The management of confirmed Chlamydia trachomatis infection incorporates appropriate antimicrobial therapy, partner notification (see section 5), advice to abstain from sex until both the index case and current partner(s) have been treated, and relevant health education (see section 6).

4.1 Choice of antimicrobial agent

The choice of antimicrobial agent is governed by efficacy, incidence of side effects, cost, and compliance.

There are no randomised controlled trials (RCTs) of the treatment of genital chlamydial infection with any agents compared to placebo, as the original trials of antimicrobial agents for the treatment of non-gonococcal urethritis (NGU) established the efficacy of tetracyclines and erythromycin long before Chlamydia trachomatis was identified.^119,120,121 Once it became clear that Chlamydia trachomatis was the aetiological agent in 50% of cases of NGU, it was ethically unjustifiable to carry out placebo-controlled trials of antichlamydial agents. Rather, newer agents have been compared with older drugs such as tetracyclines or erythromycin.^{119,122, 123,124,125,126} Evidence level IIb

The newer tetracyclines, minocycline and doxycycline are as effective as older tetracyclines and erythromycin, as is ofloxacin. Ciprofloxacin and norfloxacin have been shown to be ineffective.¹²⁷ Doxycycline is generally better tolerated than minocycline¹²⁸ and as a result has tended to be used as the control against which other drugs are compared. As erythromycin has rarely been used in RCTs, the group could find insufficient evidence to support its use, except in the treatment of uncomplicated infection in pregnancy. Although equally effective, the four times a day regimen of older treatments meant that doxycycline was more often used as a comparator in studies. Evidence level IIa

Given the high cure rate (>90%) with all the agents used, equivalence of effectiveness of therapy, rather than improved effectiveness, was sought. All treatment regimens reviewed are oral, for outpatient use.

It has been shown that compliance with oral therapy for STIs over several days is sub-optimal, and gets worse the more frequent the daily dosage. Compliance may be poor for many reasons, ranging from patients being asymptomatic, the symptoms of infection clearing quickly, the presence of side effects, through to the chaotic lifestyle of some patients.^{129,130,131,132} Evidence level IIa

4.2 Uncomplicated infection

Azithromycin 1g stat, ofloxacin 200 or 300mg twice daily for seven days, minocycline 100mg for nine days and lymecycline 300 mg for 10 days are all as effective as doxycycline 100mg twice daily for seven days.^{127,133,134,135,136,137,138,139,140,141,142,143,144} Evidence level Ib

Uncomplicated genital Chlamydia trachomatis infection may be treated with any one of the following (listed alphabetically): azithromycin 1g stat doxycycline 100 mg twice daily for 7 days lymecycline 300 mg once a day for 10 days minocycline 100 mg once a day for 9 days ofloxacin 200 mg twice daily for 7 days.

Taking into account the issue of compliance with therapy, it is recommended that uncomplicated genital Chlamydia trachomatis infection is treated with azithromycin 1g stat.

4.3 Uncomplicated infection in pregnancy

In women with ongoing pregnancy erythromycin may not be well tolerated and there is evidence that amoxycillin 500mg three times a day for seven days is equivalent to erythromycin 500mg four times a day for seven days in the treatment of uncomplicated genital chlamydial infection.^145,146 In vitro studies suggest that amoxycillin may not always eradicate chlamydial infection but may render the infection latent.¹⁴⁷ A small study has shown that some infants develop chlamydial infection despite apparently successful treatment of the mother.¹⁴⁸ Therefore a negative test of cure does not necessarily equate with absence of transmission during delivery. ^145,146 Evidence level Ia

Uncomplicated genital chlamydial infection in pregnancy should be treated with: erythromycin 500mg four times a day for 7 days or amoxycillin 500mg three times a day for 7 days.

When women have been treated with amoxycillin in pregnancy, practitioners should maintain a high index of suspicion should symptoms suggestive of chlamydial infection develop in the infant.

Women undergoing TOP should routinely be tested for chlamydial infection (see section 3.2) There is evidence that giving antichlamydial therapy at the time of the procedure reduces the risk of PID regardless of the result of the test,⁷⁴ but the test should still be performed to allow partner notification to prevent reinfection. Evidence level Ib

All women undergoing TOP should receive antimicrobial therapy effective against chlamydial infection at the time of the procedure.

4.4 Upper genital tract infection in women
(CHLAMYDIAL SALPINGITIS / PID)

All studies on the treatment of pelvic inflammatory disease use clinical end-points as their primary assessment of efficacy. There are no satisfactory studies where microbial test of cure for chlamydial infection is the primary end-point.

The current Centers for Disease Control (CDC) treatment guidelines³ for PID incorporate anti-gonococcal therapy. Their recommendations are based on the high prevalence of gonorrhoea in the USA and are not directly applicable to Scotland, where the incidence is lower. Adapting the guidelines for the UK, where there is presently a low prevalence of gonorrhoea, the following are recommended as treatment for chlamydial salpingitis. Evidence level IV

The recommended treatment for upper genital tract infection in women is doxycycline 100 mg twice daily for a minimum of 10 days plus metronidazole 200mg three times a day or 400 mg twice daily for the first 7 days.

Ofloxacin 400 mg twice daily may be used as an alternative to doxycycline.

Clindamycin 450 mg four times a day may be used as an alternative to metronidazole.

4.5 Upper genital tract infection in men
(CHLAMYDIAL EPIDIDYMO-ORCHITIS)

The literature search undertaken for this guideline did not identify any reliable evidence on the treatment of upper genital tract infection in men. Historically, tetracyclines have been used successfully, with current practice favouring doxycycline and oxytetracycline.¹⁴⁹ Evidence level IV

The recommended treatment for upper genital tract chlamydial infection in men is: doxycycline 100 mg twice daily for 7-14 days or oxytetracycline 250 mg four times a day for 7-14 days

4.6 Initiation of treatment

In symptomatic patients treatment should be initiated at the first consultation rather than awaiting laboratory confirmation of infection. There is evidence in PID that delay in starting treatment increases the risk of impaired fertility.³⁹ Partners should be treated without waiting for laboratory confirmation.¹⁵⁰ Evidence level IIb

Initiate treatment without waiting for laboratory confirmation of infection in patients with symptoms and signs attributable to chlamydial infection and their sexual partners.

4.7 Follow up and test of cure

The quality of evidence available to determine the role of test of cure is inevitably poor. Many patients fail to return and thus cannot be included in studies. However, conclusions can still be drawn regarding the management of the self-selecting group of patients who return for follow-up.^{151,152,153,154,155,156} These studies provided no conclusive evidence as to the optimal timing of follow-up. However, prolonged delay on follow-up increases the risk of re-infection from untreated partners. Evidence level III

Follow up should be offered approximately 2-3 weeks after initiating therapy.

Patients should be interviewed at follow-up with regard to compliance with therapy and risk of re-infection.

In those patients who have been compliant with therapy and in whom there is no risk of reinfection, a test of cure need not be performed.

Some patients, especially those who had asymptomatic chlamydial infection, may prefer the reassurance of test of cure.

Health professionals should be aware that if a test of cure is to be done using a molecular amplification assay, it should not be done within three weeks to avoid false positive results due to persistence of non-viable organisms.¹⁵⁷ Evidence level IIb

Test of cure/re-infection established by molecular amplification assay should be performed a minimum of three weeks after the initiation of therapy, to avoid false positive results.