SUBJECTS AND METHODS

A prevalence study of 519 men and 464 women attending the Örebro STD clinic was performed between 1 February and 31 July 2000 comparing signs and symptoms between M genitalium and C trachomatis genital infections. Two of 519 men had gonorrhoea but were negative for C trachomatis and M genitalium. In three of 464 attending women, samples for M genitalium were not taken. M genitalium was detected in 26 women and 34 men, and four of each gender, had a concurrent infection with C trachomatis. Patients with urethritis (>4 PMNL/high power field) and/or cervicitis (PMNL >epithelial cells in vaginal wet mount) were treated with doxycycline, 200 mg the first day and 100 mg the following 8 days, or lymecycline 300 mg twice daily for 10 days. However, some patients were treated otherwise, because of conditions such as epididymitis, prostatitis, and suspected low compliance, and therefore three of the M genitalium positive male patients were treated with ofloxacin, 30 days of doxycycline, or single dose azithromycin, respectively. All patients not receiving treatment initially but having a positive M genitalium test were treated with azithromycin 500 mg the first day and 250 mg for the following 4 days. Steady partners to patients with an M genitalium infection were treated with azithromycin for 5 days. All M genitalium patients were asked to return 4–5 weeks after treatment commenced. After the follow up visit, those treated with tetracyclines initially but still M genitalium positive or with remaining symptoms of urethritis or cervicitis were treated with a 5 day course of azithromycin.

Attending men had first void urine (FVU) samples collected. C trachomatis was detected by the Cobas Amplicor Chlamydia trachomatis test (Roche Diagnostic Systems, Inc, Branchburg, NJ, USA). M genitalium was detected by polymerase chain reaction (PCR) using primers detecting the M genitalium 16S rRNA gene.⁵ All positive results were confirmed by a PCR detecting the MgPa adhesin gene.⁶ Samples for Neisseria gonorrhoeae (culture) were taken in 88 men.

Women were tested for M genitalium in FVU and from endocervical specimens as described above. C trachomatis was detected in FVU and endocervix by PCR and culture, respectively. Endocervical and urethral samples were cultured for N gonorrhoeae in 65 women. Sampling for N gonorrhoeae culture was only performed on patients at risk, because of the low prevalence in Sweden.

RESULTS

Three of 34 M genitalium positive men were not treated with the standard treatment and were excluded in the treatment comparison. Those with a concurrent C trachomatis infection were treated with tetracyclines (n=3) or ofloxacin (n=1). At follow up all were C trachomatis negative, but those receiving tetracyclines were still M genitalium positive. Out of 20 men treated with either doxycycline (n=14) or lymecycline (n=6), 16 reattended and 10/16 (63 %) were still M genitalium positive after a median of 43 days (mean 39, range 27–90 days). After a second treatment with azithromycin eight of 10 reattended after a median of 38 days (mean 42, range 31–79) and were all M genitalium negative. All eight of 11 initially treated with azithromycin who reattended were M genitalium negative at the follow up visit after a median of 43 days (mean 67, range 23 to 170 days) (fig 1⇓). Among the M genitalium positive men initially treated with azithromycin, a subgroup of six had symptomatic urethritis. These patients could be compared to 15 M genitalium positive patients with symptomatic urethritis who received tetracyclines. None of those receiving the 5 day course of azithromycin were positive at follow up whereas 10 of the 15 (67%) in the tetracycline group were still M genitalium positive at follow up (Fisher’s exact test =0.0124). None had a concurrent C trachomatis or N gonorrhoeae infection.

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Figure 1

Outcome of antibiotic treatment in 31 M genitalium (Mg) infected men. The figures in bars indicate number of patients.

Fourteen M genitalium positive women were treated with tetracyclines (eight with doxycycline and six with lymecycline). Four of the women treated with lymecycline had a concomitant C trachomatis infection. Ten of the 14 (71%) women were still M genitalium positive, at the follow up visit after a median of 35.5 days (mean 42, range 24–90 days). These women were then treated with a 5 day course of azithromycin and all 10 reattended after a median of 31 days (mean 44, range 22–98 days) and were at that time M genitalium negative. Of 12 women initially treated with azithromycin (all C trachomatis negative) 10 reattended after a median of 32 days (mean 40, range 23–89 days) and were all M genitalium negative (fig 2⇓). N gonorrhoeae was not isolated from any patient.

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Figure 2

Outcome of antibiotic treatment in 26 M genitalium (Mg) infected women. The figures in bars indicate number of patients.

DISCUSSION

Tetracyclines are widely used worldwide as a treatment for NGU. This treatment is excellent for chlamydial infections and most failures are the result of lack of compliance of treatment or re-infection.⁷ It is well known that tetracycline treatment might fail in NCNGU and the proposed treatment of choice in those cases is erythromycin or azithromycin.^8,9 In vitro, M genitalium is less susceptible to tetracyclines but there are no published controlled treatment studies.⁴

The treatment groups from the present study of M genitalium infected patients were not equal in symptoms and signs and therefore not directly comparable, but in a subgroup of M genitalium infected men with symptomatic urethritis there was a statistically significant difference indicating that azithromycin could be more efficient than tetracyclines.

The widely used treatment for urethritis and cervicitis with tetracyclines does not appear to be sufficient to eradicate M genitalium and this should be considered in treatment guidelines. A randomised controlled treatment trial is urgently needed to evaluate the efficacy of azithromycin at different dosages.