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In Vitro Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae.

ABSTRACT: Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

SUBMITTER: Miari VF

PROVIDER: S-EPMC5610491 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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In Vitro Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae.

Miari Victoria F VF Solanki Priya P Hleba Yonek Y Stabler Richard A RA Heap John T JT

Antimicrobial agents and chemotherapy 20170922 10

Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae. ...[more]

PMID: 28784667

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Project description:ObjectivesMDR and XDR Neisseria gonorrhoeae strains remain major public health concerns internationally, and quality-assured global gonococcal antimicrobial resistance (AMR) surveillance is imperative. The WHO global Gonococcal Antimicrobial Surveillance Programme (GASP) and WHO Enhanced GASP (EGASP), including metadata and WGS, are expanding internationally. We present the phenotypic, genetic and reference genome characteristics of the 2024 WHO gonococcal reference strains (n = 15) for quality assurance worldwide. All superseded WHO gonococcal reference strains (n = 14) were identically characterized.Material and methodsThe 2024 WHO reference strains include 11 of the 2016 WHO reference strains, which were further characterized, and four novel strains. The superseded WHO reference strains include 11 WHO reference strains previously unpublished. All strains were characterized phenotypically and genomically (single-molecule PacBio or Oxford Nanopore and Illumina sequencing).ResultsThe 2024 WHO reference strains represent all available susceptible and resistant phenotypes and genotypes for antimicrobials currently and previously used (n = 22), or considered for future use (n = 3) in gonorrhoea treatment. The novel WHO strains include internationally spreading ceftriaxone resistance, ceftriaxone resistance due to new penA mutations, ceftriaxone plus high-level azithromycin resistance and azithromycin resistance due to mosaic MtrRCDE efflux pump. AMR, serogroup, prolyliminopeptidase, genetic AMR determinants, plasmid types, molecular epidemiological types and reference genome characteristics are presented for all strains.ConclusionsThe 2024 WHO gonococcal reference strains are recommended for internal and external quality assurance in laboratory examinations, especially in the WHO GASP, EGASP and other GASPs, but also in phenotypic and molecular diagnostics, AMR prediction, pharmacodynamics, epidemiology, research and as complete reference genomes in WGS analysis.

Project description:OBJECTIVE:To investigate the in vitro antimicrobial susceptibility and resistant trends of Neisseria gonorrhoeae strains isolated in Guangzhou, from 1996 to 2001. METHODS:The agar dilution method was used to determine the minimum inhibitory concentrations (MICs) to four antimicrobials, penicillin G, ciprofloxacin, ceftriaxone, and spectinomycin. The resistance of all strains to four antibiotics was interpreted according to criteria used in the project of surveillance of gonococcal antibiotic susceptibility in the WHO Western Pacific Region. Penicillinase producing N gonorrhoeae (PPNG) was analysed by the paper acidometric method. RESULTS:793 consecutive N gonorrhoeae isolates collected in Guangzhou were studied from 1996 to 2001. A total of 55 strains of PPNG were identified and the prevalence rapidly spread from 2% to 21.8%. Of the four antibiotics examined, ceftriaxone and spectinomycin appeared to be the most effective agents although two spectinomycin resistant strains were isolated in 1996. Their MIC(50), MIC(90), and geometric mean MIC (MICmean) were all between the sensitive ranges of the interpretative criteria and remained stable over the years. However, resistance increased continuously to penicillin G and dramatically to ciprofloxacin. In 1996-2001, MIC(50), MIC(90), and MICmean of penicillin G increased from 1 micro g/ml to 2 micro g/ml, 4 micro g/ml to 32 micro g/ml, and 0.68 micro g/ml to 2.35 micro g/ml, respectively; those of ciprofloxacin steeply increased from 0.12 micro g/ml to 4 micro g/ml, 2 micro g/ml to 32 micro g/ml, and 0.14 micro g/ml to 2.62 micro g/ml in 1996-9, respectively, and then declined slightly in 2000-1. The prevalence of resistant isolates spread from 57.2% to 81.8% for penicillin G and from 17.6% to 72.7% for ciprofloxacin over the 6 years. CONCLUSION:Resistance to penicillin and ciprofloxacin increased greatly during 1996-2001. Ceftriaxone and spectinomycin should be used as the first line agents in treating gonorrhoea. It is of great importance to continuously survey the susceptibilities of N gonorrhoeae to antibiotics in controlling the spread of gonococcal infections.

Project description:BackgroundThe increasing rate of antimicrobial-resistant Neisseria gonorrhoeae poses a considerable public health threat due to the difficulty in treating gonococcal infections. This study examined antimicrobial resistance (AMR) to drugs recommended for gonorrhea treatment between 2015 and 2017, and the AMR determinants and genetic compositions of plasmids in 3 gonococcal strains with high-level penicillin resistance.MethodsWe collected 117 N. gonorrhoeae isolates from patients with gonococcal infections who attended Siriraj Hospital, Bangkok, Thailand, between 2015 and 2017. Minimum inhibitory concentrations (MICs) of penicillin, tetracycline, ciprofloxacin, azithromycin, spectinomycin, cefixime, and ceftriaxone were determined by the agar dilution method. PCR amplification and sequencing of 23S rRNA and mtrR (a negative regulator of MtrCDE efflux pump) were performed. Whole genomes of 3 PPNG strains with high-level penicillin resistance (MIC ≥ 128 μg/ml) were sequenced using Illumina and Nanopore sequencing platforms.ResultsThe proportions of N. gonorrhoeae isolates with resistance were 84.6% for penicillin, 91.5% for tetracycline, and 96.6% for ciprofloxacin. All isolates were susceptible to spectinomycin, azithromycin, cefixime, and ceftriaxone. An adenine deletion within a 13 bp inverted repeat sequence in the mtrR promoter and an H105Y mutation in the mtrR coding region were found in the N. gonorrhoeae isolate with the highest azithromycin MIC value (1 μg/ml). Three high-level penicillin-resistant isolates contained nonmosaic type II penA and had mutations in penB and the mtrR coding region. All isolates with high-level penicillin resistance carried the conjugative plasmids with or without the Dutch type tetM determinant, the beta-lactamase plasmid (Rio/Toronto), and the cryptic plasmid.ConclusionsThe gonococcal population in Thailand showed high susceptibility to ceftriaxone and azithromycin, current dual therapy recommended for gonorrhea treatment. As elevated MIC of azithromycin has been observed in 1 strain of N. gonorrhoeae, expanded and enhanced surveillance of antimicrobial susceptibility and study of genetic resistance determinants are essential to improve treatment guidelines.

Dataset Information

In Vitro Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae.

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<i>In Vitro</i> Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae.

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