Gonorrhea and Chlamydia

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 

Sepsis

In today’s podcast, we try to provide an update on sepsis for OB/GYN’s. It’s a long one but hopefully full of lots of good information for your practice and knowledge.

Sepsis definitions have changed recently, put forth in 2016 the Third International Consensus Conference for the Definitions of Sepsis and Septic Shock Task Force. These marked a major departure from previous iterations, which were defined by the “SIRS” or “Systemic Inflammatory Response Syndrome” criteria. This also ushered in a new scoring system for sepsis evaluation, known as the Sequential Organ Failure Assessment tool, and a quick bedside version known as qSOFA.

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Common obstetric and gynecologic etiologies include urinary tract infections and pyelonephritis; chorioamnionitis/endometritis; wound infections and necrotizing fasciitis; septic abortions; toxic shock syndrome; and ruptured tuboovarian abscess. Non-obstetric or non-gynecologic causes should also be considered. Some of these more common etiologies include gastrointestinal causes, such as appendicitis, diverticulitis, or peritonitis; respiratory causes, such as influenza or pneumonia; and skin infections including cellulitis. 

In our hospital, we remember the primary interventions for sepsis using the acronym “BLAST”: Blood Cultures, Labs/Lactate, Antibiotics, Saline, Time.

B: Blood Cultures; L: Lactate/Laboratories

With the suspicion for sepsis, laboratory evaluation is essential. CBC, BMP, lactic acid, and blood cultures are often part of the initial workup.

Lactic acid production partially results from the shift of aerobic to anaerobic cellular metabolism, so it functions as a proxy marker of poor tissue perfusion. In sepsis, higher lactic acid levels have been associated with worsened outcomes. Surviving Sepsis Campaign guidelines do recommend guiding resuscitation to lactate normalization.  The SMFM consensus statement does recommend lactate measurement for suspected sepsis in pregnancy.

Blood cultures are important to obtain upfront, prior to the initiation of antibiotic therapy. Even with an initial antibiotic exposure, blood cultures can become useless. Two sets of peripheral blood cultures, with each set consisting of aerobic and anaerobic cultures, are recommended (13). If an infection site is suspected and can be easily accessed for culture in a timely manner, cultures are recommended prior to antibiotic initiation.  

In obstetric patients, the most common causes of sepsis include septic abortion, chorioamnionitis and postpartum endometritis, urinary tract infections, pneumonia, and gastrointestial origins such as appendicitis.

A: Antibiotics

Empiric antimicrobial therapy should be broad in coverage, but also directed towards the most likely source, if one is known. The SMFM consensus statement, the Surviving Sepsis Campaign, and the SEP-1 core measure promote administration of appropriate antibiotic therapy within three hours of presentation. Mortality risk in septic shock appears time-dependent with respect to antibiotic therapy based on observational data.

Combination or “double coverage” therapy for critically ill or neutropenic patients (using two antibiotics to cover the same spectrum of pathogen) is not recommended. However, one notable exception is a source of sepsis more commonly encountered by gynecologists: toxic shock syndrome (TSS).

TSS results from the production of noxious exotoxins by Streptococcus and is described with retained objects, such as tampons, in the vagina. The antibiotic therapy of choice in this case is a combination of penicillin and clindamycin, as clindamycin acts as a transcription inhibitor to the production of bacterial exotoxins.

S: Saline

Crystalloid fluid is the choice for initial resuscitation in severe sepsis or septic shock. The landmark trial on early-goal directed therapy (EGDT), published by Rivers in 2001, randomized patients to standard therapy versus targeted fluid therapy with placement of both central venous and arterial lines, with strict goals for mean arterial pressure (MAP), central venous pressure (CVP,) venous oxygen saturation, hematocrit, and urine output. Fluid administered prior to randomization in both arms was 20-30 cc/kg over 30 minutes. This has ultimately become the standard of care for initial fluid resuscitation.

In pregnancy, this may be overly aggressive, and predispose patients to pulmonary edema; thus, the SMFM consensus statement on sepsis in pregnancy recommends an initial bolus of 1-2 L. Frequent reevaluation of volume status should be performed.

