Mycoplasma genitalium: another important pathogen of nongonococcal urethritis

PURPOSE: We reviewed findings on the pathogenic role of Mycoplasma genitalium in nongonococcal urethritis and the treatment of men with M. genitalium positive nongonococcal urethritis. MATERIALS AND METHODS: We reviewed literature selected from peer reviewed journals listed in MEDLINE and from resources cited in those articles from 1967 to January 2001. RESULTS: M. genitalium was first isolated from 2 men with nongonococcal urethritis and thereafter it was shown to cause urethritis in subhuman primates inoculated intraurethrally. This mycoplasma has been detected significantly more often in patients with acute nongonococcal urethritis, particularly in those with nonchlamydial nongonococcal urethritis, than in those without urethritis. The prevalence of M. genitalium positive nonchlamydial nongonococcal urethritis is 18.4% to 45.5% of all nonchlamydial nongonococcal urethritis cases. In addition, the persistence of M. genitalium in the urethra after antimicrobial chemotherapy is associated with persistent or recurrent nongonococcal urethritis. M. genitalium is highly susceptible to tetracycline, macrolide and some new fluoroquinolones. The regimen of 100 mg. doxycycline orally twice daily for 7 days, which is recommended for chlamydial nongonococcal urethritis, seems to be effective for M. genitalium positive nongonococcal urethritis, although clinical data to substantiate this regimen are limited. CONCLUSIONS: The various results reported to date tend to support the proposition that M. genitalium is a pathogen of nongonococcal urethritis. However, currently diagnostic methods for this important mycoplasma are not available in clinical practice. Because of the possible association of the posttreatment presence of M. genitalium in the urethra with persistent or recurrent nongonococcal urethritis, eradication of this mycoplasma from the urethra is essential for managing M. genitalium positive disease. However, clinical data on treating M. genitalium positive nongonococcal urethritis are extremely limited. Thus, further studies are required to develop new diagnostic methods that would be available in clinical settings and establish a new treatment algorithm for nongonococcal urethritis, including M. genitalium positive disease.     

PCR检测衣原体及其在男性尿道感染中的意义

应用聚酶链反应（ＰＣＲ）检测６０４例临床已确诊的男性泌尿系感染患者沙眼衣原体（ＣＴ）感染情况，发现ＣＴ阳性率为：急性淋菌性尿道炎（ＡＧＵ）占２６．９％（１１７／４３５），淋菌感染后尿道炎（ＰＧＵ）占４８．５％（３２／６６），非淋菌性尿道炎（ＮＧＵ）占３１．１％（３２／１０３）。认为ＰＣＲ技术是临床快速诊断男性ＣＴ尿道炎的有效方法。     

Urethritis in white men--a microbiological appraisal.

The incidence of infections with Neisseria gonorrhoeae, Chlamydia trachomatis and mycoplasmas has been assessed in White men with urethritis who were attending a Johannesburg clinic for sexually transmitted diseases. Infection with N. gonorrhoeae was demonstrated in 54% of 212 patients with urethritis. C. trachomatis was isolated from 37% of patients with non-gonococcal urethritis, and from 25% with proven gonococcal infection. Although T-mycoplasmas were isolated significantly more often from patients with urethritis (41%) than from controls (23%) (P less than 0,05) their role in the aetiology of urethritis is uncertain.     

Bacteriological and clinical studies on levofloxacin in male gonococcal urethritis]

We performed basic and clinical studies in male gonococcal urethritis on a new oral antimicrobial agent, levofloxacin (LVFX, DR-3355), a new quinolone derivative. The antibacterial activity of LVFX against clinical strains of Neisseria gonorrhoeae was roughly comparable to that of ofloxacin, and ciprofloxacin. LVFX was administered to 10 males with gonococcal urethritis, 200 mg twice a day (8 cases) or 100 mg twice a day for 3 days (2 cases). Clinical evaluation was made according to the criteria of the Japanese UTI Committee. Overall efficacy rate was 100% (10/10). In the complication of chlamydia trachomatis (2 cases), efficacy rate was 100% (2/2). No subjective or objective adverse reactions occurred.     

