Symptomatic Non-gonococcal Urethritis Research Articles

Incidence of Nongonococcal Urethritis in Men Who Have Sex With Women and Associated Risk Factors.

Incidence and risk factors for nongonococcal urethritis (NGU) remain poorly defined. We conducted a cohort study to estimate the incidence of NGU and identify risk factors in men who have sex with women. We enrolled cisgender male sexually transmitted disease clinic attendees 16 years or older who reported exclusively female partners. At enrollment and 6 monthly follow-up visits, men underwent a clinical examination, provided urethral swab and urine specimens, completed a sexual behavior survey and biweekly diaries, and were tested for Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) using Aptima assays (Hologic, Inc). Nongonococcal urethritis was defined as ≥5 polymorphonuclear leukocytes per high-power field plus either urethral symptoms or visible discharge. We estimated the incidence of NGU overall, asymptomatic and symptomatic NGU, non-CT/non-MG NGU, and CT/MG-associated NGU using Poisson regression for clustered outcomes. We performed relative risk binomial regression for clustered data to identify characteristics associated with incident NGU. From August 2014 to July 2018, 307 participants at risk for NGU contributed 109.4 person-years. Median age was 32 years, and 52% were White. At enrollment, 107 men had NGU; of these, 88% were symptomatic, 27% had CT, and 22% had MG. Fifty men had 60 cases of incident NGU (incidence rate, 56 per 100 person-years; 95% confidence interval, 43-74). Unlike prevalent NGU at enrollment, CT/MG-associated incident NGU was rare (incidence rate, 7; 95% confidence interval [CI], 4-15), and most (78%) incident NGU was asymptomatic. Risk factors for incident NGU were ≤ high school education (adjusted rate ratio [ARR], 2.45; 95% CI, 1.19-5.00), history of CT (ARR, 2.15; 95% CI, 1.08-4.27), history of NGU (ARR, 2.67; 95% CI, 1.27-5.62), and NGU at enrollment (ARR, 2.03; 95% CI, 1.04-3.98). Neither condom use nor having a new partner was associated with incident NGU; Black race was only associated with incident symptomatic and non-CT/non-MG NGU. Incidence of NGU was high, predominantly non-CT/non-MG and asymptomatic. Future studies should investigate the etiology and clinical significance of asymptomatic NGU.

No Pathogen-Specific Sign or Symptom Predicts the Etiology of Monomicrobial Nongonococcal Urethritis in Men.

Identifying pathogen-specific signs or symptoms of nongonococcal urethritis could improve syndromic management accuracy. We evaluated nongonococcal urethritis signs and symptoms in 220 men with single-pathogen infections (Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, or Ureaplasma urealyticum) or idiopathic urethritis. No individual sign or symptom accurately predicted the infectious etiology.

Mycoplasma genitalium Infection in Men

Mycoplasmagenitalium is one of the major causes of nongonococcal urethritis (NGU) worldwide but an uncommon sexually transmitted infection (STI) in the general population. The risk of sexual transmission is probably lower than for Chlamydia trachomatis. Infection in men is usually asymptomatic and it is likely that most men resolve infection without developing disease. The incubation period for NGU caused by Mycoplasma genitalium is probably longer than for NGU caused by C. trachomatis. The clinical characteristics of symptomatic NGU have not been shown to identify the pathogen specific etiology. Effective treatment of men and their sexual partner(s) is complicated as macrolide antimicrobial resistance is now common in many countries, conceivably due to the widespread use of azithromycin 1 g to treat STIs and the limited availability of diagnostic tests for M. genitalium. Improved outcomes in men with NGU and better antimicrobial stewardship are likely to arise from the introduction of diagnostic M. genitalium nucleic acid amplification testing including antimicrobial resistance testing in men with symptoms of NGU as well as in their current sexual partner(s). The cost effectiveness of these approaches needs further evaluation. The evidence that M. genitalium causes epididymo-orchitis, proctitis, and reactive arthritis and facilitates human immunodeficiency virus transmission in men is weak, although biologically plausible. In the absence of randomized controlled trials demonstrating cost effectiveness, screening of asymptomatic men cannot be recommended.

