scholarly journals Emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains harbouring a novel mosaic penA gene in China

2020 ◽  
Vol 75 (4) ◽  
pp. 907-910 ◽  
Author(s):  
Leshan Xiu ◽  
Qianqin Yuan ◽  
Yamei Li ◽  
Chi Zhang ◽  
Lingli Tang ◽  
...  

Abstract Objectives The continuous emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains threatens the effectiveness of current treatment regimens for gonorrhoea. The objective of the present study was to characterize three ceftriaxone-resistant N. gonorrhoeae strains with a novel mosaic penA allele isolated in China. Methods Three ceftriaxone-resistant Neisseria gonorrhoeae strains (GC150, GC161 and GC208) isolated in 2017 were characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST), MLST and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR). Recombination analyses were performed using the SimPlot software. Results Three strains had the same antibiotic resistance profiles, with resistance to ceftriaxone (MIC 0.5 mg/L), ciprofloxacin (MIC 8.0 mg/L), penicillin (MIC 2.0 mg/L) and tetracycline (MIC 2.0–8.0 mg/L). STs were assigned as MLST7360, NG-MAST14292 and NG-STAR1611/NG-STAR1612. The penA gene of these three strains differed from previous ceftriaxone-resistant gonococcal strains and harboured a novel mosaic allele (penA-121.001). Like N. gonorrhoeae FC428, a widely disseminated ceftriaxone-resistant strain that was initially described in Japan in 2015, all strains also possessed substitutions A311V and T483S in PBP2, which are associated with resistance to ceftriaxone. Potential recombination events were detected in penA between N. gonorrhoeae strain FC428 and commensal Neisseria species. Our results provide further evidence that the commensal Neisseria species (Neisseria cinerea and Neisseria perflava) can serve as a reservoir of ceftriaxone resistance-mediating penA sequences in clinical gonococcal strains. Conclusions The emergence of such strains may be the result of the interspecies recombination of penA genes between N. gonorrhoeae strain FC428 and commensal Neisseria species.

1999 ◽  
Vol 43 (6) ◽  
pp. 1367-1372 ◽  
Author(s):  
Marilyn C. Roberts ◽  
Whasun O. Chung ◽  
Darcie Roe ◽  
Minsheng Xia ◽  
Carolina Marquez ◽  
...  

ABSTRACT Two Neisseria gonorrhoeae isolates from Seattle and two isolates from Uruguay were resistant to erythromycin (MIC, 4 to 16 μg/ml) and had reduced susceptibility to azithromycin (MIC, 1 to 4 μg/ml) due to the presence of the self-mobile rRNA methylase gene(s)ermF or ermB and ermF. The two Seattle isolates and one isolate from Uruguay were multiresistant, carrying either the 25.2-MDa tetM-containing plasmid (Seattle) or a β-lactamase plasmid (Uruguay). Sixteen commensal Neisseria isolates (10 Neisseria perflava-N. sicca, 2 N. flava, and 4N. mucosa) for which erythromycin MICs were 4 to 16 μg/ml were shown to carry one or more known rRNA methylase genes, includingermB, ermC, and/or ermF. Many of these isolates also were multiresistant and carried thetetM gene. This is the first time that a complete transposon or a complete conjugative transposon carrying an antibiotic resistance gene has been described for the genus Neisseria.


2019 ◽  
Vol 70 (6) ◽  
pp. 1169-1175 ◽  
Author(s):  
Huan V Dong ◽  
Loc Q Pham ◽  
Hoa T Nguyen ◽  
Minh X B Nguyen ◽  
Trung V Nguyen ◽  
...  

