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1.
Emerg Microbes Infect ; 9(1): 517-519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116136

RESUMO

We report a recent (2018) gonorrhoeal urethritis caused by a multidrug-resistant Neisseria gonorrhoeae strain in China. The isolated N. gonorrhoeae strain from a male and female pair expressed high-level resistance to spectinomycin (SPC), azithromycin, and other antibiotics but was sensitive to ceftriaxone. The SPC high-level resistance (MIC = 2048 mg/L) was due to a small deletion in rspE that caused two amino acid changes in ribosomal protein S5.


Assuntos
Farmacorresistência Bacteriana Múltipla , Neisseria gonorrhoeae/efeitos dos fármacos , Espectinomicina/farmacologia , China , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/metabolismo , Fenótipo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
4.
BMC Infect Dis ; 19(1): 1040, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822275

RESUMO

BACKGROUND: European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA). METHODS: We compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance. RESULTS: There was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between - 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from - 9.5 to 2.7%) and ciprofloxacin (from - 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate. CONCLUSIONS: The overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Neisseria gonorrhoeae/efeitos dos fármacos , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Cefixima/farmacologia , Cefixima/uso terapêutico , Ciprofloxacino/farmacologia , Ciprofloxacino/uso terapêutico , União Europeia , Gonorreia/diagnóstico , Gonorreia/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação
5.
BMC Infect Dis ; 19(1): 1085, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881862

RESUMO

BACKGROUND: Does the emergence of antimicrobial resistance in Neisseria gonorrhoeae include the erasure of highly susceptible strains or does it merely involve a stretching of the MIC distribution? If it was the former this would be important to know as it would increase the probability that the loss of susceptibility is irreversible. METHODS: We conducted a historical analysis based on a literature review of changes of N. gonorrhoeae MIC distribution over the past 75 years for 3 antimicrobials (benzylpenicillin, ceftriaxone and azithromycin) in five countries (Denmark, Japan, South Africa, the United Kingdom and the United States). RESULTS: Changes in MIC distribution were most marked for benzylpenicillin and showed evidence of a right shifting of MIC distribution that was associated with a reduction/elimination of susceptible strains in all countries. In the case of ceftriaxone and azithromycin, where only more recent data was available, right shifting was also found in all countries but the extent of right shifting varied and the evidence for the elimination of susceptible strains was more mixed. CONCLUSIONS: The finding of right shifting of MIC distribution combined with reduction/elimination of susceptible strains is of concern since it suggests that this shifting may not be reversible. Since excess antimicrobial consumption is likely to be responsible for this right shifting, this insight provides additional impetus to promote antimicrobial stewardship.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia/tratamento farmacológico , Testes de Sensibilidade Microbiana/tendências , Neisseria gonorrhoeae/efeitos dos fármacos , Penicilina G/uso terapêutico , Gestão de Antimicrobianos/métodos , Azitromicina/efeitos adversos , Ceftriaxona/efeitos adversos , Dinamarca , Humanos , Japão , Penicilina G/efeitos adversos , África do Sul , Reino Unido , Estados Unidos
6.
BMC Bioinformatics ; 20(Suppl 15): 535, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874612

