title: Emerging azithromycin-resistance among the Neisseria gonorrhoeae strains isolated in Hungary.
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.
authors.affiliation: Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, 41 Mária Street, Budapest, Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Brunner
authors.affiliation: Department of Laboratory Medicine, Semmelweis University, 41 Mária Street, Budapest, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Nemes-Nikodem
authors.affiliation: Institute of Medical Microbiology, Semmelweis University, 4 Nagyvárad Square, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Jeney
authors.affiliation: Institute of Medical Microbiology, Semmelweis University, 4 Nagyvárad Square, Budapest, Hungary.
authors.forename: Dora
authors.initials: D
authors.lastname: Szabo
authors.affiliation: Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, 41 Mária Street, Budapest, Hungary.
authors.forename: Marta
authors.initials: M
authors.lastname: Marschalko
authors.affiliation: Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, 41 Mária Street, Budapest, Hungary.
authors.forename: Sarolta
authors.initials: S
authors.lastname: Karpati
authors.affiliation: Institute of Medical Microbiology, Semmelweis University, 4 Nagyvárad Square, Budapest, Hungary. ostorhazi.eszter@med.semmelweis-univ.hu.
authors.forename: Eszter
authors.initials: E
authors.lastname: Ostorhazi
mesh_terms: D000328:Adult; D000483:Alleles; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D020682:Cefixime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006069:Gonorrhea / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D008297:Male; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D018272:Porins / Q000235:genetics / Q000378:metabolism; D015995:Prevalence; D000198:Spectinomycin / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013752:Tetracycline / Q000494:pharmacology; D033882:Transferrin-Binding Protein B / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D018272:Porins; D033882:Transferrin-Binding Protein B; C057699:porin protein, Neisseria; D002939:Ciprofloxacin; D002443:Ceftriaxone; D017963:Azithromycin; D000198:Spectinomycin; D020682:Cefixime; D013752:Tetracycline
keywords: Azithromycin-resistance; Neisseria gonorrhoeae; Phylogenetic tree; Sequence types