Treatment of Pelvic Inflammatory Disease (PID)
For mild-to-moderate PID, treat with ceftriaxone 250 mg IM once plus doxycycline 100 mg orally twice daily for 14 days, adding metronidazole 500 mg orally twice daily for 14 days to cover anaerobes. 1, 2
Diagnostic Criteria Before Treatment
Initiate empiric antibiotics immediately when all three minimum criteria are present: 3, 2
- Lower abdominal tenderness
- Adnexal tenderness
- Cervical motion tenderness
Do not delay treatment while awaiting culture results—PID is a clinical diagnosis and early therapy prevents infertility, ectopic pregnancy, and chronic pelvic pain. 1, 2
Additional findings that strengthen the diagnosis include oral temperature >38.3°C, abnormal cervical/vaginal discharge, elevated ESR or CRP, and laboratory confirmation of N. gonorrhoeae or C. trachomatis. 3, 2 However, a negative cervical test does not exclude upper tract infection. 1
Outpatient Treatment Regimen (Mild-to-Moderate PID)
The CDC-recommended outpatient regimen is: 1, 2, 4
- Ceftriaxone 250 mg IM single dose (or cefoxitin 2 g IM plus probenecid 1 g orally)
- Plus doxycycline 100 mg orally twice daily for 14 days
- Plus metronidazole 500 mg orally twice daily for 14 days
The metronidazole component provides essential anaerobic coverage against bacterial vaginosis-associated organisms and Bacteroides fragilis, which are frequently involved in the polymicrobial etiology of PID. 1, 5, 6 While some older guidelines listed metronidazole as optional, current evidence supports routine inclusion given the high prevalence of anaerobes in PID. 1, 7
Azithromycin (1 g orally weekly for 2 weeks) is an alternative to doxycycline and probably improves cure rates in mild-moderate PID compared to doxycycline based on high-quality trial data. 8 However, doxycycline remains the standard recommendation for C. trachomatis coverage. 3, 1
Criteria for Hospitalization and Parenteral Therapy
Admit immediately for IV antibiotics when any of the following are present: 1, 2, 4
- Pregnancy (doxycycline is contraindicated)
- Suspected tubo-ovarian abscess
- Severe illness with nausea, vomiting, high fever, or inability to tolerate oral medications
- Diagnostic uncertainty (cannot exclude appendicitis, ectopic pregnancy, or other surgical emergencies)
- Adolescent patient (unpredictable compliance and serious long-term sequelae risk)
- HIV infection
- Failure to improve on outpatient therapy within 72 hours
- Inability to arrange follow-up within 72 hours
Inpatient Treatment Regimens
Regimen A (CDC Preferred for Most Hospitalized Patients)
Cefoxitin 2 g IV every 6 hours OR cefotetan 2 g IV every 12 hours, plus doxycycline 100 mg orally or IV every 12 hours. 3, 1, 2
- Continue IV therapy for at least 48 hours after substantial clinical improvement (defervescence, reduced abdominal tenderness, decreased cervical/uterine/adnexal tenderness). 1, 2
- Then switch to oral doxycycline 100 mg twice daily to complete a total of 14 days. 1, 2
- Oral doxycycline provides bioavailability comparable to IV and may be used throughout when GI function is normal. 2
Regimen B (Alternative, Preferred for Tubo-Ovarian Abscess)
Clindamycin 900 mg IV every 8 hours plus gentamicin loading dose 2 mg/kg IV/IM, then 1.5 mg/kg every 8 hours. 3, 1, 2
- Continue for at least 48 hours after substantial clinical improvement. 1, 2
- Transition to oral doxycycline 100 mg twice daily OR clindamycin 450 mg orally four times daily to complete 14 days. 2
- Clindamycin-based therapy is preferred when tubo-ovarian abscess is present due to superior anaerobic coverage compared to doxycycline. 3, 1, 2
Antimicrobial Coverage Rationale
All regimens must cover the polymicrobial etiology: 3, 1, 6, 7
- Neisseria gonorrhoeae (cephalosporin provides coverage)
- Chlamydia trachomatis (doxycycline or azithromycin required)
- Anaerobes including Bacteroides fragilis, Peptococcus, Peptostreptococcus (metronidazole or clindamycin)
- Gram-negative facultative bacteria including E. coli (cephalosporin or gentamicin)
- Streptococci (covered by cephalosporins)
Even when N. gonorrhoeae or C. trachomatis are isolated from the endocervix, anaerobes and gram-negative rods are frequently present in the upper tract. 5, 6 This bacterial synergism and coinfection necessitate broad-spectrum coverage. 5
Special Populations and Considerations
Pregnant patients: Must be hospitalized for parenteral therapy; use clindamycin-based regimen (Regimen B) as doxycycline is contraindicated. 2, 4
Beta-lactam allergy: Use clindamycin 900 mg IV every 8 hours plus gentamicin; fluoroquinolone-based regimens have limited supporting data. 2
HIV-positive patients: Treatment regimens do not change, but hospitalization should be strongly considered. 4
Intrauterine device in place: Treatment does not change; IUD removal is not routinely required. 4
Regional antibiotic resistance: In areas with high quinolone resistance for N. gonorrhoeae, cephalosporins remain the preferred agents. 1
Follow-Up and Partner Management
Re-evaluate within 72 hours for clinical improvement (defervescence, reduced tenderness). 1, 2 Lack of improvement mandates hospital admission for parenteral therapy. 1, 2
All sexual partners from the preceding 60 days must be evaluated and empirically treated for C. trachomatis and N. gonorrhoeae, regardless of symptoms, to prevent reinfection. 1, 2, 4 Expedited partner therapy is recommended where legal. 4
Critical Pitfalls to Avoid
Do not use single-dose or short-course therapy alone—a single IM injection without oral continuation is inadequate and increases risk of treatment failure and long-term sequelae. 1
Do not omit anaerobic coverage—the infection is polymicrobial even when a specific pathogen is identified. 5, 6
Do not discharge hospitalized patients before 48 hours of clinical improvement on IV antibiotics. 1, 2
Do not assume negative cervical testing excludes upper tract infection—treat empirically based on clinical criteria. 1
Do not delay treatment in adolescents—they should be strongly considered for hospitalization due to unpredictable compliance and potentially severe long-term reproductive consequences. 9, 2