T: Time

The SEP-1 core measure from CMS is predicated on two major time points, with time starting at the time of patient presentation with severe sepsis or septic shock. The SEP-1 bundle requirements at three hours and six hours are shown in Figure 2. The entirety of the “BLAST” protocol covers the initial, “three hour” time point.

The next marker is six hours, which states there should be a redrawn lactate if there was a diagnosis of severe sepsis or septic shock. There also should be a full physical examination, The reexamination can include central venous pressure measurement, central venous oxygen measurement, a bedside cardiovascular ultrasound, or a passive leg raise test as well. For obstetricians and gynecologists, likely the physical examination and passive leg raise are the most easily performed. This may not work in pregnancy due to aortocaval compression; thus, SMFM recommends continued bolus with small fluid volumes (250 - 500 cc) and close monitoring of vital signs to determine if patients are fluid responsive.

If patients in septic shock do not respond to fluid and are persistently hypotensive despite adequate fluid resuscitation, the SEP-1 core measure requires administration of vasopressors by the six hour mark. Norepinephrine is the primary choice in sepsis both in and out of pregnancy. Norepinephrine is associated with lower rates of arrhythmia and overall mortality compared with other vasopressors.

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We go into a lot more detail in the podcast on some additional points, but be sure to check out the SMFM Sepsis guideline for all the deep reading on this topic!

Chorioamnionitis and Endometritis

Today we dive into intraamniotic infection (IAI), more commonly known as chorioamnionitis or endometritis. CO 712 reviews a lot of the surprisingly limited evidence on the management of IAI, and the essentials you need to know for your labor floor and for CREOGs.

IAI is an important topic because of its morbidity. 2-5% of term deliveries are complicated by chorioamnionitis. It is associated with acute neonatal morbidity, including things such as pneumonia, meningitis, sepsis, and death. Treatment intrapartum is associated with an over 10-fold decrease in GBS-neonatal sepsis. Maternal morbidities include dysfunctional labor curves that lead to further intervention, increased risk of postpartum hemorrhage due to atony, and peritonitis, sepsis, ARDS, and rarely death.

Risk factors for IAI include a longer length of labor and longer length of ROM. Additionally, it is thought that multiple digital vaginal exams in the setting of ROM  can increase risk. Other, less obvious risk factors include cervical insufficiency, nulliparity, meconium-stained fluid, use of internal fetal or uterine contraction monitoring, presence of genital tract pathogens (ie. STIs, GBS, BV), alcohol and tobacco use, and of course previous history of chorioamnionitis.

The gold standard diagnosis is made off of a gram stain or culture of amniotic fluid, but this is obviously problematic! So in reality, there are three categories of IAI or IAI-risk that help guide clinicians into deciding therapy:

1. Isolated Maternal Fever: Single oral temperature of 39 C or greater OR an oral temperature of 38-38.9 C that persists when the temp is repeated after 30 minutes.

2. Suspected intraamniotic infection: Based on clinical criteria, which includes maternal fever PLUS one of maternal leukocytosis, fetal tachycardia, or purulent or malodorous amniotic fluid. 

3. Confirmed intraamniotic infection: Based on the gold standard of culture/gram stain.

Does every fever intrapartum need to be treated?

There are lots of things that can cause fever intrapartum or immediately postpartum other than chorioamnionitis, such as:

• Misoprostol use and other types of drug fevers.

• Epidural use.

• Other sources of infection (ie. UTI, respiratory infection).

• Also… being in a hot room (girl, labor is hard work)!

For isolated maternal fever of 38-38.9, CO 712 states that without other clinical criteria indicating infection and with/without persistent temperature elevation: 

1. Few data exist to guide appropriate management of women with isolated intrapartum fever in absence of other clinical signs suggesting intra-amniotic infection.

2. Consider antibiotics, but should definitely still communicate to pediatric team.

Our tendency is to treat persistent temperatures in this range in most cases.

Antibiotic Therapy: from CO 712:

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ACOG CO 712

Once postpartum, antibiotics should not need to continue based on principle. Instead, antimicrobial therapy should be based on risk factors for postpartum endometritis:

• Women who deliver vaginally may NOT require antibiotics postpartum as they are less likely to develop endometritis.