Abstract Background Neisseria gonorrhoeae (NG) infections are a global health burden. NG resistance to cephalosporins, which is increasingly reported, is an imminent threat to public health. Many hypothesize that commensal Neisseria species are an important reservoir for genetic material conferring antimicrobial resistance in NG; however, clinical data are lacking. Methods Men who have sex with men (MSM) in Hanoi, Vietnam, completed a questionnaire regarding antibiotic use. We collected pharyngeal specimens, cultured Neisseria species, and measured minimum inhibitory concentrations (MICs) to ciprofloxacin, cefixime, ceftriaxone, and cefpodoxime. Using MIC criteria for antimicrobial susceptibility in NG, we categorized the Neisseria species and compared mean MIC levels between different antibiotic user groups. Results Of 207 participants, 38% used at least 1 antibiotic in the past 6 months; 52% without a prescription. A median of 1 Neisseria species was cultured from each participant (range, 1–4) with 10 different Neisseria species identified overall. The proportion of Neisseria with reduced susceptibility to ciprofloxacin was 93%, cefpodoxime 84%, cefixime 31%, and ceftriaxone 28%. Antibiotic use within the past month was strongly associated with Neisseria species having increased MICs to cefixime, ceftriaxone, and cefpodoxime (mean MIC ratios of 6.27, 4.11, and 7.70, respectively), compared with those who used antibiotics between 1 and 6 months prior (P < .05, all comparisons). Conclusions MSM in our study often used antibiotics without a prescription. At least 1 commensal Neisseria species colonized all men. Recent use of any antibiotics may select for oropharyngeal Neisseria species with antimicrobial resistance. The normal flora of the oropharynx may be an important source of antimicrobial resistance in Neisseria gonorrhoeae.


Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 515
Author(s):  
Chris Kenyon ◽  
Jolein Laumen ◽  
Sheeba Manoharan-Basil

The development of new gonorrhoea treatment guidelines typically considers the resistance-inducing effect of the treatment only on Neisseria gonorrhoeae. Antimicrobial resistance in N. gonorrhoeae has, however, frequently first emerged in commensal Neisseria species and then been passed on to N. gonorrhoeae via transformation. This creates the rationale for considering the effect of gonococcal therapies on resistance in commensal Neisseria. We illustrate the benefits of this pan-Neisseria strategy by evaluating three contemporary treatment options for N. gonorrhoeae—ceftriaxone plus azithromycin, monotherapy with ceftriaxone and zoliflodacin.


mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Adam L. Bailey ◽  
Robert F. Potter ◽  
Meghan A. Wallace ◽  
Caitlin Johnson ◽  
Gautam Dantas ◽  
...  

ABSTRACT The objectives of this study were to perform genomic and phenotypic characterization of antimicrobial resistance in Neisseria gonorrhoeae isolates recovered from urine samples from patients in St. Louis, MO, USA. Sixty-four clinical isolates were banked over a 2-year period and subjected to antimicrobial susceptibility testing (AST) by Kirby-Bauer disk diffusion (penicillin, tetracycline, cefuroxime, and ciprofloxacin) and gradient diffusion (tetracycline, doxycycline, azithromycin, ceftriaxone, cefixime, ciprofloxacin, gemifloxacin, and delafloxacin). The medical records for the patients were evaluated to determine the demographics, location, and prescribed treatment regimen. Isolate draft genomes were assembled from Illumina shotgun sequencing data, and resistance determinants were identified by ResFinder and PointFinder. Of the 64 isolates, 97% were nonsusceptible to penicillin, with resistant isolates all containing the blaTEM-1b gene; 78 and 81% of isolates were nonsusceptible to tetracycline and doxycycline, respectively, with resistant isolates all containing the tet(M) gene. One isolate was classified as non-wild-type to azithromycin, and all isolates were susceptible to ceftriaxone; 89% of patients received this combination of drugs as first-line therapy. Six percent of isolates were resistant to ciprofloxacin, with most resistant isolates containing multiple gyrA and parC mutations. Correlation between disk and gradient diffusion AST devices was high for tetracycline and ciprofloxacin (R2 > 99% for both). The rates of N. gonorrhoeae antibiotic resistance in St. Louis are comparable to current rates reported nationally, except ciprofloxacin resistance was less common in our cohort. Strong associations between specific genetic markers and phenotypic susceptibility testing hold promise for the utility of genotype-based diagnostic assays to guide directed antibiotic therapy. IMPORTANCE Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is most commonly diagnosed using a DNA-based detection method that does not require growth and isolation of N. gonorrhoeae in the laboratory. This is problematic because the rates of antibiotic resistance in N. gonorrhoeae are increasing, but without isolating the organism in the clinical laboratory, antibiotic susceptibility testing cannot be performed on strains recovered from clinical specimens. We observed an increase in the frequency of urine cultures growing N. gonorrhoeae after we implemented a total laboratory automation system for culture in our clinical laboratory. Here, we report on the rates of resistance to multiple historically used, first-line, and potential future-use antibiotics for 64 N. gonorrhoeae isolates. We found that the rates of antibiotic resistance in our isolates were comparable to national rates. Additionally, resistance to specific antibiotics correlated closely with the presence of genetic resistance genes, suggesting that DNA-based tests could also be designed to guide antibiotic therapy for treating gonorrhea.


