Shanghai Neisseria gonorrhoeae Isolates Exhibit Resistance to Extended-Spectrum Cephalosporins and Clonal Distribution

Abstract

The emergence of Neisseria gonorrhoeae strains with resistance (R) to extended-spectrum cephalosporins (ESCs R ) represents a public health threat of untreatable gonococcal infections. This study was designed to determine the prevalence and molecular mechanisms of ESC R of Shanghai N. gonorrhoeae isolates. A total of 366 N. gonorrhoeae isolates were collected in 2017 in Shanghai. Susceptibility to ceftriaxone (CRO), cefixime (CFM), azithromycin (AZM), ciprofloxacin (CIP), spectinomycin, penicillin, and tetracycline was determined using the agar dilution method. A subset of 124 isolates was subjected to phylogenetic analysis for nine antimicrobial resistance-associated genes, i.e., penA , porB , ponA , mtrR , 23S rRNA, gyrA , parC , 16S rRNA, and rpsE . Approximately 20.0% of the isolates exhibited CFM R [minimum inhibitory concentration (MIC) >0.125 mg/L], and 5.5% were CRO R (MIC > 0.125 mg/L). In total, 72.7% of ESC R isolates were clonal and associated with mosaic penA 10 and 60 alleles. Non-mosaic penA 18 allele and substitutions of PenA A501T, G542S, and PorB1b G213S/Y were observed in non-clonal ESC R . Approximately 6.8% of the isolates showed AZM MIC above the epidemiological cutoff (ECOFF, 1 mg/L), were associated with 23S rRNA A2059G mutation, and did not exhibit clonal distribution. Almost all isolates were CIP R (resistance to ciprofloxacin) and associated with GyrA-91/92 and ParC-85/86/87/88/89/91 alterations. Isolates with ParC S88P substitution were clustered into the ESC R clade. The Shanghai isolates exhibited a high level of ESC R and distinct resistant patterns.

Loop-Mediated Isothermal Amplification Assay for Identifying Neisseria gonorrhoeae Nonmosaic penA- Targeting Strains Potentially Eradicable by Cefixime

“…Conversely, in penA 101.001, 8 strains showed a CFM MIC of ≤0.064 mg/L, and 12 strains showed CFM MIC values of >0.064 mg/L. Incorporating an assay system that can simultaneously identify the PBP2-501 mutant may enhance the detection of strains with MIC values of ≤0.064 mg/L in certain regions where PBP2-501 mutant strains with CFM MIC values of >0.064 mg/L are isolated ( 34 , 43 ).…”

“…In this context, our approach is expected to be effective in real-world clinical settings worldwide. In certain regions, multiple strains carrying mosaic penA have been isolated ( 45 ), and other studies have also reported some strains carrying nonmosaic penA that had a CFM MIC of >0.064 mg/L ( 34 , 39 , 43 , 46 ). There are regional differences in drug susceptibility and penA type of the isolated strains of N. gonorrhoeae ( 3 , 39 ), and several factors other than solely the penA type are predicted to be involved in elevating the CFM MIC ( 19 ).…”

Antimicrobial Susceptibility of Ertapenem in Neisseria gonorrhoeae Isolates Collected Within the China Gonococcal Resistance Surveillance Programme (China-GRSP) 2018

“…The antimicrobial resistance of N. gonorrhoeae remains a severe issue for public health. Ceftriaxone-resistant isolates have been reported in many countries over the world, 2,3,12,13,21,22 which suggests the importance of finding alternative treatments. The recommended strategies from the World Health Organization include "increasing the therapeutic dose", "new antimicrobial drugs development", "recycle "old" antimicrobial agents", etc.…”

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Tetracycline Antibiotics from 9 Provinces in China Since 2020

“…Forty N. gonorrhoeae isolates with tigecycline MIC >0.25mg/L and 40 N. gonorrhoeae isolates with tigecycline MIC ≤0.25mg/L were randomly selected to investigate the possible resistance determinants of tigecycline and the source of the correlation between the MICs of tigecycline and other antibiotics. PCR was utilized to amplify five loci ( rpsJ, mtrR, porB, tetM and 23S rRNA ) using previously reported primers 14 , 15 ( Table 1 ). DNAs were sequenced using Sanger sequencing.…”