Emergence of Mycoplasma genitalium strains showing mutations associated with macrolide and fluoroquinolone resistance in the region Dresden, Germany

Among 323 specimens from male patients with symptoms of non-gonococcal urethritis, Mycoplasma genitalium was detected in 19 samples by real-time PCR. Mutations of 23S rRNA gene associated with macrolide resistance were confirmed in 10 strains. Amino acid changes at positions 81 and 83 of ParC protein were demonstrated indicating quinolone resistance of two strains.

Mycoplasma genitalium – The missing pathogen?

M. genitalium has become an established cause of sexually transmitted urethritis and cervicitis, and there is increasing evidence that it may cause upper genital tract disease in women. Detection by nucleic acid amplification tests is currently the only diagnostic method available, but no FDA approved assays are currently available, and the CE marked tests suffer from limited clinical evaluation. In most settings, M. genitalium infections explain 15-25% of symptomatic non-gonococcal urethritis, but as diagnosis of the infection is not routinely carried out, treatment is usually syndromic. A few randomized trials have evaluated treatment of M. genitalium, and have compared only doxycycline 200 mg daily for 7 days with a 1 g single dose of azithromycin. Together with results from open trials, it is obvious that doxycycline is inefficient in eradicating M. genitalium, showing eradication rates around 35%. The eradication rate after azithromycin 1 g single dose is significantly better, but differs greatly between studies. Thus, older studies appear to have higher eradication rates than the most recent one, where no significant difference between azithromycin and doxycycline could be demonstrated. Furthermore, a lower eradication rate is reported in studies from centres where azithromycin has been used as the primary treatment for chlamydial and idiopathic urethritis and cervicitis, suggesting that selection for macrolide resistance may be rapid and widespread. At present, the only second line antibiotic that has been shown to have a high activity against macrolide resistant M. genitalium is moxifloxacin. However, this drug is significantly more expensive and has a less favourable safety profile than macrolides, and multidrug resistant infections have emerged, primarily in patients with contact to South East Asia. Consequently, there is an urgent need for clinical trials with possible alternative drugs. Such trials should preferably also address the treatment efficacy in chlamydial and idiopathic urethritis and cervicitis as a single treatment covering these conditions would be advantageous.

Point: New Trichs for “Old” Dogs: Prospects for Expansion of Trichomonas vaginalis Screening

The urogenital protozoan Trichomonas vaginalis was first recognized nearly 2 centuries ago by the French clinician, researcher, and microscopist Donne. Since that time, roles for the protozoan's pathogenicity have been described for both females and males. Females who are symptomatic for trichomoniasis may present with vulvar irritation and a diffuse, yellow green, and malodorous vaginal discharge. Males with T. vaginalis infection can present with signs and symptoms of nongonococcal urethritis (1). Because of the nonulcerative nature of its presentation, trichomoniasis has been characterized largely as a disease of nuisance, particularly in females. Moreover, although T. vaginalis has been recognized as the most common nonviral etiology of sexually transmitted infection (STI),3 estimates of its prevalence have varied, largely because of inaccurate laboratory diagnostics. Trichomoniasis is not a nationally notifiable disease in the US, and recommendations for T. vaginalis screening are not broad-ranging. The CDC states that diagnostic testing for T. vaginalis should proceed in females with vaginal discharge (1) and can be considered for females at higher risk for infection (new/multiple sexual partners, commercial sex workers, injection drug use, previous history of STI). Screening may also be indicated for HIV-positive sexually active females. However, recent data are beginning to change the outlook on trichomoniasis in the US and may eventually call for a recasting of T. vaginalis–screening recommendations. This commentary provides clinical, social, and laboratory-based rationales for expansion of T. vaginalis screening. Approximately 50%–60% of T. vaginalis infections in women are asymptomatic (2). Mathematical modeling has projected the mean duration of T. vaginalis infection in women at 3–5 years (3). These data constitute a problematic scenario for at least 2 reasons: ( a ) T. vaginalis infection provides a potentially persistent and indolent conduit for subsequent sexual transmission, and ( b ) historical data demonstrate that approximately one-third of asymptomatic infections progress to …