2011 ◽  
Vol 16 (43) ◽  
Author(s):  
M Unemo ◽  
D Golparian ◽  
A Stary ◽  
A Eigentler

We describe the first cefixime-resistant Neisseria gonorrhoeae strain in Austria that caused treatment failure. It follows the first five cases in Europe of cefixime treatment failure, reported in Norway in 2010 and the United Kingdom in 2011. Effective treatment of gonorrhoea is crucial for public health control and, at present, requires substantially enhanced awareness, more frequent test-of-cure, interaction with experts after therapeutic failure, tracing and therapy of contacts, and surveillance of gonococcal antimicrobial resistance and treatment failures worldwide.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mary Wandia Kivata ◽  
Margaret Mbuchi ◽  
Fredrick Eyase ◽  
Wallace Dimbuson Bulimo ◽  
Cecilia Katunge Kyanya ◽  
...  

Abstract Background Treatment of gonorrhea is complicated by the development of antimicrobial resistance in Neisseria gonorrhoeae (GC) to the antibiotics recommended for treatment. Knowledge on types of plasmids and the antibiotic resistance genes they harbor is useful in monitoring the emergence and spread of bacterial antibiotic resistance. In Kenya, studies on gonococcal antimicrobial resistance are few and data on plasmid mediated drug resistance is limited. The present study characterizes plasmid mediated resistance in N. gonorrhoeae isolates recovered from Kenya between 2013 and 2018. Methods DNA was extracted from 36 sub-cultured GC isolates exhibiting varying drug resistance profiles. Whole genome sequencing was done on Illumina MiSeq platform and reads assembled de-novo using CLC Genomics Workbench. Genome annotation was performed using Rapid Annotation Subsystem Technology. Comparisons in identified antimicrobial resistance determinants were done using Bioedit sequence alignment editor. Results Twenty-four (66.7%) isolates had both β-lactamase (TEM) and TetM encoding plasmids. 8.3% of the isolates lacked both TEM and TetM plasmids and had intermediate to susceptible penicillin and tetracycline MICs. Twenty-six (72%) isolates harbored TEM encoding plasmids. 25 of the TEM plasmids were of African type while one was an Asian type. Of the 36 isolates, 31 (86.1%) had TetM encoding plasmids, 30 of which harbored American TetM, whereas 1 carried a Dutch TetM. All analyzed isolates had non-mosaic penA alleles. All the isolates expressing TetM were tetracycline resistant (MIC> 1 mg/L) and had increased doxycycline MICs (up to 96 mg/L). All the isolates had S10 ribosomal protein V57M amino acid substitution associated with tetracycline resistance. No relation was observed between PenB and MtrR alterations and penicillin and tetracycline MICs. Conclusion High-level gonococcal penicillin and tetracycline resistance in the sampled Kenyan regions was found to be mediated by plasmid borne blaTEM and tetM genes. While the African TEM plasmid, TEM1 and American TetM are the dominant genotypes, Asian TEM plasmid, a new TEM239 and Dutch TetM have emerged in the regions.


