 |
 |
 |
   |
||||||||
|
Warning:
This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:
- STD Treatment Guidelines at http://www.cdc.gov/STD/treatment
1998 Guidelines for Treatment of Sexually Transmitted Disease
Date: 01/23/98
Source: 47(RR-1);1-118
SUGGESTED CITATION: Centers for Disease Control and Prevention. 1998 Guidelines for Treatment of Sexually Transmitted Diseases. MMWR 1998;47(No. RR-1): {inclusive page numbers}.
The material in this report was prepared for publication by: National Center for HIV, STD and TB Prevention, Division of Sexually Transmitted Diseases Prevention
PELVIC INFLAMMATORY DISEASE (PID)
PID comprises a spectrum of inflammatory disorders of the upper female genital tract, including any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. Sexually transmitted organisms, especially N. gonorrhoeae and C. trachomatis, are implicated in most cases; however, microorganisms that can be part of the vaginal flora (e.g., anaerobes, G. vaginalis, H. influenzae, enteric Gram-negative rods, and Streptococcus agalactiae) also can cause PID. In addition, M. hominis and U. urealyticum might be etiologic agents of PID.
Diagnostic Considerations
Acute PID is difficult to diagnose because of the wide variation in the symptoms and signs. Many women with PID have subtle or mild symptoms that do not readily indicate PID. Consequently, delay in diagnosis and effective treatment probably contributes to inflammatory sequelae in the upper reproductive tract. Laparoscopy can be used to obtain a more accurate diagnosis of salpingitis and a more complete bacteriologic diagnosis. However, this diagnostic tool often is not readily available for acute cases, and its use is not easy to justify when symptoms are mild or vague. Moreover, laparoscopy will not detect endometritis and may not detect subtle inflammation of the fallopian tubes. Consequently, a diagnosis of PID usually is based on clinical findings. The clinical diagnosis of acute PID also is imprecise. Data indicate that a clinical diagnosis of symptomatic PID has a PPV for salpingitis of 65%-90% in comparison with laparoscopy. The PPV of a clinical diagnosis of acute PID differs depending on epidemiologic characteristics and the clinical setting, with higher PPV among sexually active young (especially teenaged) women and among patients attending STD clinics or from settings in which rates of gonorrhea or chlamydia are high. In all settings, however, no single historical, physical, or laboratory finding is both sensitive and specific for the diagnosis of acute PID (i.e., can be used both to detect all cases of PID and to exclude all women without PID). Combinations of diagnostic findings that improve either sensitivity (i.e., detect more women who have PID) or specificity (i.e., exclude more women who do not have PID) do so only at the expense of the other. For example, requiring two or more findings excludes more women who do not have PID but also reduces the number of women with PID who are identified.
Many episodes of PID go unrecognized. Although some cases are asymptomatic, others are undiagnosed because the patient or the health-care provider fails to recognize the implications of mild or nonspecific symptoms or signs (e.g., abnormal bleeding, dyspareunia, or vaginal discharge {atypical PID}). Because of the difficulty of diagnosis and the potential for damage to the reproductive health of women even by apparently mild or atypical PID, health-care providers should maintain a low threshold for the diagnosis of PID. Even so, the long-term outcome of early treatment of women with asymptomatic or atypical PID is unknown. The following recommendations for diagnosing PID are intended to help health-care providers recognize when PID should be suspected and when they need to obtain additional information to increase diagnostic certainty. These recommendations are based partially on the fact that 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 of PID should be initiated in sexually active young women and others at risk for STDs if all the following minimum criteria are present and no other cause(s) for the illness can be identified:
Lower abdominal tenderness,
Adnexal tenderness, and
Cervical motion tenderness.
More elaborate diagnostic evaluation often is needed, because incorrect diagnosis and management might cause unnecessary morbidity. These additional criteria may be used to enhance the specificity of the minimum criteria listed previously. Additional criteria that support a diagnosis of PID include the following:
Oral temperature greater than 101 F (greater than 38.3 C),
Abnormal cervical or vaginal discharge,
Elevated erythrocyte sedimentation rate,
Elevated C-reactive protein, and
Laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis.
The definitive criteria for diagnosing PID, which are warranted in selected cases, include the following:
Histopathologic evidence of endometritis on endometrial biopsy,
Transvaginal sonography or other imaging techniques showing thickened fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex, and
Laparoscopic abnormalities consistent with PID.
Although treatment can be initiated before bacteriologic diagnosis of C. trachomatis or N. gonorrhoeae infection, such a diagnosis emphasizes the need to treat sex partners.
Treatment
PID treatment regimens must provide empiric, broad-spectrum coverage of likely pathogens. Antimicrobial coverage should include N. gonorrhoeae, C. trachomatis, anaerobes, Gram-negative facultative bacteria, and streptococci. Although several antimicrobial regimens have been effective in achieving a clinical and microbiologic cure in randomized clinical trials with short-term follow-up, few investigations have a) assessed and compared these regimens with regard to elimination of infection in the endometrium and fallopian tubes or b) determined the incidence of long-term complications (e.g., tubal infertility and ectopic pregnancy).