Detection of Chlamydia trachomatis with a direct specimen test (MicroTrack) in urethritis patients

The urethral smear specimens from 197 male urethritis patients attending our department and 4 affiliated hospitals were examined for Chlamydia trachomatis between April, 1984 and May, 1985, using fluorescein-labeled monoclonal antibodies (Direct Specimen Test; MicroTrack, Syva Co., USA). C. trachomatis was detected in 7 (25.0%) out of 28 patients with gonococcal urethritis, and 83 (49.1%) out of 169 patients with nongonococcal urethritis. The detection rates were almost comparable to those of other reports that used the cell culture method. The direct test is a time-saving, non-culture method useful for the diagnosis of chlamydial infection.     

Diagnosis of gonococcal urethritis and chlamydial urethritis by polymerase chain reaction]

A polymerase chain reaction (PCR) method was compared to standard methods (cultures for Neisseria gonorrhoeae and Chlamydia trachomatis and an enzyme-immunoassay for C. trachomatis) in diagnosis of gonococcal and chlamydial urethritis in 40 male patients with urethritis. Gonococcal urethritis was diagnosed by detection of a 206 bp DNA fragment amplified by PCR with N. gonorrhoeae-specific primers. Chlamydial urethritis was diagnosed by detection of a 242 bp DNA fragment amplified by PCR with C. trachomatis-specific primers. Gonococcal and chlamydial urethritis, gonococcal and non-chlamydial urethritis, non-gonococcal and chlamydial urethritis, and non-gonococcal and non-chlamydial urethritis were diagnosed in 8, 10, 14 and 8 patients, respectively, by the PCR method. In 9 patients with gonococcal and chlamydial urethritis, 10 with gonococcal and non-chlamydial urethritis, 12 with non-gonococcal and chlamydial urethritis, and 9 with non-gonococcal and non-chlamydial urethritis, diagnosed by the standard methods, the coincidence rates of the PCR to the standard methods were 78% (7/9), 90% (9/10), 100% (12/12), and 89% (8/9), respectively. The overall coincidence rate between the PCR and the standard methods in diagnosis of urethritis were high (90%). In addition, N.gonorrhoeae and C.trachomatis could be simultaneously detected from one urethral sample in approximately 6 hours by means of the PCR. Thus, the PCR method could clinically be applied and would offer several advantages to diagnosis of urethritis, compared to the standard methods.     

Uretritis masculina. Una revisión del método ideal de diagnóstico

Male urethritis is an inflammation of the urethra and the periurethral glands; it is widely classified as gonococcal or non-gonococcal. The most frequent microorganisms responsible are Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum.In the last three decades, the diagnosis of sexually transmitted diseases depended almost exclusively on traditional methods, such as culture, enzyme immunoassay, fluorescent antibody staining, and hybridization, until the appearance of molecular techniques.Clinical syndromes such as urethritis are rarely specific for a single microorganism, so screening strategies should allow multiple agents to be considered. Multiplex PCR is the fastest and most sensitive technique for the diagnosis of gonococcal and non-gonococcal urethritis.Male urethritis without treatment is one of the main health problems related to reproductive and sexual function, constituting one of the main causes of infertility. The objective of this mini-review was to analyze the epidemiology, causes, diagnosis, and complications of male urethritis.     

Acute urethritis caused by Neisseria meningitidis and Chlamydia trachomatis

A 16-year-old heterosexual man presented to our hospital with a purulent urethral discharge and pain at voiding. These symptoms began seven days after oral-genital contact (fellatio) with his partner. A Gram-stained smear from the urethral discharge showed Gram-negative diplococci, and the antigen of Chlamydia trachomatis from urine was positive. We initially made a diagnosis of urethritis caused by Neisseria gonorrhoeae and C. trachomatis. However, N. meningitidis was isolated by culture. Clinicians should pay attention to the possibility of N. meningitidis infection in all cases resembling gonococcal urethritis.     