Epidemiological and clinical rationale for screening and diagnosis of Mycoplasma genitalium infections

1. Chris L. McGowin, PhD[⇑][1] 1. Louisiana State University Health Sciences Center, Department of Microbiology, Immunology and Parasitology, New Orleans, LA 2. Rodney E. Rohde, PhD, MS, SV, SM(ASCP)CM, MBCM 1. Clinical Laboratory Science Program, College of Health Professions, Texas State University, San Marcos, TX 3. Gerald Redwine, MEd, MT(ASCP) 1. Clinical Laboratory Science Program, College of Health Professions, Texas State University, San Marcos, TX 1. Address for Correspondence: Chris L. McGowin, PhD, Louisiana State University Health Sciences Center, Department of Microbiology, Immunology and Parasitology, 1901 Perdido St.; MEB 6214, New Orleans, LA 70112-2822, 504 568-7281, cmcgow{at}lsuhsc.edu 1. Discuss the historical and epidemiological background of Mycoplasma genitalium 2. Justify the clinical rationale for M. genitalium testing 3. Describe the diagnosis of M. genitalium 4. Define M. genitalium non-gonococcal urethritis and cervicitis 5. Explain the syndromic management and antimicrobial resistance associated with M. genitalium Mycoplasma genitalium has been the focus of basic scientific and synthetic biology research as the organism with the smallest genome of all known human bacterial pathogens. As a sexually transmitted organism, substantial clinical and epidemiologic evidence now exists that warrant further consideration of M. genitalium as a priority for diagnostic testing. In the early 1980's, M. genitalium was first identified from two men with symptomatic non-gonococcal urethritis (NGU) – an inflammatory syndrome most often attributed to infections with Neisseria gonorrhoeae or Chlamydia trachomatis . Since then, epidemiologic studies of clinical disease, several animal models, and the results of many basic scientific investigations point towards M. genitalium as a urogenital pathogen with significant implications for reproductive and sexual health. It is now unequivocally known that M. genitalium is found in approximately 15-25% of patients with NGU and in more than one third of non-chlamydial NGU cases.1 Importantly, M. genitalium establishes both acute and chronic infections in the urogenital tract of men and women. This article aims to concisely address the rationale for continued investigation of M. genitalium as a sexually transmitted infection (STI) and for the implementation of diagnostic testing paradigms in the USA. Epidemiology of M. genitalium As an emerging urogenital pathogen, the vast majority of M. genitalium research has been focused on the epidemiologic characteristics and associations with disease syndromes – first in men, and more recently in women. With regard to the “emergence” of M. genitalium infections, it should be clarified that no reports have indicated an increase in… ABBREVIATIONS: CDC - Centers for Disease Control and Prevention, FDA - Food and Drug Administration, HPV - Human Papilloma Virus, LDT - laboratory developed tests, MDx - molecular diagnostics, NAAT - nucleic acid amplification test, NGU - non-gonococcal urethritis, NPV - negative predictive value, PPV - positive predictive value, RUO - research use only, STD - sexually transmitted disease, STI - sexually transmitted infection, ART - anti-retroviral therapy, LOD, limit of detection, LOQ, limit of quantification 1. Discuss the historical and epidemiological background of Mycoplasma genitalium 2. Justify the clinical rationale for M. genitalium testing 3. Describe the diagnosis of M. genitalium 4. Define M. genitalium non-gonococcal urethritis and cervicitis 5. Explain the syndromic management and antimicrobial resistance associated with M. genitalium [1]: #corresp-1

Bacterial loads of Ureaplasma urealyticum contribute to development of urethritis in men

