An Update on Pelvic Inflammatory Disease

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We last covered PID and TOA on the podcast in February 2019 — and since then, as with our gonorrhea and chlamydia update, have some new updates to reflect the 2021 CDC Treatment Guidelines.

What is PID/TOA? 

  • PID: pelvic inflammatory disease 

    • This is a wide variety of inflammatory disorders of the upper female genital tract, including: 

      • Endometritis

      • Salpingitis

      • TOA: tubo-ovarian abscess

      • Pelvic peritonitis 

    • Caused by many infectious diseases. 

      • Most common: N. gonorrhoeae and C. trachomatis (gonorrhea and chlamydia)

        • 50% of PID diagnoses test positive for GC/CT, though this proportion is decreasing.

    • Other organisms that can be implicated:

      • Anaerobes, 

      • G. vaginalis 

      • H. influenzae

      • Enteric GNRs

      • Strep agalactiae

      • Cytomegalovirus 

      • Trichomonas (Trichomonas vaginalis)

      • Mycoplasima hominis and M. genitalium

      • Ureaplasma urealyticum

Diagnosis of PID

  • Can be difficult because of many vague symptoms, and some are asymptomatic 

  • Differential diagnosis is broad for abdominopelvic pain: 

    • Appendicitis 

    • Ectopic pregnancy

    • Ovarian torsion or ovarian cysts

    • Diverticulitis

    • Functional GI pain, IBS, IBD

    • Etc. etc. etc. 

  • A presumptive dx should be made, and treatment started,

    • In sexually active women and those at risk for STIs experiencing pelvic/lower abdominal pain, if no other cause for illness can be identified,

    • and if they have 1 or more of these minimum clinical criteria: 

    • Cervical motion tenderness 

    • Uterine tenderness 

    • Adnexal tenderness  

  • One or more of the following can be used to enhance specificity of the minimal clinical criteria: 

    • Oral temp > 101 F (38.3) 

    • Abnormal cervical mucopurulent discharge or friability 

    • Presence of abundant WBC on saline microscopy of vaginal fluid 

    • Elevated erythrocyte sedimentation rate 

    • Elevated C-reactive protein 

    • Laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis 

  • Even more specific criteria can include:

  • Endometrial biopsy with histopathologic evidence of endometritis 

  • TVUS or MRI showing thickened, fluid-filled tubes with or without free fluid or tubo-ovarian complex

  • Laparoscopic findings of PID (Fitz-Hugh-Curtis syndrome) 

What should I do if I think someone has PID?

  • Testing:

  • HIV

    • Testing recommended by CDC “in all persons seeking STI testing who do not have a known diagnosis of HIV.” 

  • GC/CT

    • 50% will test positive, so they are high yield for PID testing.

    • NAAT testing is preferred method.

      • Patient self-collected swabs are just as accurate as clinician-collected.

      • First void urine is most sensitive; decreases with later voids during the day.

        • Urine testing may miss over 400k infections per year in USA - vaginal swab testing should be offered first, and patient-collected may help improve acceptability.

  • Imaging

    • Not recommended outright by CDC in PID evaluation.

    • Will frequently be part of your evaluation in a differential diagnosis

      • TVUS - may continue to have cervical motion tenderness, can demonstrate TOA. Can also demonstrate other GYN pathologies.

      • CT/MRI - unlikely to demonstrate specific findings for PID outside of large TOAs.

  • Treatment:

    • Primary Considerations: 

  • Choice of medication:

    • Treatment is empiric, requiring broad spectrum coverage of likely pathogens

    • All treatment types should be effective against gonorrhea and chlamydia 

  • Need for hospitalization:

    • Recommended if:

      • A surgical emergency (ie. appendicitis) cannot be excluded

      • Presence of tubo-ovarian abscess 

      • Pregnancy

      • Severe illness including nausea, vomiting, or high fever,

      • Inability to tolerate or follow outpatient regimen

      • Failed outpatient therapy based on follow up

    • Parenteral treatments

      • Ceftriaxone (1g IV q24 hrs) + doxycycline (100 mg oral or IV q12hrs) + metronidazole (500mg oral or IV q12h).

      • Cefoxitin (2g IV q6hrs) + doxycycline (100mg oral or IV q12hrs) 

      • Cefotetan (2g IV q12h) + doxycycline (100mg oral or IV q12hrs)

    • Because of pain associated with IV infusion, doxycycline should be given orally whenever possible.

