Recurrent Non-gonococcal Urethritis Research Articles

Identification and Characteristics of Multidrug-Resistant Ureaplasm urealyticum and Mycoplasma hominis Isolates among Female Patients with Recurrent Non-Gonococcal Urethritis in a Tertiary Hospital, China

Background: Concerns are increasing over the mechanisms of drug resistance pathogens among non-gonococcal urethritis (NGU) or cervicitis. The study aims to explore the distribution of Ureaplasm urealyticum (U. urealyticum) and Mycoplasma homins (M. homins) isolates, characteristics of multidrug resistance, and the underlying mechanism to allow clinicians to deliver rational therapy for NGU. Methods: Samples from cervical secretions of 246 patients with NGU were collected. Mycoplasma culture and drug susceptibility tests were performed, respectively. The resistance genes were detected by multiplex Polymerase Chain Reaction (PCR), and the PCR products were cloned and sequenced. Results: Out of 246 samples, the overall prevalence of U. urealyticum and/or M. hominis infection was 39.02% (96/246). In 96 culture positive samples, the overall infection rate of U. urealyticum was higher than that of the single M. hominis (46.87% vs. 28.13%) (p < 0.05), and the coinfection rate was 25.00% (24/96). Each U. urealyticum and M. hominis isolate exhibited resistance to at least three types of antimicrobial agents (manifest by more than 70% resistance to erythromycin, tetracycline, ciprofloxacin, and spiramycin, followed by ofloxacin, roxithromycin, azithromycin and josamycine (with resistance thereto of more than 50%)). More than 80% of U. urealyticum and M. hominis isolates were susceptible to minomycine and doxycycline, whereas 81.16% and 77.44% of both U. urealyticum and M. hominis isolates were also susceptible to minomycine and doxycycline. Surprisingly, the resistance rate of the mixed infection was higher that of erythromycin, tetracycline and ciprofloxacin comparison to the single infection (p < 0.05). All tetracycline-resistant isolates carried the tetM gene and 50% of erythromycin-resistant isolates carried the ermA gene. Conclusions: Among outpatients with recurrent NGU, the U. urealyticum infection dominated, followed by M. hominis, mixed U. urealyticum and M. hominis infection. Minomycine and doxycycline are recommended for empirical clinical treatment. The determination of U. urealyticum and M. hominis infection, antibiotic susceptibility testing is crucial for effective therapy.

Persistent Chlamydia trachomatis genital infection: laboratory diagnosis and treatment

If Chlamydia trachomatis (Ct) can not be cleared in time after invading human genital tract, it tends to cause persistent infection and induce severe sequelae, such as tubal infertility. Laboratory examination is of great value in the diagnosis of persistent Ct infection. Combined detection of antibodies to CT443 and CT381, or antibodies to Ct heat shock protein 60 (HSP60) , CT376, CT557 and CT443, can predict female tubal infertility with a specificity of 100% and a high sensitivity. Nucleic acid amplification techniques can be used to detect low Ct loads and to increase detection rates of Ct in patients with persistent infection. In clinic, antibacterial agents are the mainstay of treatment for Ct infection. Azithromycin in combination with metronidazole for 5 days or doxycycline combined with metronidazole for 7 days can be recommended for the treatment of persistent or recurrent nongonococcal urethritis. However, further studies are needed to confirm the efficacy of tryptophan metabolism-related drugs and glucocorticoids in the auxiliary treatment of persistent Ct infection. Key words: Chlamydia trachomatis; Reproductive tract infections; Clinical laboratory techniques; Diagnosis; Therapeutic uses

P086 An audit of the management of persistent and recurrent non-gonococcal urethritis (pNGU) in a large London teaching hospital

