title: Azithromycin-resistant Neisseria gonorrhoeae isolates in Guangzhou, China (2009-2013): coevolution with decreased susceptibilities to ceftriaxone and genetic characteristics.
abstract: BACKGROUND
  The recent emergence of azithromycin-resistant (AZM-R) N. gonorrhoeae isolates that have coevolved decreased susceptibility to extended-spectrum cephalosporins has caused great concern. Here we investigated the prevalence of decreased susceptibility to ceftriaxone (CRO(D)) in AZM-R isolates and genetically characterized AZM-R isolates in Guangzhou, China from 2009 to 2013.
  
  
  METHODS
  The minimum inhibitory concentration (MIC) of AZM and ceftriaxone was determined using an agar-dilution method. All AZM-R isolates were screened for mutations in 23S rRNA, mtrR and penA genes and genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST).
  
  
  RESULTS
  Of the 485 identified N. gonorrhoeae isolates, 445 (91.8%) were isolated from male urethritis subjects, and 77 (15.9%) were AZM-R (MIC ≥ 1 mg/L), including 33 (6.8%) with AZM low-level resistant (AZM-LLR, MIC = 1 mg/L) and 44 (9.1%) with AZM middle-level resistant (AZM-MLR, MIC ≥ 2 mg/L). Significantly more CRO(D) (MIC ≥ 0.125 mg/L) showed in AZM-MLR isolates (43.2%, 19/44) as compared with that in AZM-LLR isolates (18.2%, 6/33) (p < 0.05). For the 23S rRNA, mtrR, penA or combined 23S rRNA/MtrR/penA mutations, no significant difference was found between AZM-LLR isolates and AZM-MLR isolates (P > 0.05); similar results were detected between combined AZM-LLR/CRO(D) isolates and combined AZM-MLR/CRO(D) isolates (P > 0.05). No mutation A2059G or AZM high-level resistant (AZM-HLR, MIC ≥ 256 mg/L) isolate was detected. Among 77 AZM-R isolates, 67 sequence types (STs) were identified by NG-MAST, of which 30 were novel. Most STs were represented by a single isolate.
  
  
  CONCLUSIONS
  The AZM-R together CRO(D) isolates are now present in Guangzhou, China, which deserve continuous surveillance and the mechanism of concurrent resistance needs further study.
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Jing-Yao
authors.initials: JY
authors.lastname: Liang
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Cao
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Bi
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Ri-Dong
authors.initials: RD
authors.lastname: Yang
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Liang
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Xing-Dong
authors.initials: XD
authors.lastname: Ye
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Chen
authors.affiliation: Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, PR China. gzpfbfzs@yahoo.com.|Department of Dermatology, Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, PR China. gzpfbfzs@yahoo.com.
authors.forename: Xi-Bao
authors.initials: XB
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002443:Ceftriaxone / Q000494:pharmacology*; D002681:China / Q000453:epidemiology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005838:Genotype; D006069:Gonorrhea / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012338:RNA, Ribosomal, 23S / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012338:RNA, Ribosomal, 23S; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; D002443:Ceftriaxone; D017963:Azithromycin
keywords: Antimicrobial resistance; Azithromycin; NG-MAST; Neisseria gonorrhoeae