INTRODUCTION — Pelvic inflammatory disease (PID) refers to acute infection of the upper genital tract structures in females, 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 "Pelvic inflammatory disease: Clinical manifestations and diagnosis".)
The treatment of PID will be reviewed here. The pathogenesis of, risk factors for, and sequelae following PID are discussed separately. The management of tubo-ovarian abscess is discussed separately. (See "Pelvic inflammatory disease: Pathogenesis, microbiology, and risk factors" and "Long-term complications of pelvic inflammatory disease" and "Management and complications of tubo-ovarian abscess".)
MICROBIOLOGIC CONSIDERATIONS — Acute pelvic inflammatory disease (PID) is an ascending polymicrobial infection caused by cervical microorganisms (including Chlamydia trachomatis and Neisseria gonorrhoeae, and potentially Mycoplasma genitalium), as well as the vaginal microflora, including anaerobic organisms, enteric gram-negative rods, streptococci, genital mycoplasmas, and Gardnerella vaginalis, which is associated with bacterial vaginosis . Treatment of PID generally requires broad antimicrobial coverage, particularly among those with severe disease requiring hospitalization. (See "Pelvic inflammatory disease: Pathogenesis, microbiology, and risk factors", section on 'Microbiology' and 'Antibiotic selection' below.)
Chlamydia and gonorrhea — PID is primarily a disease of sexually active females. The two most important sexually transmitted organisms associated with acute PID, C. trachomatis and N. gonorrhoeae, should be the main targets for treatment. Even if endocervical testing is not positive for either of these pathogens, they should still be covered, as upper tract infection cannot be ruled out .
Drug resistance is an ongoing challenge in the therapy of gonococcal infections. As an example, the prevalence of fluoroquinolone resistance in N. gonorrhoeae reaches nearly 100 percent in some regions, and these agents are no longer recommended for treatment of N. gonorrhoeae infections. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Antibiotic resistance'.)
Anaerobic bacteria — Anaerobic bacteria, in particular organisms associated with bacterial vaginosis, are frequently recovered from the upper genital tract of females with acute PID [3,4]. Whether antibiotic therapy for PID should routinely include anaerobic coverage has been controversial [2,5]. However, based on accumulating evidence, we favor including anaerobic coverage in treatment regimens for PID, including mild to moderate PID that is treated in the outpatient setting . This approach is consistent with guidelines from the United States Centers for Disease Control and Prevention  and the European Sexually Transmitted Infections Guidelines Editorial Board . (See 'Antibiotic selection' below and 'Outpatient therapy' below.)
Although several studies of females with PID have demonstrated the presence of anaerobes in the genital tract at initial presentation, several regimens without dedicated anaerobic coverage (eg, ceftriaxone plus doxycycline) result in excellent clinical cure rates among females with mild to moderate PID [5,8]. However, there may be benefits to anaerobic coverage beyond short-term clinical response:
●In one trial of 233 females with mild to moderate PID who were randomly assigned to receive ceftriaxone (single dose) and doxycycline for 14 days with either metronidazole (500 mg twice daily) or placebo for 14 days, clinical improvement rates at three days were similar in the two groups (82.8 versus 80.3 percent, respectively) . However, at 30 days, females in the metronidazole group had a lower rate of pelvic tenderness (9 versus 20 percent); there was also a trend toward higher 30-day clinical cure rates with metronidazole (96 versus 90 percent), but this was not statistically significant. Females who received metronidazole were less likely to have bacterial vaginosis (21 versus 54 percent), and there was a nonsignificant trend toward fewer T. vaginalis infections as well (5 versus 12 percent). Metronidazole was also associated with lower rates of isolating anaerobic bacteria from endometrium at 30 days, although the clinical significance of this finding is uncertain.
There has been concern that the additional gastrointestinal side effects of anaerobic therapy (eg, metronidazole) would result in nonadherence and inadequately treated PID. However, in the trial described above, rates of adherence were similar with regimens with and without metronidazole .
M. genitalium — M. genitalium infection has been associated with symptomatic PID. However, we do not suggest including targeted M. genitalium coverage in empiric PID regimens. Recommended treatment regimens are not highly effective against M. genitalium, yet clinical response rates are high.
