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

Lin, Eric Y; Adamson, Paul C; Ha, Seung Min; Klausner, Jeffrey D.

doi:10.1128/spectrum.02065-21

Cited by 7 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the increasing international spread of ceftriaxone-resistant strains, there is a need to strengthen international cooperation to monitor and trace the spread of ceftriaxone-resistant clones. 28,29 Infection and Drug Resistance 2023:16 https://doi.org/10.2147/IDR.S396793 DovePress 1445 Spectinomycin, an amino cyclohexanol antibiotic found in Streptomyces, demonstrates strong antibacterial effect on N. gonorrhoeae. In our study, among 1710 clinical strains of N. gonorrhoeae collected in Zhejiang province from 2007 to 2021, only 3 and 1 spectinomycin-resistant strains were found in 2018 and 2019, respectively.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007

Zhang¹,

Hu²,

Huang³

et al. 2023

IDR

View full text Add to dashboard Cite

This study aimed to assess the drug susceptibility of clinical isolates of Neisseria gonorrhoeae to spectinomycin, ceftriaxone and azithromycin. Moreover, the temporal trends in the minimum inhibitory concentration (MIC) of five antibiotics from Zhejiang, China, are also in the scope of this study. Methods: A total of 1710 gonococcal clinical strains were collected between 2007 and 2021 from health-care institutions in Zhejiang. The MICs of ceftriaxone, azithromycin, spectinomycin, penicillin and ciprofloxacin were assessed by agar dilution method on 1710 Neisseria gonorrhoeae isolates. Count data were expressed as strains and rates, and MICs distribution was elucidated using descriptive statistics. Results: The total resistance rates of gonococci to azithromycin, spectinomycin, penicillin and ciprofloxacin in this study were 19.3%, 0.3%, 75.4% and 99.7%, respectively. Conclusion:The in vitro results showed a high prevalence of resistance to ciprofloxacin and penicillin. Azithromycin resistance rate has exceeded 5%, suggested a high prevalence of resistance. Ceftriaxone and spectinomycin are suggested based on this study for the treatment of Neisseria gonorrhoeae in Zhejiang.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007

Zhang¹,

Hu²,

Huang³

et al. 2023

IDR

View full text Add to dashboard Cite

show abstract

“…This continued evolution in the pathogen population means that routine surveillance will be a critical part of regularly assessing sequence-based diagnostics that predict resistance phenotype from genotype. 89,121,122…”

Section: Root Mean Squared Errormentioning

confidence: 99%

“…Escape could be achieved through mutations around a probe's target that reduce binding and thus the diagnostic's sensitivity, through dropping the probe's target altogether, or through developing novel resistance mutations or novel combinations of mutations (a particular concern for N. gonorrhoeae , given that it is highly recombinogenic). This continued evolution in the pathogen population means that routine surveillance will be a critical part of regularly assessing sequence‐based diagnostics that predict resistance phenotype from genotype 89,121,122 …”

Section: Framework For Machine Learning Models For Antimicrobial Susc...mentioning

confidence: 99%

Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests

Martin

Mortimer

Grad

2022

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Neisseria gonorrhoeae is an urgent public health threat due to the emergence of antibiotic resistance. As most isolates in the United States are susceptible to at least one antibiotic, rapid molecular antimicrobial susceptibility tests (ASTs) would offer the opportunity to tailor antibiotic therapy, thereby expanding treatment options. With genome sequence and antibiotic resistance phenotype data for nearly 20,000 clinical N. gonorrhoeae isolates now available, there is an opportunity to use statistical methods to develop sequence-based diagnostics that predict antibiotic susceptibility from genotype. N. gonorrhoeae, therefore, provides a useful example illustrating how to apply machine learning models to aid in the design of sequence-based ASTs. We present an overview of this framework, which begins with establishing the assay technology, the performance criteria, the population in which the diagnostic will be used, and the clinical goals, and extends to the choices that must be made to arrive at a set of features with the desired properties for predicting susceptibility phenotype from genotype. While we focus on the example of N. gonorrhoeae, the framework generalizes to other organisms for which large-scale genotype and antibiotic resistance data can be combined to aid in diagnostics development.

