Efficacy of standard therapies againstUreaplasmaspecies and persistence among men with non-gonococcal urethritis enrolled in a randomised controlled trial

Abstract

Objective U. urealyticum biovar 2 (UU-2) but not U. parvum (UP) has been associated with non-gonococcal urethritis (NGU), but little is known about species-specific responses to standard therapies. We examined species-specific treatment outcomes and followed men with treatment failure for 9 weeks. Methods From May 2007-July 2011, men aged ≥16 attending an STD clinic in Seattle, Washington with NGU (urethral discharge or urethral symptoms plus ≥5 PMNs/HPF) were enrolled in a double-blind, randomized trial. Participants received active azithromycin (1g) + placebo doxycycline or active doxycycline (100mg bid × 7d) + placebo azithromycin. Ureaplasmas were detected in culture followed by species-specific PCR. Outcomes were assessed at 3, 6, and 9 weeks. At 3 weeks, men with persistent Ureaplasmas received “reverse therapy” (e.g., active doxycycline if they first received active azithromycin). At 6 weeks, persistently-positive men received moxifloxacin (400mg × 7d). Results Of 490 men, 107 (22%) and 60 (12%) were infected with UU-2 and UP, respectively, and returned at 3 weeks. Persistent infection was similar for UU-2-infected men initially treated with azithromycin or doxycycline (25% vs. 31%, P=0.53), but differed somewhat for men with UP (45% vs. 24%; P=0.11). At 6 weeks, 57% of UU-2-infected and 63% of UP-infected men who received both drugs had persistent infection. Failure after moxifloxacin occurred in 30% and 36%, respectively. Persistent detection of UU-2 or UP was not associated with signs/symptoms of NGU. Conclusion Persistent infection after treatment with doxycycline, azithromycin, and moxifloxacin was common for UU and UP, but not associated with persistent urethritis.

Should we be testing for urogenital Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum in men and women? – a position statement from the European STI Guidelines Editorial Board

“…U. urealyticum is moderately sensitive to 14‐membered macrolides. In general, urogenital M. hominis , U. parvum and U. urealyticum can be difficult to eradicate in many individuals because of true antimicrobial resistance but also because of lower activity of the antimicrobials at low pH and lack of bactericidal activity . Additionally, suboptimal antimicrobial susceptibility testing methods, including many commercial kits, are frequently used .…”

“…In general, urogenital M. hominis, U. parvum and U. urealyticum can be difficult to eradicate in many individuals because of true antimicrobial resistance but also because of lower activity of the antimicrobials at low pH and lack of bactericidal activity. 4,27,[78][79][80] Additionally, suboptimal antimicrobial susceptibility testing methods, including many commercial kits, are frequently used. 80 The extensive treatment of these commonly colonizing commensals with suboptimal antimicrobial regimens selects for antimicrobial resistance in these bacteria and in many of the more severe bacterial 'true' STI agents as well as in the general microbiota.…”

“…• Ureaplasma urealyticum in high bacterial loads might cause a small proportion of male NGU, but the majority of men and women infected/colonized with U. urealyticum do not develop disease. Antimicrobial treatment which results in eradication is difficult, 4,27,78,79 and cure is not associated with eradication. 78 Treatment may result in development of antimicrobial resistance in urogenital mycoplasmas but also in other bacteria including the traditional, more severe 'true' STI agents.…”

Current understanding and treatment of intra‐amniotic infection with Ureaplasma spp.

“…The efficacy of azithromycin is different for U. parvum and U. urealyticum . In one study, after treatment with azithromycin, persistent urethritis was more commonly observed in patients infected with U. urealyticum than in those infected with U. parvum …”

Highlights from this issue

“…However Sviben et al 's data suggest that detection in men could reach worthwhile levels6 in symptomatic men. The question of what pathogens we should test for is further complicated by an RCT by Khrosopour et al ,7 showing that while persistence of ureaplasma species was common after treatment with standard therapies, it was not associated with persistent urethritis.…”