Project description:During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.
Project description:We have characterized in detail a new ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain (FC428) isolated in Japan in 2015. FC428 differed from previous ceftriaxone-resistant strains and contained a novel mosaic penA allele encoding a new mosaic penicillin-binding protein 2 (PBP 2). However, the resistance-determining 3'-terminal region of penA was almost identical to the regions of two previously reported ceftriaxone-resistant strains from Australia and Japan, indicating that both ceftriaxone-resistant strains and conserved ceftriaxone resistance-determining PBP 2 regions might spread.
Project description:BackgroundGlobally, decreased susceptibility to ceftriaxone in Neisseria gonorrhoeae is rising. We aimed to compile a global collection of N. gonorrhoeae strains and assess the genetic characteristics associated with decreased susceptibility to ceftriaxone.MethodsWe performed a literature review of all published reports of N. gonorrhoeae strains with decreased susceptibility to ceftriaxone (>0.064 mg/L minimum inhibitory concentration) through October 2019. Genetic mutations in N. gonorrhoeae genes (penA, penB, mtrR, and ponA), including determination of penA mosaicism, were compiled and evaluated for predicting decreased susceptibility to ceftriaxone.ResultsThere were 3821 N. gonorrhoeae strains identified from 23 countries and 684 (18%) had decreased susceptibility to ceftriaxone. High sensitivities or specificities (>95%) were found for specific genetic mutations in penA, penB, mtrR, and ponA, both with and without determination of penA mosaicism. Four algorithms to predict ceftriaxone susceptibility were proposed based on penA mosaicism determination and penA or non-penA genetic mutations, with sensitivity and specificity combinations up to 95% and 62%, respectively.ConclusionMolecular algorithms based on genetic mutations were proposed to predict decreased susceptibility to ceftriaxone in N. gonorrhoeae. Those algorithms can serve as a foundation for the development of future assays predicting ceftriaxone decreased susceptibility within N. gonorrhoeae globally.
Project description:Ceftriaxone remains a first-line treatment for patients infected by Neisseria gonorrhoeae in most settings. We investigated the possible spread of a ceftriaxone-resistant FC428 N. gonorrhoeae clone in Japan after recent isolation of similar strains in Denmark (GK124) and Canada (47707). We report 2 instances of the FC428 clone in Australia in heterosexual men traveling from Asia. Our bioinformatic analyses included core single-nucleotide variation phylogeny and in silico molecular typing; phylogenetic analysis showed close genetic relatedness among all 5 isolates. Results showed multilocus sequence type 1903; N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) 233; and harboring of mosaic penA allele encoding alterations A311V and T483S (penA-60.001), associated with ceftriaxone resistance. Our results provide further evidence of international transmission of ceftriaxone-resistant N. gonorrhoeae. We recommend increasing awareness of international spread of this drug-resistant strain, strengthening surveillance to include identifying treatment failures and contacts, and strengthening international sharing of data.
Project description:BACKGROUND: Neisseria gonorrhoeae can rapidly develop resistance to antimicrobial agents. Over the last years, decreased gonococcal susceptibility to third-generation cephalosporins, especially cefixime, emerged worldwide. Therefore, current international guidelines recommend dual therapy for gonorrhoea with ceftriaxone plus either azithromycin or doxycycline. Gonococcal susceptibility data in Switzerland are sparse. METHODS: We investigated the prevalence of antibiotic susceptibility of N. gonorrhoeae in specimens collected between 1990 and 2012 at the University of Zurich, Switzerland. Minimum inhibitory concentrations (MICs) for cefixime, ceftriaxone, ciprofloxacin, and penicillin were determined by Etests. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used to define reduced susceptibility. RESULTS: A total of 320 isolates were tested. Between 1990 and 2006 all tested samples were susceptible to both cephalosporins. Subsequently, the prevalence of elevated MICs for cefixime increased to 10.4% (2007/2008), 11.5% (2009/2010), and 11.4% (2011/2012); and for ceftriaxone to 2.4% (2007/2008), 4.7% (2009/2010), and 0% (2011/2012), respectively. The prevalence of resistance to ciprofloxacin (72.7%) and penicillin (22.7%) was high in 2011/2012. CONCLUSIONS: Decreasing susceptibility of N. gonorrhoeae to third-generation cephalosporins in Switzerland supports treatment recommendations with ceftriaxone plus azithromycin or doxycycline. Health-care providers need to be aware of possible treatment failures with cephalosporins. Continued surveillance of gonococcal antimicrobial resistance is essential.
Project description:We report the complete genome sequence of ceftriaxone-resistant Neisseria gonorrhoeae SS3160, harboring the mosaic penA-60.001 allele. This Japanese isolate has a unique sequence type (ST), ST13429, which was determined by multilocus sequence typing from the chromosome sequence (2,214,955?bp). It carries two plasmids, pConjugative (39,057?bp) and pCryptic (4,207?bp).
Project description:We identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in a patient in Canada. This isolate carried the penA-60 allele, which differs substantially from its closest relative, mosaic penA XXVII (80% nucleotide identity). Epidemiologic and genomic data suggest spread from Asia. Antimicrobial susceptibility surveillance helps prevent spread of highly resistant N. gonorrhoeae strains.
Project description:We report a case of Neisseria gonorrhoeae with a non-mosaic penA allele that exhibited decreased susceptibility to extended-spectrum cephalosporins, including a ceftriaxone minimum inhibitory concentration of 0.5 μg/mL. An analysis of resistance determinants suggested that the observed phenotype might have resulted from the combined effects of mutations in multiple genes.
Project description:In July 2018, a case of Neisseria gonorrhoeae associated with ceftriaxone treatment failure was identified in Alberta, Canada. We identified the isolate and nucleic acid amplification testing (NAAT) specimen as the ceftriaxone-resistant strain multilocus sequence type 1903/NG-MAST 3435/NG-STAR 233, originally identified in Japan (FC428), with the same penA 60.001 mosaic allele and genetic resistance determinants. Core single-nucleotide variant (SNV) analysis identified 13 SNVs between this isolate and FC428. Culture-independent surveillance by PCR for the A311V mutation in the penA allele and N. gonorrhoeae multiantigen sequence typing directly from NAAT transport media positive for N. gonorrhoeae by NAAT did not detect spread of the strain. We identified multiple sequence types not previously detected in Alberta by routine surveillance. This case demonstrates the benefit of using culture-independent methods to enhance detection, public health investigations, and surveillance to address this global threat.