while in the hospital to begin treatment immediately to increase the effectiveness of antibiotic treatment. Hospitalization may be necessary if tubo-ovarian abscess, very ill, immunodeficient, pregnancy, incompetence, or because this or something else life threatening can not be ruled out. Treating partners for STD's is a very important part of treatment and prevention. Anyone with PID and partners of patients with PID since six months prior to diagnosis should be treated to prevent reinfection. Psychotherapy is highly recommended to women diagnosed with PID as the fear of redeveloping the disease after being cured may exist. It is important for a patient to communicate any issues and/or uncertainties they may have to a doctor, especially a specialist such as a gynecologist, and in doing so, to seek follow-up care.

Medical Therapy

PID can be cured with several types of antibiotics. A health care provider will determine and prescribe the best therapy. However, antibiotic treatment does not reverse any damage that has already occurred to the reproductive organs. If a woman has pelvic pain and other symptoms of PID, it is critical that she seek care immediately. Prompt antibiotic treatment can prevent severe damage to reproductive organs. The longer a woman delays treatment for PID, the more likely she is to become infertile or to have a future ectopic pregnancy because of damage to the fallopian tubes.

Because of the difficulty in identifying organisms infecting the internal reproductive organs and because more than one organism may be responsible for an episode of PID, PID is usually treated with at least two antibiotics that are effective against a wide range of infectious agents. These antibiotics can be given by mouth or by injection. The symptoms may go away before the infection is cured. Even if symptoms go away, the woman should finish taking all of the prescribed medicine. This will help prevent the infection from returning. Women being treated for PID should be re-evaluated by their health care provider three days after starting treatment to be sure the antibiotics are working to cure the infection. In addition, a woman’s sex partner(s) should be treated to decrease the risk of re-infection, even if the partner(s) has no symptoms. Although sex partners may have no symptoms, they may still be infected with the organisms that can cause PID.

Hospitalization to treat PID may be recommended if the woman

(1) Is severely ill (e.g., nausea, vomiting, and high fever)

(2) Is pregnant

(3) Does not respond to or cannot take oral medication and needs intravenous antibiotics

(4) Has an abscess in the fallopian tube or ovary (tubo-ovarian abscess) or

(5) Needs to be monitored to be sure that her symptoms are not due to another condition that would require emergency surgery (e.g., appendicitis).

No evidence is available to suggest that adolescents benefit from hospitalization for treatment of PID. The decision to hospitalize adolescents with acute PID should be based on the same criteria used for older women. Younger women with mild-to-moderate acute PID have similar outcomes with either outpatient or inpatient therapy, and clinical response to outpatient treatment is similar among younger and older women.

If symptoms continue or if an abscess does not go away, surgery may be needed.

Empiric Treatment

Treatment is usually started empirically because of the terrible complications. The optimal treatment regimen and long-term outcome of early treatment of women with asymptomatic or subclinical PID are unknown. Diagnosis and management of other common causes of lower abdominal pain (e.g., ectopic pregnancy, acute appendicitis, and functional pain) are unlikely to be impaired by initiating empiric antimicrobial therapy for PID.

Empiric treatment for PID should be initiated in sexually active young women and other women at risk for STDs if they are experiencing pelvic or lower abdominal pain, if no cause for the illness other than PID can be identified, and if one or more of the following minimum criteria are present on pelvic examination:

• Cervical motion tenderness

or

• Uterine tenderness

or

• Adnexal tenderness.

Shown below is a table summarizing the preferred and alternative empiric treatment for Pelvic inflammatory disease (includes salpingitis, tubo-ovarian abscess and pelvic peritonitis).

PID TREATMENT Preferred Regimen Outpatient ▸ Ceftriaxone 250 mg IM or IV x 1 dose PLUS ▸ Metronidazole 500 mg po bid x 14 days PLUS ▸ Doxycycline 100 mg po bid x 14 days OR ▸ Cefoxitin 2 gm IM with Probenecid 1 gm po both as single dose PLUS ▸ Doxycycline 100 mg po bid x 14 days PLUS ▸ Metronidazole 500 mg bid x 14 days Inpatient ▸ Cefoxitin 2 gm IV q6h PLUS ▸ Doxycycline 100 mg IV/po q12h Alternative Regimen Outpatient ▸ Ceftriaxone 250 mg IM or IV x 1 dose PLUS ▸ Azithromycin 1 gm po weekly x 2 weeks Inpatient ▸ Clindamycin 900 mg IV q8h PLUS ▸ Gentamicin 2 mg/kg loading dose, then 1.5 mg/kg q8h or 4.5 mg/kg once/day then Doxycycline 100 mg po bid x 14 days OR ▸ Amp-Sulb 3 gm IV q6h PLUS ▸ Doxycycline 100 mg IV/po q12h

Follow-Up

Patients should demonstrate substantial clinical improvement (e.g., defervescence; reduction in direct or rebound abdominal tenderness; and reduction in uterine, adnexal, and cervical motion tenderness) within 3 days after initiation of therapy. Patients who do not improve within this period usually require hospitalization, additional diagnostic tests, and surgical intervention.

If no clinical improvement has occurred within 72 hours after outpatient oral or parenteral therapy, further assessment should be performed. Subsequent hospitalization and an assessment of the antimicrobial regimen and diagnostics (including the consideration of diagnostic laparoscopy for alternative diagnoses) are recommended in women without clinical improvement. Women with documented chlamydial or gonococcal infections have a high rate of reinfection within 6 months of treatment. Repeat testing of all women who have been diagnosed with chlamydia or gonorrhea is recommended 3–6 months after treatment, regardless of whether their sex partners were treated. All women diagnosed with acute PID should be offered HIV testing.