Background/introduction The British Association of Sexual Health and HIV (BASHH) released a new national guideline on the management of non-gonococcal urethritis (NGU) in 2015. This audit was completed to assess compliance and identify areas for service improvement. Aim(s)/objectives To compare the management of pNGU against national guidelines. Methods A retrospective case note review was performed for all patients having two or more NGU code (C4N) over a 12-month period from 1 st April 2014. We collected demographic details, presenting symptoms, signs, investigations, management and number of visits. Results 130 patients were identified from three different clinics within the same Trust. A total of 282 visits were recorded. 35.4% of visits were diagnosed as NGU and 66.2% as pNGU. We achieved 100% compliance with all four of BASHH auditable out comes (i.e. screening for C. trachomatis (CT) and gonorrhoea, documented offer of written information, delivery of first-line therapy and partner notification). Only one patient was diagnosed with CT. In recurrent visits, only 31.0% of further investigations were done and 12.6% of them were treated as pNGU according to the guideline. 55.2% of the patients had 4 or more visits. Discussion/conclusion We demonstrated high levels of compliance with national guidelines for managing NGU. However, management of patients with pNGU was sub-optimal with a lack of appropriate investigations and incorrect treatment regimes. Low levels of CT positivity in this cohort demonstrate the importance of further investigations. Correct pNGU treatment may also lead to fewer visits and reduced burden on the service.

Management of non-gonococcal urethritis.

Non-gonococcal urethritis (NGU), or inflammation of the urethra, is the most common treatable sexually transmitted syndrome in men, with approximately 20-50 % of cases being due to infection with Chlamydia trachomatis and 10-30 % Mycoplasma genitalium. Other causes are Ureaplasma urealyticum, Trichomonas vaginalis, anaerobes, Herpes simplex virus (HSV) and adenovirus. Up to half of the cases are non-specific. Urethritis is characterized by discharge, dysuria and/or urethral discomfort but may be asymptomatic. The diagnosis of urethritis is confirmed by demonstrating an excess of polymorpho-nuclear leucocytes (PMNLs) in a stained smear. An excess of mononuclear leucocytes in the smear indicates a viral etiology. In patients presenting with symptoms of urethritis, the diagnosis should be confirmed by microscopy of a stained smear, ruling out gonorrhea. Nucleid acid amplifications tests (NAAT) for Neisseria gonorrhoeae, C. trachomatis and for M. genitalium. If viral or protozoan aetiology is suspected, NAAT for HSV, adenovirus and T. vaginalis, if available. If marked symptoms and urethritis is confirmed, syndromic treatment should be given at the first appointment without waiting for the laboratory results. Treatment options are doxycycline 100 mg x 2 for one week or azithromycin 1 gram single dose or 1,5 gram distributed in five days. However, azithromycin as first line treatment without test of cure for M. genitalium and subsequent Moxifloxacin treatment of macrolide resistant strains will select and increase the macrolide resistant strains in the population. If positive for M. genitalium, test of cure samples should be collected no earlier than three weeks after start of treatment. If positive in test of cure, moxifloxacin 400 mg 7–14 days is indicated. Current partner(s) should be tested and treated with the same regimen. They should abstain from intercourse until both have completed treatment. Persistent or recurrent NGU must be confirmed with microscopy. Reinfection and compliance must be considered. Evidence for the following recommendations is limited, and is based on clinical experience and guidelines. If doxycycline was given as first therapy, azithromycin five days plus metronidazole 4–500 mg twice daily for 5–7 days should be given. If azithromycin was prescribed as first therapy, doxycycline 100 mg x 2 for one week plus metronidazole, or moxifloxacin 400 mg orally once daily for 7–14 days should be given.

Trichomonas vaginalis infection: How significant is it in men presenting with recurrent or persistent symptoms of urethritis?

Persistent or recurrent non-gonococcal urethritis has been reported to affect up to 10-20% of men attending sexual health clinics. An audit was undertaken to review the management of persistent or recurrent non-gonococcal urethritis in men presenting at Whittall Street Clinic, Birmingham, UK. Detection of Trichomonas vaginalis infection was with the newly-introduced nucleic acid amplification test. A total of 43 (8%) of 533 men treated for urethritis re-attended within three months with persistent or recurrent symptoms. Chlamydia trachomatis infection was identified in 13/40 (33%), T. vaginalis in 1/27 (4%) and Mycoplasma genitalium in 6/12 (50%). These findings suggest that the prevalence of T. vaginalis infection remains low in our clinic population and may not contribute significantly to persistent or recurrent non-gonococcal urethritis.