There are no data on the benefits of screening and treating females with acute PID for M. genitalium, and there is no consensus on whether PID treatment regimens should include coverage for this organism. (See "Mycoplasma genitalium infection in males and females".)
THRESHOLD FOR TREATMENT — Clinicians should maintain a low threshold of suspicion for the diagnosis and treatment of PID. The presumptive clinical diagnosis of PID is made in sexually active young women or women at risk for sexually transmitted infections (STIs) who present with pelvic or lower abdominal pain and have evidence of cervical motion, uterine, or adnexal tenderness on exam . Occasionally, acute PID can occur in females without recent sexual activity. Treatment is indicated for patients with this presumptive clinical diagnosis of PID, even if findings are subtle or minimal, since the risk of long-term complications is higher if treatment is withheld or delayed [1,2].
The evaluation and diagnosis of PID is discussed in detail elsewhere. (See "Pelvic inflammatory disease: Clinical manifestations and diagnosis", section on 'Evaluation' and "Pelvic inflammatory disease: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
Evaluation for and diagnosis of tubo-ovarian abscess, a complication of PID, is also discussed in detail elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of tubo-ovarian abscess", section on 'Evaluation of patients with suspected TOA'.)
INDICATIONS FOR HOSPITALIZATION — Most females with PID can be safely treated in outpatient settings. Indications for hospitalization and parenteral antibiotics include :
●Severe clinical illness (eg, fever ≥38.5°C [101°F], nausea and vomiting)
●Complicated PID with pelvic abscess (including tubo-ovarian abscess) (see "Epidemiology, clinical manifestations, and diagnosis of tubo-ovarian abscess", section on 'Diagnosis')
●Possible need for invasive diagnostic evaluation for alternate etiology (eg, appendicitis or ovarian torsion) or surgical intervention for suspected ruptured tubo-ovarian abscess
●Inability to take oral medications
●Lack of response or tolerance to oral medications
●Concern for nonadherence to therapy
There has been a trend towards outpatient treatment of PID, with only the minority of females being hospitalized [9,10]. Support for outpatient therapy for mild or moderate PID comes from the Pelvic Inflammatory Disease Evaluation Clinical Health trial (ie, PEACH trial) . In that trial, 831 females with lower abdominal pain, uterine or adnexal tenderness, and mucopurulent cervicitis or untreated gonococcal or chlamydial infection were randomly assigned to inpatient therapy with intravenous cefoxitin for at least 48 hours plus doxycycline or outpatient therapy with a single intramuscular dose of cefoxitin with probenecid plus doxycycline. Short-term clinical and microbiologic outcomes and long-term reproductive outcomes (eg, ectopic pregnancy, chronic pelvic pain) were similar between the two groups.
There are no clinical data to suggest that older age or HIV infection should be considered criteria for hospitalization [2,12].
ANTIBIOTIC SELECTION — Antibiotic therapy is the cornerstone of pelvic inflammatory disease (PID) treatment. The therapeutic regimens for PID should provide broad empiric coverage for the wide array of implicated pathogens, although the optimal treatment regimen remains undefined [13-16]. Regimen options depend on whether the patient is initially hospitalized or managed as an outpatient, which generally depends on the severity of infection (algorithm 1) (see 'Indications for hospitalization' above). The selection of a regimen additionally takes into account cost, convenience of administration, safety, formulary availability, and allergy history. (See 'Hospitalized patients' below and 'Outpatient therapy' below.)
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 [13,17,18]. However, the available clinical data have limitations. Some studies did not use objective criteria to define PID, some have evaluated subjective pain outcomes without blinding of investigators, and few randomized trials have long-term data on outcomes, such as risk of infertility, ectopic pregnancy, and chronic pelvic pain following treatment.
Evaluation of regimen efficacy is also hampered by the inability to distinguish between relapse versus reinfection. As an example, 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 females had evidence of at least one of these infections at baseline; by 30 days after treatment, approximately 3 percent still had evidence of either infection, but whether this reflected relapse (and thus treatment failure) or new infection is uncertain .