Epidemiological and therapeutic studies on gonococcal infections--one shot therapy by spectinomycin--[Sapporo Clinical Research Group for STD]

From January through March of 1985, the Sapporo Clinical Research Group for STD treated 69 cases of gonococcal infections (61 cases of male gonococcal urethritis and 8 cases of female gonococcal cervicitis) at its facilities in Sapporo City. The therapeutic efficacy of one shot therapy of Spectinomycin (SPCM) was investigated, and an epidemiological study on the cases and bacteriological studies on the isolated strains of Neisseria gonorrhoeae were made. The male patients were between 19 and 55 years old, with a peak age distribution in the younger half of the twenties. The female patients were between 18 and 40 years old. The major source of infections was a so-called special massage parlor which accounted for 36.1% of male cases. The isolation rate of PPNG were 16.7% (11/66). The MIC (inoculum size; 10(6) CFU/ml) of SPCM ranged from 3.13 to 25 micrograms/ml regardless of beta-lactamase production. In male patients, the eradication rate (efficacy rate) of N. gonorrhoeae by SPCM was 94.7% on the first day, 93.6% on the third day and 100% on the seventh day after 2 g one shot therapy. In female patients, the rate was 100% on the third and seventh day after 2 g one shot therapy, and 75% on the first day, 66.7% on third day and 100% on seventh day after 4 g one shot therapy. We considered that one shot therapy of SPCM was effective for gonococcal infection also in the present time. Especially SPCM was effective for infections by PPNG, since it was not resolved by beta-lactamase of N. gonorrhoeae. Positive rate of Chlamydia trachomatis was 16.3% in male gonococcal urethritis, and the serous discharge tended to remain longer in the positive patients than in the negative patients. There was only one side effect (1.4%), therefore SPCM was recognized to be a safely administrated antimicrobial agent.     

Detection of Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum (biovar 1) and Ureaplasma urealyticum (biovar 2) in patients with non-gonococcal urethritis using polymerase chain reaction-microtiter plate hybridization

AIM: To use polymerase chain reaction (PCR)-microtiter plate hybridization assays to detect Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum (biovar 1) and Ureaplasma urealyticum (biovar 2) in first-voided urine specimens from patients with non-gonococcal urethritis (NGU). METHODS: A total of 153 male patients with NGU, who visited one of 24 clinics in Japan, were recruited for this study. All were examined using PCR-microtiter plate hybridization assays for the presence of M. genitalium, M. hominis, U. parvum (biovar 1) and U. urealyticum (biovar 2) in first-voided urine specimens. They were also examined for the presence of Chlamydia trachomatis. RESULTS: Of these 153 patients, 73 (47.7%) were positive for C. trachomatis. Overall, the prevalence was 17.0% for M. genitalium, 16.3% for U. urealyticum (biovar 2), 7.8% for U. parvum (biovar 1) and 2.6% for M. hominis. In the 80 patients with non-chlamydial NGU, the prevalence of M. genitalium, U. urealyticum (biovar 2), U. parvum (biovar 1) and M. hominis was 23.8%, 18.8%, 8.8% and 2.6%, respectively. CONCLUSIONS: This study shows the prevalence of mycoplasmas and ureaplasmas in NGU in Japan. M. genitalium and U. urealyticum (biovar 2) might be pathogens of NGU and could be associated with persistent and recurrent urethritis. When patients with NGU are treated, such pathogens should be taken into account. This PCR-microtiter plate hybridization assay provides a useful method for diagnosing NGU caused by M. genitalium and U. urealyticum (biovar 2).     

Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of cefetamet pivoxil

We studied the epidemiology of 109 cases of gonococcal infections (105 males with urethritis and 4 females with cervicitis), together with the basic and clinical effects of cefetamet pivoxil in the cases. The peak of age distribution of the male patients was in the younger half of their twenties, and all of the 4 female cases were between 20 and 39 years old. The major source of infections in the males younger than 25 years old was their girl friends or so-called pick-up friends, and that of the males older than 25 years old workers serving at an amusement center, for example, bars and so-called special massage parlor, which accounted for about three fourths of the male cases between 35 and 44 years old. The distribution of the MIC (inoculum size; 10(6) CFU/ml) of Cefetamet against beta-lactamase non penicillinase producing Neisseria gonorrhoeae (non-PPNG) ranged from 0.025 to 0.1 microgram/ml and that against beta-lactamase producing Neisseria gonorrhoeae ranged from 0.025 to 0.05 microgram/ml. The isolation rate of PPNG was 10.2% (9/88). In male patients with gonococcal urethritis, the efficacy rate was 100% on days 3 and 7 for 1,000 mg single dose and 7-day treatment and 500 mg single dose treatment. One of the cases treated with 250 mg single dose therapy was unchanged at 3, but the efficacy rate of the remaining cases was 100% at day 7. Complicated urethritis with C. trachomatis was noticed in 25.7% (5/105) of the male urethritis and in 25.0% (1/4) of the female cervicitis cases. The only side effect was diarrhea observed in 1 of the 124 case (0.8%).     

