Global Resistance of Neisseria gonorrhoeae

When Theory Becomes Reality

David A. Lewis

Disclosures

Curr Opin Infect Dis. 2014;27(1):62-67. 

In This Article

Abstract and Introduction

Abstract

Purpose of review Neisseria gonorrhoeae has demonstrated a remarkable genetic capacity to acquire antimicrobial resistance (AMR) determinants. This review focuses on the recent developments in respect of third generation extended spectrum cephalosporin (ESC)-resistant gonorrhoea and the search for future treatment options.

Recent findings The estimated incidence of new gonorrhoea cases is increasing, and the antimicrobial resistance profile of N. gonorrhoeae is worsening. The most significant recent finding has been the emergence of extensively drug-resistant (XDR) N. gonorrhoeae characterized by very high ceftriaxone minimum inhibitory concentrations. A national switch from cefixime to high-dose ceftriaxone as first-line antigonococcal therapy in England and Wales, as well as parts of Japan, has been accompanied by a reduction in the prevalence of oral ESC-resistant gonococci. Azithromycin given in combination with either gentamicin or gemifloxacin has been shown to be an effective alternative antigonococcal therapy. Both ertapenem and solithromycin have good in-vitro activity against ESC-resistant N. gonorrhoeae strains.

Summary Current strategies to control gonococcal AMR should focus on the use of higher doses of ceftriaxone given as part of dual therapy and further evaluation of alternative drug combinations. The emergence of XDR gonorrhoea argues for enhanced efforts to develop novel antimicrobial agents and a gonococcal vaccine.

Introduction

Neisseria gonorrhoeae, a Gram-negative diplococcus, is the aetiological agent responsible for gonorrhoea. Although gonorrhoea is mostly acquired through sexual intercourse, it may be transmitted by direct inoculation to the eye of both neonates and adults. Untreated gonorrhoea may result in several complications, such as pelvic inflammatory disease, infertility, ectopic pregnancy, epididymo-orchitis and disseminated gonococcal infection. The most recent 2008 WHO estimates have documented a 21% global increase in the total number of new cases of gonorrhoea in adults compared with 2005, with an estimated 106 million adults being infected with N. gonorrhoeae in 2008.[1]

Since the first introduction of sulphonamides to treat gonorrhoea in the 1930s, the gonococcus has shown a remarkable genetic capacity to develop antimicrobial resistance (AMR) to sequential antimicrobial agents introduced for the treatment of gonorrhoea.[2] Importantly, N. gonorrhoeae is naturally competent for the uptake of extracellular DNA, which enables the bacterium to acquire resistance determinants through transformation. AMR may be divided into chromosomally mediated and plasmid-mediated resistance. Chromosomal mutations typically affect drug-target interactions or the functioning of the multidrug-resistance efflux pump.[3] Plasmids may contain resistance determinants and be passed from one gonococcus to another through conjugation. For N. gonorrhoeae, plasmid-mediated resistance has been described for penicillin and tetracycline.[3]

With rising rates of AMR, we are running out of available treatment options for gonorrhoea. This review will first briefly review the key historical milestones in the development of AMR to earlier therapies and then summarize recent literature in the past 1–2 years (2011–2013) with particular focus on resistance to the third generation extended spectrum cephalosporins (ESCs) and potential options for the future.

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