When the new Centers for Disease Control and Prevention (CDC) recommendations1 regarding the treatment of uncomplicated gonorrhea (and indirectly chlamydia) debuted like a slice of antibiotic resistance doom, it felt like another “gift” had arrived from 2020. Intramuscular (IM) ceftriaxone dosing has increased from 250 mg to 500 mg (or 1 g for weight ≥150 kg). Empiric chlamydia coverage switched from a single dose of 1 g of azithromycin to doxycycline 100 mg PO BID for 7 days. Being deferential to CDC expertise, many providers accepted them uncritically. Compliance rates with a switch from a 1-time to a 7-day regimen are not addressed, especially worrisome for a condition that can be minimally or asymptomatic.
A young woman presents with new and concerning discharge after an unprotected encounter. Her pregnancy test is negative. After agreement for empiric treatment, the patient then refuses empiric treatment when told about the new guidelines (2 injections and 14 chances for esophagitis). Patient specifically asks for the old regime or will just leave against medical advice.
It is important to note that the evidence of ceftriaxone, cefixime, and azithromycin resistance for gonorrhea is substantial.2 Observational data from across the United States and world demonstrate worsening resistance patterns. Many of our pharmacy colleagues are working on obtaining 500 mg/2 mL ceftriaxone for injection vials, so it can be given in single injection (or two for morbidly obese patients). While this guideline may be existentially troubling, this change is practically feasible and should become standard of care.
Read more about the Trick of the Trade on administering IV instead of IM ceftriaxone for gonorrohea.
The evidence basis for the change to doxycycline for treatment of chlamydia co-infection coverage is substantially weaker. It is also decidedly mute on the risks of partial or non-compliance with treatment. The question then becomes: How profound is the treatment effect and how does it balance against its risks?
The guideline states, as evidence for the doxycycline switch:
“A recent investigation comparing children who received twice-yearly azithromycin with children who received placebo found that the gut’s resistome, a reservoir of antimicrobial resistance genes in the body, had increased determinants of macrolide and nonmacrolide resistance, including beta-lactam antibiotics, among children receiving azithromycin (10).3 A higher proportion of macrolide resistance in nasopharyngeal Streptococcus pneumoniae was demonstrated in communities receiving mass administration of oral azithromycin (11).4 Azithromycin resistance has been demonstrated in another STI, Mycoplasma genitalium, and sexually transmissible enteric pathogens (e.g., Shigella and Campylobacter) (12–14)5-7. In addition, evidence supports increasing concern for the efficacy of azithromycin to treat chlamydial infections, especially rectal infections (15,16)8,9.”
Citations 10 and 11 speak in generalities of resistance patterns, with citation 11 being a secondary analysis of a mass azithromycin treatment trial of young children in Niger. Citations 12-14 discuss rates of coinfection treatment failure – an important consideration, but only secondarily relevant. That leaves 2 citations (15 and 16)– one a meta-analysis and one a small poster that isn’t even available online related to known anorectal chlamydia.
That really leaves the meta-analysis8 to answer our question: how best do we protect the reproductive health of our patients in the setting of diagnostic uncertainty?
The meta-analysis is somewhat messy with substantial heterogeneity in many relevant subgroups.8 A single study comprises the majority of the evidence that shows doxycycline superiority in non-gonococcal urethritis.10 It was from 2011 and revealed that while doxycycline may be better for chlamydia treatment, azithromycin was better for coinfection treatment (such as shigella or mycoplasma). And to top the whole thing, the doxycycline superiority line reads:
“We found a pooled efficacy difference in favor of doxycycline of 1.5%… to 2.6%.”
In men with symptomatic urethritis, the superiority of doxycycline increases to 7% (an NNT of 14). If you ignore the heterogeneity and pool everyone, we arrive with an overall NNT for doxycycline over azithromycin of 38 (fixed effects model size was a 2.6% advantage). If the above study10 was removed, the pooled difference would have been non-significant with an NNT of at least 50.
Having thought perhaps they just didn’t include all the evidence, a secondary literature review was undertaken. A few small case studies11 and older observational studies12,13 were found, which showed a potential treatment failure rate of azithromycin of up to 8%, but comparable rates with doxycycline.12 That’s it. There is also genuine concern that use of azithromycin may induce resistance not only for itself but other antibiotic classes3,4 but this concern is based on fecal biome sampling from toddlers and requires a couple of steps to be relevant to our question. Doxycycline, an essential medication in its own right, for treatment of tick-borne disease, ascending genital tract infections, COPD exacerbation and MRSA, also requires our stewardship.