    • Oral and IV doxycycline and metronidazole have similar bioavailability

  • Alternative regimens pending allergies and antibiotic availability:

    • Clindamycin (900 mg IV q8hrs) + gentamicin (2mg/kg loading dose IV or IM, then maintenance of 1.5mg/kg every 8 hrs, or single daily dosing of 3-5mg/kg) 

    • Ampicillin-sulbactam (Unasyn) 3g IV q6hrs + doxycycline 100mg q12hrs  

  • Goal of parenteral therapy will be to transition to oral antibiotics within 24-48 hours if clinical improvement.

    • Those with TOA should have at least 24 hours of inpatient observation

    • IM/Oral treatment - For continuation of inpatient treatment, or start here in those with mild-to-moderate symptoms of acute PID. 

  • Clinical outcomes are similar to those treated with IV therapy, but if women don’t respond in 72 hours, should be re-evaluated and treated with IV

    • Ceftriaxone 500mg IM x1 + doxycycline 100mg BID x14 days + metronidazole 500 mg BID x14 days 

    • Cefoxitin 2g IM + Probenecid 1g orally + doxycyline 100mg BID x14 days + metronidazole 500mg BID x14 days 

    • Some other 3rd generation cephalosporin + doxy + metronidazole 

  • If starting with outpatient treatment, improvement should be documented by follow up within 72 hours.

    • If no improvement has occurred, then hospitalization, assessment of the antimicrobial regimen, and considering potential additional diagnostics (imaging, laparoscopy) are indicated.

  • Retesting should occur at 3 months after treatment, regardless of treatment of sex partners, to assess for reinfection.

    • Patients should refrain from sex until treatment is completed, symptoms resolved, and sex partners have been treated.

    • Sex partners within previous 60 days of patients with PID should also be treated presumptively for gonorrhea and chlamydia

      • This is regardless of PID etiology or pathogens isolated 

      • Consider expedited partner therapy (EPT).

Managing TOAs 

  • Surgical drainage indicated if:

    • Failure to respond to treatment within 48-72 hours 

    • Clinical decline (ie. becoming septic) 

  • Likelihood of need for surgical intervention is related to the size of TOA: 

    • 60% of those with abscess >10cm 

    • 30% in 7-9cm 

    • 15% in those of 4-6 cm

Special considerations for treatment in certain populations:

  • Pregnancy

    • Pregnant patients with PID are at high risk of morbidity, pregnancy loss, preterm delivery.

    • Hospitalization and consultation with ID are recommended.

  • Persons with HIV

    • Patients with HIV may be more likely to have TOA, though symptoms are similar overall to those without HIV.

    • No data currently to suggest more aggressive therapy is needed in patients with HIV.

  • If patient has an IUD:

    • IUD is not required to be removed with a diagnosis of PID.

    • However, if there is no clinical improvement in 48-72 hours, then should consider removing the IUD.

Gonorrhea and Chlamydia

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We talked about most STIs in a series back at the beginning of 2019! This podcast is an update to the treatment guidelines and will replace our last episode on gonorrhea and chlamydia, as these two bugs had some changes in treatment with the 2021 CDC STI guidelines.

First of all, why are we doing these two STDs together? 

  • Because they have a lot of common symptomatology 

  • They may come together (ie. if you have one, you may have the other) 

  • We usually order the two tests together (say it in one breath anyway in the clinic or the ED) 

What are gonorrhea and chlamydia and why do we care? 

  • Both are sexually transmitted infections that anyone can get if they are sexually active (any kind of sex), and there is vertical transmission between mother and child 

  • Gonorrhea 

    • Caused by bacteria Neisseria gonorrhoeae (gram negative diplococci) 

    • 1.6 million new infections annually in the US

      • More than 50% occur in patients aged 15-24

    • Usually symptomless but in men can cause burning with urination, penile discharge, or even testicular pain 

    • In women, 50% are symptomless but can lead to burning with urination, vaginal discharge, intermenstrual bleeding/postcoital spotting, pelvic pain

    • Can also affect other areas like throat or anus 

    • If untreated, it can lead to pelvic inflammatory disease and infertility. Additionally, at risk for disseminated gonococcal infection 

      • Skin pustules/petechiae, septic arthritis, meningitis, endocarditis 

      • Very rare (0.6-3% of infected women and 0.4-0.7% of infected men 

      • In pregnant patients: septic abortion, chorio, neonatal blindness 

  • Chlamydia 

    • Caused by bacteria Chlamydia trachomatis (gram negative bacteria that only replicates in host cells).

