Disseminated Neisseria gonorrhea of the wrist.
Ontology highlight
ABSTRACT:
SUBMITTER: Douedi S
PROVIDER: S-EPMC7210423 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Similar Datasets
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.
| S-EPMC5875269 | biostudies-literature
Project description:Gonorrhea is one of the most common, but still hidden and insidious, sexually transmitted diseases caused by Neisseria gonorrhoeae (gonococci). However, the diagnosis and treatment of gonorrhea are hampered by antigenic variability among gonococci, the lack of acquired immunity, and antimicrobial resistance. Further, strains resistant to cephalosporins, including ceftriaxone, the last line of defense, represent a growing threat, which prompted us to develop gonococci-specific diagnostic antibodies with broad-spectrum binding to gonococci strains to generate gonorrhea-detecting reagents. This study reports the identification of gonococci antibodies via bio-panning on gonococci cells using scFv-phage libraries. Reformatting the lead scFv-phage Clones 1 and 4 to a multivalent scFv1-Fc-scFv4 maxibody increased the sensitivity by up to 20-fold compared to the single scFv-Fc (maxibody) alone. Moreover, the multivalent maxibody showed broader cross-reactivity with clinical isolates and the ceftriaxone antibiotic-resistant World Health Organization (WHO) reference strain L. In contrast, the selected antibodies in the scFv-phage, maxibody, and multivalent maxibody did not bind to N. sicca, N. meningitides, and N. lactamica, suggesting the clinical and pharmaceutical diagnostic value of these selected antibodies for gonorrheal infections. The present study illustrates the advantages and potential application of multivalent maxibodies to develop rapid and sensitive diagnostic reagents for infectious diseases and cancer.
| S-EPMC8004885 | biostudies-literature
Project description:ABSTRACT Neisseria gonorrhoeae is a Gram-negative bacterium that causes the sexually transmitted infection gonorrhea. N. gonorrhoeae has progressively developed resistance to all currently prescribed antibiotics, and no vaccine is available. Here, we report the closed, completed, annotated genome sequences for seven N. gonorrhoeae strains obtained by single-molecule real-time (SMRT) long-read genome sequencing.
| S-EPMC8552677 | biostudies-literature
Project description:Using crude whole-genome assemblies, we analyzed 25 isolates of Neisseria gonorrhoeae by using a high-resolution single nucleotide polymorphism (SNP) approach for nine housekeeping genes, characterizing penA alleles, and antimicrobial susceptibility phenotypes coupled with population structure analysis. Two clonal complexes, characterized by their spatial and geographical persistence, were identified. In addition, the clonal spread of penicillin-resistant/intermediate phenotypes and a novel introduction of the azithromycin resistance phenotype in Saskatchewan, Canada, were ascertained using this method.
| S-EPMC4187769 | biostudies-literature
Project description:Recently, the first Neisseria gonorrhoeae strain (H041) that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, the last remaining option for empirical first-line treatment, was isolated. We performed a detailed characterization of H041, phenotypically and genetically, to confirm the finding, examine its antimicrobial resistance (AMR), and elucidate the resistance mechanisms. H041 was examined using seven species-confirmatory tests, antibiograms (30 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of ESC resistance determinants (penA, mtrR, penB, ponA, and pilQ). Transformation, using appropriate recipient strains, was performed to confirm the ESC resistance determinants. H041 was assigned to serovar Bpyust, MLST sequence type (ST) ST7363, and the new NG-MAST ST4220. H041 proved highly resistant to ceftriaxone (2 to 4 μg/ml, which is 4- to 8-fold higher than any previously described isolate) and all other cephalosporins, as well as most other antimicrobials tested. A new penA mosaic allele caused the ceftriaxone resistance. In conclusion, N. gonorrhoeae has now shown its ability to also develop ceftriaxone resistance. Although the biological fitness of ceftriaxone resistance in N. gonorrhoeae remains unknown, N. gonorrhoeae may soon become a true superbug, causing untreatable gonorrhea. A reduction in the global gonorrhea burden by enhanced disease control activities, combined with wider strategies for general AMR control and enhanced understanding of the mechanisms of emergence and spread of AMR, which need to be monitored globally, and public health response plans for global (and national) perspectives are important. Ultimately, the development of new drugs for efficacious gonorrhea treatment is necessary.
