pelvic inflammatory disease

INTRODUCTION  —

 Pelvic inflammatory disease (PID) refers to acute infection of the upper genital tract structures in women, involving any or all of the uterus, oviducts, and ovaries; this is often accompanied by involvement of the neighboring pelvic organs. Involvement of these structures results in endometritis, salpingitis, oophoritis, peritonitis, perihepatitis and tubo-ovarian abscess.

Sexually transmitted agents, such as Neisseria gonorrhoeae and Chlamydia trachomatis are often implicated, although vaginal flora may also play an important role . Post-operative pelvic cellulitis and abscess, pregnancy-related pelvic infection, and pelvic infection secondary to spread of another infection (appendicitis, diverticulitis, tumor, tuberculous peritonitis, actinomycosis, others) produce a very similar clinical picture, and indeed are referred to as PID by some. However, the etiologic differences among these processes have significant implications for treatment and prevention.

The last 30 years have witnessed an interesting, if circular, evolution of the clinical approach to the diagnosis of PID. Diagnostic procedures to document PID at one time replaced a primary clinical diagnosis. It is now appreciated that PID represents a spectrum of infection, that there is no single diagnostic gold standard, and that the practical value of clinical diagnosis retains central importance.

CLINICAL FEATURES  —

 The clinical diagnosis of PID is imprecise . Lower abdominal pain is the cardinal presenting symptom in women with PID although the character of the pain may be quite subtle. The recent onset of pain that worsens during coitus or with jarring movement may be the only presenting symptom of PID; the onset of pain during or shortly after menses is particularly suggestive . The abdominal pain is usually bilateral and rarely of more than two weeks' duration.

Abnormal uterine bleeding occurs in one-third or more of patients with PID . New vaginal discharge, urethritis, proctitis, fever, and chills can be associated signs but are neither sensitive nor specific for the diagnosis. The presence of PID is less likely if symptoms referable to the bowel or urinary tract predominate. While it is 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 .

Evaluation of the patient for risk factors for sexually transmitted disease and those that increase the probability of PID can be quite helpful. 

Risk factors for STD include:

• Age less than 25 years
• Young age at first sex
• Nonbarrier contraception
• New, multiple, or symptomatic sexual partners
• Oral contraception
• Cervical ectopy

Factors that potentially facilitate PID include:

• Previous episode of PID
• Sex during menses
• Vaginal douching
• Bacterial vaginosis
• Intrauterine device

On physical examination, only about one-half of patients with PID have fever. Abdominal examination reveals diffuse tenderness greatest in the lower quadrants, which may or may not be symmetrical. Rebound tenderness and decreased bowel sounds are common. Marked tenderness in the right upper quadrant does not exclude PID, since approximately 10 percent of these patients have perihepatitis (Fitz-Hugh Curtis syndrome). 

On pelvic examination, the finding of a purulent endocervical discharge and/or acute cervical motion and adnexal tenderness with bimanual examination is strongly suggestive of PID. Rectovaginal examination should reveal the uterus and adnexae to be the focus of tenderness. Other diagnoses should be considered if uterine and adnexal tenderness are not prominent. One study found that adnexal tenderness was the sign that correlated best with the finding of endometritis on endometrial biopsy . However, significant lateralization of adnexal tenderness is uncommon in PID. The presence of a palpable adnexal mass is equally likely to represent tuboovarian abscess complicating PID and other diseases processes in the differential diagnosis. 

Subclinical PID  —

 Lower genital tract infection with gonorrhea, chlamydia, or bacterial vaginosis is a risk factor for subclinical PID, defined histologically by the presence of neutrophils and plasma cells in endometrial tissue . Women with tubal factor infertility apparently induced by past episodes of PID often give no history of PID . As an example, in one study of 112 infertile women, 36 had adhesions or distal tube occlusion suggestive of PID by laparoscopy but only 11 had a history of this diagnosis . In addition, up to one-third of women without a history of PID harbor persistent Chlamydia trachomatis in the upper genital tract despite the absence of clinical findings except infertility .

Based upon these observations, it seems clear that subclinical PID severe enough to produce significant sequelae is common. Subclinical episodes are particularly common among oral contraceptive users . This was illustrated in a study in which 43 women with endometritis but no clinical signs of PID were four times more likely to have used oral contraceptives than 111 control patients with clinical PID and endometritis.