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to global public health because it makes standard treatments ineffective and contributes to the spread of infections. It is important to understand AMR's biological mechanisms for the development of new drugs and more rapid and accurate clinical diagnostics. The increasing availability of whole-genome SNP (single nucleotide polymorphism) information, obtained from whole-genome sequence data, along with AMR profiles provides an opportunity to use feature selection in machine learning to find AMR-associated mutations. This work describes the use of a supervised feature selection approach using deep neural networks to detect AMR-associated genetic factors from whole-genome SNP data. RESULTS: The proposed method, DNP-AAP (deep neural pursuit - average activation potential), was tested on a Neisseria gonorrhoeae dataset with paired whole-genome sequence data and resistance profiles to five commonly used antibiotics including penicillin, tetracycline, azithromycin, ciprofloxacin, and cefixime. The results show that DNP-AAP can effectively identify known AMR-associated genes in N. gonorrhoeae, and also provide a list of candidate genomic features (SNPs) that might lead to the discovery of novel AMR determinants. Logistic regression classifiers were built with the identified SNPs and the prediction AUCs (area under the curve) for penicillin, tetracycline, azithromycin, ciprofloxacin, and cefixime were 0.974, 0.969, 0.949, 0.994, and 0.976, respectively. CONCLUSIONS: DNP-AAP can effectively identify known AMR-associated genes in N. gonorrhoeae. It also provides a list of candidate genes and intergenic regions that might lead to novel AMR factor discovery. More generally, DNP-AAP can be applied to AMR analysis of any bacterial species with genomic variants and phenotype data. It can serve as a useful screening tool for microbiologists to generate genetic candidates for further lab experiments.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Sequenciamento Completo do Genoma , Genômica , Humanos , Neisseria gonorrhoeae/efeitos dos fármacos
7.
BMC Infect Dis ; 19(1): 991, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752720

RESUMO

BACKGROUND: Male urethritis is primary sexually transmitted. Northern Territory (NT) has the highest rates of gonococcal infection in Australia and local guidelines recommend empiric treatment with azithromycin and ceftriaxone for all men presenting with urethritis. As gonococcal drug resistance is a growing concern, this study aims to improve empiric use of ceftriaxone through examining local patterns of male urethritis, comparing cases of gonococcal urethritis (GU) to controls with non-gonococcal urethritis (NGU). METHODS: A retrospective study was undertaken of all men with symptomatic urethritis presenting to Darwin sexual health clinic from July 2015 to July 2016 and aetiology of urethritis in this population was described. Demographic, risk profile, and clinical features of GU cases were compared to NGU controls. RESULTS: Among n = 145 men, the most common organisms identified were Chlamydia trachomatis (23.4%, SE 3.5%) and Neisseria gonorrhoeae (17.2%, SE 3.1%). The main predictors of GU were any abnormalities on genital examination (aOR 10.4, 95% CI 2.1 to 50.8) and a history of urethral discharge (aOR 5.7, 95% CI 1.4 to 22.6). Aboriginal patients (aOR 3.0, 95% CI 0.9 to 9.6) and those over 30 years of age (aOR 1.4, 95% CI 0.3 to 7.0) were more likely to have GU in the unadjusted analysis, but not in the adjusted model. CONCLUSION: This is the first study looking at patterns of male urethritis in urban NT and the results support a move towards adopting national guidelines to use ceftriaxone for empiric management of syndromic urethritis only in high-risk patients. In addition to traditional demographic risk factors, clinical features remain an important component of risk stratification.


Assuntos
Infecções por Chlamydia/epidemiologia , Gonorreia/epidemiologia , Uretrite/epidemiologia , Adulto , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Azitromicina/uso terapêutico , Estudos de Casos e Controles , Ceftriaxona/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/efeitos dos fármacos , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Humanos , Masculino , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , Northern Territory/epidemiologia , Estudos Retrospectivos , Uretrite/diagnóstico , Uretrite/tratamento farmacológico , Uretrite/microbiologia
8.
Emerg Microbes Infect ; 8(1): 1546-1549, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661379

RESUMO

The growing multidrug-resistant Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. During 2017-2018, we identified a rare multidrug-resistant (ceftriaxone and azithromycin) strain (GC250) and four strains (GC185, GC195, GC196 and GC249) with both resistance to ceftriaxone and decreased susceptibility to azithromycin. All strains belonged to NG-STAR ST1143, including the mosaic penA-60.001, which is closely related to ceftriaxone resistance. The characterization of antimicrobial resistance (AMR) determinants and phylogenetic analysis showed these five strains were closely related to internationally spreading ceftriaxone-resistant N. gonorrhoeae FC428, but with higher azithromycin MIC. Findings here demonstrated that this clone not only initiated clonal expansion in China, but acquired azithromycin resistance.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Ceftriaxona/farmacologia , Farmacorresistência Bacteriana Múltipla , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/isolamento & purificação , China , Feminino , Heterossexualidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/classificação , Neisseria gonorrhoeae/genética , Filogenia
9.
Mem Inst Oswaldo Cruz ; 114: e190079, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411309

