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Current and future antimicrobial treatment of gonorrhoea: the rapidly evolving Neisseria gonorrhoeae continues to challenge
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Ctr Gonorrhoea & Other STIs, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Microbiol, Örebro University Hospital, Örebro, Sweden.
2015 (English)In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, article id 364Article, review/survey (Refereed) Published
Abstract [en]

Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs previously and currently recommended for empirical monotherapy of gonorrhoea. In vitro resistance, including high-level, to the last option ceftriaxone and sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged. In response, empirical dual antimicrobial therapy (ceftriaxone 250-1000 mg plus azithromycin 1-2 g) has been introduced in several particularly high-income regions or countries. These treatment regimens appear currently effective and should be considered in all settings where local quality assured AMR data do not support other therapeutic options. However, the dual antimicrobial regimens, implemented in limited geographic regions, will not entirely prevent resistance emergence and, unfortunately, most likely it is only a matter of when, and not if, treatment failures with also these dual antimicrobial regimens will emerge. Accordingly, novel affordable antimicrobials for monotherapy or at least inclusion in new dual treatment regimens, which might need to be considered for all newly developed antimicrobials, are essential. Several of the recently developed antimicrobials deserve increased attention for potential future treatment of gonorrhoea. In vitro activity studies examining collections of geographically, temporally and genetically diverse gonococcal isolates, including multidrug-resistant strains particularly with resistance to ceftriaxone and azithromycin, are important. Furthermore, understanding of effects and biological fitness of current and emerging (in vitro induced/selected and in vivo emerged) genetic resistance mechanisms for these antimicrobials, prediction of resistance emergence, time-kill curve analysis to evaluate antibacterial activity, appropriate mice experiments, and correlates between genetic and phenotypic laboratory parameters, and clinical treatment outcomes, would also be valuable. Subsequently, appropriately designed, randomized controlled clinical trials evaluating efficacy, ideal dose, toxicity, adverse effects, cost, and pharmacokinetic/pharmacodynamics data for anogenital and, importantly, also pharyngeal gonorrhoea, i.e. because treatment failures initially emerge at this anatomical site. Finally, in the future treatment at first health care visit will ideally be individually-tailored, i.e. by novel rapid phenotypic AMR tests and/or genetic point of care AMR tests, including detection of gonococci, which will improve the management and public health control of gonorrhoea and AMR. Nevertheless, now is certainly the right time to readdress the challenges of developing a gonococcal vaccine.

Place, publisher, year, edition, pages
2015. Vol. 15, article id 364
Keywords [en]
Gonorrhoea, Neisseria gonorrhoeae, Treatment, Ceftriaxone, Azithromycin, Antimicrobial resistance, Treatment failure
National Category
Infectious Medicine
Research subject
Infectious Diseases
Identifiers
URN: urn:nbn:se:oru:diva-45804DOI: 10.1186/s12879-015-1029-2ISI: 000359901400001PubMedID: 26293005Scopus ID: 2-s2.0-84939529739OAI: oai:DiVA.org:oru-45804DiVA, id: diva2:854213
Note

Funding Agencies:

Örebro University Hospital, Department of Laboratory Medicine

Research Committee of Örebro County

Örebro University Hospital Foundation, Örebro, Sweden

Available from: 2015-09-16 Created: 2015-09-15 Last updated: 2018-07-01Bibliographically approved

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Unemo, Magnus

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