Emergence of a Neisseria gonorrhoeae clone with reduced cephalosporin susceptibility between 2014 and 2019 in Amsterdam, The Netherlands, revealed by genomic population analysis

Abstract

Background Emerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of resistant strains and those with reduced susceptibility. Objectives For the purpose of epidemiological surveillance, genomic population analysis was performed on Ng isolates from Amsterdam with a focus on isolates with reduced susceptibility to ceftriaxone. Methods WGS data were obtained from 318 isolates from Amsterdam, the Netherlands between 2014 and 2019. Isolates were typed according to MLST, Ng Multi-Antigen Sequence Typing (NG-MAST) and Ng Sequence Typing for Antimicrobial Resistance (NG-STAR) schemes and additional resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch and non-Dutch MLST7827 isolates. Results MLST7363 and MLST1901 were the predominant strains having reduced susceptibility to ceftriaxone during 2014–16; MLST7827 emerged and dominated during 2017–19. NG-STAR38 and NG-MAST2318/10386 were predominant among MLST7827 isolates. MLST7827 reduced susceptibility isolates carried a non-mosaic 13.001 penA allele with an A501V mutation and porB1b G120K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch and other European MLST7827 isolates. Conclusions MLST7827 isolates with reduced ceftriaxone susceptibility have emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB1b G120K/A121D mutations was strongly associated with reduced susceptibility to ceftriaxone. Genetic clustering of Dutch and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Close monitoring of the spread of this strain having an alarming susceptibility profile is needed.

Reliability of Genetic Alterations in Predicting Ceftriaxone Resistance in Neisseria gonorrhoeae Globally

“…From our analysis, we outlined different combinations of genetic mutations and different scenarios needed to obtain high positive and negative predictive values in predicting ceftriaxone's decreased susceptibility. At a 1.1% prevalence as reported by an sexually transmitted infection (STI) clinic in Amsterdam ( 28 ), all the molecular markers resulted in extremely high negative predictive values >99% with positive predictive values <10%. In populations like those, molecular assays might not be useful given the high proportion of false-positive to true positive tests.…”

Trends and regional variations of gonococcal antimicrobial resistance in the Netherlands, 2013 to 2019

“…Molecular epidemiology of decreased susceptibility to ceftriaxone and resistance to azithromycin have been studied in more detail in the Amsterdam region (SHC region 1), providing 52% of all strains included in this study. Resistance and decreased susceptibility were restricted to certain clonal strain populations which appeared and disappeared over time [18][19][20]. Further study on strains from other regions would be required to assess whether a nationwide spread of clonal strain populations is related to the observed trends in resistance and decreased susceptibility.…”

The Neisseria gonorrhoeae Accessory Genome and Its Association with the Core Genome and Antimicrobial Resistance

“…A subset of 765 N. gonorrhoeae isolates was chosen that was representative of the total N. gonorrhoeae genomes found in PubMLST. This data set of 765 isolates included (i) 380 isolates from a Dutch surveillance study containing many different MLSTs ( 28 ) and (ii) 385 isolates chosen to be representative of all MLSTs, core genome groups, and geographical origins available in PubMLST (Table S1). The extent to which this data set was representative of the diversity found in all 8,013 publicly available isolates was assessed through the use of a minimum spanning tree generated using the PubMLST plugin GrapeTree ( 29 ).…”