Initial parenteral therapy — Initial therapy consists of a combination parenteral regimen that provides antimicrobial coverage against a wide range of bacteria, including C. trachomatis, N. gonorrhoeae, streptococci, gram-negative enteric bacilli (Escherichia coli, Klebsiella spp, and Proteus spp), and anaerobic organisms (ie, bacterial vaginosis-associated flora) (algorithm 1).
We suggest one of the following regimens, which are consistent with first-line regimens recommended by the United States Centers for Disease Control and Prevention (CDC) :
●Ceftriaxone (1 g intravenously every 24 hours) plus doxycycline (100 mg orally or intravenously every 12 hours) plus metronidazole (500 mg orally or intravenously every 12 hours)
●Cefoxitin (2 g intravenously every six hours) plus doxycycline (100 mg orally or intravenously every 12 hours)
●Cefotetan (2 g intravenously every 12 hours) plus doxycycline (100 mg orally or intravenously every 12 hours)
Oral administration of doxycycline is generally preferred, if the patient can tolerate it, because of the pain associated with intravenous drug administration. The bioavailabilities of the oral and parenteral formulations are equivalent for both doxycycline and metronidazole.
Combination regimens that include a cephalosporin and doxycycline have been shown in several trials to result in short-term clinical cure rates of more than 80 to 90 percent of cases [17,18]. They have excellent in vitro activity against N. gonorrhoeae and C. trachomatis [2,19]. Cefoxitin and cefotetan have intrinsic anaerobic activity; metronidazole is added to the ceftriaxone-based regimen to provide anaerobic activity. (See 'Anaerobic bacteria' above.)
Alternative regimens have more limited clinical data to support their use for hospitalized patients or have other drawbacks. We do not routinely use them for patients with PID, but it is reasonable to use them in case of allergy to or unavailability of the preferred regimens:
●Clindamycin (900 mg intravenously every eight hours) plus gentamicin (3 to 5 mg/kg intravenously daily or 2 mg/kg intravenously once followed by 1.5 mg/kg every eight hours). In a meta-analysis of 10 studies comparing a cephalosporin (usually in combination with doxycycline) with clindamycin plus gentamicin for severe PID, short-term clinical and microbiologic cure were similar with each regimen . However, this regimen may be associated with a higher risk of toxicity than preferred regimens. In vitro activity against N. gonorrhoeae and C. trachomatis is moderate . (See "Dosing and administration of parenteral aminoglycosides", section on 'Gentamicin and tobramycin dosing in adults'.)
●Ampicillin-sulbactam (3 g intravenously every six hours) plus doxycycline (100 mg twice daily). This regimen has activity against N. gonorrhoeae, C. trachomatis, and anaerobes. Clinical data to support its use are limited. In one trial of 103 females hospitalized with PID, the regimen resulted in a similar clinical cure rate as cefoxitin plus doxycycline regimen (86 versus 89 percent) .
●Azithromycin (500 mg intravenously daily for one to two days followed by 250 mg orally daily to complete a seven-day course) plus metronidazole (500 mg twice daily for 14 days). This dose of azithromycin, with or without metronidazole, resulted in similarly high clinical and microbiologic cure rates (>95 percent) for mild to moderate PID compared with a combination beta-lactam and doxycycline regimen . However, the regimen has not been evaluated in patients with severe PID, and it should only be considered when N. gonorrhoeae infection has been excluded or is unlikely because it does not provide coverage against that pathogen. When using azithromycin for PID, we favor adding metronidazole for anaerobic coverage. (See 'Anaerobic bacteria' above.)
Transition to oral therapy — Patients can usually be transitioned from parenteral to oral therapy after 24 to 48 hours of sustained clinical improvement, as reflected by resolution of fever, nausea, vomiting, and severe abdominal pain, if initially present (algorithm 1) .
Oral therapy consists of doxycycline 100 mg twice daily and metronidazole 500 mg twice daily to complete a 14-day course. This regimen is also appropriate for females whose PID was complicated by pelvic abscess and females with documented Trichomonas vaginalis infection or bacterial vaginosis because it provides coverage for anaerobic bacteria. (See 'Anaerobic bacteria' above.)