An indolent presentation of PID with low-grade fever, weight loss, and abdominal pain, has also been reported with actinomycosis. An association between an indwelling IUD and risk of actinomycosis has been suggested, although this relationship remains unclear.  

Perihepatitis  —

 Perihepatitis (Fitz-Hugh Curtis Syndrome) was first associated with gonococcal salpingitis in 1920  and subsequently with Chlamydia . It consists of infection of the liver capsule and peritoneal surfaces of the anterior right upper quadrant, with minimal stromal hepatic involvement. It manifests as a patchy purulent and fibrinous exudate in the acute phase ("violin string" adhesions), most prominently affecting the anterior surfaces of the liver (not the liver parenchyma). Thus, aminotransferases are also usually normal .

Symptoms are typically the sudden onset of severe right upper quadrant abdominal pain with a distinct pleuritic component, sometimes referred to the right shoulder. The severity of the pain in this location may mask the diagnosis of PID and lead to concerns regarding cholecystitis . Aminotransferases are abnormal in approximately one-half of patients with perihepatitis .

DIAGNOSTIC CONSIDERATIONS  —

 There are several important concepts about PID that must be appreciated:

• PID represents a spectrum of clinical disease, from endometritis to fatal intraabdominal sepsis.
• There are multiple gold standards in use to establish the diagnosis, because no one among them is adequate alone. Older studies defining PID by a single standard, such as laparoscopic visualization of gross salpingitis, are now felt to lack sensitivity .

The following discussion will review the tests that have been used to confirm the diagnosis of PID and diagnostic criteria that have been proposed. As will be seen, none of these tests is highly specific and sensitive. Thus, in many cases, clinicians must have a low threshold for considering the diagnosis and be prepared to initiate empiric antibiotic therapy.

Plasma cell endometritis  — Plasma cell endometritis (PCE) has been identified as an important component of PID . In one study of 45 women admitted for acute PID, PCE was documented in 26 (87 percent) of 30 women with gross salpingitis; four of five women with PCE and no salpingitis had positive tests for chlamydia and/or gonorrhea in the genital tract and were also felt to have PID. In addition, the density of the plasma cell infiltrate correlated with the clinical severity of disease.

Several other studies have confirmed these findings . In one report, endometritis was present in one-third of 44 patients with confirmed PID, four of whom had negative laparoscopic findings for salpingitis; the specificity of endometritis for the diagnosis of PID was 92 percent with a positive predictive value of 77 percent . PCE correlates closely with the follicular/proliferative phase of the menstrual cycle, the interval during which most cases of PID arise .

Other evidence, however, tempers enthusiasm for linking the finding of PCE with the diagnosis of PID. PCE occurs among asymptomatic women with no other evidence of PID (eg, in 42 percent of women with isolated bacterial vaginosis and 13 percent with no genital tract infection) . Furthermore, one study found a poor correlation between PCE and the clinical findings classically associated with PID . Whether PCE when found alone is representative of the subclinical cases of PID discussed above or is, in some cases, a benign finding remains to be elucidated.

Laparoscopy  — 

The diagnosis of PID had been almost exclusively a clinical one until a pivotal 1969 study in which laparoscopy was performed in 814 women with a clinical diagnosis of PID . The presence of PID was verified by laparoscopy in 532 patients and other disorders were diagnosed in 98; 184 patients were classified as normal because of a negative laparoscopy.

Almost a generation of physicians were trained to diagnose PID based upon clinical correlates derived from this study since laparoscopy was difficult to justify in all suspected cases of acute PID and was not always available . Subsequent studies from the 1990s found the sensitivity of laparoscopy to be as low as 50 percent with a specificity approaching 100 percent . Thus, laparoscopy has substantial value in confirming the diagnosis of PID but is not sensitive enough to be considered a diagnostic gold standard. We recommend laparoscopy for the following:

• A sick patient with high suspicion of a competing diagnosis (usually appendicitis, etc.)
• An acutely ill patient who has failed outpatient treatment for PID
• Any patient not clearly improving after approximately 72 hours of inpatient treatment for PID

Consent for laparotomy at the same procedure should be obtained in advance for these patients. We do not recommend endometrial biopsy for PCE at present unless the procedure is part of a protocol.

Diagnostic criteria and guidelines  —

 The index of suspicion for the clinical diagnosis of PID should be high, especially in adolescent women, even if they deny sexual activity. The current favored approach to the diagnosis of PID is multifaceted .

