Treatment Effectiveness of Azithromycin and Doxycycline in Uncomplicated Rectal and Vaginal Chlamydia trachomatis Infections in Women: A Multicenter Observational Study (FemCure)

Nicole H T M Dukers-Muijrers, Petra F G Wolffs, Henry De Vries, Hannelore M Götz, Titia Heijman, Sylvia Bruisten, Lisanne Eppings, Arjan Hogewoning, Mieke Steenbakkers, Mayk Lucchesi, Maarten F Schim van der Loeff, Christian J P A Hoebe, Nicole H T M Dukers-Muijrers, Petra F G Wolffs, Henry De Vries, Hannelore M Götz, Titia Heijman, Sylvia Bruisten, Lisanne Eppings, Arjan Hogewoning, Mieke Steenbakkers, Mayk Lucchesi, Maarten F Schim van der Loeff, Christian J P A Hoebe

Abstract

Background: Rectal infections with Chlamydia trachomatis (CT) are prevalent in women visiting a sexually transmitted infection outpatient clinic, but it remains unclear what the most effective treatment is. We assessed the effectiveness of doxycycline and azithromycin for the treatment of rectal and vaginal chlamydia in women.

Methods: This study is part of a prospective multicenter cohort study (FemCure). Treatment consisted of doxycycline (100 mg twice daily for 7 days) in rectal CT-positive women, and of azithromycin (1 g single dose) in vaginally positive women who were rectally untested or rectally negative. Participants self-collected rectal and vaginal samples at enrollment (treatment time-point) and during 4 weeks of follow-up. The endpoint was microbiological cure by a negative nucleic acid amplification test at 4 weeks. Differences between cure proportions and 95% confidence intervals (CIs) were calculated.

Results: We analyzed 416 patients, of whom 319 had both rectal and vaginal chlamydia at enrollment, 22 had rectal chlamydia only, and 75 had vaginal chlamydia only. In 341 rectal infections, microbiological cure in azithromycin-treated women was 78.5% (95% CI, 72.6%-83.7%; n = 164/209) and 95.5% (95% CI, 91.0%-98.2%; n = 126/132) in doxycycline-treated women (difference, 17.0% [95% CI, 9.6%-24.7%]; P < .001). In 394 vaginal infections, cure was 93.5% (95% CI, 90.1%-96.1%; n = 246/263) in azithromycin-treated women and 95.4% (95% CI, 90.9%-98.2%; n = 125/131) in doxycycline-treated women (difference, 1.9% [95% CI, -3.6% to 6.7%]; P = .504).

Conclusions: The effectiveness of doxycycline is high and exceeds that of azithromycin for the treatment of rectal CT infections in women.

Clinical trials registration: NCT02694497.

Keywords: Chlamydia trachomatis; rectal; treatment effectiveness; women.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Study design. Abbreviations: STI, sexually transmitted infection; T-1, STI clinic testing consultation, T0, enrollment; T1, follow-up (week 4).
Figure 2.
Figure 2.
Flowchart of chlamydia infections in the analyses.