| S-EPMC3122416 | biostudies-literature
Project description:Neisseria gonorrhoeae strains with resistance to extended-spectrum cephalosporins (ESCs), last options for first-line monotherapy of gonorrhoea, likely emerged and initially disseminated in Japan, followed by international transmission. In recent years, multi-locus sequence typing (MLST) ST1901 and N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolates with the mosaic penicillin-binding protein (PBP) 2 XXXIV have accounted for most ESC resistance globally. Our aim was to elucidate the initial emergence and transmission of ESC-resistant strains by detailed examination of N. gonorrhoeae isolates from 1995 to 2005 in Kanagawa, Japan.N. gonorrhoeae isolates were examined phenotypically (n?=?690) and genetically (n?=?372) by agar dilution method (cefixime, ceftriaxone and ciprofloxacin), penA gene sequencing, MLST and NG-MAST.Already in 1995, one cefixime-resistant (CFM-R) isolate was found, which is the first CFM-R isolate described globally. After 1996, the prevalence of CFM-R and CFM-decreased susceptibility (CFM-DS) isolates significantly increased, with the peak resistance level in 2002 (57.1% CFM-R). In 1997-2002, the CFM-R MLST ST7363 strain type with the mosaic PBP 2 X was predominant among CFM-R/DS isolates. The first CFM-R/DS MLST ST1901 clone(s), which became the predominant CFM-R/DS strain type(s) already in 2003-2005, possessed the mosaic PBP 2 X, which was possibly originally transferred from the MLST ST7363 strains, and subsequently acquired the mosaic PBP 2 XXXIV. The first MLST ST1901 and NG-MAST ST1407 isolate was identified in Kanagawa already in 2003.The two main internationally spread cefixime-resistant gonococcal clones, MLST ST7363 and ST1901 (NG-MAST ST1407 most frequent internationally) that also have shown their capacity to develop high-level ceftriaxone resistance (superbugs H041 and F89), likely emerged, evolved and started to disseminate in the metropolitan area, including Kanagawa, in Japan, which was followed by global transmission.
| S-EPMC4574456 | biostudies-literature
Project description:There is a pressing need for drug development for gonorrhea. Here we describe a pharmacokinetic (PK)/pharmacodynamic (PD) analysis of extended-spectrum cephalosporins (ESC) against drug-susceptible and drug-resistant gonococcal strains in a murine genital tract infection model. The PK determined in uninfected mice displayed a clear dose-response in plasma levels following single doses of ceftriaxone (CRO) (intraperitoneal) or cefixime (CFM) (oral). The observed doses required for efficacy against ESC-susceptible (ESCs) strain FA1090 were 5 mg/kg of body weight (CRO) and 12 mg/kg (CFM); these doses had estimated therapeutic times (the time that the free drug concentration remains above the MIC [fT MIC]) of 24 h and 37 h, respectively. No single dose of CRO or CFM was effective against ESC-resistant (ESCr) strain H041. However, fractionation (three times a day every 8 h [TIDq8h]) of a 120-mg/kg dose of CRO resulted in estimated therapeutic times in the range of 23 h and cleared H041 infection in a majority (90%) of mice, comparable to the findings for gentamicin. In contrast, multiple CFM doses of 120 or 300 mg/kg administered TIDq8h cleared infection in ≤50% of mice, with the therapeutic times estimated from single-dose PK data being 13 and 27 h, respectively. This study reveals a clear relationship between plasma ESC levels and bacterial clearance rates in the gonorrhea mouse model. The PK/PD relationships observed in mice reflected those observed in humans, with in vivo efficacy against an ESCs strain requiring doses that yielded an fT MIC in excess of 20 to 24 h. PK data also accurately predicted the failure of single doses of ESCs against an ESCr strain and were useful in designing effective dosing regimens.
| S-EPMC6395893 | biostudies-other
Project description:We describe a sexual network consisting of 1 nonbinary-gendered participant and 2 male and 4 female participants in Australia, 2018. Six of 7 participants had oropharyngeal gonorrhea in the absence of urogenital gonorrhea. This observation supports a new paradigm of gonorrhea transmission in which oropharyngeal gonorrhea can be transmitted through tongue kissing.