For those who cannot tolerate doxycycline, azithromycin (500 mg for one to two days followed by 250 mg once daily to complete a 14-day course) is an alternative; for those who cannot tolerate metronidazole, clindamycin 450 mg orally every six hours is an alternative. (See 'Anaerobic bacteria' above.)
Additional management considerations, including other potential antibiotic regimens, for females with a tubo-ovarian abscess are discussed elsewhere. (See "Management and complications of tubo-ovarian abscess", section on 'Clinical approach'.)
Outpatient therapy — For females with mild to moderate PID who can tolerate oral medications and are expected to reasonably adhere to therapy, we suggest the following regimen (algorithm 1) :
●A single intramuscular dose of a long-acting cephalosporin plus doxycycline (100 mg orally twice daily for 14 days) plus metronidazole (500 mg orally twice daily for 14 days)
The optimal choice of a cephalosporin is uncertain. We prefer ceftriaxone (500 mg for individuals <150 kg or 1 g for individuals ≥150 kg, intramuscularly in a single dose) to use in combination with doxycycline and metronidazole, as it is the recommended cephalosporin for coverage of gonorrhea. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on '"High" dose intramuscular (IM) ceftriaxone'.)
Other appropriate cephalosporins to use with doxycycline and metronidazole include cefoxitin (2 g intramuscularly) with probenecid (1 g orally), cefotaxime (1 g intramuscularly), and ceftizoxime (1 g intramuscularly). Cephalosporin-based regimens result in clinical and microbiologic cure rates of approximately 90 percent or higher [17,18]. The approach to patients with allergies that potentially preclude cephalosporin administration is discussed elsewhere. (See 'Penicillin-allergic patients' below.)
We favor the routine addition of metronidazole for coverage of anaerobic organisms based on evidence of improved longer-term outcomes compared with regimens without anaerobic coverage. (See 'Anaerobic bacteria' above.)
An alternative to doxycycline is azithromycin (either 500 mg daily for one to two days then 250 mg orally for a 14-day course or 1 g once per week for two weeks), to be given with the single cephalosporin dose and metronidazole. Small clinical trials suggest clinical efficacy , although data on microbiologic cures are not available, and azithromycin results in lower microbiologic cure rates for C. trachomatis in some anatomic locations compared with doxycycline. (See "Treatment of Chlamydia trachomatis infection", section on 'Doxycycline as preferred agent'.)
Directed therapy and duration — The empirically chosen antibiotic regimen is generally continued for the duration of the course. The therapy should not be modified or cut short if N. gonorrhoeae or C. trachomatis is not identified in clinical specimens.
The optimal duration of therapy is unknown. We treat for a total of 14 days. Most studies have used this duration of therapy, and it is standard in other guidelines [2,7]. Shorter courses of therapy have not been explored, mainly related to concerns regarding eradication of C. trachomatis in the setting of upper tract disease .
ADJUNCTIVE CARE — Patients who are hospitalized for severe or complicated pelvic inflammatory disease (PID) may also warrant volume repletion, particularly if nausea/vomiting prevents oral intake. Other supportive measures include antiemetic, analgesic, and antipyretic medications.
Surgical interventions are usually reserved for patients with tubo-ovarian abscesses that are associated with sepsis, are large, or do not improve with medical therapy. This is discussed in detail elsewhere. (See "Management and complications of tubo-ovarian abscess", section on 'Clinical approach'.)
Medication adherence — Compliance with a long course of oral antibiotics can be problematic . Patients should be educated about the importance of medication adherence and clinical outcomes.
Sexual activity — Females with pelvic inflammatory disease (PID) should be counseled to refrain from sexual activity until they have completed therapy, their symptoms have resolved, and sex partners have been evaluated and/or treated for potential sexually transmitted infections (STIs) (see 'Management of sex partners' below). Clinicians should also counsel patients regarding the route of acquisition for STIs and future safe sex practices. (See "Prevention of sexually transmitted infections", section on 'Prevention counseling' and "Prevention of sexually transmitted infections", section on 'Male condom use'.)
Screening and prevention of STIs — All patients diagnosed with acute PID should be screened for other important STIs, including HIV and syphilis. (See "Screening for sexually transmitted infections".)