  1. However, give an additional dose if bacteremia or persistent fever are present.

• Women undergoing cesarean deliveries should receive at least one additional dose of antimicrobial agents after delivery is recommended.

  1. One additional dose of chosen regimen + clindamycin 900 mg IV or metronidazole 500 mg IV.

Postpartum endometritis occurs when infection is not totally cleared out after delivery and affects the endometrium. Risk factors include chorioamnionitis, cesarean delivery, prolonged labor or ROM, manual placental removal, and all the chorioamnionitis risk factors above.

The diagnosis is based on the presence of postpartum fever, along with tachycardia, uterine tenderness, foul smelling lochia, and/or leukocytosis.

Treating endometritis occurs most commonly with clindamycin and gentamicin, with the addition of ampicillin (“triple therapy”) for GBS-positive patients. The patient should be treated until 24-48 hours afebrile. Additional oral antibiotic therapy after successful IV therapy is not required as RCTs have demonstrated no improved outcomes. And of course if someone isn’t looking better, consider source control measures (i.e., D&C for retained POCs) or a different source of infection.

Infection Prevention and Gynecologic Surgery

Shout out to Taylor DeGiulio for today’s episode idea! We’re doing a pretty close reading of ACOG PB 195 if you want to follow along!

SSI represents the most common complication after GYN surgery, however definitions of this may surprise you. The National Surgical Quality Improvement Program (NSQIP) divides SSI up into three broad categories, with their definitions below:

1. Superficial incisional: occurs within 30 days of surgery, involving only skin or subcutaneous tissue.

2. Deep incisional: occurs within 30 days of surgery without an implant, or within 1 year of surgery with an implant, and involves deep soft tissues (rectus muscle, fascia).

3. Organ space: occurs within 30 days of surgery without an implant, or within 1 year of surgery with an implant, and involves any other area manipulated during operative procedure (i.e., osteomyelitis if bone, endometritis or vaginal cuff for GYN, etc.)

• In addition to satisfying these time and location definitions, an SSI also must have one of the following characteristics present:

  • Purulent drainage from the area of infection.

  • Spontaneous dehiscence or deliberate opening of a wound by the surgeon, with organisms subsequently obtained from an aseptically collected culture; or not cultured, but the patient displays signs/symptoms) of infection (i.e., fever, localized pain or tenderness, redness, etc.).

  • Abscess or other evidence of infection noted on examination.

  • Diagnosis of infection made by surgeon or attending physician.

In GYN surgery, our threats for infection lie primarily from vaginal organisms or skin organisms; however we may also come into contact with fecal content or enteric contents as well. Thinking about the organisms we’re helping to bolster defense against will help in selecting a preventive antibiotic. Thinking about the wound class is a simple way to characterize this:

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ACOG PB 195

ACOG also recommends a number of perioperative considerations/techniques to reduce SSI:

1. Treat remote infections - this one seems pretty obvious. If there’s an infection going on, like a skin infection or a UTI, it’s likely best to postpone surgery in favor of treating the infection!

2. Do not shave the incision site - Preoperative shaving by patients themselves has actually been shown to be likely harmful, increasing the risk of infection by introducing a nidus for infection remote from surgery. If hair needs to be clipped, it should be done immediately pre-op with electric clippers.

3. Prevent preop hyperglycemia - blood glucose should be targeted to < 200 mg/dL for both non-diabetic and diabetic patients before proceeding with surgery. Performing a preoperative random blood sugar prior to major surgery is a practice our hospital has implemented to identify diabetes in our patients, and to prevent SSI.

4. Advise patients to shower or bathe with full body soap on at least the night before surgery -We found it fairly surprising that no particular soap is recommended over another. Many offices offer patients a chlorhexidine soap for use the night before surgery. The soap significantly reduces risk of cellulitis versus no bathing.

5. Use alcohol-based preop skin prep, unless contraindicated - chlorhexidine-alcohol combinations have been proven in RCTs and meta-analyses to be superior to povidine-iodine for preoperative skin preparation. For mucosal sites such as the vagina, where high alcohol concentrations should not be used due to irritation risk, povidine-iodine or chlorexidine soap solutions should be used.