Prediction of the persistence of Mycoplasma genitalium after antimicrobial chemotherapy by quantification of leukocytes in first-void urine from patients with non-gonococcal urethritis

Mycoplasma genitalium is regarded as another pathogen of male non-gonococcal urethritis (NGU). Failure to eradicate this mycoplasma is associated with persistent or recurrent NGU, but this mycoplasma is not routinely examined in clinical practice. In cases of M. genitalium-positive NGU, therefore, some criteria are needed to assess the success or failure of antimicrobial chemotherapy other than microbiological outcomes. We enrolled 49 men with M. genitalium-positive non-chlamydial NGU. At successive visits after treatment, we inquired about their symptoms, observed their urethral meatus for urethral discharge, and examined their first-void urine (FVU) for quantification of leukocytes and for the persistence of M. genitalium. M. genitalium was eradicated in 34 patients after treatment, whereas the mycoplasma persisted in 15. Urethritis symptoms and urethral discharges were not found to be predictors of the persistence of M. genitalium up to the 25th day after the start of treatment. Leukocyte counts in FVU from the patients with persistence of M. genitalium were significantly higher than those from the patients with eradication of the mycoplasma. Leukocyte counts of 10 leukocytes/μl or more between the 18th and 24th day after the start of treatment were most significantly associated with the persistence of M. genitalium. Quantification of leukocytes in FVU would appear to be crucial to judge the outcome of treatment in patients with non-chlamydial NGU and could be helpful to predict the persistence of M. genitalium after treatment when M. genitalium is not routinely examined in clinical specimens in clinical practice.

Antimicrobial chemotherapy of Mycoplasma genitalium-positive non-gonococcal urethritis

Mycoplasma genitalium is an important pathogen of acute non-gonococcal urethritis (NGU) in men and plays a significant role in persistent or recurrent NGU. In the management of patients with M. genitalium-positive NGU, eradication of the mycoplasma from the urethra is necessary to prevent persistent or recurrent NGU. Therefore, M. genitalium should be considered for antimicrobial chemotherapy of NGU. This article reviews the in vitro antimicrobial activities of antibiotics against M. genitalium and the efficacies of various antibiotic regimens against M. genitalium-positive NGU, including the doxycycline and azithromycin regimens recommended as first-line treatments for NGU in the guidelines. Selection of macrolide-resistant M. genitalium by treatment with the single-dose regimen of 1-g azithromycin and mechanisms of macrolide resistance in M. genitalium are discussed. The effectiveness of the moxifloxacin regimen against persistent or recurrent NGU, unsuccessfully treated with azithromycin and/or doxycycline regimens, is emphasized.

Clinical and microbiological outcomes in treatment of men with non-gonococcal urethritis with a 100-mg twice-daily dose regimen of sitafloxacin

Several microorganisms cause non-gonococcal urethritis (NGU). Failure to eradicate Mycoplasma genitalium from the urethra could be associated with persistent or recurrent urethritis; thus, the choice of antibiotics with activities potent enough to eradicate M. genitalium is crucial in the treatment of NGU. In in vitro studies, sitafloxacin has been shown to be highly active against Chlamydia trachomatis and M. genitalium. We treated 89 males with NGU, including 15 patients with persistent or recurrent NGU and 1 patient with post-gonococcal urethritis, with a 100-mg twice-daily dose regimen of sitafloxacin to assess its efficacy against NGU. We examined first-void urine samples for the presence of C. trachomatis, M. genitalium, Ureaplasma parvum, and Ureaplasma urealyticum. After treatment, we evaluated 73 patients for clinical outcomes and 44 for microbiological outcomes. Symptoms were alleviated in 62 (84.9%) patients, who were judged clinically cured. Microorganisms detected before treatment were eradicated in 42 (95.5%) patients, who were judged microbiologically cured. Regarding microbiological outcomes of specific microorganisms, eradication rates of C. trachomatis (n=33), M. genitalium (n=11), and U. urealyticum (n=10) were 100%, 100%, and 80.0%, respectively. In all 5 patients with M. genitalium-positive persistent or recurrent NGU who had experienced treatment failures with antibiotics, the mycoplasma was eradicated. These results suggested that the sitafloxacin regimen used, which was effective on both M. genitalium and C. trachomatis infections, could be useful as an appropriate option as first- and second-line treatment of NGU.

