Standard Treatment Regimens for Nongonococcal Urethritis Have Similar but Declining Cure Rates: A Randomized Controlled Trial

Manhart, Lisa E.; Gillespie, Catherine W.; Lowens, M Sylvan; Khosropour, Christine M; Colombara, Danny V.; Golden, Matthew R.; Hakhu, Navneet R.; Thomas, Katherine K.; Hughes, James P.; Jensen, Nicole L.; Totten, Patricia A.

doi:10.1093/cid/cis1022

Cited by 177 publications

(194 citation statements)

References 27 publications

Supporting

Mentioning

183

Contrasting

Unclassified

Order By: Relevance

“…The prevalence of pathogens identified in both studies is reassuringly similar, and these data confirm C. trachomatis and M. genitalium are less likely to be detected in MSM. The estimates for C. trachomatis and M. genitalium are also in keeping with other estimates from our service and region (17)(18)(19)(20). It was interesting to note that even in the presence of a bacterial pathogen, MSM reported more consistent condom use for anal sex than MSW for vaginal sex and that MSM with idiopathic NGU were also substantially more likely to report engaging in only nonpenetrative anal/ vaginal sexual activity with their partners in the prior 3 months.…”

Section: Discussionsupporting

confidence: 83%

Characteristics of Acute Nongonococcal Urethritis in Men Differ by Sexual Preference

et al. 2014

View full text Add to dashboard Cite

N ucleic acid amplification techniques (NAAT) have allowed greater understanding of the variety of pathogens involved in acute nongonococcal urethritis (NGU) (1). This has included the recent recognition of Mycoplasma genitalium, herpes simplex virus (HSV), and adenoviruses as urethral pathogens (2-5), although in a significant proportion of cases no urethral pathogen is currently identified. The role of Ureaplasma urealyticum in NGU has been somewhat controversial, but recent evidence implicates specific biovars and possibly higher bacterial loads as causally associated with acute NGU (6-8). Sporadic case reports implicate other bacteria such as Haemophilus species (Haemophilus influenzae and Haemophilus parainfluenzae), Streptococcus species (Streptococcus pneumoniae and Streptococcus pyogenes), and Moraxella catarrhalis in acute NGU, following orogenital sex (9-11); however, their etiologic role has not been established in case-control studies.Diagnostic and management approaches to acute NGU do not differentiate between men who have sex with men (MSM) and men who have sex with women (MSW). Yet sexual behaviors differ considerably between these groups, and it is therefore likely that the spectrum of pathogens varies. In support of this, a previous case-control study of NGU in our service found that Chlamydia trachomatis or M. genitalium were more likely to be associated with female partners, while viruses, such as HSV and adenovirus, were associated with a recent history of male sexual partners (2). Further elucidation of the etiology of this common syndrome, and developing an understanding of how sexual practices influence the detection of urethral pathogens, could improve the management of men and their partners (1,12,13). In this study, we examined behavioral, demographic, and laboratory characteristics of a large series of MSW and MSM with acute urethral symptoms over a 6-year period. We aimed to determine if there were key differences between MSW and MSM with acute NGU in the spectrum of pathogens involved and whether there were differences in sexual behavior preceding the acquisition of NGU. MATERIALS AND METHODSStudy population. We retrospectively reviewed the electronic case record database of Melbourne Sexual Health Centre, the main public sexually transmitted diseases clinic in Melbourne, Australia, from January 2006 to December 2011. Patients were required to have the diagnosis of acute NGU entered into the electronic medical record, with one or more of the following acute urethral symptoms for less than 1 month's duration: urethral discharge and urethral irritation, discomfort, or itch; patients also needed to fulfill the conventional laboratory definition of urethritis, namely, 5 or more polymorphic neutrophilic lymphocytes/high-powered field (Ն5 polymorphonuclear leukocytes [PMNL]/high-powered field [HPF]) on urethral Gram stain. Importantly, only a single first episode of acute NGU per case over the study period was included. All subsequent

show abstract

Section: Discussionsupporting

confidence: 83%

Characteristics of Acute Nongonococcal Urethritis in Men Differ by Sexual Preference

et al. 2014

View full text Add to dashboard Cite

show abstract

“…This study, to our knowledge, is the first to investigate macrolide susceptibility among low-risk women and suggests that M. genitalium strains circulating in this population are more susceptible to these antibiotics than those in higherrisk populations such that AZM is less effective (12,47). AZM treatment failures using the 1-g dose have ranged from 15 to 60% (47)(48)(49).…”

Section: Discussionmentioning

confidence: 88%

“…Since AZM is commonly used to treat male NGU and is also included in the current CDC treatment guidelines for gonorrheae, it remains imperative to monitor resistance patterns for M. genitalium and other bacterial STIs since virtually all men with urethritis receive AZM. In patients with AZM-resistant M. genitalium infections, moxifloxacin is the recommended and most commonly used antibiotic (12,47), but reports of resistance are emerging (50).…”

Section: Discussionmentioning

confidence: 99%

Mycoplasma genitalium Infection Is Associated with Microscopic Signs of Cervical Inflammation in Liquid Cytology Specimens

