Pelvic Inflammatory Disease Empiric Therapy

Empiric treatment for pelvic inflammatory disease (PID) should be initiated in sexually active young women and women at risk for sexually transmitted diseases if they are experiencing lower abdominal pain and pelvic tenderness. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9]}

In addition, PID empiric therapy is warranted if one or more of the following are present on pelvic examination; cervical motion tenderness, uterine tenderness, or adnexal tenderness.

Empiric therapy should be broad spectrum and should include regiments that are effective against Neisseria gonorrhoeae and Chlamydia trachomatis.

There is no agreement amongst experts on whether treatment of PID should include anaerobic coverage. Outpatient regimens provided below have moderate coverage, while inpatient regimens have excellent coverage. Some experts recommend that all women should be covered for anaerobes, while others recommend that only women with severe disease requiring hospitalization, or those with tubo-ovarian abscesses should be covered. 

Parenteral therapy for severe PID 

Recommended by the CDC. Results in cure in > 90% of patients: 

• Cefoxitin 2 grams IV every 6 hours plus doxycycline 100 mg IV or orally every 12 hours or

• Cefotetan 2 grams IV every 12 hours plus  doxycycline 100 mg IV or orally every 12 hours or

• Clindamycin 900 mg IV every 8 hours plus gentamicin loading dose 2 mg/kg IV, followed by a maintenance dose of 1.5 mg/kg every 8 hours. Single daily dosing of gentamicin (3-5 mg/kg) can be substituted for three times daily dosing.

Alternative regimen per CDC with limited data:

• Ampicillin-sulbactam 3 grams IV every 6 hours plus doxycycline 100 mg IV or orally every 12 hours

Note: If patient able to tolerate oral medication, oral doxycycline preferred to IV secondary to discomfort from IV administration. Patients should complete 14 day course of doxycycline (100mg twice daily). If a pelvic abscess is also present, patients should also be treated with oral clindamycin 450mg every 6 hours or metronidazole 500mg every 8 hours for 14 days, in addition to doxycycline. 

Outpatient oral therapy for mild to moderate PID

As recommended by the CDC:

• Ceftriaxone 250 mg intramuscularly 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 gram intramuscularly in a single dose plus  probenecid 1 gram orally 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

• 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.

Of the regimens listed above for treatment of mild to moderate PID, ceftriaxone has the best coverage against gonococcal disease and this is the preferred antibiotic in conjunction with doxycycline. Metronidazole should be added for women with trichomonas vaginalis or bacterial vaginosis.

Alternative oral therapy for penicillin- or cephalosporin-allergic patients

• Patients with a history of a severe penicillin allergy who cannot tolerate cephalosporins or a known cephalosporin allergy may be prescribed fluoroquinolones (levofloxacin 500 mg orally daily or ofloxacin 400 mg orally twice a day for 14days), with or without metronidazole (500 mg orally twice a day for 14 days). This regimen should only be used for individuals in whom suspicion of N gonorrhoeae is low or resistance in the community is less than 5%.

• If N gonorrhoeae is the suspected pathogen, fluoroquinolones are no longer recommended secondary to increased resistance.

• If considering a fluoroquinolone, the patient must be cultured for N gonorrhoeae.

• If cultures return with quinolone-resistant N gonorrhoeae (QRNG), or if susceptibility to antimicrobials cannot be assessed, parenteral cephalosporin therapy is recommended. If cephalosporin therapy is not feasible, azithromycin 2 grams orally should be added to the quinolone-based regimen.
• The patient can also be hospitalized and started on clindamycin 900mg intravenously every 8 hours plus gentamicin loading dose (2mg/kg) followed by the maintenance dose (1.5 mg/kg) every 8 hours. If the patient improves with inpatient regimen, treatment may be changed to oral doxycycline 100mg orally every 12 hours for 14 days.

CDC guidelines on treatment of PID

In 2021, the Centers for Disease Control and Prevention (CDC) updated its clinical practice guidelines on the treatment of sexually transmitted infections. ^[10] These are some of the highlights of the recommendations for the treatment of PID.

The recommended parenteral treatment regimens for PID are as follows:

• Ceftriaxone 1 g IV every 24 hours PLUS
• Doxycycline at 100 mg PO or IV every 12 hours PLUS
• Metronidazole at 500 mg PO or IV every 12 hours

OR

• Cefotetan at 2 g IV every 12 hours PLUS
• Doxycycline at 100 mg PO or IV every 12 hours

OR

• Cefoxitin at 2 g IV every 6 hours PLUS
• Doxycycline at 100 mg PO or IV every 12 hours

Alternative parenteral treatment regimens are as follows:

• Ampicillin-sulbactam at 3 g IV every 6 hours PLUS
• Doxycycline at 100 mg PO or IV every 12 hours

OR

• Clindamycin at 900 mg IV every 8 hours PLUS
• Gentamicin loading dose IV or IM (2 mg/kg body weight), followed by a maintenance dose (1.5 mg/kg body weight) every 8 hours; can substitute single daily dosing (3-5 mg/kg body weight)

The recommended intramuscular or oral regimens for PID are as follows:

• Ceftriaxone at 500 mg IM in a single dose (for persons weighing ≥150 kg, administer 1 g of ceftriaxone) PLUS
• Doxycycline at 100 mg PO BID for 14 days with metronidazole at 500 mg PO BID for 14 days

OR

• Cefoxitin at 2 g IM in a single dose and probenecid at 1 g PO administered concurrently in a single dose PLUS
• Doxycycline at 100 mg PO BID for 14 days with metronidazole at 500 mg PO BID for 14 days

OR

• Other parenteral third-generation cephalosporin (eg, ceftizoxime, cefotaxime) PLUS
• Doxycycline at 100 mg PO BID for 14 days with metronidazole at 500 mg PO BID for 14 days