Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015-2017. 2019

Boris Shaskolskiy, and Ekaterina Dementieva, and Ilya Kandinov, and Marina Filippova, and Natalia Petrova, and Xenia Plakhova, and Alexander Chestkov, and Alexey Kubanov, and Dmitry Deryabin, and Dmitry Gryadunov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

The goal of this work was to study the phenotypic susceptibility and resistance determinants of N. gonorrhoeae isolates to beta-lactam antimicrobials (benzylpenicillin and ceftriaxone). A total of 522 clinical isolates collected in Russia in 2015-2017 were analysed for susceptibility using the agar dilution method. DNA loci involved in antimicrobial resistance were identified using DNA microarray analysis and sequencing. Resistance to benzylpenicillin remained high, with 7.7% of isolates resistant (MICpen > 1 mg/L) and 47.5% of isolates showing intermediate susceptibility (MICpen = 0.12-1 mg/L). The most frequent resistance determinant (72.4% isolates) was the Asp345 insertion in penA, both as a single mutation and in combination with other mutations, particularly with the substitution Leu421Pro in ponA (39.0%). Mutations affecting the influx and efflux of drugs were also found, including amino acid substitutions in PorB (26.8% isolates) and delA in the promoter region of mtrR (22.8%). The accumulation of mutations in chromosomal genes (penA, pon, porA, and mtrR) led to a stepwise increase in MICpen to values characteristic of intermediate resistance. The presence of blaTEM plasmids was found in 25 isolates (4.8%), resulting in a strong increase in resistance to penicillin (MICpen > 16 mg/L) compared with the chromosomal mutations; 23 plasmids were of the African type with TEM-1 beta-lactamase, and two plasmids were of the Toronto/Rio type with TEM-135 beta-lactamase. Only three isolates were found with reduced susceptibility to ceftriaxone, with MICcef = 0.12-0.25 mg/L. Sequencing of penA did not reveal mutations associated with resistance to third-generation cephalosporins, and the gene structure was non-mosaic. The majority of isolates (21 of 25) carrying the blaTEM plasmid also contained the conjugative plasmid with tetM (resistance to tetracyclines), consistent with previously reported data that the presence of the conjugative plasmid facilitates the transfer of other plasmids associated with antimicrobial resistance.

UI MeSH Term Description Entries
D008297 Male Males
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009344 Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of GONORRHEA. Diplococcus gonorrhoeae,Gonococcus,Gonococcus neisseri,Merismopedia gonorrhoeae,Micrococcus der gonorrhoe,Micrococcus gonococcus,Micrococcus gonorrhoeae
D010400 Penicillin G A penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on GAMMA-AMINOBUTYRIC ACID mediated synaptic transmission. Benzylpenicillin,Benpen,Benzylpenicillin Potassium,Coliriocilina,Crystapen,Or-pen,Parcillin,Pekamin,Pengesod,Penibiot,Penicilina G Llorente,Penicillin G Jenapharm,Penicillin G Potassium,Penicillin G Sodium,Penicillin GrĂ¼nenthal,Penilevel,Peniroger,Pfizerpen,Sodiopen,Sodipen,Sodium Benzylpenicillin,Sodium Penicillin,Unicilina,Ursopen,Van-Pen-G
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D002443 Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Benaxona,Cefatriaxone,Cefaxona,Ceftrex,Ceftriaxon,Ceftriaxon Curamed,Ceftriaxon Hexal,Ceftriaxona Andreu,Ceftriaxona LDP Torlan,Ceftriaxone Irex,Ceftriaxone Sodium,Ceftriaxone Sodium, Anhydrous,Ceftriaxone, Disodium Salt,Ceftriaxone, Disodium Salt, Hemiheptahydrate,Lendacin,Longacef,Longaceph,Ro 13-9904,Ro-13-9904,Ro13-9904,Rocefalin,Rocefin,Rocephin,Rocephine,Tacex,Terbac,Anhydrous Ceftriaxone Sodium,Ro 13 9904,Ro 139904,Ro13 9904,Ro139904
D004252 DNA Mutational Analysis Biochemical identification of mutational changes in a nucleotide sequence. Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D005260 Female Females
D006069 Gonorrhea Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, NEISSERIA GONORRHOEAE, was isolated by Neisser in 1879. Neisseria gonorrhoeae Infection
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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