Dehon¹,

McGowin²

2014

J Clin Microbiol

View full text Add to dashboard Cite

Cervicitis is a common clinical finding often attributed to sexually transmitted infections (STIs), but no etiologic agent is identified in the majority of cases. In this study, we comparatively assessed inflammation among the common infectious etiologies of cervicitis and assessed the potential value of liquid cytology specimens for predicting STIs. Among 473 Louisiana women at low risk for acquiring STIs, the prevalences of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in liquid-based cytology specimens were 1.5, 2.1, 0.6, and 4.4%, respectively. N. gonorrhoeae and human papillomavirus 18 (HPV18) infections were significantly more common among subjects infected with M. genitalium. Using direct microscopy, we observed significant increases in leukocyte infiltrates among subjects with monoinfections with M. genitalium or C. trachomatis compared to women with no detectable STIs. Inflammation was highest among subjects with M. genitalium. Using a threshold of >2 leukocytes per epithelial cell per high-powered field, the positive predictive values for M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis were 100, 70, 67, and 20%, respectively. Several novel M. genitalium genotypes were identified, all of which were predicted to be susceptible to macrolide antibiotics, suggesting that different strains may circulate among low-risk women and that macrolide resistance is substantially lower than in high-risk populations. This study highlights the capacity of M. genitalium to elicit cervical inflammation and, considering the strong epidemiologic associations between M. genitalium and human immunodeficiency virus (HIV), provides a potential mechanism for acquisition and shedding of HIV via chronic leukocyte recruitment to the cervical mucosa.

show abstract

“…Most early studies have shown insufficient microbiological and clinical cure rates with tetracyclines, whereas azithromycin (1-g single dose) appeared to be superior but far from perfect, with cure rates rarely exceeding 85% (16)(17)(18). However, more recent randomized clinical trials from the United States have shown a decreasing cure rate after azithromycin 1-g single-dose therapy, with a microbiological cure rate of 67% among patients included between 2006 and 2009 (19) reduced to 40% among patients included between 2007 and 2011 (20). Moxifloxacin is currently the most commonly used second-line antibiotic in patients failing azithromycin treatment (11,21).…”

mentioning

confidence: 99%

In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains

Jensen

Fernandes

Unemo

2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Mycoplasma genitalium, first isolated in 1980 (1), has become well established as an etiological agent of sexually transmitted infections (reviewed in reference 2). Several studies have demonstrated the association between M. genitalium and urethritis in men and urethritis, cervicitis, endometritis, and pelvic inflammatory disease in women (3-7). The prevalence of M. genitalium in men with nonchlamydial nongonococcal urethritis (NCNGU) ranges from 10% to 35% (2), and in men and women in the general population, it ranges from 1% to 3.3% (8-10).Persistence of M. genitalium is associated with recurrent or persistent nongonococcal urethritis (NGU), as illustrated by the findings of Bradshaw et al. (11) showing that 91% of patients with persistent M. genitalium infection experienced persistent symptoms compared to 17% of patients in whom M. genitalium was eradicated. In men with persistent NCNGU after doxycycline therapy, as many as 41% were found to be M. genitalium positive (12).M. genitalium, like other mycoplasmas, lacks a rigid peptidoglycan-containing cell wall (13). Hence, ␤-lactam antibiotics and other antibiotics targeting the cell wall are not active. Early in vitro studies showed that M. genitalium was highly susceptible to macrolides, particularly to azithromycin, but that it had reduced susceptibility to tetracyclines and older quinolones, such as norfloxacin and ciprofloxacin (14). Ketolides (15), which are related to macrolides such as azithromycin, and some of the newer fluoroquinolones, such as moxifloxacin, have sufficiently low MICs in vitro to be clinically useful (14).Currently, no evidence-based guidelines specifically for the treatment of M. genitalium infection have been developed. Most early studies have shown insufficient microbiological and clinical cure rates with tetracyclines, whereas azithromycin (1-g single dose) appeared to be superior but far from perfect, with cure rates rarely exceeding 85% (16-18). However, more recent randomized clinical trials from the United States have shown a decreasing cure rate after azithromycin 1-g single-dose therapy, with a microbiological cure rate of 67% among patients included between 2006 and 2009 (19) reduced to 40% among patients included between 2007 and 2011 (20). Moxifloxacin is currently the most commonly used second-line antibiotic in patients failing azithromycin treatment (11, 21). However, the side effects, cost, and risk of selection for antimicrobial resistance limit the use of moxifloxacin.Macrolide resistance in M. genitalium is primarily caused by mutations in nucleotide 2058 or 2059 (Escherichia coli numbering) in region V of the 23S rRNA gene and is commonly selected during treatment with macrolides (22, 23). The increasing level of macrolide resistance challenges the use of azithromycin as the first-line treatment for NGU, and new treatment options are needed, in particular in light of emerging resistance to moxifloxacin, as well (24).In this study, we evaluated the in vitro activity of the newly developed fluoroketolide solithr...

show abstract

Standard Treatment Regimens for Nongonococcal Urethritis Have Similar but Declining Cure Rates: A Randomized Controlled Trial

Abstract: Clinical and microbiologic cure rates for NGU were somewhat low and there was no significant difference between azithromycin and doxycycline. Mycoplasma genitalium treatment failure was extremely common. Clinical Trials Registration.NCT00358462.

Cited by 177 publications

References 27 publications

Characteristics of Acute Nongonococcal Urethritis in Men Differ by Sexual Preference

Characteristics of Acute Nongonococcal Urethritis in Men Differ by Sexual Preference

Mycoplasma genitalium Infection Is Associated with Microscopic Signs of Cervical Inflammation in Liquid Cytology Specimens

In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains

Contact Info

Product

Resources

About