2000 ◽  
Vol 44 (11) ◽  
pp. 3184-3185 ◽  
Author(s):  
Albert J. de Neeling ◽  
Marga van Santen-Verheuvel ◽  
Joke Spaargaren ◽  
Rob J. L. Willems

ABSTRACT Surveillance of antibiotic resistance in Neisseria gonorrhoeae showed a decrease in the percentage of β-lactamase-producing isolates but an increase in intermediately penicillin-resistant strains and strains resistant to a high level of tetracycline. MICs for the ciprofloxacin-resistant isolates that emerged increased, and these isolates had mutations in gyrAand parC similar to those observed in the Far East.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Koji Yahara ◽  
Kevin C. Ma ◽  
Tatum D. Mortimer ◽  
Ken Shimuta ◽  
Shu-ichi Nakayama ◽  
...  

Abstract Background Antimicrobial resistance in Neisseria gonorrhoeae is a global health concern. Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to third-generation cephalosporins, mainly due to mosaic penA alleles. These two STs were first detected in Japan; however, the timeline, mechanism, and process of emergence and spread of these mosaic penA alleles to other countries remain unknown. Methods We studied the evolution of penA alleles by obtaining the complete genomes from three Japanese ST-1901 clinical isolates harboring mosaic penA allele 34 (penA-34) dating from 2005 and generating a phylogenetic representation of 1075 strains sampled from 35 countries. We also sequenced the genomes of 103 Japanese ST-7363 N. gonorrhoeae isolates from 1996 to 2005 and reconstructed a phylogeny including 88 previously sequenced genomes. Results Based on an estimate of the time-of-emergence of ST-1901 (harboring mosaic penA-34) and ST-7363 (harboring mosaic penA-10), and > 300 additional genome sequences of Japanese strains representing multiple STs isolated in 1996–2015, we suggest that penA-34 in ST-1901 was generated from penA-10 via recombination with another Neisseria species, followed by recombination with a gonococcal strain harboring wildtype penA-1. Following the acquisition of penA-10 in ST-7363, a dominant sub-lineage rapidly acquired fluoroquinolone resistance mutations at GyrA 95 and ParC 87-88, by independent mutations rather than horizontal gene transfer. Data in the literature suggest that the emergence of these resistance determinants may reflect selection from the standard treatment regimens in Japan at that time. Conclusions Our findings highlight how antibiotic use and recombination across and within Neisseria species intersect in driving the emergence and spread of drug-resistant gonorrhea.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Jolein Gyonne Elise Laumen ◽  
Christophe Van Dijck ◽  
Saïd Abdellati ◽  
Irith De Baetselier ◽  
Gabriela Serrano ◽  
...  

AbstractNon-pathogenic Neisseria are a reservoir of antimicrobial resistance genes for pathogenic Neisseria meningitidis and Neisseria gonorrhoeae. Men who have sex with men (MSM) are at risk of co-colonization with resistant non-pathogenic and pathogenic Neisseria. We assessed if the antimicrobial susceptibility of non-pathogenic Neisseria among MSM differs from a general population and if antimicrobial exposure impacts susceptibility. We recruited 96 participants at our center in Belgium: 32 employees, 32 MSM who did not use antibiotics in the previous 6 months, and 32 MSM who did. Oropharyngeal Neisseria were cultured and identified with MALDI-TOF–MS. Minimum inhibitory concentrations for azithromycin, ceftriaxone and ciprofloxacin were determined using E-tests® and compared between groups with non-parametric tests. Non-pathogenic Neisseria from employees as well as MSM were remarkably resistant. Those from MSM were significantly less susceptible than employees to azithromycin and ciprofloxacin (p < 0.0001, p < 0.001), but not ceftriaxone (p = 0.3). Susceptibility did not differ significantly according to recent antimicrobial exposure in MSM. Surveilling antimicrobial susceptibility of non-pathogenic Neisseria may be a sensitive way to assess impact of antimicrobial exposure in a population. The high levels of antimicrobial resistance in this survey indicate that novel resistance determinants may be readily available for future transfer from non-pathogenic to pathogenic Neisseria.


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