ABSTRACT
We report two extensively drug-resistant (XDR) Neisseria gonorrhoeae (NG) isolates combining high-level resistance to azithromycin and resistance to ceftriaxone, obtained in France from two heterosexual patients, one of whom returned from Cambodia. Whole genome sequencing identified MLST ST16406, the mosaic penA-60.001 which caused ceftriaxone resistance in the internationally spreading FC428 clone, and the A2059G mutation in the 23S rRNA gene. The NG isolates F93 and F94 were related to XDR isolates detected in Austria and the United Kingdom in 2022.
Subject(s)
Ceftriaxone , Gonorrhea , Humans , Azithromycin/pharmacology , Ceftriaxone/pharmacology , France , Gonorrhea/diagnosis , Gonorrhea/drug therapy , Multilocus Sequence Typing , Neisseria gonorrhoeae/geneticsABSTRACT
This paper reports on the design of a series of 10 novel lipophilic piperazinyl derivatives of the 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, their synthesis, their characterisation by 1H, 13C and 19F NMR, IR spectroscopy and HRMS, as well as their biological activity against bacteria of medical interest. Among these derivatives, 2 were as potent as the parent quinolone against Neisseriagonorrhoeae whereas all the compounds displayed lower activity than the parent quinolone against other bacteria of medical interest. Our results showing that the increased lipophilicity was deleterious for antibacterial activity may help to design new quinolone derivatives in the future, especially lipophilic quinolones which have been poorly investigated previously.
Subject(s)
Anti-Bacterial Agents/pharmacology , Neisseria gonorrhoeae/drug effects , Quinolones/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Dose-Response Relationship, Drug , Hydrophobic and Hydrophilic Interactions , Microbial Sensitivity Tests , Molecular Structure , Quinolones/chemical synthesis , Quinolones/chemistry , Structure-Activity RelationshipABSTRACT
We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2â¯g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC-199, and the novel mosaic penA-237.001, which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001, reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.
Subject(s)
Ceftriaxone , Gonorrhea , Humans , Female , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic use , Neisseria gonorrhoeae , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Multilocus Sequence Typing , Gonorrhea/diagnosis , Gonorrhea/drug therapy , Microbial Sensitivity Tests , Drug Resistance, Bacterial/geneticsABSTRACT
BACKGROUND: The resistance to all aminoglycosides (AGs) conferred by 16S rRNA methyltransferase enzymes (16S-RMTases) is a major public health concern. OBJECTIVES: To characterize the resistance genotype, its genetic environment and plasmid support, and the phylogenetic relatedness of 16S-RMTase-producing Escherichia coli from France. METHODS: We screened 137 E. coli isolates resistant to all clinically relevant AGs from nine Parisian hospitals for 16S-RMTases. WGS was performed on clinical isolates with high-level AG resistance (MIC ≥256 mg/L) and their transformants. RESULTS: Thirty of the 137 AG-resistant E. coli produced 16S-RMTases: 11 ArmA, 18 RmtB and 1 RmtC. The 16S-RMTase producers were also resistant to third-generation cephalosporins (90% due to a blaCTX-M gene), co-trimoxazole, fluoroquinolones and carbapenems (blaNDM and blaVIM genes) in 97%, 83%, 70% and 10% of cases, respectively. Phylogenomic diversity was high in ArmA producers, with 10 different STs, but a similar genetic environment, with the Tn1548 transposon carried by a plasmid closely related to pCTX-M-3 in 6/11 isolates. Conversely, RmtB producers belonged to 12 STs, the most frequent being ST405 and ST complex (STc) 10 (four and four isolates, respectively). The rmtB gene was carried by IncF plasmids in 10 isolates and was found in different genetic environments. The rmtC gene was carried by the pNDM-US plasmid. CONCLUSIONS: ArmA and RmtB are the predominant 16S-RMTases in France, but their spread follows two different patterns: (i) dissemination of a conserved genetic support carrying armA in E. coli with high levels of genomic diversity; and (ii) various genetic environments surrounding rmtB in clonally related E. coli.
Subject(s)
Drug Resistance, Bacterial , Escherichia coli , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Escherichia coli/genetics , France , Genomics , Methyltransferases/genetics , Microbial Sensitivity Tests , Phylogeny , Plasmids/genetics , RNA, Ribosomal, 16S/genetics , beta-Lactamases/geneticsABSTRACT
We report two cases of multidrug-resistant Neisseria gonorrhoeae urogenital infection with ceftriaxone resistance in a heterosexual couple in south-western France who were successfully treated with a single, high dose of intramuscular ceftriaxone (1 g). Whole genome sequencing of isolate F91 identified MLST13871, NG-MAST1086, NG-STAR233. Patient history revealed the isolate F91 was most likely acquired during a trip to Cambodia and belongs to the successful multidrug-resistant FC428 Asian clone.