show abstract

“…For example, according to the latest Gonococcal Isolate Surveillance Project (GISP) report 12 ∼15% of surveyed isolates were resistance to penicillin, ∼20% resistant to tetracycline, 33.2% to ciprofloxacin, 5.8% to azithromycin, and 0.3% to cefixime in the United States; and although resistance (≥ 0.25 μg/ml ) was not observed in 2020 to ceftriaxone, isolates with reduced susceptibly have been identified in previous years (2017-2019) as a part of the GISP collection 12 . Additionally, surveillance studies in other countries have identified higher rates of circulating ceftriaxone resistance (e.g., 4.2% in Taiwan 13 , 16% in in Guangdong, China 14 ); with recent observations indicating global dissemination (Japan, China, Europe, Australia, North America and Southeast Asia) of high-level ceftriaxone-resistant strains 15–20 . Though the genetic basis of some resistance phenotypes appears to be exclusively encoded by recurrently acquired mutations (i.e., ciprofloxacin resistance is almost always caused by amino acid substitutions in the DNA gyrase subunit A (GyrA S91F and D95G/D95A 21,22 )); the complete genetic bases of other resistance phenotypes is currently not fully described and/or is clearly imparted by multiple additive or epistatically-interacting loci (i.e., penicillin 23–27 and azithromycin 22,28 resistance).…”

Section: Introductionmentioning

confidence: 99%

Rolling the evolutionary dice:Neisseriacommensals as proxies for elucidating the underpinnings of antibiotic resistance mechanisms and evolution in human pathogens

Frost,

Charron-Smith,

Cotsonas

et al. 2023

Preprint

View full text Add to dashboard Cite

Species within the genusNeisseriaare especially adept at sharing adaptive allelic variation across species’ boundaries, with commensal species repeatedly transferring resistance to their pathogenic relativeN. gonorrhoeae. However, resistance in commensalNeisseriais infrequently characterized at both the phenotypic and genotypic levels, limiting our ability to predict novel and potentially transferable resistance mechanisms that ultimately may become important clinically. Unique evolutionary starting places of eachNeisseriaspecies will have distinct genomic backgrounds, which may ultimately control the fate of evolving populations in response to selection, as epistatic and additive interactions may coerce lineages along divergent evolutionary trajectories. However alternatively, similar genetic content present across species due to shared ancestry may constrain the adaptive solutions that exist. Thus, identifying the paths to resistance across commensals may aid in characterizing theNeisseriaresistome – or the reservoir of alleles within the genus, as well as its depth. Here, we usein vitroevolution of four commensal species to investigate the potential for and repeatability of resistance evolution to two antimicrobials, the macrolide azithromycin and the β-lactam penicillin. After 20 days of selection, commensals evolved elevated minimum inhibitory concentrations (MICs) to penicillin and azithromycin in 11/16 and 12/16 cases respectively. Almost all cases of resistance emergence converged on mutations within ribosomal components or themtrRCDEefflux pump for azithromycin-based selection, andmtrRCDEorpenAfor penicillin selection; thus, supporting constrained adaptive solutions despite divergent evolutionary starting points across the genus for these particular drugs. However, continuing to explore the paths to resistance across different experimental conditions and genomic backgrounds, which could shunt evolution down alternative evolutionary trajectories, will ultimately flesh out the fullNeisseriaresistome.

show abstract

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

Abstract: Antimicrobial resistance in Neisseria gonorrhoeae ( N. gonorrhoeae ), the causative agent of gonorrhea, is rising globally. Ceftriaxone is the last remaining antibiotic for empirical treatment of gonorrhea.

Cited by 7 publications

References 38 publications

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007

Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests

Rolling the evolutionary dice:Neisseriacommensals as proxies for elucidating the underpinnings of antibiotic resistance mechanisms and evolution in human pathogens

Contact Info

Product

Resources

About