References

    1. Unemo M, Bradshaw CS, Hocking JS, et al. . Sexually transmitted infections: challenges ahead. Lancet Infect Dis 2017; 17:e235–79.
    1. Hocking JS, Kong FY, Timms P, Huston WM, Tabrizi SN. Treatment of rectal chlamydia infection may be more complicated than we originally thought. J Antimicrob Chemother 2015; 70:961–4.
    1. Dewart CM, Bernstein KT, DeGroote NP, Romaguera R, Turner AN. Prevalence of rectal chlamydial and gonococcal infections: a systematic review. Sex Transm Dis 2018; 45:287–93.
    1. Dukers-Muijrers NH, Schachter J, van Liere GA, Wolffs PF, Hoebe CJ. What is needed to guide testing for anorectal and pharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae in women and men? Evidence and opinion. BMC Infect Dis 2015; 15:533.
    1. Chan PA, Robinette A, Montgomery M, et al. . Extragenital infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae: a review of the literature. Infect Dis Obstet Gynecol 2016; 2016:5758387.
    1. van Liere GAFS, Dukers-Muijrers NHTM, Levels L, Hoebe CJPA. High proportion of anorectal Chlamydia trachomatis and Neisseria gonorrhoeae after routine universal urogenital and anorectal screening in women visiting the sexually transmitted infection clinic. Clin Infect Dis 2017; 64:1705–10.
    1. Chandra NL, Broad C, Folkard K, et al. . Detection of Chlamydia trachomatis in rectal specimens in women and its association with anal intercourse: a systematic review and meta-analysis. Sex Transm Infect 2018; 94:320–6.
    1. Heijne JCM, van Liere GAFS, Hoebe CJPA, Bogaards JA, van Benthem BHB, Dukers-Muijrers NHTM. What explains anorectal chlamydia infection in women? Implications of a mathematical model for test and treatment strategies. Sex Transm Infect 2017; 93:270–5.
    1. Davies B, Turner KME, Frølund M, et al. . Danish Chlamydia Study Group Risk of reproductive complications following chlamydia testing: a population-based retrospective cohort study in Denmark. Lancet Infect Dis 2016; 16:1057–64.
    1. Kong FY, Tabrizi SN, Law M, et al. . Azithromycin versus doxycycline for the treatment of genital chlamydia infection: a meta-analysis of randomized controlled trials. Clin Infect Dis 2014; 59:193–205.
    1. Geisler WM, Uniyal A, Lee JY, et al. . Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N Engl J Med 2015; 373:2512–21.
    1. Kong FY, Tabrizi SN, Fairley CK, et al. . The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis. J Antimicrob Chemother 2015; 70:1290–7.
    1. Lau A, Kong F, Fairley CK, et al. . Treatment efficacy of azithromycin 1 g single dose versus doxycycline 100 mg twice daily for 7 days for the treatment of rectal chlamydia among men who have sex with men—a double-blind randomised controlled trial protocol. BMC Infect Dis 2017; 17:35.
    1. Li B, Hocking JS, Bi P, Bell C, Fairley CK. The efficacy of azithromycin and doxycycline treatment for rectal chlamydial infection: a retrospective cohort study in South Australia. Intern Med J 2018; 48:259–64.
    1. Gratrix J, Brandley J, Dane M, et al. . A retrospective review of treatment failures using azithromycin and doxycycline in the treatment of rectal chlamydia infections in women and men who have sex with men. Sex Transm Dis 2016; 43:110–2.
    1. Dukers-Muijrers NH, Wolffs PF, Eppings L, et al. . Design of the FemCure study: prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care. BMC Infect Dis 2016; 16:381.
    1. Lanjouw E, Ouburg S, de Vries HJ, Stary A, Radcliffe K, Unemo M. 2015 European guideline on the management of Chlamydia trachomatis infections. Int J STD AIDS 2016; 27:333–48.
    1. Ding A, Challenor R. Rectal chlamydia in heterosexual women: more questions than answers. Int J STD AIDS 2014; 25:587–92.
    1. Janssen KJ, Hoebe CJ, Dukers-Muijrers NH, Eppings L, Lucchesi M, Wolffs PF. Viability-PCR shows that NAAT detects a high proportion of DNA from non-viable Chlamydia trachomatis. PLoS One 2016; 11:e0165920.
    1. Bom RJ, van der Helm JJ, Schim van der Loeff MF, et al. . Distinct transmission networks of Chlamydia trachomatis in men who have sex with men and heterosexual adults in Amsterdam, the Netherlands. PLoS One 2013; 8:e53869.
    1. Janssen KJH, Dirks JAMC, Dukers-Muijrers NHTM, Hoebe CJPA, Wolffs PFG. Review of Chlamydia trachomatis viability methods: assessing the clinical diagnostic impact of NAAT positive results. Expert Rev Mol Diagn 2018; et al.:739–47.
    1. Dukers-Muijrers NH, Speksnijder AG, Morré SA, et al. . Detection of anorectal and cervicovaginal Chlamydia trachomatis infections following azithromycin treatment: prospective cohort study with multiple time-sequential measures of rRNA, DNA, quantitative load and symptoms. PLoS One 2013; 8:e81236.
    1. Versteeg B, Bruisten SM, Heijman T, et al. . Monitoring therapy success of urogenital Chlamydia trachomatis infections in women: a prospective observational cohort study. PLoS One 2017; 12:e0185295.
    1. Lewis R, Tanton C, Mercer CH, et al. . Heterosexual practices among young people in Britain: evidence from three national surveys of sexual attitudes and lifestyles. J Adolesc Health 2017; 61:694–702.
    1. Horner P. The case for further treatment studies of uncomplicated genital Chlamydia trachomatis infection. Sex Transm Infect 2006; 82:340–3.
    1. Kong FY, Tabrizi SN, Fairley CK, et al. . Higher organism load associated with failure of azithromycin to treat rectal chlamydia. Epidemiol Infect 2016; 144:2587–96.
    1. Foschi C, Salvo M, Cevenini R, Marangoni A. Chlamydia trachomatis antimicrobial susceptibility in colorectal and endocervical cells. J Antimicrob Chemother 2018; 73:409–13.
    1. Horner PJ. Azithromycin antimicrobial resistance and genital Chlamydia trachomatis infection: duration of therapy may be the key to improving efficacy. Sex Transm Infect 2012; 88:154–6.
    1. World Health Organization. Guidelines for the management of sexually transmitted infections. Geneva, Switzerland: WHO, 2004.
    1. Thanh NX, Akpinar I, Gratrix J, et al. . Benefit of adjunct universal rectal screening for chlamydia genital infections in women attending Canadian sexually transmitted infection clinics. Int J STD AIDS 2017; 28:1311–24.
    1. Khosropour CM, Manhart LE, Colombara DV, et al. . Suboptimal adherence to doxycycline and treatment outcomes among men with non-gonococcal urethritis: a prospective cohort study. Sex Transm Infect 2014; 90:3–7.
    1. Augenbraun M, Bachmann L, Wallace T, Dubouchet L, McCormack W, Hook EW 3rd. Compliance with doxycycline therapy in sexually transmitted diseases clinics. Sex Transm Dis 1998; 25:1–4.

Source: PubMed

3
Prenumerera