RESUMO

A total of 124 Neisseria gonorrhoeae isolates recovered during a 12-year period (2003-2015) from outpatients assisted at Centro de Referência e Treinamento DST/AIDS-CRT of São Paulo city, Brazil, were analysed. The following resistance rates were observed: penicillin-59.6%, ciprofloxacin-15.3%, and azithromycin-6.7%. Although reduced susceptibility to these drugs was observed since 2003, no ceftriaxone-resistant isolates were detected. Ciprofloxacin- and azithromycin non-susceptible isolates were grouped in 11 clusters. Mutations were detected in GyrA and ParC of isolates 124 and 260, and a C2611T substitution on 23S rRNA alleles was also observed in isolate 260. Both isolates belonged to ST1901/ST6210 (MSLT/NG-MAST schemes).


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Mutação , Fatores de Tempo , População Urbana
10.
Emerg Infect Dis ; 25(9): 1660-1667, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31407661

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Resistência às Cefalosporinas/genética , Gonorreia/epidemiologia , Neisseria gonorrhoeae/isolamento & purificação , Alberta/epidemiologia , Gonorreia/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Filogenia , Reação em Cadeia da Polimerase , Vigilância da População
12.
Nat Microbiol ; 4(11): 1941-1950, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31358980

RESUMO

The sexually transmitted pathogen Neisseria gonorrhoeae is regarded as being on the way to becoming an untreatable superbug. Despite its clinical importance, little is known about its emergence and evolution, and how this corresponds with the introduction of antimicrobials. We present a genome-based phylogeographical analysis of 419 gonococcal isolates from across the globe. Results indicate that modern gonococci originated in Europe or Africa, possibly as late as the sixteenth century and subsequently disseminated globally. We provide evidence that the modern gonococcal population has been shaped by antimicrobial treatment of sexually transmitted infections as well as other infections, leading to the emergence of two major lineages with different evolutionary strategies. The well-described multidrug-resistant lineage is associated with high rates of homologous recombination and infection in high-risk sexual networks. A second, multisusceptible lineage is more associated with heterosexual networks, with potential implications for infection control.


Assuntos
Farmacorresistência Bacteriana Múltipla , Gonorreia/microbiologia , Neisseria gonorrhoeae/classificação , Análise de Sequência de DNA/métodos , África , Antibacterianos/farmacologia , DNA Bacteriano/genética , Europa (Continente) , Evolução Molecular , Recombinação Homóloga , Humanos , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Filogenia , Filogeografia
13.
mSphere ; 4(4)2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31341071

RESUMO

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 bla TEM-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 (R 2 > 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.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Gonorreia/microbiologia , Gonorreia/urina , Neisseria gonorrhoeae/genética , Adolescente , Adulto , Estudos Transversais , Feminino , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neisseria gonorrhoeae/efeitos dos fármacos , Fenótipo , Análise de Sequência de DNA , Sequenciamento Completo do Genoma , Adulto Jovem
16.
J Med Microbiol ; 68(7): 991-995, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31162022

