Azithromycin resistant gonococci: a literature review

Awoke Derbie, Daniel Mekonnen, Yimtubezinash Woldeamanuel, Tamrat Abebe

Gonorrhea is the second most common sexually transmitted bacterial infection (STI) next to Chlamydia. Untreated cases could results in major complications like pelvic inflammatory disease (PID), ectopic pregnancy, infertility, miscarriage, fetal death and congenital infections. Gonorrhea has been treated with antibiotics for more than eight decades. However, the emergence and spread of antimicrobial resistance (AMR) in gonococcus seriously compromises the management of the disease. The aim of this review was to describe the current developments in the field of azithromycin resistant gonococci. Literatures published in English in the last 10 years were retrieved from PubMed, SCOPUS, Google scholar, Cochrane library and the Google databases using relevant searching terms. Gonococcus is capable of using a number of strategies to confer resistance as the bacterium has an extraordinary capacity to alter its genome. So far the accumulated data on the field showed that the world is heading towards a pandemic of extensively drug-resistant (XDR) gonococcus which is now seems to be evolving into a true "superbug". Hence, in the near future gonorrhea may become untreatable on the international basis unless new drugs become available. An antibiotic resistance in gonococcus has been noted beginning in 1940s against sulfonamides. Since then, resistance has rapidly emerged to penicillins, tetracyclines, macrolides, fluoroquinolones, and cephalosporins. Currently, in most nations, the injectable extended-spectrum cephalosporin (ESC), i.e. ceftriaxone based therapy is the only remaining option for gonorrhea. Based on the WHO and the US-CDC recommendations, countries are increasingly using a combination of cephalosporin and azithromycin for the treatment of gonorrhoea. Azithromycin revolutionized gonoccocal therapy as it shortened treatment time by more than half from 7 to 14 days and improved patient compliance due to high tissue levels and long half-life. However, constantly emerging reports from different parts of the globe showed that N. gonorrhoeae is developing significant level of resistance against azithromycin, and so far more than 33% level of resistance was reported. Two strategies have been commonly implicated in gonococcal resistance against azithromycin: over expression of an efflux pump (due to mutations at mtrR coding region) and decreased antimicrobial affinity (due to mutations in genes encoding the 23S ribosomal subunit). With no alternative antimicrobial treatment options for gonorrhoea and only a few new drugs in the development pipeline, it is necessary to monitor drug resistance and optimize treatment regimens regularly. Moreover, investigations for novel drugs should be wired.