What are the updated treatment recommendations for chlamydia and gonococcal infections?

The 2021 Guidelines
In July 2021 the Centers for Disease Control and Prevention (CDC) updated their guidelines for sexually transmitted infections.¹ These guidelines replace the 2015 guidelines with several updates to screening, diagnosing, and treating various sexually transmitted infections.² The focus of this review is the updated treatment recommendations for patients with chlamydia or gonococcal infections.

Recommended treatment options for patients with chlamydia or gonococcal infections
The CDC recommendations for chlamydia and gonococcal infections in 2015 and 2021 are summarized in the Table. A key change is the removal of azithromycin as a recommended regimen for chlamydia as well as its removal in combination with ceftriaxone for gonococcal infections.

Chlamydia
Over 1.8 million cases of chlamydia were reported in the US in 2019 making it the most common bacterial infection in this country.³ Complications of chlamydial infections can include pelvic inflammatory disease (PID), ectopic pregnancy, and infertility.¹ Chlamydia screening in women less than 25 years of age (and in older women at increased risk) has been shown to reduce PID.⁴

For patients diagnosed with chlamydia, prompt treatment is warranted, and treatment of sexual partners is recommended.¹ Recent evidence indicates that doxycycline is effective for urogenital, rectal, and oropharyngeal chlamydia infections, and it is now the preferred option to azithromycin. Although azithromycin continues to be sufficiently effective for urogenital chlamydial infections, it has been found to be less effective in rectal chlamydial infections. A 2019 Cochrane review found higher microbiological failure with azithromycin in men treated for chlamydia infections (risk ratio [RR] 2.45; 95% CI, 1.36 to 4.41).⁵ The risk of microbiologic failure in women was not significantly different between treatments (RR 1.71; 95% CI, 0.48 to 6.16). A 2021 systematic review in patients with rectal chlamydia found a higher microbiological cure rate with doxycycline than azithromycin (RR 1.21; 95% CI, 1.15 to 1.28).⁶ It should be noted that the guidelines do consider the potential for nonadherence with the 7-day regimen of doxycycline.¹ In cases where there is significant concern for adherence, the 1-dose azithromycin regimen can be considered; however, the guidelines suggest that posttreatment testing may be necessary due to lower efficacy with azithromycin treatment. In addition to azithromycin changes, erythromycin was also removed as an alternative regimen largely due to gastrointestinal adverse effects associated with its use. The guidelines also recommend that any sexual partner within the last 60 days be evaluated and treated.

Pregnant women should not be treated with doxycycline – azithromycin remains the treatment of choice for pregnant patients with test of cure 4 weeks after completion of therapy.¹ Erythromycin is the recommended treatment for neonates, infants, and children who weigh less than 45 kg with azithromycin the preferred regimen for those weighing at least 45 kg or at least 8 years of age.

Gonococcal infections
Over 600,000 gonococcal infections were reported in the US in 2019 making it the second most common bacterial infection.³ Coinfections with chlamydia are common, and patients with gonorrhea should be treated for chlamydia if coinfection has not been ruled out.⁷ Gonorrhea is associated with numerous health problems including preterm birth, low birth weight, infant death, neonatal ophthalmia, PID, schizophrenia in offspring, and prostate problems.⁸

Rapid evolution of treatment for gonococcal infections has been necessary based on antimicrobial resistance.^1,7 Historically, fluoroquinolones were a treatment option for patients with gonococcal infections, but fluoroquinolone-resistant Neisseria gonorrhoeae emerged in the early 2000s eliminating this as a treatment strategy.⁷ Although dual therapy with ceftriaxone and azithromycin was previously recommended, the addition of azithromycin is no longer recommended due to concerns of the microbiome and the effect of azithromycin overuse on the susceptibility of other organisms.¹ Alternatives to ceftriaxone are lacking and concerns over N. gonorrhoeae resistance to ceftriaxone are mounting.⁹ Oral cephalosporins are not recommended with the exception of cefixime (800 mg) when ceftriaxone is not available or feasible.¹

At this time the CDC does not recommend a test of cure for patients with uncomplicated urogenital or rectal gonorrhea; however, patients with pharyngeal gonorrhea should return 1 to 2 weeks after treatment for testing.¹ Similar to chlamydia, sexual partners should be treated.

Pregnant women can be treated with ceftriaxone 500 mg similar to nonpregnant patients with gonococcal infections.¹ Patients with gonococcal conjunctivitis should be treated with a 1 g ceftriaxone dose.

Conclusion

Updated treatment recommendations are available for chlamydia and gonococcal infections. These guidelines significantly reduce the use of azithromycin and remove several alternative options for chlamydia infections. Clinicians should closely monitor for updated treatment guidance, particularly in the case of gonococcal infections where treatment options are extremely limited and drug resistance is a concern.

References

1. Workowski KA, Bachmann, LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. doi:10.15585/mmwr.rr7004a1
2. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015 Aug 28;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137.
3. Sexually transmitted disease surveillance 2019. Centers for Disease Control and Prevention. Reviewed April 13, 2021. Accessed December 3, 2021. https://www.cdc.gov/std/statistics/2019/tables/1.htm
4. Cantor A, Dana T, Griffin JC, et al. Screening for chlamydial and gonococcal infections: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;326(10):957-966. doi:10.1001/jama.2021.10577
5. Páez-Canro C, Alzate JP, González LM, Rubio-Romero JA, Lethaby A, Gaitán HG. Antibiotics for treating urogenital Chlamydia trachomatis infection in men and non-pregnant women. Cochrane Database Syst Rev. 2019;1(1):CD010871. doi:10.1002/14651858.CD010871.pub2
6. Chen LF, Wang TC, Chen FL, et al. Efficacy of doxycycline versus azithromycin for the treatment of rectal chlamydia: a systematic review and meta-analysis. J Antimicrob Chemother. 2021;76(12):3103-3110. doi:10.1093/jac/dkab335
7. Dombrowski JC. Chlamydia and Gonorrhea. Ann Intern Med. 2021;174(10):ITC145-ITC160. doi:10.7326/AITC202110190
8. Whelan J, Eeuwijk J, Bunge E, Beck E. Systematic literature review and quantitative analysis of health problems associated with sexually transmitted Neisseria gonorrhoeae infection. Infect Dis Ther. 2021;10(4):1887-1905. doi:10.1007/s40121-021-00481-z
9. Unemo M, Seifert HS, Hook EW 3rd, Hawkes S, Ndowa F, Dillon JR. Gonorrhoea. Nat Rev Dis Primers. 2019;5(1):79. doi:10.1038/s41572-019-0128-6

Prepared by:
Courtney Krueger, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

January 2022

The information presented is current as December 3, 2021. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.