They should also be evaluated for indications for vaccinations to prevent other STIs, including:
●Hepatitis B vaccination for those who have no evidence of immunity to hepatitis B virus (eg, through vaccination history or serologic testing). (See "Hepatitis B virus immunization in adults".)
●Human papillomavirus vaccination for those within the appropriate age range if they have not previously been vaccinated. (See "Human papillomavirus vaccination".)
Management of sex partners — Male sex partners of females with PID should be examined and treated if they had sexual contact with the patient during the 60 days prior to the patient's onset of symptoms, regardless of the woman's STI test results. Evaluation and treatment of the sex partner is essential to decrease the risk of reinfection. Regimens should include antibiotics with activity against N. gonorrhoeae and C. trachomatis; these regimens are discussed elsewhere. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Initial treatment of urogenital infection'.)
Expedited partner therapy, in which treatment of sex partners is facilitated by prescribing antibiotics for the partner without direct evaluation, is discussed elsewhere. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Management of sexual partners'.)
FOLLOW-UP — Close follow-up is essential. 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) .
Those who have no clinical improvement after this period warrant further diagnostic evaluation for complications (eg, pelvic abscesses) or for alternate diagnoses. Patients initially treated as outpatients warrant hospitalization and parenteral therapy. For those who were already on parenteral therapy, the initial regimen should be evaluated to ensure that it provided appropriate coverage (eg, for N. gonorrhoeae and anaerobes), and it should be adjusted if not. (See 'Initial parenteral therapy' above and "Pelvic inflammatory disease: Clinical manifestations and diagnosis", section on 'Additional evaluation for diagnostic uncertainty'.)
For females who had documented C. trachomatis or N. gonorrhoeae infection, additional follow-up, including retesting, is discussed elsewhere. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Patient follow-up' and "Treatment of Chlamydia trachomatis infection", section on 'Follow-up testing'.)
Assess whether cephalosporin can be used — For patients with penicillin allergies, our approach depends on the type and severity of the allergy and the risk for gonococcal infection. Most patients with a penicillin allergy can still receive a cephalosporin.
●Patients with a penicillin allergy that was mild and had no features of an IgE-mediated reaction (eg, a maculopapular or morbilliform rash without angioedema, respiratory symptoms, or hypotension) can receive a third-generation cephalosporin (eg, ceftriaxone) normally (algorithm 2). If needed, they can receive a second-generation cephalosporin (eg, cefoxitin or cefotetan) with a test dose procedure.
●Patients with a penicillin allergy that did have features of an IgE-mediated reaction (eg, anaphylaxis or angioedema) can receive a third-generation cephalosporin (eg, ceftriaxone) with a test dose procedure (algorithm 2).
A test dose procedure consists of giving one-tenth of the full dose (either intramuscularly or intravenously) and observing the patient for 30 to 60 minutes. If no reaction develops, the remainder of the dose can be given with continued observation for another hour. (See "Choice of antibiotics in penicillin-allergic hospitalized patients", section on 'Test dose procedure (graded challenge)'.)
For patients who receive a cephalosporin for PID treatment, it should be administered with doxycycline and metronidazole. (See 'Initial parenteral therapy' above and 'Outpatient therapy' above.)
If the beta-lactam allergy precludes cephalosporin use (eg, Stevens-Johnson Syndrome), patients who warrant hospitalization can receive clindamycin and gentamicin, as outlined above. (See 'Hospitalized patients' above.)
For outpatients who cannot use a cephalosporin, the management options depend on the risk for gonorrhea, as outlined below.
For outpatients who cannot receive cephalosporins — For those who cannot use a cephalosporin, options for outpatient therapy are limited. The main outpatient alternative is a fluoroquinolone-containing regimen. However, while certain fluoroquinolones have activity against C. trachomatis, high rates of fluoroquinolone resistance among N. gonorrhoeae isolates limit the utility of such regimens for PID. Thus, the approach to empiric management in this setting depends on the risk for fluoroquinolone-resistant N. gonorrhoeae (information on the community prevalence of resistance may be obtained from the local department of public health):
●High risk of resistant gonorrhea – For females with PID in a region where the prevalence of fluoroquinolone resistance in N. gonorrhoeae is ≥5 percent, we suggest hospitalization for treatment with clindamycin (900 mg intravenously every 8 hours) plus gentamicin (3 to 5 mg/kg intravenously once daily) until clinical improvement, at which point the regimen can be transitioned to oral therapy. (See 'Transition to oral therapy' above.)