Ureaplasma urealyticum could be a pathogen of non-gonococcal urethritis (NGU) in men. However, ureaplasma is often detected in men without NGU, and the proportion of cases possibly attributable to this pathogen is still undefined. We attempted to determine the bacterial loads of U. urealyticum significantly associated with NGU. The 16S rRNA genes of U. urealyticum were quantified by a real-time polymerase chain reaction-based assay in first-void urine (FVU) from 26 asymptomatic and 25 symptomatic men positive for U. urealyticum. The leucocyte counts in first-void urine (FVU) were determined as an objective measure of inflammatory response to ureaplasma in the hosts by automated quantitative urine particle analysis. Positive correlations were observed between copies of the 16S rRNA genes of U. urealyticum per ml and the leucocyte counts per µl in FVU (r = 0.49, p = 0.0003). Loads of ≥10(4) copies of the 16S rRNA gene of U. urealyticum/ml, corresponding to ≥5 × 10(3) cells of U. urealyticum/ml in FVU, were significantly associated with the presence of urethritis symptoms (p < 0.0001) and with higher leukocyte counts in FVU (p < 0.0001). The bacterial load of U. urealyticum, possibly of ≥5 × 10(3) cells of U. urealyticum/ml in FVU, could be significantly associated with the development of symptomatic NGU.

P1.029 Bacterial Vaginosis Associated Bacteria Are Detected Together with Ureaplasmas in Men But Not Associated with Non-Gonococcal Urethritis

BackgroundLittle is known about the presence of bacterial vaginosis (BV) associated bacteria in men, but male partners of women with BV have been reported to have a high risk of...

S08.4 Mycoplasma Genitalium : Implications For Disease, Treatment and the Public Health

M. genitalium is an established cause of sexually transmitted urethritis and cervicitis, and may cause upper tract disease in women. Detection by nucleic acid amplification tests is currently the only...

Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis Infections in Men With Nongonococcal Urethritis: Predictors and Persistence After Therapy

Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV) are sexually transmitted infections (STIs) associated with nongonococcal urethritis (NGU). We assessed their predictors and persistence after treatment. We analyzed data from an NGU treatment trial among symptomatic heterosexual men aged 16-45 years from STI clinics. Nucleic acid amplification tests detected CT, MG, and TV at baseline and at 1 and 4 weeks after therapy. Associations between variables and STI detection were investigated. Among 293 participants, 44% had CT, 31% had MG, and 13% had TV at baseline. In multivariate analysis, CT infection was associated with young age and STI contact. Young age was also associated with MG, and having ≥ 1 new partner was negatively associated with TV. We detected persistent CT in 12% and MG in 44% of participants at 4 weeks after therapy, which were associated with signs and symptoms of NGU. Persistent CT was detected in 23% of participants after azithromycin treatment vs 5% after doxycycline treatment (P = .011); persistent MG was detected in 68% of participants after doxycycline vs 33% after azithromycin (P = .001). All but 1 TV infection cleared after tinidazole. Persistent CT and MG after treatment of NGU are common, and were associated with clinical findings and drug regimen.

P3-S7.14 The association of Ureaplasma urealyticum with male non-gonococcal urethritis

BackgroundThe aetiology of non-gonococcal urethritis (NGU) is unexplained in 30–50% of cases. The role of ureaplasmas is not clear. We detected Ureaplasma urealyticum (Uu) and U parvum (Up) by quantitative...

Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis

To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

Mycoplasma genitalium is associated with symptomatic and asymptomatic non-gonococcal urethritis in men

Objectives:To examine the prevalence of Mycoplasma genitalium in a large number of male patients attending a sexually transmitted infections (STI) clinic and to determine if there is an association with...