    • 4 million new infections annually in the US

      • More than 65% occur in patients aged 15-24

      • Some estimates show at any given time, 1 in 20 sexually active women aged 15-24 has active chlamydia infection in the US.

    • Again, usually symptomless (70-80%), but can cause vaginal discharge and burning with urination in women 

    • In men, can have discharge from penis, burning with urination, pain and swelling in testicles. 

    • Rectal, oral/throat infections are also possible.

    • If untreated, can also cause PID and infertility in women → around 15% of women will develop.

    • Also can cause chlamydia conjunctivitis or trachoma → blindness 

    • Reactive arthritis → can’t see, can’t pee, can’t climb a tree = arthritis, conjunctivitis, urethral inflammation 

How do we diagnose them? 

  • Usually a urine test, but can also do endocervical swab, vaginal swab, rectal swab, or pharyngeal swab 

    • Nucleic acid amplification test = gold standard 

  • Who should be tested? 

    • CDC recommends screening:

      • Of anyone with concern for symptoms;

      • Annually for GC/chlamydia for all sexually active women younger than 25 years 

      • Opportunistic screening for older women with identified risk factors (ie. new or multiple sexual partners or sex partner who recently had an STI) 

    • For men: once a year for GC/chlamydia for all sexually active MSM, and more frequently (q3-6 months) for MSM who have HIV or if they have multiple or anonymous partners 

How do we treat gonorrhea and chlamydia? - note, this is only for adolescents and adults 

  • Treating gonorrhea (NOT disseminated) 

    • Gonorrhea is becoming more and more resistant to antibiotics, and we are down to one class of antibiotic that really treats it: cephalosporins 

    • CDC recommends: ceftriaxone 500mg IM x1

      • This is an update to the previous recommendations, which used 250mg. This reflects the changing state of antibiotic resistance of gonorrhea.

      • Test of cure is recommended for throat infections and for pregnant patients, but not necessarily for genital or rectal infections.

    • If cephalosporin allergic:

      • Gentamicin 240mg IM in single dose, AND Azithromycin 2g orally in single dose.

  • Treating chlamydia 

    • Recommended regimen by the CDC: Doxycycline 100mg PO twice daily for 7 days.

      • Alternative regimens include:

        • Azithromycin 2g orally, single dose

        • Levofloxacin 500 mg orally for 7 days 

    • Azithromycin has lower efficacy amongst persons with concomitant rectal infection, which is why the doxycycline regimen is preferred.

      • Repeat screening may be needed to ensure efficacy of the single-dose azithro regimen.

  • Expedited partner treatment - treat the sexual partner of the patient diagnosed with chlamydia or gonorrhea without first examining the sexual partner 

    • CDC says: EPT is a useful option to facilitate partner management in states where it is permissible, and reduces re-infection risk for the patient while treating the partner.

    • Should always counsel the patient that partner and patient should refrain from having intercourse for at least 7 days after all partners have been treated.

GC/chlamydia in pregnancy 

  • Screen in first trimester and if positive, should be treated

    • Exception: for chlamydia, Azithromycin 1g orally x1 is the recommended regimen.

    • These medications are safe during pregnancy, and risks outweigh the benefits of not treating

    • Expedited partner treatment is recommended where permissible.

    • Test of cure is recommended in three weeks (and should also screen in 3rd trimester again)

  • Pregnancy-specific risks of non-treatment

    • Vertical transmission to newborn 

    • Chlamydia: conjunctivitis (5-14 days after birth), and pneumonia (4-12 weeks of age) 

    • Gonorrhea: conjunctivitis (more purulent compared to watery discharge of chlamydia… both can lead to blindness!) 

      • Gentamicin/erythomycin eye gel helps to prevent these and why we use it!

    • Otherwise: septic abortions, intact chorio, etc. 