A minimal set of clinical criteria has been recommended by the CDC for empirical treatment of PID, including cervical motion tenderness or uterine or adnexal tenderness in the presence of lower abdominal or pelvic pain. The following additional criteria can also be used to support a clinical diagnosis of PID :

• Oral temperature >101° F (>38.3°C)
• Abnormal cervical or vaginal mucopurulent discharge
• Presence of abundant numbers of white blood cells (WBCs) on saline microscopy of vaginal secretions
• Elevated erythrocyte sedimentation rate
• Elevated C-reactive protein

Patients with pelvic pain and tenderness and any one or more of the following are currently considered "confirmed" cases:

• Acute or chronic (plasma cell) endometritis or acute salpingitis on histologic evaluation of a biopsy
• Demonstration of N. gonorrhoeae or C. trachomatis in the genital tract
• Gross salpingitis visualized at laparoscopy or laparotomy
• Isolation of pathogenic bacteria from a clean specimen from the upper genital tract
• Inflammatory/purulent pelvic peritoneal fluid without another source

The Centers for Disease Control and Prevention (CDC) also has issued guidelines for the "definitive" diagnosis of PID in symptomatic patients . One or more of the following three findings are required:

• Histologic evidence of endometritis in a biopsy
• An imaging technique revealing thickened fluid-filled tubes/oviducts with or without free pelvic fluid or tuboovarian complex
• Laparoscopic abnormalities consistent with PID (eg, tubal erythema, edema, adhesions; purulent exudate or cul-de-sac fluid; abnormal fibriae)

Standards for the diagnosis of subclinical PID, assuming that it exists, remain to be established.

DIFFERENTIAL DIAGNOSIS  — 

In addition to PID, the differential diagnosis of lower abdominal pain in a young woman includes the following conditions:

• Gastrointestinal: Appendicitis, cholecystitis, constipation, gastroenteritis, inflammatory bowel disease
• Renal: Cystitis, pyelonephritis, nephrolithiasis, urethritis
• Obstetric/Gynecologic: Dysmenorrhea, ectopic pregnancy, intrauterine pregnancy complication, ovarian cyst, ovarian torsion, ovarian tumor

In a woman with right upper quadrant pain related to Fitz-Hugh Curtis syndrome, aminotransferases are usually normal; in contrast, a patient with acute viral hepatitis would be expected to have significant abnormalities of aminotransferases .

DIAGNOSTIC TESTING  —

 Noninvasive diagnostic tests for PID include general laboratory studies looking for signs of inflammation, culture testing and microscopy of cervical or vaginal secretions, and imaging studies.

All patients who are diagnosed with acute PID should also be tested for HIV infection .

Laboratory tests  —

 Laboratory testing for patients suspected of PID always begins with a pregnancy test to rule out ectopic pregnancy and complications of an intrauterine pregnancy. Blood counts have limited value. Although PID is usually an acute process, less than half of PID patients exhibit leukocytosis . A hematocrit of less than 0.30 makes PID less likely, relative to hemorrhagic conditions such as ovulatory ovarian bleeding and ectopic pregnancy .

Gram stain and microscopic examination of vaginal discharge may provide useful information. If a cervical Gram stain is positive for Gram negative intracellular diplococci when interpreted by an experienced microscopist, the probability of PID greatly increases; if negative, it is of little use .

One study of 120 women showed that increased white blood cells (WBC) in vaginal fluid was the most sensitive single laboratory test for PID (78 percent for ≥3 WBC per high power field (hpf) compared with 57, 70, and 71 percent respectively for serum WBC, erythrocyte sedimentation rate (ESR), and C reactive protein) . However, the specificity was only 39 percent.

A meta-analysis also concluded that there was no single test or combination that was both sensitive and specific for the diagnosis of PID . However, certain combinations may have a high negative predictive value. In the series of 120 women described above, the probability of PID was only 11 percent in women with the combination of a normal peripheral WBC and ≤3 WBC/hpf from vaginal fluid; no patient had PID if the ESR also was normal. The ovarian tumor marker CA-125 is apparently elevated in all cases of PID.

We recommend the following laboratory tests:

• Pregnancy test
• Microscopic exam of vaginal discharge in saline
• Complete blood counts
• Nucleic acid amplification tests for chlamydia and gonococcus
• Urinalysis
• C-reactive protein (optional)
• HIV testing
• Hepatitis B surface antigen and surface antibody
• Testing for syphilis

Imaging techniques  —

 Several studies have evaluated sonographic findings in PID with mixed results; a transvaginal rather than transabdominal approach is required .