All regimens should be effective against N. gonorrhoeae and C. trachomatis, because negative endocervical screening does not preclude upper-reproductive tract infection. Although the need to eradicate anaerobes from women who have PID has not been determined definitively, the evidence suggests that this may be important. Anaerobic bacteria have been isolated from the upper-reproductive tract of women who have PID, and data from in vitro studies have revealed that anaerobes such as Bacteroides fragilis can cause tubal and epithelial destruction. In addition, BV also is diagnosed in many women who have PID. Until treatment regimens that do not adequately cover these microbes have been shown to prevent sequelae as well as the regimens that are effective against these microbes, the recommended regimens should have anaerobic coverage. Treatment should be initiated as soon as the presumptive diagnosis has been made, because prevention of long-term sequelae has been linked directly with immediate administration of appropriate antibiotics. When selecting a treatment regimen, health-care providers should consider availability, cost, patient acceptance, and antimicrobial susceptibility.
In the past, many experts recommended that all patients who had PID be hospitalized so that bed rest and supervised treatment with parenteral antibiotics could be initiated. However, hospitalization is no longer synonymous with parenteral therapy. No currently available data compare the efficacy of parenteral with oral therapy or inpatient with outpatient treatment settings. Until the results from ongoing trials comparing parenteral inpatient therapy with oral outpatient therapy for women who have mild PID are available, such decisions must be based on observational data and consensus opinion. The decision of whether hospitalization is necessary should be based on the discretion of the health-care provider.
The following criteria for HOSPITALIZATION are based on observational data and theoretical concerns:
Surgical emergencies such as appendicitis cannot be excluded;
The patient is pregnant;
The patient does not respond clinically to oral antimicrobial therapy;
The patient is unable to follow or tolerate an outpatient oral regimen;
The patient has severe illness, nausea and vomiting, or high fever;
The patient has a tubo-ovarian abscess; or
The patient is immunodeficient (i.e., has HIV infection with low CD4 counts, is taking immunosuppressive therapy, or has another disease).
Most clinicians favor at least 24 hours of direct inpatient observation for patients who have tubo-ovarian abscesses, after which time home parenteral therapy should be adequate.
There are no efficacy data comparing parenteral with oral regimens. Experts have extensive experience with both of the following regimens. Also, there are multiple randomized trials demonstrating the efficacy of each regimen. Although most trials have used parenteral treatment for at least 48 hours after the patient demonstrates substantial clinical improvement, this is an arbitrary designation. Clinical experience should guide decisions regarding transition to oral therapy, which may be accomplished within 24 hours of clinical improvement.
Parenteral Regimen A
Cefotetan 2 g IV every 12 hours,
OR
Cefoxitin 2 g IV every 6 hours,
PLUS
Doxycycline 100 mg IV or orally every 12 hours.
NOTE: Because of pain associated with infusion, doxycycline should be administered orally when possible, even when the patient is hospitalized. Both oral and IV administration of doxycycline provide similar bioavailability. In the event that IV administration is necessary, use of lidocaine or other short-acting local anesthetic, heparin, or steroids with a steel needle or extension of the infusion time may reduce infusion complications. Parenteral therapy may be discontinued 24 hours after a patient improves clinically, and oral therapy with doxycycline (100 mg twice a day) should continue for a total of 14 days. When tubo-ovarian abscess is present, many health-care providers use clindamycin or metronidazole with doxycycline for continued therapy rather than doxycycline alone, because it provides more effective anaerobic coverage.
Clinical data are limited regarding the use of other second- or third-generation cephalosporins (e.g., ceftizoxime, cefotaxime, and ceftriaxone), which also might be effective therapy for PID and might replace cefotetan or cefoxitin. However, they are less active than cefotetan or cefoxitin against anaerobic bacteria.
Parenteral Regimen B
Clindamycin 900 mg IV every 8 hours,
PLUS
Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing may be substituted.
NOTE: Although use of a single daily dose of gentamicin has not been evaluated for the treatment of PID, it is efficacious in other analogous situations. Parenteral therapy may be discontinued 24 hours after a patient improves clinically, and continuing oral therapy should consist of doxycycline 100 mg orally twice a day or clindamycin 450 mg orally four times a day to complete a total of 14 days of therapy. When tubo-ovarian abscess is present, many health-care providers use clindamycin for continued therapy rather than doxycycline, because clindamycin provides more effective anaerobic coverage.
Alternative Parenteral Regimens
Limited data support the use of other parenteral regimens, but the following three regimens have been investigated in at least one clinical trial, and they have broad spectrum coverage.