A final “fun fact” we had dug out in the original GC/CT episode…

  • There is no consensus as to why gonorrhea is called the clap… but some theories: 

    • Old English word “clappan” means throbbing or beating -- could mean the burning during urination with gonorrhea 

    • Proposed treatment during medieval times of “clapping” the penis or slamming the penis between both hands on a hard surface to get rid of the discharge/pus 






Monkeypox for the OB/GYN

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Reading/sources:

What is monkeypox and how is it transmitted? 

  • Name and type of virus 

    • WHO is planning to rename the virus to reduce stigma and racist overtones - but this hasn’t happened yet! 

    • Orthopoxvirus (genus of Poxviridae family) and has features similar to smallpox or variola 

      • DNA genome

      • There are two different strains: the Congo basin clade and the west African clade 

        • Congo basin clade has historically caused more severe disease and is thought to be more transmissible 

        • The West African clade seems to be the dominant circulating strain → case fatality ratio of 3% to 6% 

  • Cases and outbreak 

    • First case was in 1970 in the Democratic Republic of Congo

    • First case in the US in this outbreak was on 5/17/2022 

    • Most recent reports from the CDC states (as of 8/31/2022) - there have been 18,989 total confirmed monkeypox cases in the US 

    • Demographics 

      • There is not complete demographics data for everyone

      • Most recent data from mid August from the CDC shows that only 1.5% of all cases were in women and transgender men

      • No deaths have been reported in this population  

  • Transmission 

    • Human to human transmission can occur from

      • Direct contact with infected rash, scab, or body fluid 

      • Respiratory secretions during prolonged or intimate physical contact 

      • Contact with contaminated items, such as clothing or bedding 

    • A person with monkeypox infection is considered contagious from initial viral prodrome and development of rash until lesions have full healed and new skin has formed over the scabs 

    • Unclear if transmission can also occur through vaginal or seminal fluids 

    • Perinatal infection can occur through transplacental transmission or during close contact during and after birth 

    • Zoonotic transmission can also occur following direct contact with blood, bodily fluids, or cutaneous/mucosal lesion of infected animals 

Clinical Presentation 

  • Current outbreak 

    • Many of the initial patients in this outbreak have shown painful genital and perianal lesions, oral lesions, and proctitis in the setting of mild or no prodromal symptoms 

  • Clinical course 

    • Average time between contact with monkeypox and symptoms is 5-13 days, with range of 4-17 days 

    • Classic features of infection: 

      • Fever, lymphadenopathy, malaise, headache, muscleaches 

      • Can have lymphadenopathy

      • Rash develops approximately 1-4 days after prodromal symptoms → deep-seated vesicular or pustular, often beginning centrally and spreading to the limbs 

      • Rash can last 2-4 weeks, progressing through stages includes macules, papules, vesicles, pustules, and even scabs and crusts 

      • Rash can leave scars

  • From the Green Journal article (not sure we can use?) 

Pregnancy Implications of Monkeypox 

  • Not very much is known: 

    • We reviewed that the monkeypox virus can be transmitted to the fetus during pregnancy or to the newborn by close contact during and after birth 

    • There has been an increased risk of maternal mortality and morbidity documented with other poxviruses, but it’s unknown if pregnant people are more susceptible to monkeypox or if disease is more severe in pregnancy 

    • One publication looked at 5 cases of documented perinatal outcomes 

      • 2 = SAB 

      • 1 = stillbirth 

      • 1 = preterm birth 

Evaluation for individual with suspected monkeypox 

  • Routine screening is not recommended for asymptomatic patients 

  • If suspicion of monkeypox virus infection:

    • Collect recent travel history, ask specifically about countries where monkeypox has been reported 

    • If rash or anogenital lesions, ask about close contact or sexual exposure to someone with monkeypox 

    • Full body skin exam, including oral mucosa, genital, and rectal areas, + evaluate lymph nodes 

    • Isolation from others

    • Consultation with infectious disease 

  • Diagnosis 

    • Two-step process requiring initial identification of an orthopoxvirus 

    • If orthopoxvirus is confirmed, specimens are sent for monkeypox virus-specific testing 

    • Multiple samples should be collected, ideally from different lesions (2-3 from different areas of the body with diff appearance) for PCR testing 

    • Please follow your own hospital’s guidelines on how to obtain these samples!