RESUMO

In 2018, the European Centre for Disease Prevention and Control reported the first cases of extensively drug-resistant Neisseria gonorrhoeae infections in Europe. Seeking new options for antimicrobial therapy we investigated the susceptibility of N. gonorrhoeae to nitroxoline (NIT) and mecillinam (MCM), both of which are currently only indicated to treat uncomplicated urinary tract infections. Clinical N. gonorrhoeae isolates with non-susceptibility to penicillin from two German medical centres were included (n =27). Most isolates were also non-susceptible to a range of other anti-gonococcal antimicrobials (cefotaxime, ciprofloxacin, azithromycin, tetracycline). All isolates were further characterized by multi-locus sequence typing. MICs of penicillin and cefotaxime were determined by agar gradient diffusion. Production of penicillinase was tested by cefinase disk test. Susceptibility of MCM was investigated by agar dilution, NIT by agar dilution and disk diffusion. Penicillin MICs ranged from 0.125 to 64 mg l-1 and MICs of cefotaxime ranged from < 0.016 to 1 mg l-1 . Five isolates were penicillinase-producers. MICs of MCM ranged from 16 to > 128 mg l-1 whereas MICs of NIT ranged from 0.125 to 2 mg l-1 . NIT disk diffusion (median zone diameter 32 mm) correlated well with results from agar dilution. We demonstrated excellent in vitro activity of NIT against clinical N. gonorrhoeae isolates with non-susceptibility to standard anti-gonococcal antibiotics. MCM activity was unsatisfactory. Correlation of agar dilution and disk diffusion in NIT susceptibility testing is an important aspect with potential clinical implications.


Assuntos
Andinocilina/farmacologia , Anti-Infecciosos Urinários/farmacologia , Neisseria gonorrhoeae/efeitos dos fármacos , Nitroquinolinas/farmacologia , Farmacorresistência Bacteriana Múltipla , Humanos , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/genética
17.
Infez Med ; 27(2): 212-221, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31205048

RESUMO

Gonorrhea can be traced back to the earliest records of the human race even if Albert Neisser first described gonococcus in 1879. The Romans, Jews and Arabs all have documents referring to gonorrhea and each society had their own description of symptoms and treatment. The Roman physician Galen in 130 AD described the disease as an "involuntary escape of semen". The word itself derives from the Greek, meaning "the flow of seed". Gonorrhea is currently the second most commonly notifiable sexually transmitted infection (STI) reported to Centers for Disease Control and Prevention (CDC), second only to chlamydial infection. Gonorrhea notifications have been on the rise all over the world and in several European countries since the early 2000s, particularly in populations with higher frequency of spread of STIs, such as men who have sex with men and young heterosexual individuals of both sexes. Having been recognized at least 3500 years ago, the fight against the disease began infinitely before the antibiotic era, using healing compounds. In the absence of an ideal vaccine, the most important challenge today is the emergence of the multidrug-resistant gonorrhea, which is currently the main reason for public concern responsible for the evolution of N. gonorrheae into a superbug. N. gonorrheae strains resistant to extended spectrum cephalosporin (ESC) form a threat to effective control of gonorrhea for which there are currently ongoing clinical trials to evaluate the efficacy and safety profile of old and new antimicrobial molecules for monotherapy and as dual therapy of gonorrhea. In this paper we investigated the remedies and treatments employed against gonorrhea during the 19th century in Ferrara, referring to Campana's Pharmacopoeia and unpublished manuscripts concerning the treatment of this disease in medical practice. The remedies for gonorrhea adopted in the city were in line with those utilized in other countries. Among these, copaiba oleoresins have been demonstrated to have been efficacious in the past against gonococcal disease in popular medical use and, recently, against a large number of bacteria, fungi and protozoa, which will call for more in vitro and clinical studies to evaluate their real effectiveness on the N. gonorrheae bacterium.


Assuntos
Gonorreia/história , Gonorreia/terapia , Antibacterianos/história , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Gonorreia/epidemiologia , Gonorreia/microbiologia , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , Humanos , Masculino , Neisseria gonorrhoeae/efeitos dos fármacos
18.
Methods Mol Biol ; 1997: 37-58, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119616