Given patient non-compliance with filling and completing ED prescriptions approach rates of 20%,14,15 the recommendation for a 7-day course of doxycycline for chlamydia over single-dose azithromycin is fraught with peril. Additionally, consider that the patient may be relatively asymptomatic, placing them even more at risk for medication non-compliance for the 7-day course of doxycycline. Contrast this with the risks of pelvic inflammatory disease and infertility if untreated.
Given the sparse, heterogenous literature, we should have strong reservations about recommending doxycycline for patients for whom chlamydia has not been excluded. New gonorrhea treatment recommendations should be followed and efforts made to stock appropriate concentrations of ceftriaxone. A single-dose of azithromycin may be a reasonable alternative for your patient for non-gonococcal disease, after considering and discussing the risks and benefits. Pregnant patients require close follow up but should also continue to receive azithromycin.
If you are prescribing doxycycline, remember:
If you are prescribing azithromycin, remember:
You explain to your patient that the new guidelines should be followed for gonorrhea, and so she receives 500 mg of IM ceftriaxone. While the new guideline for doxycycline MAY be slightly more effective for the treatment of chlamydia, using shared decision making, she receives the old regimen (single-dose azithromycin). You verbally emphasize and document in the discharge instructions the importance they follow up with either their PCP, gynecologist, or the local sexually transmitted infection clinic for a recheck, if their symptoms don’t resolve within 7 days.
A 78-year-old male is brought in from his nursing home for evaluation of hypotension. He has a prior history of multiple strokes and is bed bound. He arrives febrile, tachycardic, and hypotensive. On your physical exam, you notice that he has an indwelling foley catheter. The catheter tubing and bag have a vibrant purple color. You wonder if this unusual urine color could be caused by something insidious. Could this be related to a toxin, medication, or infection?(more…)
Welcome to the AIR Renal/Genitourinary Module! After carefully reviewing all relevant posts from the top 50 sites of the Social Media Index, the ALiEM AIR Team is proud to present the highest quality online content related to renal and genitourinary emergencies. 6 blog posts within the past 12 months (as of May 2020) met our standard of online excellence and were curated and approved for residency training by the AIR Series Board. We identified 1 AIR and 5 Honorable Mentions. We recommend programs give 3 hours (about 30 minutes per article) of III credit for this module.
Interested in taking the renal/GU quiz for fun or asynchronous (Individualized Interactive Instruction) credit? Please go to the above link. You will need to create a free, 1-time login account.
|emDocs||Complications of Nephrostomy Tubes: ED Presentations, Evaluation, and Management||Michael J. Yoo, MD||11/11/2019||AIR|
|RebelEM||Post Contrast Acute Kidney Injury||Salim Rezaie, MD||1/16/2020||HM|
|EMCrit||The Myth of Contrast Nephropathy||Josh Farkas, MD||5/2/2019||HM|
|EMCrit||Non-Anion Gap Metabolic Acidosis (NAGMA)||Josh Farkas, MD||9/19/2019||HM|
|emDocs||[email protected]: Kidney Transplant Complications||Rachel Bridwell, MD||12/29/2019||HM|
|CanadiEM||Testicular Torsion||Subhrata Verma||11/12/2019||HM|
(AIR = Approved Instructional Resource; HM = Honorable Mention)
Thank you to the Society of Academic Emergency Medicine (SAEM) and the Council of EM Residency Directors (CORD) for jointly sponsoring the AIR Series! We are thrilled to partner with both on shaping the future of medical education.
A 25-year-old man presents with 6 hours of penile pain and swelling after recreational penile injection of Trimix (alprostadil, papaverine, and phentolamine). He denies any history of sickle cell disease or penile trauma. On exam, he is in moderate discomfort and has a tumescent penis with a soft glans. You suspect the patient is suffering from ischemic, low-flow priapism. Manual compression and ice application have been attempted with no significant improvement in the patient’s clinical status.
Production and use of free open access medical education resources (FOAM) has had a meteoric rise over the last decade.1–4 ALiEM works hard to produce content, disseminate knowledge, and consolidate resources in a democratic and accessible way. However, we recognize that FOAM comes with its own limitations:
Case: A 58-year-old male with no past medical history presents to the emergency department for evaluation of right lower quadrant abdominal pain associated with right scrotal swelling. The patient reports that he had a colonoscopy the day before to remove a 20 mm polyp, which had been seen on an outpatient CT scan. He states that he noticed that his right scrotum appeared slightly swollen immediately away after the procedure, but since then the swelling had increased and he developed mild right lower quadrant abdominal pain. Physical examination reveals mild tenderness to the right lower quadrant and swelling of the right scrotum with palpable crepitus of the right scrotum and inguinal canal. There is no overlying skin discoloration. What is the most likely diagnosis?