Management of Sex Partners

Male partners of women who have PID often are asymptomatic.

Male sex partners of women with PID should be examined and treated if they had sexual contact with the patient during the 60 days preceding the patient’s onset of symptoms. If a patient’s last sexual intercourse was >60 days before onset of symptoms or diagnosis, the patient’s most recent sex partner should be treated. Patients should be instructed to abstain from sexual intercourse until therapy is completed and until they and their sex partners no longer have symptoms. Evaluation and treatment are imperative because of the risk for reinfection of the patient and the strong likelihood of urethral gonococcal or chlamydial infection in the sex partner. Male partners of women who have PID caused by C. trachomatis and/or N. gonorrhoeae frequently are asymptomatic.

Sex partners should be treated empirically with regimens effective against both of these infections, regardless of the etiology of PID or pathogens isolated from the infected woman. Even in clinical settings in which only women are treated, arrangements should be made to provide care or appropriate referral for male sex partners of women who have PID. Expedited partner treatment and enhanced patient referral are alternative approaches to treating male partners of women who have chlamydia or gonococcal infections.

Special Considerations

Pregnancy

Because of the high risk for maternal morbidity and preterm delivery, pregnant women who have suspected PID should be hospitalized and treated with parenteral antibiotics.

HIV Infection

Differences in the clinical manifestations of PID between HIV-infected women and HIV-negative women have not been well delineated. In previous observational studies, HIV-infected women with PID were more likely to require surgical intervention; more comprehensive observational and controlled studies now have demonstrated that HIV-infected women with PID have similar symptoms when compared with uninfected controls, except they were more likely to have a tubo-ovarian abscess; both groups of women responded equally well to standard parenteral and oral antibiotic regimens. The microbiologic findings for HIV-positive and HIV-negative women were similar, except HIV-infected women had higher rates of concomitantM. hominis, candida, streptococcal, and HPV infections and HPV-related cytologic abnormalities. Regardlesss of these data, whether the management of immunodeficient HIV-infected women with PID requires more aggressive interventions (e.g., hospitalization or parenteral antimicrobial regimens) has not been determined.

Intrauterine Contraceptive Devices

IUDs are popular contraceptive choices for women. Both levonorgestrel and copper-containing devices are marketed in the United States. The risk for PID associated with IUDuse is primarily confined to the first 3 weeks after insertion and is uncommon thereafter. Given the popularity of IUDs, practitioners might encounter PID in IUD users. Evidence is insufficient to recommend that the removal of IUDs in women diagnosed with acute PID. However, caution should be exercised if the IUD remains in place, and close clinical follow-up is mandatory. The rate of treatment failure and recurrent PID in women continuing to use an IUD is unknown, and no data have been collected regarding treatment outcomes by type of IUD (e.g., copper or levonorgestrel).

Oral Treatment

Outpatient, oral therapy can be considered for women with mild-to-moderately severe acute PID, because the clinical outcomes among women treated with oral therapy are similar to those treated with parenteral therapy. The following regimens provide coverage against the frequent etiologic agents of PID. Patients who do not respond to oral therapy within 72 hours should be reevaluated to confirm the diagnosis and should be administered parenteral therapy on either an outpatient or inpatient basis.

Recommended Regimen

---

Ceftriaxone 250 mg IM in a single dose PLUS Doxycycline 100 mg orally twice a day for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days

---

OR

---

Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose PLUS Doxycycline 100 mg orally twice a day for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days

---

OR

---

Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) PLUS Doxycycline 100 mg orally twice a day for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days

---

The optimal choice of a cephalosporin is unclear; although cefoxitin has better anaerobic coverage, ceftriaxone has better coverage against N. gonorrhoeae. A single dose of cefoxitin is effective in obtaining short-term clinical response in women who have PID. However, the theoretical limitations in coverage of anaerobes by recommended cephalosporin antimicrobials might require the addition of metronidazole to the treatment regimen. Adding metronidazole also will effectively treat BV, which is frequently associated with PID. No data have been published regarding the use of oral cephalosporins for the treatment of PID.

Alternative Oral Regimens

Although information regarding other outpatient regimens is limited, other regimens have undergone at least one clinical trial and have demonstrated broad spectrum coverage. In a single clinical trial, amoxicillin/clavulanic acid and doxycycline were effective together in obtaining short-term clinical response; however, gastrointestinal symptoms might limit compliance with this regimen. Azithromycin has demonstrated short-term effectiveness in one randomized trial, and in another study, it was effective when used combination with ceftriaxone 250 mg IM single dose and azithromycin 1 g orally once a week for 2 weeks. When considering alternative regimens, the addition of metronidazole should be considered because anaerobic organisms are suspected in the etiology of PID and metronidazole will also treat BV.

As a result of the emergence of quinolone-resistant Neisseria gonorrhoeae, regimens that include a quinolone agent are no longer recommended for the treatment of PID. If parenteral cephalosporin therapy is not feasible, use of fluoroquinolones (levofloxacin 500 mg orally once daily or ofloxacin 400 mg twice daily for 14 days) with or without metronidazole (500 mg orally twice daily for 14 days) can be considered if the community prevalence and individual risk for gonorrhea are low. Diagnostic tests for gonorrhea must be performed before instituting therapy and the patient managed as follows if the test is positive.

• If the culture for gonorrhea is positive, treatment should be based on results of antimicrobial susceptibility.
• If the isolate is determined to be quinolone-resistant N. gonorrhoeae (QRNG) or if antimicrobial susceptibility

cannot be assessed (e.g., if only NAAT testing is available), parenteral cephalosporin is recommended. However, if cephalosporin therapy is not feasible, the addition of azithromycin 2 g orally as a single dose to a quinolone-based PID regimen is recommended.