If there are major barriers to intravenous antibiotics, other alternative regimens for gonorrhea can be substituted into the outpatient therapy regimens for PID (eg, gentamicin 240 mg intramuscularly once plus azithromycin 2 g orally once in addition to metronidazole); however, there are no data to inform PID outcomes with these regimens. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Alternate regimens'.)
In such individuals, we submit cervical specimens for culture for N. gonorrhoeae and request that susceptibility testing be performed on any isolate. If the patient has persistent symptoms, an infectious diseases consultation should be obtained. If retreatment is appropriate, potential options include desensitization to a cephalosporin or alternative regimens based on susceptibility testing. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Monitoring for and managing treatment failure'.)
●Low risk of resistant gonorrhea – For females who have a low risk of fluoroquinolone-resistant N. gonorrhoeae (ie, infection acquired in a region where the prevalence is <5 percent, postmenopausal females who develop PID following uterine instrumentation), a fluoroquinolone-containing regimen can be used. This consists of either the combination of levofloxacin 500 mg orally once daily plus metronidazole 500 mg orally twice daily or monotherapy with moxifloxacin 400 mg orally once daily; each regimen is given for 14 days.
Prior to use of a fluoroquinolone-containing regimen, we submit cervical specimens for culture for N. gonorrhoeae and request that susceptibility testing be performed on any isolate. If testing confirms susceptibility to fluoroquinolones, the fluoroquinolone-containing regimen can be continued. If a fluoroquinolone-resistant isolate is identified, an infectious diseases consultation should be obtained. Potential treatment options include desensitization to a cephalosporin or alternative regimens based on susceptibility testing. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Monitoring for and managing treatment failure'.)
In the absence of resistance, fluoroquinolones are clinically effective against PID. In a meta-analysis of randomized trials, there was no evidence of a clear difference in clinical cure for PID of any severity with fluoroquinolones compared with cephalosporin-based regimens or clindamycin plus an aminoglycoside, but the included trials were conducted prior to the increased prevalence of fluoroquinolone-resistant gonorrhea .
In situations in which N. gonorrhoeae has been excluded (ie, known negative NAAT) and the patient cannot receive a cephalosporin or a fluoroquinolone, an alternative regimen is azithromycin (500 mg orally daily for one to two days followed by 250 mg daily or 1 g orally once per week for two weeks) with metronidazole (500 mg orally twice daily) for a total of 14 days .
Molecular tests that can identify mutations associated with fluoroquinolone resistance in N. gonorrhoeae can help streamline this approach by identifying individuals who have susceptible infection and could thus use a fluoroquinolone; however, these tests are not widely available. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on 'Fluoroquinolones'.)
Females with IUDs — Intrauterine devices (IUDs) do not appear to be associated with an increased risk of PID . Removal of an IUD in a woman who develops PID is not necessary. However, she should be followed closely, as with all females with PID, and removal may be warranted if she does not clinically improve with antibiotic therapy. This is discussed in detail elsewhere. (See "Intrauterine contraception: Management of side effects and complications", section on 'Infection and/or pelvic inflammatory disease'.)
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 . 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 once (instead of doxycycline). (See 'Initial parenteral therapy' above.)
Patients with HIV — Females with HIV appear to respond to therapy for PID as well as females without HIV . Therefore, recommended antibiotic regimens for acute PID in patients with HIV are the same as those for the general population.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sexually transmitted infections".)
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 5th to 6th 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 10th to 12th 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 education: Pelvic inflammatory disease (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Indications for treatment – The presumptive clinical diagnosis of pelvic inflammatory disease (PID) is made in sexually active young women or women at risk for sexually transmitted infections (STIs) who present with pelvic or lower abdominal pain and have evidence of cervical motion, uterine, or adnexal tenderness on exam. Treatment is indicated for patients with this presumptive clinical diagnosis of PID, even if findings are subtle or minimal, since the risk of long-term complications is higher if treatment is withheld or delayed. (See 'Threshold for treatment' above.)