6. Maintain appropriate aseptic technique - Of course, right? But in addition, our surgical technique does matter! Effective hemostasis while preserving vital blood supply, maintaining normothermia and reducing operative time, gentle tissue handling, avoiding inadvertent injuries, using drains when appropriate, and eradicating dead space can all help to reduce risk of SSI.

7. Minimize OR traffic - safety bundles that have included components to reduce opening of OR doors during cases have been shown to reduce SSI.

8. For hysterectomy, consider preop screening for bacterial vaginosis - prior to routine use of antibiotic prophylaxis for hysterectomy, use of metronidazole pre-op in patients who screened positive for BV reduced SSI. These studies haven’t been repeated with systematic antibiotic prophylaxis, but given the data, ACOG does state that screening is reasonable at the preop visit.

Alright, now time for the antibiotics! We dive deeper in the podcast, but PB 195 will give you the quick version here in the tables:

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ACOG PB 195

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ACOG PB 195

HIV in the Non-Pregnant Patient

We jump back to our STI saga to cover HIV today. ACOG PB 167 and CO 596 make for supplementary reading for this show.

The CDC and USPSTF recommend at least one-time HIV screening in most women. The CDC goes further to recommend up to annual screening in certain high-risk groups, including IV drug users, > 1 sex partner annually or known sex partner with HIV, those who exchange sex for money or goods, and MSM.

Screening is important, because almost 25% of new cases occur in women, and heterosexual intimate contact is the most common form of disease spreading. ACOG subscribes to a philosophy of “opt out” testing, by which HIV screening should be considered routine, with the patient able to opt out. Physicians need to document the reason for this in their notes. Screening tests are broken into rapid and confirmatory. A positive rapid screen should always be followed with a confirmatory test, as the rapid screens have high sensitivity, but lower specificity.

GYN care may vary somewhat with positive HIV status. For Pap smears, PB 167 describes an appropriate algorithm for dealing with initial screening and some positive results:

ACOG PB 167

We spend some time reviewing the treatment of other STIs in the podcast briefly, all of which are reviewed in PB 167 as well. Highlights include:

• Using 1 week rather than single-dose metronidazole treatment for trichomonal infections

• Re-testing any positive GC/CT testing result at 3 months, due to high risk of re-infection

• Screening for most STIs at entry to care for HIV-affected patients.

Birth control is also another important topic for HIV-affected patients. ACOG and the CDC recommend use of dual-contraception — that is, a barrier method and a hormonal method — to prevent viral spread. Certain forms of hormonal contraception may be affected by antiretroviral drugs:

• CHCs: The NNRTI non nucleoside reverse transcriptase inhibitor efavirenz and certain protease inhibitors (-navir) may decrease efficacy of combined methods by reducing contraceptive hormone levels; however, they are considered US MEC Category 2.

  • The exception to this rule is fosamprenavir, as CHCs also lead to decreased levels of this protease inhibitor (US MEC 3).

• Etonogestrel implant:  Similarly to CHCs, there are theoretical risks in decreased contraceptive effectiveness for patients on efavirenz; however, the implant remains US MEC 2.

• DMPA: MEC category 1 for all users, except for those on fosamprenavir; there is limited evidence DMPA decreases fosamprenavir levels like CHCs (US MEC 2).

• IUDs: MEC category 1 for all users!

• Emergency contraception: for oral medicatons such as levenorgestrel and ulipristal, these should be offered to HIV-affected women as the benefits of emergency contraception are considered to outweigh the risks in this group. Similarly to CHCs, there is theoretical risk of decreased efficacy of these methods among women taking efavirenz.

Finally, in a preview to our next episode, we talk about preconception counseling for HIV-affected patients. The goal for any patient with HIV is to achieve a negative viral load, and for OB-GYNs, this is important to limit vertical transmission. Efavirenz has been associated with neural tube defects, so should be avoided in pregnancy if possible.

Conceiving is safest through artificial insemination. However, if natural conception is desired. OB-GYNs should discuss limiting unprotected intercourse to ovulatory times, and using pre-exposure prophylaxis for the patient, or her partner, in serodiscordant couples. This generally involves a daily regimen of tenofovir/emtricitabine (Truvada) for 1 month prior to, and 1 month after, conception. Risk reduction is estimated to be somewhere between 63-75%, and the best-available data suggests this is likely safe.