Markedly Increasing Antibiotic Resistance and Dual Treatment of Neisseria gonorrhoeae Isolates in Guangdong, China, from 2013 to 2020

Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0229421. doi: 10.1128/aac.02294-21. Epub 2022 Mar 29.

Abstract

The emergence of multidrug resistance in Neisseria gonorrhoeae is concerning, especially the cooccurrence of azithromycin resistance and decreased susceptibility to extended-spectrum cephalosporin. This study aimed to confirm the antibiotic resistance trends and provide a solution for N. gonorrhoeae treatment in Guangdong, China. A total of 5,808 strains were collected for assessment of antibiotic MICs. High resistance to penicillin (53.80 to 82%), tetracycline (88.30 to 100%), ciprofloxacin (96 to 99.8%), cefixime (6.81 to 46%), and azithromycin (8.60 to 20.03%) was observed. Remarkably, spectinomycin and ceftriaxone seemed to be the effective choices, with resistance rates of 0 to 7.63% and 2.00 to 16.18%, respectively. Moreover, the rates of azithromycin resistance combined with decreased susceptibility to ceftriaxone and cefixime reached 9.28% and 8.64%, respectively. Furthermore, genotyping identified NG-STAR-ST501, NG-MAST-ST2268, and MLST-ST7363 as the sequence types among representative multidrug-resistant isolates. Evolutionary analysis showed that FC428-related clones have spread to Guangdong, China, which might be a cause of the rapid increase in extended-spectrum cephalosporin resistance currently. Among these strains, the prevalence of N. gonorrhoeae was extremely high, and single-dose ceftriaxone treatment might be a challenge in the future. To partially relieve the treatment pressure, a susceptibility test for susceptibility to azithromycin plus extended-spectrum cephalosporin dual therapy was performed. The results showed that all the representative isolates could be effectively killed with the coadministration of less than 1 mg/liter azithromycin and 0.125 mg/liter extended-spectrum cephalosporin, with a synergistic effect according to a fractional inhibitory concentration (FIC) of <0.5. In conclusion, dual therapy might be a powerful measure to treat refractory N. gonorrhoeae in the context of increasing antibiotic resistance in Guangdong, China.

Keywords: FC428; N. gonorrhoeae; dual therapy; genotyping; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin / pharmacology
  • Azithromycin / therapeutic use
  • Cefixime / pharmacology
  • Ceftriaxone / pharmacology
  • Ceftriaxone / therapeutic use
  • Cephalosporin Resistance
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use
  • China / epidemiology
  • Drug Resistance, Bacterial
  • Gonorrhea* / drug therapy
  • Gonorrhea* / epidemiology
  • Humans
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Neisseria gonorrhoeae*

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Ceftriaxone
  • Azithromycin
  • Cefixime