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Where did it all go wrong? Azithromycin, a second generation macrolide antimicrobial, has been demonstrated to be highly efficacious both in vitro (low minimum inhibitory concentration (MIC)) and in vivo against the common bacterial STIs Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) and has good treponemicidal activity in animal studies.1 ,2 w1 w2 What's more its long half-life particularly intracellularly enabled it to be administered as single-dose directly observed therapy, the preferred dosing schedule for STIs where poor compliance, and thus potential reduced efficacy, was considered a major concern with multidose regimens.3 Indeed its efficacy against chlamydia was considered to be so good, a test of cure was not considered necessary.
I argue that the evidence indicates that azithromycin 1 g is no longer at least 95% effective in achieving microbiological cure for bacterial STIs as recommended by WHO for first-line treatment and therefore should not be used for treatment.4 In addition, as monotherapy, it is likely to be doing harm by inducing macrolide antimicrobial resistance. First, it is necessary to consider the mode of action and pharmacokinetics of azithromycin given as a 1 g stat regimen (figure 1) and its mechanism of action; second, the mechanism of macrolide antimicrobial development and third, reappraise the evidence of efficacy in vivo against the common bacterial STIs, NG, syphilis, CT, MG and non-gonococcal urethritis (NGU).
Azithromycin is a bacteriostatic antibiotic and duration of exposure to levels >MIC 90 are likely to be important in determining microbiological cure, particularly if the micro-organism is slow growing.5 …