| S-EPMC6590767 | biostudies-literature
Project description:We evaluated microbiological correlates for the successful treatment of Neisseria gonorrhoeae isolates from a phase 2 study of gepotidacin, a novel triazaacenaphthylene antibacterial, for therapy of uncomplicated urogenital gonorrhea. Culture, susceptibility testing, genotypic characterization, and frequency of resistance (FoR) were performed for selected isolates. Microbiological success was defined as culture-confirmed eradication of N. gonorrhoeae Against 69 baseline urogenital isolates, gepotidacin MICs ranged from ?0.06 to 1?µg/ml (MIC90 = 0.5?µg/ml). For gepotidacin, the ratio of the area under the free-drug concentration-time curve to the MIC (fAUC/MIC) was associated with therapeutic success. Success was 100% (61/61) at fAUC/MICs of ?48 and decreased to 63% (5/8) for fAUC/MICs of ?25. All 3 isolates from microbiological failures were ciprofloxacin resistant, had a baseline gepotidacin MIC of 1?µg/ml, and carried a preexisting ParC D86N mutation, a critical residue for gepotidacin binding. In a test-of-cure analysis, the resistance to gepotidacin emerged in 2 isolates (MICs increased ?32-fold) with additional GyrA A92T mutations, also implicated in gepotidacin binding. Test-of-cure isolates had the same sequence type as the corresponding baseline isolates. For 5 selected baseline isolates, all carrying a ParC D86N mutation, the in vitro FoR to gepotidacin was low (10-9 to 10-10); the resistant mutants had the same A92T mutation as the 2 isolates in which resistance emerged. Five participants with isolates harboring the ParC D86N mutation were treatment successes. In summary, fAUC/MICs of ?48 predicted 100% microbiological success, including 3 isolates with the ParC D86N mutation (fAUC/MICs ? 97). Pharmacokinetic/pharmacodynamic determinations may help to evaluate new therapies for gonorrhea; further study of gepotidacin is warranted. (This study has been registered at ClinicalTrials.gov under identifier NCT02294682.).
| S-EPMC6256812 | biostudies-literature
Project description:BackgroundSyphilis and gonorrhea reached an all-time high in 2018. The resurgence of syphilis and gonorrhea requires innovative methods of sexual contact tracing that encourage disclosure of same-sex sexual contacts that might otherwise be suppressed. Over 75% of Grindr mobile phone application users report seeking "friendship," so this study asked people diagnosed with syphilis and gonorrhea to identify their friends.MethodsPatients at the two Baltimore sexually transmitted infection (STI) clinics and the Baltimore City Health Department were asked 12 questions to elicit members of their friendship networks before eliciting sexual networks. The study included 353 index cases and 172 friendship contacts, yielding a friendship network of 331 non-isolates (n = 331) and sexual-only network of 140 non-isolates. The data were plotted and analyzed using exponential family random graph analysis.ResultsEliciting respondents' in-person social contacts yielded 12 syphilis cases and 6 gonorrhea cases in addition to the 16 syphilis cases and 4 gonorrhea cases that would have been found with sexual contacts alone. Syphilis is clustered within sexual (odds ratio = 2.2, 95% confidence interval (1.36, 3.66)) and social contacts (OR = 1.31, 95% CI (1.02, 1.68)). Gonorrhea is clustered within reported social (OR = 1.56, 95% CI (1.22, 2.00)) but not sexual contacts (OR = 0.98, 95% CI (0.62, 1.53)).ConclusionsEliciting friendship networks of people diagnosed with syphilis and gonorrhea may find members of their sexual networks, drug use networks, or people of similar STI risk. Friendship networks include more diagnosed cases of syphilis and gonorrhea than sexual networks alone, especially among populations with many non-disclosing men who have sex with men (MSM) and women who have sex with women (WSW). Future research should evaluate whether this friendship network method of contact tracing can be implemented by adapting automated mobile phone COVID-19 contact tracing protocols, if these COVID-19 contact tracing methods are able to maintain anonymity and public trust.
| S-EPMC7575333 | biostudies-literature