●Targeted pathogens – Treatment of PID consists of 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, including anaerobic organisms. Although Mycoplasma genitalium is associated with PID, routine testing for or empiric therapy of that organism is not clearly necessary. (See 'Microbiologic considerations' above.)
●Indications for hospitalization – These include (see 'Indications for hospitalization' above):
•Severe clinical illness (eg, high fever, nausea/vomiting preventing oral intake, severe abdominal pain)
•Suspected pelvic abscess
•A possible alternative diagnosis that could warrant surgery (eg, appendicitis)
●Antibiotic regimens for hospitalized patients
•Initial parenteral therapy – For patients who are hospitalized for PID, we suggest initial parenteral therapy with a second-generation cephalosporin plus doxycycline (algorithm 1) (Grade 2B). We also suggest inclusion of anaerobic coverage (Grade 2C). Appropriate regimens include ceftriaxone (1 g intravenously every 24 hours) plus doxycycline plus metronidazole (500 mg twice daily); cefoxitin (2 g intravenously every six hours) plus doxycycline; and cefotetan (2 g intravenously every 12 hours) plus doxycycline. The doxycycline dose is 100 mg every 12 hours. (See 'Initial parenteral therapy' above.)
•Transition to oral antibiotics – The parenteral regimen can be transitioned to oral therapy after 24 to 48 hours of sustained clinical improvement. We suggest doxycycline 100 mg twice daily plus metronidazole (500 mg orally twice daily) to complete a 14-day course (Grade 2C). (See 'Transition to oral therapy' above.)
●Antibiotic regimens for outpatients – For patients with mild or moderate PID who are treated as outpatients, we suggest ceftriaxone as a single intramuscular dose (500 mg, or 1 g for individuals ≥150 kg) plus doxycycline (100 mg orally twice daily for 14 days) plus metronidazole (500 mg twice daily for 14 days) rather than other regimens (algorithm 1) (Grade 2C). This regimen provides coverage for C. trachomatis, N. gonorrhoeae, and anaerobic bacteria. (See 'Outpatient therapy' above.)
●Approach to penicillin allergies – Most penicillin allergies do not prelude cephalosporin use. In such cases, the same regimens as recommended for those without allergies can be used. For patients who cannot use a cephalosporin, our approach depends on their risk of fluoroquinolone-resistant N. gonorrhoeae. (See 'Penicillin-allergic patients' above.)
●Counseling – Patients should be counseled on the importance of medication adherence, refraining from sexual activity until treatment completion and symptom resolution, safe sex practices, and screening and prevention of other STIs. Male sexual contacts within the 60 days prior to the patient's onset of symptoms should be examined and/or treated to decrease the risk of reinfection. (See 'Counseling' above.)
●Follow-up – Close follow-up is essential. Patients receiving outpatient therapy should be evaluated for clinical improvement within 72 hours. Those who have not improved warrant hospitalization, parenteral therapy, and further workup. (See 'Follow-up' above.)
5 : Anaerobes in pelvic inflammatory disease: implications for the Centers for Disease Control and Prevention's guidelines for treatment of sexually transmitted diseases.
6 : A Randomized Controlled Trial of Ceftriaxone and Doxycycline, With or Without Metronidazole, for the Treatment of Acute Pelvic Inflammatory Disease.
8 : Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease in outpatients.
9 : Direct medical cost of pelvic inflammatory disease and its sequelae: decreasing, but still substantial.
11 : 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.
15 : Microbial causes of proven pelvic inflammatory disease and efficacy of clindamycin and tobramycin.
19 : Comparison of three regimens recommended by the Centers for Disease Control and Prevention for the treatment of women hospitalized with acute pelvic inflammatory disease.
20 : Randomized comparison of ampicillin-sulbactam to cefoxitin and doxycycline or clindamycin and gentamicin in the treatment of pelvic inflammatory disease or endometritis.
21 : 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.
22 : Pelvic inflammatory disease: findings during inpatient treatment of clinically severe, laparoscopy-documented disease.
23 : Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial.
25 : High failure rates in outpatient treatment of salpingitis with either tetracycline alone or penicillin/ampicillin combination.
26 : Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study.
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