Bacteriological and clinical studies on fleroxacin in male gonococcal urethritis

We performed basic and clinical studies on the effects of a new oral antimicrobial agent, fleroxacin (FLRX), a new quinolone derivative in male gonococcal urethritis. The antibacterial activity of FLRX against clinical strains of Neisseria gonorrhoeae was roughly comparable to that of norfloxacin and ofloxacin. FLRX was administered to 58 males with gonococcal urethritis. Two different schedules of administration were adopted. One was a single-dose of 300 mg given orally (17 cases) and the other was the oral administration of 200 mg once a day for 3 to 10 days (41 cases). Clinical evaluation was made according to the criteria of the Japanese UTI Committee. The overall efficacy rate was 98% (49/50). For complications of Chlamydia trachomatis (11 cases), the efficacy rate was 90.9% (10/11). No subjective or objective adverse reaction occurred.     

Clinical observation of non-gonococcal urethritis

Sixty-one male urethritis cases, 28 gonococcal urethritis and 33 nongonococcal urethritis (NGU), were out-patients at the Department of Urology, Asahi General Hospital, during the 4 months, Oct. 1, 1984-Jan. 31, 1985. Thirteen of the 33 NGU patients (39.4%) were infected with C. trachomatis (CT). The efficacy of Doxycycline and the route of infection was studied in the cases of CT-positive CT-negative-NGU. CT infection from prostitutes was not so frequent as in the other pathogen infection of NGU. The efficacy of Doxycycline (100 mg b.i.d. for 2 weeks) against CT infection was excellent in the disappearance of subjective complaints and that of white blood cells in the urethral discharge in the CT positive-NGU group (13/13), in comparison with CT negative-NGU group (7/18). The efficacy of Doxycycline against CT was also confirmed from the follow-up study by the isolation of CT and by detection of CT antigen from urethral swabs using FITC conjugated monoclonal antibody against CT antigen.     

Detection of Chlamydia trachomatis in urethra of patients with urogenital infection

Between January, 1984 and August 1986, we examined 151 male patients with urogenital infections including 114 cases of urethritis, 18 cases of epididymitis, 19 cases of prostatitis at the outpatient clinic of the department of urology, Toho University's Ohmori Hospital. The positive rate for Chlamydia trachomatis from the urethra based on cell cultures was 29.0%, (30.5% for urethritis, 27.8% for epididymitis, and 21.1% for prostatitis). The positive rate for non-gonorrheal urethritis was 33.0% and chlamydia infections were complicated by gonorrheal urethritis in 23.3% of the cases. The mean age of the patients with positive Chlamydia trachomatis was 31.9 years. The route of infection in 77.8% of the cases was sexual intercourse the most common cause of which was infection from a prostitute in 62.1% of the cases. The latent period was in most cases from 2-3 weeks.     

Clinical observations on urethritis over the last eight years in Gifu City Hospital

Clinical observations were made on patients with urethritis, syphilis, chancroid, genital herpes and venereal warts for the last eight years at Gifu City Hospital. The patients with urethritis, genital herpes and venereal warts tended to increase yearly, and the number of the cases with urethritis increased about 2.5 times in the eight years. Slightly more patients had nongonococcal urethritis than gonococcal urethritis excluding 1981. Of the patients with gonococcal urethritis seen between 1977 and 1979, 58% were treated with benzylpenicillin intramuscularly, and 43% of the patients seen between 1980 and 1984 were treated with a concomitant therapy of spectinomycin intramuscularly and minocycline or doxycycline orally. The cure rate for each treatment was 94% and 97%, respectively. Of the patients with nongonococcal urethritis seen between 1980 and 1984, 89% were treated with minocycline or doxycycline orally, and the cure rate was 97%. On the other hand, the cure rate was 43% for the treatment between 1977 and 1979, only 10% of whom had received treatment with minocycline or doxycycline.     