Ofloxacin 400 mg IV every 12 hours,
PLUS
Metronidazole 500 mg IV every 8 hours.
OR
Ampicillin/Sulbactam 3 g IV every 6 hours,
PLUS
Doxycycline 100 mg IV or orally every 12 hours.
OR
Ciprofloxacin 200 mg IV every 12 hours,
PLUS
Doxycycline 100 mg IV or orally every 12 hours,
PLUS
Metronidazole 500 mg IV every 8 hours.
Ampicillin/sulbactam plus doxycycline has good coverage against C. trachomatis, N. gonorrhoeae, and anaerobes and appears to be effective for patients who have tubo-ovarian abscess. Both IV ofloxacin and ciprofloxacin have been investigated as single agents. Because ciprofloxacin has poor coverage against C. trachomatis, it is recommended that doxycycline be added routinely. Because of concerns regarding the anaerobic coverage of both quinolones, metronidazole should be included with each regimen.
Oral Treatment
As with parenteral regimens, clinical trials of outpatient regimens have provided minimal information regarding intermediate and long-term outcomes. The following regimens provide coverage against the frequent etiologic agents of PID, but evidence from clinical trials supporting their use is limited. Patients who do not respond to oral therapy within 72 hours should be reevaluated to confirm the diagnosis and be administered parenteral therapy on either an outpatient or inpatient basis.
Regimen A
Ofloxacin 400 mg orally twice a day for 14 days,
PLUS
Metronidazole 500 mg orally twice a day for 14 days.
Oral ofloxacin has been investigated as a single agent in two well-designed clinical trials, and it is effective against both N. gonorrhoeae and C. trachomatis. Despite the results of these trials, ofloxacin's lack of anaerobic coverage is a concern; the addition of metronidazole provides this coverage.
Regimen B
Ceftriaxone 250 mg IM once,
OR
Cefoxitin 2 g IM plus Probenecid 1 g orally in a single dose concurrently once,
OR
Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime),
PLUS
Doxycycline 100 mg orally twice a day for 14 days. (Include this regimen with one of the above regimens.)
The optimal choice of a cephalosporin for Regimen B is unclear; although cefoxitin has better anaerobic coverage, ceftriaxone has better coverage against N. gonorrhoeae. Clinical trials have demonstrated that a single dose of cefoxitin is effective in obtaining short-term clinical response in women who have PID; however, the theoretical limitations in its coverage of anaerobes may require the addition of metronidazole. The metronidazole also will effectively treat BV, which also is frequently associated with PID. No data have been published regarding the use of oral cephalosporins for the treatment of PID.
Alternative Oral Regimens
Information regarding other outpatient regimens is limited, but one other regimen has undergone at least one clinical trial and has broad spectrum coverage. Amoxicillin/clavulanic acid plus doxycycline was effective in obtaining short-term clinical response in a single clinical trial; however, gastrointestinal symptoms might limit the overall success of this regimen. Several recent investigations have evaluated the use of azithromycin in the treatment of upper-reproductive tract infections; however, the data are insufficient to recommend this agent as a component of any of the treatment regimens for PID.
Follow-Up
Patients receiving oral or parenteral therapy 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 demonstrate improvement within this time period usually require additional diagnostic tests, surgical intervention, or both.
If the health-care provider prescribes outpatient oral or parenteral therapy, a follow-up examination should be performed within 72 hours, using the criteria for clinical improvement described previously. Some experts also recommend rescreening for C. trachomatis and N. gonorrhoeae 4-6 weeks after therapy is completed. If PCR or LCR is used to document a test of cure, rescreening should be delayed for 1 month after completion of therapy.
Management of Sex Partners
Sex partners of patients who have PID should be examined and treated if they had sexual contact with the patient during the 60 days preceding onset of symptoms in the patient. The evaluation and treatment are imperative because of the risk for reinfection 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 often are asymptomatic.
Sex partners should be treated empirically with regimens effective against both of these infections, regardless of the apparent etiology of PID or pathogens isolated from the infected woman.
Even in clinical settings in which only women are treated, special arrangements should be made to provide care for male sex partners of women who have PID. When this is not feasible, health-care providers should ensure that sex partners are referred for appropriate treatment.
Special Considerations
Pregnancy
Because of the high risk for maternal morbidity, fetal wastage, 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 early observational studies, HIV-infected women with PID were more likely to require surgical intervention. In a subsequent and more comprehensive observational study, HIV-infected women who had PID had more severe symptoms than HIV-negative women but responded equally well to standard parenteral antibiotic regimens. In another study, the microbiologic findings for HIV-infected and HIV-negative women were similar, except for higher rates of concomitant Candida and HPV infections and HPV-related cytologic abnormalities among HIV-infected women. Immunosuppressed HIV-infected women who have PID should be managed aggressively using one of the parenteral antimicrobial regimens recommended in this report.