Induced Macrolide Resistance in Mycoplasma genitalium Isolates from Patients with Recurrent Nongonococcal Urethritis

Mycoplasma genitalium accounts for as much as 15 to 20% of cases of male nongonococcal urethritis (NGU) (7). It is also implicated in female cervicitis and increasingly so in pelvic inflammatory disease (3). Since it is a fastidious microorganism that is very difficult to culture, nucleic acid amplification tests (NAAT) have become invaluable in its detection and microbiological evaluation. Currently recommended treatments of NGU include multidoses of doxycycline (100 mg twice daily for 7 days) or a single dose of azithromycin (1 g). With regard to M. genitalium-positive NGU, a recent randomized study has shown multidose treatment with doxycycline to be inferior to single-dose azithromycin (cure rates of 45% versus 87%, respectively) (8). However, even single-dose azithromycin can be associated with treatment failure rates of up to 28% (2). An extended 5-day course of azithromycin (500 mg on day 1, followed by 250 mg on days 2 to 5) has a much higher cure rate of up to 96% (1) but becomes less efficacious when used after initial treatment failure with single-dose azithromycin (6). Jensen et al. (4) have shown that macrolide resistance in M. genitalium can be induced by insufficient therapy with single-dose azithromycin and found the resistance to be strongly associated with three single-base mutations (A2058C, A2058G, A2059G) in region V of the 23S rRNA gene (4). They developed a conventional PCR to detect all of these mutations. In September 2009, we started M. genitalium NAAT testing of genital samples from selected patients with recurrent NGU at the Christchurch Sexual Health Centre, Christchurch, New Zealand. The PCR was performed as described by Jensen et al. (5) with the 2× Universal TaqMan gene expression master mix (Applied Biosystems, Life Technologies, Foster City, CA). Between September 2009 and October 2010, 52 samples were collected and M. genitalium was detected in 11 (21%) samples. The nucleic acid extracts were stored at −80°C until October 2010, when we retrospectively performed PCR and DNA sequencing on these extracts to look for the single-base mutations mentioned above, using the method described by Jensen et al. (4). Of the 11 nucleic acid extracts, we were able to amplify and sequence the 23S rRNA genes of 9 extracts. PCR of the other 2 nucleic acid extracts did not yield an amplicon upon repeat testing, probably due to nucleic acid degradation during storage. Of the 9 sequenced nucleic acid extracts, 4 extracts contained the A2059G mutation, whereas none contained mutations at position 2058. We retrospectively reviewed the notes for the relevant patients (those with extracts containing the mutation) and found that all four patients had previously been treated multiple times for sexually transmitted infections. We were able to determine that three of these patients had received single-dose azithromycin between 34 and 58 days preceding the positive test for M. genitalium; the fourth patient had also received single-dose azithromycin in the few weeks preceding a positive test, but we were unable to determine the exact time frame. All four patients had received an extended course of azithromycin following the diagnosis of M. genitalium urethritis: two experienced treatment failure, whereas the other two were subsequently cured, based on the fact that M. genitalium DNA was no longer detectable. Of the 5 patients whose M. genitalium extracts did not contain any of the macrolide resistance mutations (of the 9 extracts whose rRNA genes we were able to amplify and sequence), 3 had experienced successful empirical therapy with single-dose azithromycin (2 patients) or extended-dose azithromycin (1 patient); 1 patient was lost to follow up. The remaining 1 patient had received treatment with single-dose azithromycin, but upon subsequent testing, M. genitalium DNA was detectable and in this case contained the A2059G mutation, and the patient was included in our group above. This nicely demonstrates the induction of macrolide resistance by single-dose azithromycin treatment. To our knowledge, this is the first report from New Zealand describing macrolide resistance in M. genitalium. Despite a very limited number of samples, we have evidence that the A2059G mutation conferring induced macrolide resistance is present at a high frequency in M. genitalium extracts from patients with recurrent NGU at the Christchurch Sexual Health Centre. This brings into question whether or not single-dose azithromycin should be the first-line treatment of choice for M. genitalium-positive urethritis. At the Christchurch Sexual Health Centre, the current practice is to prescribe an extended course of azithromycin for all cases of M. genitalium-positive urethritis (primarily because moxifloxacin is currently not readily accessible in New Zealand). We also note with interest that in two patients with the resistant isolate, infection was still cleared with an extended course of azithromycin. This would suggest that macrolide resistance conferred by the A2059G mutation was not absolute. Clearly, the subject of macrolide resistance in M. genitalium requires more study.