• Sonographic findings consistent with PID, especially thickened, fluid-filled oviducts, are useful to support a clinical diagnosis of PID. However, the absence of findings does not diminish the probability of PID and should not be used as a reason to delay treatment. We reserve ultrasounds for acutely ill patients with PID in whom a pelvic abscess is a consideration. One study compared pelvic ultrasonography in 60 adolescents with a clinical diagnosis of PID and 40 age-matched controls. The presence of fluid in the cul-de-sac was not helpful in distinguishing patients with PID from those without, but 19 percent of adolescents with PID in this series had a tubo-ovarian abscess demonstrated by ultrasound before clinically suspected. Given the major contribution of tubo-ovarian abscess to failure of medical therapy for PID, this information is of considerable importance.

AVAILABLE ANTIMICROBIAL AGENTS  —

 Multiple antibacterial agents with activity against the wide variety of implicated pathogens have been studied, including medications within the beta-lactam, fluoroquinolone, aminoglycoside, lincosamide and macrolide classes of drugs . Meta-analyses of selected trials have demonstrated overall clinical and microbiological cure rates of greater than 90 percent for most regimens .

The vast majority of these studies have included dual therapy arms for coverage of N. gonorrhoeae, C. trachomatis, and the wide variety of microbes associated with PID; doxycycline has been the agent of choice for coverage of C. trachomatis in most of these studies, although azithromycin also has activity against this pathogen. The combination of clindamycin and gentamicin has moderate in vitro activity against N. gonorrhoeae and C. trachomatis, while a second generation cephalosporin (eg, cefoxitin or cefotetan ) plus doxycycline have excellent in vitro activity against both pathogens . Ampicillin-sulbactam is a beta-lactam agent with broad spectrum activity, although there are scant data on its use for the treatment of PID .

Fluoroquinolones are no longer recommended in the United States for the treatment of gonorrhea or associated conditions, such as PID, due to increasing rates of resistance . 

CLINICAL TRIAL DATA

Defining treatment response  — 

Treatment response is based on both short- and long-term outcomes. Clinical cure is defined as “significant” or “complete improvement” in the signs and/or symptoms of PID. Microbiologic cure is defined as eradication of N. gonorrhoeae or C. trachomatis, if present at baseline.

Long-term sequelae of PID include infertility, ectopic pregnancy, and chronic pelvic pain.

Limitations of current data sets  — There are multiple limitations of the clinical trials of PID treatment.

Clinical efficacy  — Some studies have not used objective criteria to diagnose PID, raising concerns as to the whether the appropriate patient population was included . In addition, others have evaluated subjective improvement in pain scores without blinding of investigators. Few randomized controlled trials have long-term data on reproductive outcomes, such as risk of ectopic pregnancy following treatment.

Microbiologic efficacy  —

 Although several studies have demonstrated the presence of anaerobes at initial presentation, there are scant data on their persistence or eradication after therapy. In fact, excellent clinical cure rates among women with mild to moderate PID have been documented for several regimens with modest anaerobic coverage (eg, ceftriaxone plus doxycycline ) .

Assessment of efficacy is also hampered by diagnostic methods that do not distinguish between relapse versus reinfection. 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 women had evidence of single or dual infections at baseline; by 30 days after therapeutic invention, approximately 3 percent still had evidence of either infection, representing either reinfection or relapse.

Management of mild or moderate PID  — 

There has been a persistent trend toward outpatient treatment of PID with only 10 to 25 percent of women now being hospitalized . Clinical trial data support such an approach in patients with mild or moderate PID. The Pelvic Inflammation Disease Evaluation Clinical Health trial (ie, PEACH trial) randomly assigned 831 patients with mild or moderate PID to either :

• Inpatient therapy with intravenous cefoxitin (2 grams every 6 hours) plus doxycycline (100 mg twice daily for 14 days)

OR

• Outpatient therapy with a single intramuscular dose of cefoxitin (2 grams) plus a single dose of oral probenecid (1 gram) plus oral doxycycline (100 mg twice daily for 14 days) .

