Abstract
The emergence of Neisseria gonorrhoeae strains with resistance (R) to extended-spectrum cephalosporins (ESCsR) represents a public health threat of untreatable gonococcal infections. This study was designed to determine the prevalence and molecular mechanisms of ESCR 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 CFMR [minimum inhibitory concentration (MIC) >0.125 mg/L], and 5.5% were CROR (MIC > 0.125 mg/L). In total, 72.7% of ESCR 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 ESCR. 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 CIPR (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 ESCR clade. The Shanghai isolates exhibited a high level of ESCR and distinct resistant patterns.
Highlights
Neisseria gonorrhoeae is the causative agent of gonorrhea
According to the World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Programme (GASP), in 2016, about one-third of the participating countries reported that ≥5% of isolates are resistant to extended-spectrum cephalosporins (ESCs) (CRO and/or CFM), and half reported ≥5% resistance to azithromycin (AZMR)
We found that N. gonorrhoeae ESCR isolates were predominantly clonal in this study
Summary
The World Health Organization (WHO) estimated that N. gonorrhoeae causes more than 86.9 million new infections worldwide annually (World Health Organization [WHO], 2018). Gonococcal antimicrobial resistance (AMR) continues to spread worldwide and could lead to a pandemic of extensively drug-resistant gonococci (World Health Organization [WHO], 2018). Drug Resistance in Gonococcal Isolates [reduced susceptibility to the extended-spectrum cephalosporins (ESCs), i.e., cefixime (CFM), and ceftriaxone (CRO)], which is the first-line empirical treatment for N. gonorrhoeae infections (Unemo and Shafer, 2014; Wi et al, 2017), is becoming widely spread. According to the WHO Global Gonococcal Antimicrobial Surveillance Programme (GASP), in 2016, about one-third of the participating countries reported that ≥5% of isolates are resistant to ESCs (CRO and/or CFM), and half reported ≥5% resistance to azithromycin (AZMR). In Shanghai, the proportion of CRORS (MIC ≥ 0.125 mg/L) ranged from 7 to 13% during 1988–2013 (Gu et al, 2014)
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