Chlorhexidine rinse for prevention of urethritis in men linked to oral sex

BackgroundOral sex among teenagers is on the rise. Similarity between the oral flora and organisms recovered from nongonococcal urethritis and prostatitis, points to retrograde entry of bacteria from oral cavity into the urethra following insertive oral intercourse.Presentation of the hypothesisChlorhexidine has a wide spectrum of anti-bactericidal activity encompassing gram positive and negative bacteria. It is also effective against HIV and HBV. It produced large and prolonged reductions in salivary bacterial counts within 7-h of its use. Hence, it would seem logic to postulate that rinsing with chlorhexidine before oral sex will be effective for prevention of retrograde entry of bacteria from oral cavity into the urethra. The recommendation for rinsing will be: 15 ml of a 0.12% or 10 ml of 0.2% chlorhexidine rinse for 30 seconds. Also other drug delivery systems such as chlorhexidine chewing gum or spray can be used.Testing the hypothesisMen suffering from recurrent nongonococcal urethritis or prostatitis are good subjects for testing the hypothesis. They perform genital safe sex via consistent use of condom. Yet they generally received unprotected insertive oral intercourse. Chlorhexidine can be used for prevention of recurrences of the disease.Implications of the hypothesisThe chlorhexidine will be a new, easy, attractive and effective method for reduction of nongonococcal urethritis, prostatitis and epidydimitis following insertive oral intercourse. It is poorly absorbed from skin, mucosa and gastrointestinal tract indicating systemic safety of chlorhexidine. The agent does not cause any bacterial resistance and supra-infection.

A Randomized Comparison of Azithromycin and Doxycycline for the Treatment ofMycoplasma genitalium–Positive Urethritis in Men

Several uncontrolled observational studies have suggested that the tetracycline class of antibiotics may not be effective in treating Mycoplasma genitalium infection. The present study compared the efficacy of 1 g of azithromycin given as a single dose with that of 100 mg of doxycycline given twice a day for 7 days in eliminating M. genitalium infection. Men with signs or symptoms of urethral disease who were attending a New Orleans sexually transmitted disease clinic and who met clinical criteria for nongonococcal urethritis were enrolled in the study. They were randomized to receive either doxycycline (100 mg orally twice a day for 7 days) or azithromycin (1 g orally as a single dose). All participants were asked to return for a follow-up visit 10-17 days after enrollment. M. genitalium-positive men at enrollment were invited to return for a second follow-up visit between 31 and 41 days after enrollment. Of the 398 men who enrolled, 197 were randomized to receive azithromycin, and 201 were randomized to receive doxycycline. Thirty-six (18%) and 42 (21%) men in these 2 groups, respectively, were infected with M. genitalium. At the early initial follow-up visit, 3 (13%) of 23 azithromycin-treated men were M. genitalium positive, compared with 17 (55%) of 31 doxycycline-treated men (P = .002). Of 15 persistently infected men who were clinically cured at the early initial follow-up visit, 7 (47%) experienced clinical relapse over the subsequent 2-6 weeks. A single 1-g dose of azithromycin is more effective than multidose doxycycline for the treatment of M. genitalium-associated urethritis in men. M. genitalium may be an important cause of recurrent nongonococcal urethritis after administration of the treatment regimens currently recommended by the Centers for Disease Control and Prevention.