Eligible women had a history of lower abdominal pain, uterine or adnexal tenderness on examination, and leukorrhea/mucopurulent cervicitis or documented untreated gonococcal or chlamydial infection. Patients underwent a standardized interview, and cervical swabs were obtained for N. gonorrhoeae and C. trachomatis for polymerase chain reaction (PCR) testing. Vaginal specimens were Gram stained and examined for evidence of bacterial vaginosis by a reference laboratory. Endometrial biopsies were scored for evidence of endometritis by two reference pathologists. Long-term follow-up was conducted through periodic phone calls. Intravenous therapy continued for a minimum of 48 hours; upon clinical improvement, the patient was switched to doxycycline for a 14-day course.

This clinical trial showed that short-term clinical and microbiologic outcomes and long-term reproductive outcomes (eg, ectopic pregnancy, chronic pelvic pain) were similar between arms. Intravenous administration of doxycycline was associated with high rates of phlebitis.

INDICATIONS FOR HOSPITALIZATION  —

 Recommended indications for hospitalization and parenteral antibiotics include :

• Pregnancy
• Lack of response or tolerance to oral medications
• Nonadherence to therapy
• Inability to take oral medications due to nausea and vomiting
• Severe clinical illness (high fever, nausea, vomiting, severe abdominal pain)
• Complicated PID with pelvic abscess (including tuboovarian abscess)
• Possible need for surgical intervention or diagnostic exploration for alternative etiology (eg, appendicitis)

There are no clinical data to suggest that older age or HIV status should be considered criteria for hospitalization .

RECOMMENDED REGIMENS

General approach  — 

The therapeutic regimens for PID, discussed below, provide broad empiric coverage for the wide array of implicated pathogens, although the optimal treatment regimen remains undefined . Antibiotics selected should have activity against Neisseria gonorrhoeae and Chlamydia trachomatis, as both play a significant role in PID. As noted above, 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. Cost, convenience of administration, safety, formulary availability and allergy history are all assessed in making antimicrobial selections. The choice of antimicrobial therapy is also guided by whether the patient will be treated as an inpatient or outpatient.

Gonococcal drug resistance  — 

 the CDC guidelines state that fluoroquinolones are no longer recommended as therapy for PID if N. gonorrhoeae is a proven or suspect pathogen .

Role for anaerobic coverage  — 

There is no consensus on the degree of anaerobic coverage that is needed for PID or whether anaerobes need to be targeted at all . Anaerobic bacteria are frequently recovered from patients with acute PID; however, there are no studies to demonstrate that inclusion of anaerobic coverage is superior to antibiotic regimens with minimal coverage . Furthermore, experts are concerned that the additional gastrointestinal side effects seen with metronidazole therapy will lead to nonadherence and inadequately treated PID.

Some experts have suggested that anaerobes should be treated empirically while others suggest inclusion of anaerobic coverage among select groups of patients, such as those with severe infection requiring hospitalization and tubo-ovarian abscess . The inpatient regimens noted below have excellent anaerobic coverage while the outpatient regimens have only modest coverage. The addition of antibiotics with anaerobic activity (eg, metronidazole ) may be considered among outpatients with:

• 
  

Inpatient therapy  — Patients with severe PID should be hospitalized and treated with parenteral therapy. Indications for hospitalization are discussed above. (See 'Indications for hospitalization' above.)

First-line therapies  — For patients with severe PID, the CDC recommends either of the following parenteral regimens, which result in clinical cure of acute disease in >90 percent of PID cases :

• Cefoxitin (2 g intravenously every 6 hours) or cefotetan (2 g IV every 12 hours) plus doxycycline (100 mg orally every 12 hours).
• Clindamycin (900 mg intravenously every 8 hours) plus gentamicin loading dose (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily intravenous dosing of gentamicin may be substituted for three times daily dosing .  

These inpatient regimens provide broad coverage, including streptococci, gram-negative enteric bacilli (Escherichia coli, Klebsiella spp, and Proteus spp), and anaerobic organisms (ie, bacterial vaginosis-associated flora) . We prefer a second generation cephalosporin plus doxycycline for inpatients with PID due to its overall tolerability.

Antiemetic and antipyretic medications should be offered to those patients who are symptomatic. Transitioning from parenteral to oral therapy can usually be started after 24 hours of sustained clinical improvement, such as resolution of fever, nausea, vomiting, and severe abdominal pain, if present . Patients should complete a 14-day course of treatment with doxycycline (100 mg twice daily). Oral administration of doxycycline is generally preferred, as soon as vomiting subsides, because of the pain associated with intravenous drug administration. Importantly, the bioavailability of the oral preparation of doxycycline is equivalent to parenteral administration.