RESUMO

Gonorrhea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns globally. Dual antimicrobial therapy (mainly ceftriaxone 250-500 mg × 1 plus azithromycin 1-2 g × 1) is currently recommended in many countries. These dual therapies have high cure rates, have likely been involved in decreasing the level of cephalosporin resistance internationally, and inhibit the spread of AMR gonococcal strains. However, ceftriaxone-resistant strains are currently spreading internationally, predominately associated with travel to Asia. Furthermore, the first global treatment failure with recommended dual therapy was reported in 2016 and the first isolates with combined ceftriaxone resistance and high-level azithromycin resistance were reported in 2018 in the UK and Australia. New antimicrobials for treatment of gonorrhea are essential and, of the few antimicrobials in clinical development, zoliflodacin particularly appears promising. Holistic actions are imperative. These include an enhanced advocacy; prevention, early diagnosis, contact tracing, treatment, test-of-cure, and additional measures for effective management of anogenital and pharyngeal gonorrhea; antimicrobial stewardship; surveillance of infection, AMR and treatment failures; and intensified research, for example, regarding rapid molecular point-of-care detection of gonococci and AMR, novel AMR determinants, new antimicrobials, and an effective gonococcal vaccine, which is the only sustainable solution for management and control of gonorrhea.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/fisiologia , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Busca de Comunicante , Quimioterapia Combinada/métodos , Gonorreia/microbiologia , Gonorreia/transmissão , Saúde Holística , Humanos , Testes de Sensibilidade Microbiana/métodos , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/isolamento & purificação
19.
Methods Mol Biol ; 1997: 59-76, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119617

RESUMO

Bacterial whole-genome sequencing is now increasingly available to researchers, reference laboratories and individual healthcare institutions. It can be possible to predict antimicrobial minimum inhibitory concentrations (MICs) for Neisseria gonorrhoeae using sequencing data, for many antimicrobials within one or two MIC doubling dilutions of the phenotypic value. With emerging rapid sequencing technologies, it may be possible in future to predict antimicrobial resistance faster than existing culture-based methods. Sequencing also provides insights into the genetic mechanisms underlying antimicrobial resistance, their spread in time and space, as well as the molecular epidemiology of the gonococcal strains.


Assuntos
Farmacorresistência Bacteriana/genética , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/genética , Sequenciamento Completo do Genoma/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Variações do Número de Cópias de DNA , Análise Mutacional de DNA/métodos , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Mutação , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/isolamento & purificação , Regiões Promotoras Genéticas/genética , RNA Ribossômico 23S/genética , Sequenciamento Completo do Genoma/instrumentação
20.
Methods Mol Biol ; 1997: 413-429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119637

RESUMO

Mouse models of infection are important tools in the study of infectious disease or host the development of products to prevent or treat infections. The estradiol-treated mouse model of Neisseria gonorrhoeae genital tract infection has proved to be a valuable system for determining the importance of gonococcal factors that mediate evasion of host innate effectors in vivo or host gonococcal adaptation to hormonally driven host factors in females. Examination of mechanisms that Neisseria gonorrhoeae uses to subvert the host immune response also has been greatly aided by this whole model system, as have studies on the consequence of antibiotic resistance mutations on gonococcal fitness in vivo and the search for new antibiotics to treat antibiotic-resistant infections. The strict human specificity of N. gonorrhoeae limits the ability of experimental murine infection to mimic human infection. However, in recent years, the development of transgenic mice and protocols for supplementing mice with human factors has improved animal modeling of gonorrhea. To date, however, because the mouse estrous cycle is much shorter than the human reproductive cycle, all reported gonorrhea mouse models require treatment with estradiol and antibiotics to maintain an estrus-like state and suppress the overgrowth of inhibitory commensal flora that occurs under the influence of estrogen to allow sustained N. gonorrhoeae infection. In this chapter, we detail the methods used to (1) prepare the mice for experimental infection with N. gonorrhoeae, (2) inoculate mice and quantitatively culture vaginal swabs for noncompetitive and competitive infection experiments, and (3) monitor the host innate immune response to infection.


Assuntos
Modelos Animais de Doenças , Gonorreia/imunologia , Neisseria gonorrhoeae/imunologia , Animais , Antibacterianos/administração & dosagem , Estradiol/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/imunologia , Feminino , Gonorreia/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/patogenicidade , Vagina/imunologia , Vagina/microbiologia
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