Mycoplasma genitalium urethritis in men

Mycoplasma genitalium was first isolated from two men with non-gonococcal urethritis (NGU) and thereafter shown to produce urethritis in subhuman primates, inoculated intraurethrally. This mycoplasma has been detected significantly more often in patients with acute NGU, particularly in patients with non-chlamydial NGU, than in subjects without urethritis. The prevalence of M. genitalium-positive non-chlamydial NGU ranges from 18 to 46% of all non-chlamydial NGU cases. In addition, the persistence of M. genitalium in the urethra after antimicrobial chemotherapy is associated with persistence or recurrence of NGU. The various results reported to date tend to support the proposition that M. genitalium is a pathogen of NGU. M. genitalium is highly susceptible to tetracyclines, macrolides, and some new fluoroquinolones, but the clinical data on the chemotherapy in M. genitalium-positive NGU is extremely limited. Because of the possible association between the post-treatment presence of M. genitalium in the urethra and persistent or recurrent NGU, the eradication of this mycoplasma from the urethra is essential in the management of patients with M. genitalium-positive NGU. Further studies are required to establish the optimal chemotherapy for M. genitalium-positive NGU.

Mycoplasma genitalium in chronic non-gonococcal urethritis.

Seventy-eight men with a history of chronic urethritis were referred for investigation. Of 52 men diagnosed as having persistent or recurrent non-gonococcal urethritis (NGU) at the time of referral, 11 (21%) were infected with Mycoplasma genitalium and three with Chlamydia trachomatis. Men who were M. genitalium-positive had not previously received less antibiotic, in terms of treatment duration, than those who were M. genitalium-negative, suggesting a possible resistance to the antibiotics given. In the current investigation, of 11 M. genitalium-positive men with persistent or recurrent NGU who were treated for four to six weeks with erythromycin, 500 mg four times daily, nine (82%) responded clinically and microbiologically, but later six relapsed without M. genitalium being detected. The results of observing and investigating a patient for about one year, the only one to have concurrent chlamydial and mycoplasmal infections, is presented, a feature being the intermittent persistence of the mycoplasma.

Longitudinal quantitative detection by real-time PCR of Mycoplasma genitalium in first-pass urine of men with recurrent nongonococcal urethritis.

By using a TaqMan assay we monitored longitudinal changes in Mycoplasma genitalium loads in five men with recurrent M. genitalium-positive nongonococcal urethritis. We observed regrowth of M. genitalium persisting in hosts after treatment and a possible association of the increase in the M. genitalium load with emergence of symptoms and signs of nongonococcal urethritis in four of these patients.

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.

Erythromycin for Persistent or Recurrent Nongonococcal Urethritis

To evaluate the efficacy of a 3-week regimen of erythromycin for treatment of persistent or recurrent nongonococcal urethritis in men. A prospective, randomized, double-blind trial with follow-up at 2, 4, and 8 weeks after enrollment. Seventy-seven evaluable men with objective evidence of nongonococcal urethritis (36 in the erythromycin group and 41 in the placebo group) with a mean age of 28 years, a median duration of urethritis of 3 months, and a median number of three previous antimicrobial regimens. Erythromycin, 500 mg, or placebo four times daily for 3 weeks. After 2 weeks of treatment, urethral symptoms resolved in 13 of 25 erythromycin-treated patients compared with 8 of 34 placebo-treated patients (P = 0.03). Erythromycin also resulted in more frequent resolution of urethral discharge and leukocytosis at all visits compared with placebo but these differences were not statistically significant. First-voided urine leukocyte counts decreased, however, by a median of 89% (95% CI, -96% to -67%) in the erythromycin group compared with 23% (CI, -73% to 83%) in the placebo group after treatment (P = 0.02 for the difference in changes). Further, in men with prostatic inflammation, urinary leukocyte counts decreased by a median of 94% (CI, -99% to -83%) after treatment in erythromycin-treated patients compared with a 46% increase (CI, -57% to 290%) in placebo-treated patients (P = 0.0003 for the difference in changes). A 3-week regimen of erythromycin was more effective than placebo in improving symptoms and in reducing pyuria in men with persistent or recurrent nongonococcal urethritis, especially among men with prostatic inflammation.