    • As there aren’t really any other orthopox viruses in the US, we shouldn’t wait for the confirmatory testing before initiating infection-control procedures and preventative strategies + treatment 

  • Healthcare provider precautions 

    • Standard precautions and wear PPE: gown, gloves, eye protection, and N95 mask 

    • Any procedure where there is aerosolization (ie. intubation/extubation), should be done in airborne infection-isolation room 

Treatment 

  • Disease is usually self-limited, but disease can progress to severe, so certain populations at risk of severe disease 

    • This includes pregnant patients, people who are breastfeeding, and those with oral, ocular, genital, or anal lesions 

  • No specific treatment for monkeypox virus infection

    • However, there are 2 antivirals +immune globulin available 

    • Tecovirimat (Tpoxx) - antiviral (limited to health department/CDC Expanded access protocol) 

      • Approved by FDA for treatment of smallpox virus infection and may prove beneficial for monkeypox 

      • Available in oral and IV formulations 

      • Works by blocking cellular transmission of the virus 

      • Both forms have been used to treat patients during the current outbreak in the US

      • No human data is available during pregnancy, but no fetal toxic effects were observed in mice studies using oral medication 

      • Not known if present in breastmilk 

    •  Cidofovir - antiviral (Off-label use, available for use in outbreak setting) 

      • Approved by the FDA for treatment of CMV retinitis in patients with AIDS 

      • Can be used for orthopoxviruses in an outbreak setting 

      • In animal studies, cidofovir has been associated with embryotoxicity and teratogenicity, but no adequate or well-controlled studies in humans 

    • Brincidofovir - antiviral (availability limited to Strategic National Stockpile distribution) 

      • Approved by FDA to treat smallpox 

      • Unfortunately, in animal studies, there have been embryo-fetal toxicity demonstrated + structural malformations

      • Therefore, alternative therapy is recommended in pregnancy  

    • IVIG - also available in outbreak setting 

      • Also no human data or animal data in pregnancy 

  • Prevention 

    • Primary prevention is from isolating from individuals with infection

      • Avoid close contact and sexual activity with people with infection 

    •  Postexposure prophylaxis 

      • CDC has tools to assess the risk of monkeypox virus infection and recommends post-exposure vaccination for specific risk exposures or risk factors 

        • Criteria

          • Within 4 days of known exposure to reduce likelihood of infection or between 4-14 days to reduce severity symptoms 

          • Known contacts of monkeypox cases ID’ed by public health via case investigation 

          • Presumed contacts who meet criteria: 

            • Know that sexual partner in the past 14 days was diagnosed with monkeypox or 

            • Had multiple sexual partners in past 14 days in a jurisdiction with known monkeypox 

      • If given within 4 days of exposure, vaccine is likely to prevent monkey pox virus infection 

      • Of note, there are two types of vaccines 

        • JYNNEOS = live-non-replicated viral vaccine - There are no studies in pregnant patients

          • Pregnancy, however, is not a contraindication to post exposure prophylaxis with vaccination if the individual is otherwise eligible 

        • ACAM2000 - repliating viral vaccine licensed for prevention of smallpox 

          • Contraindicated in pregnant or breastfeeding people due to risk of pregnancy loss, congenital defects, and vaccinia virus infection 

    • Preexposure prophylaxis 

      • Attenuated live-virus vaccine and replication-competent vaccine are available 

      • Routine immunization of all healthcare workers is not currently recommended 

      • Only recommended for those whose jobs may expose them to monkeypox (ie. lab personnel and healthcare workers who administer a replication-competent vaccinia virus vaccine or anticipate caring for many patients with monkeypox) 

HIV in the Pregnant Patient

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Today we go into part 2 of our HIV series, this time focusing on pregnancy and HIV. Check out ACOG CO 752 (Prenatal and Perinatal HIV Screening) and CO 751 (Labor and Delivery Management of Women with HIV).

However, we have to give a major shout out to the OBG Project — their editors have put out an awesome summary of HIV in pregnancy and preventing vertical transmission: Check it out here.

(c) OBG Project

One of the important CREOG points on HIV in pregnancy includes drug interactions. Methergine is metabolized by CYP3A4 enzymes, which may be inhibited by certain antiretrovirals. Thus, methergine should be avoided if possible if encountering postpartum hemorrhage.

Lastly, we wanted to drive home the point again about patient autonomy, especially regarding risk of cesarean delivery. We put the ACOG CO text below for you to chew on!

ACOG CO 751