Clinical efficacy of azithromycin for male nongonococcal urethritis

The aim of this study was to confirm the clinical efficacy of a single-dose azithromycin (AZM) regimen (1000 mg) for patients with nongonococcal urethritis in real-life practice. The study finally evaluated 55 patients, 42 who were symptomatic and 13 who were asymptomatic, after excluding 40 who visited clinics only once. Sixteen of the symptomatic patients were diagnosed as having nongonococcal chlamydial urethritis, 7 as having nongonococcal nonchlamydial urethritis, and 19 as having urethritis without any microbial detection. Chlamydia trachomatis was detected in 11 asymptomatic patients, Mycoplasma genitalium in 1, and Ureaplasma urealyticum in 1. Of the patients who were microbiologically evaluated before and after single-dose AZM, microbiological cure was achieved in 87% (20/23) of those with symptomatic nongonococcal urethritis and in 100% (13/13) of those with asymptomatic nongonococcal urethritis. The clinical cure rate was 86% for the 42 symptomatic patients with detectable and undetectable pathogens. There were adverse events in 5 (9%) patients but they were commonly mild and self-limited. In conclusion, the single-dose AZM regimen was well tolerated and eradicated the estimated and potential pathogens of nongonococcal urethritis.

Treatment of men with urethritis negative for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum

Some patients with symptomatic non-gonococcal urethritis (NGU) are negative for Chlamydia trachomatis, mycoplasmas and ureaplasmas. The optimal antimicrobial chemotherapy for such NGU has not fully been elucidated, though many studies of antimicrobial chemotherapies for C. trachomatis-positive NGU have been performed. We assessed the efficacy of antimicrobial agents that are active against C. trachomatis on non-mycoplasmal, non-ureaplasmal and non-chlamydial NGU (NMNUNCNGU). One hundred men whose first-pass urine samples were negative for C. trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were treated with levofloxacin, gatifloxacin, minocycline, or clarithromycin for 7 days. Urethritis symptoms and the presence of polymorphonuclear leukocytes (PMNL) in urethral smears were assessed before and after treatment. Eighty-eight (88.0%) of 100 men with NMNUNCNGU showed no signs of urethral inflammation after treatment, but two men complained of some symptoms of urethritis. Twelve (12.0%) of 100 men had significant numbers of PMNL in urethral smears, but five of these 12 men had no symptoms of urethritis. The efficacy for normalization of urethral smears was 90.7% for clarithromycin, 89.7% for levofloxacin, 87.5% for gatifloxacin, and 75.0% for minocycline. The 12 men who showed signs of urethral inflammation were retreated with levofloxacin, gatifloxacin, minocycline or clarithromycin for an additional 7 days. The 10 men who returned after the second treatment had negative urethral smears. Our present findings suggest that antimicrobial agents active against C. trachomatis are effective against NMNUNCNGU and that a 7-day treatment regimen with an appropriate antimicrobial agent may be sufficient to manage patients with NMNUNCNGU.

Etiologies of Nongonococcal Urethritis: Bacteria, Viruses, and the Association with Orogenital Exposure

The purpose of the present study was to determine pathogens and behaviors associated with nongonococcal urethritis (NGU) and the usefulness of the urethral smear in predicting the presence of pathogens. We conducted a case-control study of men with and without symptoms of NGU. Sexual practices were measured by questionnaire. First-stream urine was tested for Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma parvum, U. urealyticum, herpes simplex virus (HSV)-1, HSV-2, adenoviruses, and Gardnerella vaginalis by polymerase chain reaction. C. trachomatis (20%), M. genitalium (9%), adenoviruses (4%), and HSV-1 (2%) were more common in cases with NGU (n = 329) after age and sexual risk were adjusted for (P< or =.01); U. urealyticum, U. parvum, and G. vaginalis were not. Infection with adenoviruses or HSV-1 was associated with distinct clinical features, oral sex, and male partners, whereas infection with M. genitalium or C. trachomatis was associated with unprotected vaginal sex. Oral sex was associated with NGU in which no pathogen was detected (P < or = .001). Fewer than 5 polymorphonuclear leukocytes (PMNLs) per high-power field (HPF) on urethral smear were present in 32%, 37%, 38%, and 44% of cases with C. trachomatis, M. genitalium, adenoviruses, and HSV, respectively. We identified adenoviruses and HSV-1 as significant causes of NGU with distinct clinical and behavioral characteristics and highlighted the association between insertive oral sex and NGU. A urethral PMNL count of > or =5 PMNLs/HPF is not sufficiently sensitive to exclude pathogens in men with urethral symptoms.

Association of Mycoplasma genitalium persistence in the urethra with recurrence of nongonococcal urethritis.