甘肃省张掖市2 356例患者泌尿生殖道衣原体、支原体感染的调查与药敏分析

目的：了解甘肃省张掖市2000-2004年间2356例可疑非淋菌性尿道炎（NGU）患者泌尿生殖道分泌物衣原体、支原体感染及药敏状况。方法：应用衣原体试剂盒（胶体金法）定性检测衣原体抗原、支原体培养及药敏选用支原体药敏试剂盒,并对10种抗生素对支原体的敏感性进行了分析。结果：2356例可疑NGU患者检出衣原体阳性者384例（16．29％）,支原体阳性者324例（13．29％）,混合感染者57例（2．42％）。支原体敏感的药物是多西环素、交沙霉素、米诺环素,耐药的是环丙沙星、氧氟沙星、克林霉素。结论：张掖地区NGU患者的病原体仍然主要是衣原体、支原体,多西环素、交沙霉素、米诺环素可作为支原体感染的首选药物,同时,NGU的病原学检测和药敏试验对其防治尤为重要。     

PCR检测沙眼衣原体及其在男性尿道感染中的意义

应用多聚酶链反应(PCR)检测604例临床已确诊的男性泌尿系感染患者衣原体(CT)感染情况,发现阳性率为:急性淋菌性尿道炎26.9％(117/435)、淋菌后尿道炎48.5％(32/66)、非淋菌性尿道炎31.1％(32/103)。认为PCR技术是临床快速诊断男性衣原体尿道炎的有效方法。     

The importance and frequency of mixed infections with Chlamydia trachomatis and mycoplasmas in acute gonococcal urethritis

Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis are frequently involved in gonococcal urethritis. We investigated 143 male White and Black patients with gonococcal urethritis (average age 22,5 years). Of these 29% had coexisting Chlam. trachomatis infection, 34% U. urealyticum infection and 13% Mycoplasma hominis infection. Conventional penicillin therapy did not affect Chlam. trachomatis, U. urealyticum or Mycoplasma hominis, which persisted in the lower urogenital tract, causing a so-called 'post-gonococcal urethritis.' Additional therapy with tetracycline or erythromycin was successful in most cases.     

Gonococcal urethritis--diagnosis and treatment.

For men with urethral discharge, a simple gram stained smear is 98% sensitive and over 99% specific in detecting gonococcal infection when compared to a single Thayer-Martin culture. The smear is less than 50% sensitive in asymptomatic urethritis. Neither Fluorescent antibody nor various serologic tests offer any diagnostic advantages over smears and/or cultures and they are not cost-effective. Treatment of gonococcal urethritis may be successfully accomplished with a variety of antibiotic regimens. Tetracycline hydrochloride (500 mg four times a day for 5 days) is highly effective, inexpensive, and is active against Chlamydia trachomatis; post gonococcal urethritis (PGU) is therefore uncommon. Aqueous Procaine Penicillin G (4.8 million units IM with 1 g of probenecid) has become the standard in the United States but suffers from higher cost, the need for refrigeration, occasional alarming toxic procaine reactions, and a high incidence of PGU. Spectinomycin 2 g IM remains expensive but is the regimen of choice for treatment failures and for Neisseria gonorrhoeae that produce penicillinase (PPNG). Other antibiotics active against PPNG are cotrimoxozole, cefoxitin, and cefuroxime. PNNG have now been reported from 27 countries throughout the world, but have attained significant prevalence in only a few areas of East Asia and West Africa. Because gonococcal patterns of antibiotic resistance are constantly changing, each region of the world needs to monitor treatment results and maintain some surveillance over sensitivity to antibiotics.     

Cytodiagnosis of Chlamydia trachomatis by the immunoperoxidase technic

The PAP-immunocytochemistry using a monoclonal antibody against Chlamydia trachomatis was applied to male patients with clinically manifest urethritis and their female sex partners. In addition, serum levels of the antibody were determined by means of an ELISA system. Immunoperoxidase reactions were recognized on urethral scrapes in 53 (33%) out of 160 cases, and on endocervical specimens in 13 (59%) out of 22 sex partners of PAP-positive patients. In patients with gonococcal urethritis, an infection of C. trachomatis was revealed immunocytochemically in 11 (31%) out of 36 cases, and in 29 (46%) out of 62 cases with non-gonococcal urethritis. Following medication with 200 mg of minocycline or doxycycline per day, PAP staining became negative in 23 (66%) out of 35 cases. The levels of serum antibody against C. trachomatis were undetectable in 8 (26%) out of 29 PAP-positive cases, but positive in 7 (15%) out of 44 PAP-negative cases.