Characteristics of inflammatory cells in urethral smears from men with non-gonococcal urethritis.

Differential cell counts in inflammatory exudates were undertaken in urethral smears from men with non-gonococcal urethritis (NGU) for the first time, recurrent NGU (presumably reinfection) after a new sexual contact, or persistent NGU (in patients with no recent history of sexual exposure). Patients experiencing first episodes of NGU had significantly higher macrophage counts, both in relative and absolute terms, than the other two groups, regardless of the presence or absence of Chlamydia trachomatis in the urethral culture. The estimated total inflammatory cell count (ETICC) in the urethral exudate was assessed by counting the number of inflammatory cells in the first voided urine. The ETICC was significantly lower in patients with persistent NGU but no recent history of sexual exposure than in patients with NGU for the first time or with NGU presumably caused by a new infection. The ETICC in all three groups of patients was significantly higher than in controls. A more precise definition of NGU or more reproducible methods of diagnosis may possibly differentiate patients without an infective cause.

Clinical and microbiological features of persistent or recurrent nongonococcal urethritis in men.

Nongonococcal urethritis, the most common sexually transmitted disease among heterosexual men in the United States, affects at least two million men each year [1, 2]. Chlamydia trachomatis causes ^40^0 of these cases, and Ureaplasma urealyticum is implicated in another 15^020(7o, but the cause of remaining cases is obscure [3]. The response to antibiotics by these men is greatly affected by whether a causative organism can be isolated. Ninety percent and 70^0 of cases of nongonococcal urethritis associated with C trachomatis and U. urealyticum, respectively, respond to antibiotic therapy [4], whereas when neither organism is isolated, ^OVo of cases persist or relapse within six weeks of treatment [4, 5]. Overall, 30(7o of patients treated for nongonococcal urethritis will have persistent or recurrent symptoms. Thus, we estimate that some 600 000 men develop the syndrome of persistent or recurrent urethritis annually in the United States. These men are subjected to repeated diagnostic evaluations, and although an infectious etiology has not been established, they often are treated with multiple courses of antibiotics. We initiated this study to better define the clinical, epidemiological, and microbiological features of persistent or recurrent nongonococcal urethritis in men.

PREVALENCE OF MYCOPLASMA GENITALIUM DETERMINED BY DNA PROBE IN MEN WITH URETHRITIS

The prevalence of urethral infection with Mycoplasma genitalium was determined by use of a DNA probe in 203 men attending a sexually transmitted disease clinic. M genitalium was detected in 3 (14%) of 21 with acute gonococcal urethritis; 3 (10%) of 30 with acute chlamydia-positive non-gonococcal urethritis (NGU); 4 (13%) of 31 with acute chlamydia-negative NGU; 10 (27%) of 37 with persistent or recurrent NGU; and 10 (12%) of 84 with no urethritis. The organism was more prevalent in homosexual (11 [30%] of 37) than in heterosexual men (19 [11%] of 166; p=0·009). These data do not support an important aetiological role for M genitalium in acute urethritis, but suggest that it may account for some cases of NGU that become persistent or recurrent. The higher prevalence of urethral infection in homosexual men suggests that M genitalium may reside in the gastrointestinal tract.

Persistent urethritis due to Ureaplasma urealyticum in conjugal or stable partnerships.

A study of four conjugal partnerships is described in which the male partners presented with persistent or recurrent non-gonococcal, non-chlamydial, but ureaplasma positive urethritis. Resolution of symptoms and signs in the male partners was achieved only after treatment to eliminate Ureaplasma urealyticum from both partners.