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Besides Chlamydia trachomatis, various microorganisms could cause non-gonococcal urethritis (NGU). Recently, Mycoplasma genitalium and Ureaplasma urealyticum (biovar 2) have been suggested to be other pathogens of NGU independent of C. trachomatis. Clinical findings of non-chlamydial NGU, including M. genitalium--or U. urealyticum-postive NGU, are not different from those of chlamydial NGU. M. genitalium and U. urealyticum (biovar 2) are susceptible to tetracyclines, macrolides, and fluoroquinolones. However, the post-treatment presence of M. genitalium in the urethra is significantly associated with persistent or recurrent urethritis. Eradication of this mycoplasma from the urethra is essential for managing M. genitalium-positive NGU. In treatment of non-chlamydial NGU, therefore, the antimicrobial agents that are active against M. genitalium should be chosen.

Genital chlamydial infection is a sexually transmitted disease (STD) of public health importance. Infection with Chlamydia trachomatis can cause urethritis, cervicitis, pharyngitis, or epididymitis, although asymptomatic infections are quite common. Chlamydial infection remains asymptomatic in approximately 50% of infected men and 70% of infected women. Genital infection with C. trachomatis markedly enhances the risk for reproductive tract sequelae in women, including tubal factor infertility and ectopic pregnancy. A proper detection of C. trachomatis and its treatment is of importance to prevent outbreaks of genital chlamydial infection. We review the pathology, diagnosis and treatment of this entity.

Two hundred and forty four men with non-gonococcal urethritis (NGU) took part in a trial of minocycline. Chlamydiae were isolated from 34%, ureaplasmas from 47.1%, and Mycoplasma hominis from 10.2%. These micro-organisms were isolated least often from men suffering their third or more attack of NGU, and men in this group failed most often to respond to minocycline. Irrespective of the micro-organisms isolated originally or the number of previous attacks, the failure rate (10%) for men receiving minocycline for 10 days was significantly less than for those receiving this antibiotic for one or two days. More than half of the men suffering third attacks from whom micro-organisms were not isolated failed to respond to these short regimens. One of the lowest failure rates (4%) after short term treatment, however, was seen in men experiencing first attacks who yielded only ureaplasmas with or without M hominis, which indicates the importance of ureaplasmas in this group of patients. Chlamydiae were not reisolated from any patient after treatment, irrespective of its duration, and the only ureaplasmas that were reisolated were from nine patients who carried tetracycline resistant strains. Reasons for the absence of chlamydiae and ureaplasmas in the presence of disease and the need to look for other microorganisms as a cause of NGU are discussed among other issues raised by these results.

A trial comparing the efficacy of three different tetracyclines, each in two different dosage regimens, in the treatment of non-specific urethritis is described. There was a significant association between the retreatment rate and sexual intercourse. Age, race, duration of symptoms, previous infection, and indulgence in alcohol did not appear to influence the results whereas treatment of sexual contacts before resumption of sexual intercourse significantly reduced the retreatment rate. Single-dose treatment with doxycycline was shown to be ineffective. Treatment with doxycycline for seven days or triple tetracycline for seven days was less effective than triple tetracycline for 21 days or oxytetracyline for seven or 21 days, all of which gave the same success rate.

We treated 289 men who had nongonococcal urethritis with minocycline, 100 mg once or twice daily for 7 to 21 days. After 21 +/- 7 days, urethritis persisted or recurred in 31 (27%) of 114 given 7-day therapy and only nine (8%) of 110 given 21-day therapy (p = 0.0005). However, by 49 +/- 14 days, the cumulative percent rate of failure was 31% for 7-day and 30% for 21-day therapy. Thus, 21-day therapy only delayed recurrence. The higher daily dosage did not improve outcome. Urethritis persisted or recurred in 19% of men with initial Chlamydia trachomatis infection. Among men without C. trachomatis, urethritis persisted or recurred in 32% with and 52% without Ureaplasma urealyticum infection (p = 0.03). At follow-up, 79% of cases of persistent or recurrent urethritis were culture negative for C. trachomatis and U. urealyticum. The cause of C. trachomatis-negative, U. urealyticum-negative nongonococcal urethritis, which was least responsive to minocycline therapy, remains uncertain.

Seventy-two men with gonococcal urethritis were given a single 300-mg dose of minocycline. The failure rate was 13% and the trial was terminated at an early stage. Failure was correlated with increased resistance of Neisseria gonorrhoeae to minocycline. The activity of penicillin, spectinomycin, erythromycin, tetracycline, sulphamethoxazole, cefuroxime, cefotaxime, rosamicin, thiamphenicol, and piperacillin against N. gonorrhoeae were examined in vitro. With the exception of spectinomycin, parallel patterns of resistance to the other antibiotics and minocycline were found. Resistance to spectinomycin was not found, confirming the usefulness of this antibiotic in the treatment of gonorrhoea. The incidence of PGU was significantly lower after a single dose of minocycline than in previous studies.

In a controlled trial of rosoxacin in patients with non-gonococcal urethritis (NGU), 150 mg of the antibiotic given twice daily for 10 days was compared with 300 mg triple tetracycline (Deteclo) given twice daily for the same period. Only six (19%) of 31 patients treated with rosoxacin were free of urethritis after 10 days; Chlamydia trachomatis was reisolated from 12 (92%) of 13 patients who were chlamydia positive originally, and Ureaplasma urealyticum was reisolated from 12 (80%) of 15 patients who were ureaplasma positive originally. In contrast, 18 (58%) of 31 patients treated with triple tetracycline were cured clinically after 10 days; C trachomatis was not reisolated from any of 10 patients who were chlamydia positive originally, and U urealyticum was reisolated from only three (17%) of 18 patients who were ureaplasma positive originally. These results were consistent with the antimicrobial inactivity of rosoxacin in vitro and they cannot be reconciled with previous reports of successful use of this antibiotic in NGU. Ureaplasmas were isolated more frequently and in larger numbers from chlamydia negative than from chlamydia positive patients, but it is probable that ureaplasmas resistant to tetracycline were not responsible for persistent urethritis.

Details are given of a double-blind trial involving 400 cases in which tetracycline 500 mg. four times a day for 7 days was compared with tetracycline 250 mg. four times a day for 14 days and also of the findings in 311 cases treated with Deteclo 300 mg. three times a day for 3 weeks. The treatment in the double-blind trial were equally effective and appeared to be as effective as the long-term Deteclo therapy. When the results of these treatments were compared with those obtained previously with tetracycline 250 mg. four times a day for 4 days and allowance was made for the time at which the latter results have been assessed, it was concluded that neither the treatment used in the double-blind trial nor Deteclo 300 mg. three times a day for 3 weeks offered any advantage over the customary treatment with tetracycline 250 mg, four times a day for 4 days.