Most patients with recurrent symptomatic nongonococcal urethritis receive negative test results for Chlamydia trachomatis and Ureaplasma urealyticum, and the cause of such recurrence usually is unknown. To assess the association of Mycoplasma genitalium with recurrent nongonococcal urethritis. In this study, 72 men with nongonococcal urethritis were treated with levofloxacin. Before and after treatment, symptoms and signs were assessed and first-pass urine was examined for C trachomatis, M genitalium, U urealyticum, and Mycoplasma hominis by polymerase chain reaction-based assays. In 6 of 45 men who had no symptoms and no evidence of inflammation after treatment, nongonococcal urethritis recurred. Of these 6 men, 5 had positive test results for M genitalium before levofloxacin treatment, which remained positive afterward. After the second treatment for recurrent nongonococcal urethritis, one man was still had a positive test result for the mycoplasma and experienced a subsequent recurrence. This study suggests that the persistence of M genitalium in the urethra may be associated with recurrence of nongonococcal urethritis.

Need for diagnostic screening of Herpes simplex virus in patients with nongonococcal urethritis.

The prevalence of various microorganisms known to cause nongonococcal urethritis, including herpes simplex virus (HSV), was evaluated. The findings suggest that HSV can be a significant etiological agent in nongonococcal urethritis (NGU) and that the necessary laboratory investigations should be performed for all patients with clinical symptoms of NGU.

Azithromycin for Empirical Treatment of the Nongonococcal Urethritis Syndrome in Men

To evaluate the use of single-dose azithromycin for empirical treatment of nongonococcal urethritis. Randomized, double-blind, multicenter trial comparing azithromycin vs doxycycline therapy, with a 2:1 randomization ratio. Patients were evaluated clinically and microbiologically for Chlamydia trachomatis and Ureaplasma urealyticum infection before therapy and at 2 and 5 weeks after study entry. Eleven sexually transmitted disease clinics throughout the United States. A total of 452 men aged 18 years or older with symptomatic nongonococcal urethritis of less than 14 days' duration. Patients were treated with either 1.0 g of azithromycin as a single oral dose or 100 mg of doxycycline taken orally twice daily for 7 days. Clinical resolution of symptoms and signs of nongonococcal urethritis, microbiological cure of C trachomatis and U urealyticum, and occurrence of adverse experiences. Of the 452 patients enrolled, 248 in the azithromycin-treated group and 123 in the doxycycline-treated group were evaluable for clinical response. The two treatment groups were comparable in terms of age, weight, ethnic distribution, sexual preference, sexual activity, and history of prior nongonococcal urethritis or gonorrhea. Sixteen percent of the azithromycin group and 24% of the doxycycline group were culture positive for C trachomatis before therapy, while 38% and 28%, respectively, were culture positive for U urealyticum. The cumulative clinical cure rate was 81% (95% confidence interval [CI], 75% to 85%) in the azithromycin-treated group and 77% (95% CI, 69% to 84%) in the doxycycline-treated group. Clinical cure rates in the two groups were also comparable when patients were stratified by presence or absence of infection with C trachomatis or U urealyticum prior to therapy. Among those infected with C trachomatis, overall microbiological cure rates were 83% (95% CI, 65% to 94%) for azithromycin-treated patients (n = 30) and 90% (95% CI, 68% to 98%) for doxycycline-treated patients (n = 21). Among those infected with U urealyticum, overall microbiological cure rates were 45% (95% CI, 34% to 57%) for azithromycin-treated patients (n = 75) and 47% (95% CI, 30% to 65%) for doxycycline-treated patients (n = 32). Adverse reactions were generally mild to moderate and occurred in 23% of the azithromycin-treated group and 29% of the doxycycline-treated group. For empirical treatment of the acute nongonococcal urethritis syndrome in men, a single oral dose of azithromycin was as effective as a standard 7-day course of doxycycline in achieving clinical cure. Further, clinical cure rates were comparable with either regimen, regardless of the presence or absence of Chlamydia or Ureaplasma infection.