Patients with a pelvic abscess should also receive oral clindamycin 450 mg every 6 hours or metronidazole 500 mg every 8 hours for a total of 14 days in addition to doxycycline . Management of the patient with complicated PID with tubo-ovarian abscess is discussed separately.

Alternative regimens  — Limited data are available on the following regimens, which are considered “alternative” by the CDC:

• Ampicillin-sulbactam (3 g intravenous every 6 hours) plus doxycycline (100 mg twice daily) led to a similar rate of clinical cure as cefoxitin (2 g every 6 hours) plus doxycycline (100 mg twice daily) among women hospitalized with PID (86 versus 89 percent) [ 16 ].
• One small trial randomly assigned patients with mild or moderate PID to azithromycin monotherapy, azithromycin plus metronidazole , or a combination regimen including a beta-lactam . Clinical and microbiological cure rates were greater than 95 percent in all arms.

Outpatient therapy  — Patients with mild or moderate PID are suitable candidates for oral therapy since clinical outcomes are equivalent with parenteral or oral therapy. 

First-line regimens  — The CDC recommends any of the following oral regimens, with or without metronidazole (500 mg twice a day for 14 days) :

• Ceftriaxone (250 mg intramuscularly in a single dose) plus doxycycline (100 mg orally twice a day for 14 days)
• Cefoxitin (2 g intramuscularly in a single dose) concurrently with probenecid (1 g orally in a single dose) plus doxycycline (100 mg orally twice a day for 14 days)
• Other parenteral third-generation cephalosporins, such as cefotaxime (1 gram intramuscularly in a single dose) or ceftizoxime (1 gram intramuscularly in a single dose) plus doxycycline (100 mg orally twice a day for 14 days)

TREATMENT OF THE PENICILLIN-ALLERGIC PATIENT  — Treatment considerations must also take into consideration any history of drug allergy and the risk for gonococcal infection. Penicillin-allergic patients who have tolerated cephalosporins may be treated with a cephalosporin-based regimen.

Patients at risk for gonorrhea  — Patients with PID who require hospitalization can be treated with clindamycin and gentamicin , as outlined above. 

However, therapeutic options for outpatient management of the penicillin allergic patient at risk for gonorrhea are limited, particularly among those with a history of severe penicillin allergy. In patients with mild or moderate PID, it is important to obtain a complete history regarding the underlying penicillin allergy so a therapeutic regimen may be constructed, as discussed below.

History of mild allergy  — A patient with a mild past reaction to a penicillin and who never reacted to a cephalosporin (or never received one) may be a candidate for treatment with intramuscular ceftriaxone .

A history of a maculopapular or morbilliform rash, without signs of IgE-mediated allergy (urticaria, angioedema, respiratory symptoms, hypotension) or desquamation, is associated with very low risk for a serious allergic reaction to ceftriaxone . Cross-reactivity between penicillins and third-generation cephalosporins is believed to be uncommon. For such patients, an initial test dose of ceftriaxone (one-tenth of the full dose, intramuscularly) can be administered with patient observation for two hours. If no reaction develops, the remainder of the dose can be given with continued observation for another hour; the patient should be discharged with doxycycline (100 mg twice daily) for 14 days. 

History of severe allergy  — Patients with severe or life-threatening penicillin allergies are not candidates for cephalosporin therapy; options for outpatient therapy are limited.

We suggest the following possible options:

• Hospitalize the patient and initiate treatment with clindamycin (900 mg intravenously every 8 hours) plus gentamicin loading dose (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily intravenous dosing of gentamicin may be substituted .

OR

• Administer a quinolone-based regimen, eg, levofloxacin (500 mg orally once daily for 14 days) AND a single dose of azithromycin (2 grams orally). This dosage of azithromycin is also used for penicillin allergic patients with uncomplicated gonococcal infection; however, this high dose of azithromycin is associated with increased rates of gastrointestinal disturbance. 

Following 24 hours of clinical improvement, treatment may be changed to doxycycline (100 mg orally every 12 hours) to complete 14 days of treatment. In the patient with uncomplicated PID, another fluoroquinolone alternative to levofloxacin is moxifloxacin (400 mg) once daily for 14 days .