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      Emerging azithromycin-resistance among the Neisseria gonorrhoeae strains isolated in Hungary

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          Abstract

          Background

          In the 1990s, azithromycin became the drug of choice for many infectious diseases but emerging resistance to the drug has only been reported in the last decade. In the last 5 years, the National Neisseria gonorrhoeae Reference Laboratory of Hungary (NNGRLH) has also observed an increased number of N. gonorrhoeae strains resistant to azithromycin. The aim of this study was to determine the most frequent sequence types (ST) of N. gonorrhoeae related to elevated levels of azithromycin MIC (minimal inhibitory concentration). Previously and currently isolated azithromycin-resistant strains have been investigated for the existence of molecular relationship.

          Methods

          Maldi-Tof technic was applied for the identification of the strains isolated from outpatients attending the reference laboratory. Testing antibiotic susceptibility of azithromycin, cefixime, ceftriaxone, tetracycline, spectinomycin and ciprofloxacin was carried out for all the identified strains, using MIC strip test Liofilchem ®. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed exclusively on azithromycin-resistant isolates. A phylogenetic tree was drawn using MEGA6 (Molecular Evolutionary Genetics Analysis Version 6.0) Neighbour-Joining method.

          Results

          Out of 192 N. gonorrhoeae isolates, 30.0 % (58/192) proved resistant to azithromycin (MIC > 0.5 mg/L). Of the azithromycin-resistant isolates, ST1407, ST4995 and ST11064 were the most prevalent. Based on the phylogenetic analysis, the latter two STs are closely related.

          Conclusions

          In contrast to West-European countries, in our region, resistance to azithromycin has increased up to 30 % in the last 5 years, so the recommendation of the European Guideline −500 mg of ceftriaxone combined with 2 g of azithromycin as first choice therapy against N. gonorrhoeae- should be seriously considered in case of Hungary.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12941-016-0166-9) contains supplementary material, which is available to authorized users.

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          Most cited references18

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          Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area.

          In large metropolitan areas, which typically have the highest rates of gonorrhea, the identification of chains of transmission by use of partner notification is problematic, and there is an increasing interest in applying molecular approaches, which would require new discriminatory high-throughput procedures for recognizing clusters of indistinguishable gonococci, procedures that identify local chains of transmission. Sequencing of internal fragments of 2 highly polymorphic loci, from 436 isolates recovered in London during a 3-month period, identified clusters of antibiotic-resistant and antibiotic-susceptible isolates with indistinguishable genotypes, the vast majority of which were also identical or closely related by other methods, and defined groups of individuals who typically had similar demographic characteristics. This discriminatory sequence-based approach produces unambiguous data that easily can be compared via the Internet and appears to be suitable for the identification of linked cases of gonorrhea and the timely identification of transmission of antibiotic-resistant strains, even within large cities.
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            2012 European guideline on the diagnosis and treatment of gonorrhoea in adults.

            Gonorrhoea is a major public health concern globally. Of particularly grave concern is that resistance to the extended-spectrum cephalosporins has emerged during the most recent years. This guideline provides recommendations regarding the diagnosis and treatment of gonorrhoea in Europe. Compared to the outdated 2009 European gonorrhoea guideline, this 2012 European gonorrhoea guideline provides up-to-date guidance on, broader indications for testing and treatment of gonorrhoea;the introduction of dual antimicrobial therapy (ceftriaxone 500 mg and azithromycin 2 g) for uncomplicated gonorrhoea when the antimicrobial sensitivity is unknown; recommendation of test of cure in all gonorrhoea cases to ensure eradication of infection and identify emerging resistance; and recommendations to identify, verify and report failures with recommended treatment regimens. Optimisations of the testing, diagnostics, antimicrobial treatment and follow-up of gonorrhoea patients are crucial in controlling the emergent spread of cephalosporin-resistant and multidrug-resistant gonorrhoea.
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              An outbreak of high-level azithromycin resistant Neisseria gonorrhoeae in England.

              To investigate a potential outbreak of high-level azithromycin resistant (HL-AziR) gonococcal infections diagnosed in eight patients attending a sexual health clinic in Leeds, North England, between November 2014 and March 2015.
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                Author and article information

                Contributors
                brunner.ale@gmail.com
                e.nikodem@gmail.com
                csjeney@gmail.com
                szabo.dora@med.semmelweis-univ.hu
                marschalko.marta@med.semmelweis-univ.hu
                karpati.sarolta@med.semmelweis-univ.hu
                ostorhazi.eszter@med.semmelweis-univ.hu
                Journal
                Ann Clin Microbiol Antimicrob
                Ann. Clin. Microbiol. Antimicrob
                Annals of Clinical Microbiology and Antimicrobials
                BioMed Central (London )
                1476-0711
                20 September 2016
                20 September 2016
                2016
                : 15
                : 53
                Affiliations
                [1 ]Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, 41 Mária Street, Budapest, Hungary
                [2 ]Department of Laboratory Medicine, Semmelweis University, 41 Mária Street, Budapest, Hungary
                [3 ]Institute of Medical Microbiology, Semmelweis University, 4 Nagyvárad Square, Budapest, Hungary
                Article
                166
                10.1186/s12941-016-0166-9
                5029006
                27646968
                2ce34deb-2a64-4bc5-9976-3f0368a1aeb1
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 February 2016
                : 13 September 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Infectious disease & Microbiology
                azithromycin-resistance,neisseria gonorrhoeae,sequence types,phylogenetic tree

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