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1.
BMC Infect Dis ; 21(1): 520, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078300

RESUMO

BACKGROUND: Limited antimicrobial resistance (AMR) data for Neisseria gonorrhoeae are available in Eastern Europe. We investigated AMR in N. gonorrhoeae isolates in the Republic of Belarus from 2009 to 2019, antimicrobial treatment recommended nationally, and treatment given to patients with gonorrhoea. METHODS: N. gonorrhoeae isolates (n = 522) cultured in three regions of Belarus in 2009-2019 were examined. Determination of minimum inhibitory concentrations (MICs) of eight antimicrobials was performed using Etest. Resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing were applied where available. A Nitrocefin test identified ß-lactamase production. Gonorrhoea treatment for 1652 patients was also analysed. Statistical significance was determined by the Z-test, Fisher's exact test, or Mann-Whitney U test with p-values of < 0.05 indicating significance. RESULTS: In total, 27.8% of the N. gonorrhoeae isolates were resistant to tetracycline, 24.7% to ciprofloxacin, 7.0% to benzylpenicillin, 2.7% to cefixime, and 0.8% to azithromycin. No isolates were resistant to ceftriaxone, spectinomycin, or gentamicin. However, 14 (2.7%) isolates had a ceftriaxone MIC of 0.125 mg/L, exactly at the resistance breakpoint (MIC > 0.125 mg/L). Only one (0.2%) isolate, from 2013, produced ß-lactamase. From 2009 to 2019, the levels of resistance to ciprofloxacin and tetracycline were relatively high and stable. Resistance to cefixime was not identified before 2013 but peaked at 22.2% in 2017. Only sporadic isolates with resistance to azithromycin were found in 2009 (n = 1), 2012 (n = 1), and 2018-2019 (n = 2). Overall, 862 (52.2%) patients received first-line treatment according to national guidelines (ceftriaxone 1 g). However, 154 (9.3%) patients received a nationally recommended alternative treatment (cefixime 400 mg or ofloxacin 400 mg), and 636 (38.5%) were given non-recommended treatment. CONCLUSIONS: The gonococcal resistance to ciprofloxacin and tetracycline was high, however, the resistance to azithromycin was low and no resistance to ceftriaxone was identified. Ceftriaxone 1 g can continuously be recommended as empiric first-line gonorrhoea therapy in Belarus. Fluoroquinolones should not be prescribed for treatment if susceptibility has not been confirmed by testing. Timely updating and high compliance with national evidence-based gonorrhoea treatment guidelines based on quality-assured AMR data are imperative. The need for continued, improved and enhanced surveillance of gonococcal AMR in Belarus is evident.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria gonorrhoeae/isolamento & purificação , República de Belarus/epidemiologia , Adulto Jovem
2.
BMC Infect Dis ; 21(1): 392, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910514

RESUMO

BACKGROUND: Algorithms that bridge the gap between syndromic sexually transmitted infection (STI) management and treatment based in realistic diagnostic options and local epidemiology are urgently needed across Africa. Our objective was to develop and validate a risk algorithm for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) diagnosis among symptomatic Rwandan women and to compare risk algorithm performance to the current Rwandan National Criteria for NG/CT diagnosis. METHODS: The risk algorithm was derived in a cohort (n = 468) comprised of symptomatic women in Kigali who sought free screening and treatment for sexually transmitted infections and vaginal dysbioses at our research site. We used logistic regression to derive a risk algorithm for prediction of NG/CT infection. Ten-fold cross-validation internally validated the risk algorithm. We applied the risk algorithm to an external validation cohort also comprised of symptomatic Rwandan women (n = 305). Measures of calibration, discrimination, and screening performance of our risk algorithm compared to the current Rwandan National Criteria are presented. RESULTS: The prevalence of NG/CT in the derivation cohort was 34.6%. The risk algorithm included: age < =25, having no/primary education, not having full-time employment, using condoms only sometimes, not reporting genital itching, testing negative for vaginal candida, and testing positive for bacterial vaginosis. The model was well calibrated (Hosmer-Lemeshow p = 0.831). Higher risk scores were significantly associated with increased prevalence of NG/CT infection (p < 0.001). Using a cut-point score of > = 5, the risk algorithm had a sensitivity of 81%, specificity of 54%, positive predictive value (PPV) of 48%, and negative predictive value (NPV) of 85%. Internal and external validation showed similar predictive ability of the risk algorithm, which outperformed the Rwandan National Criteria. Applying the Rwandan National Criteria cutoff of > = 2 (the current cutoff) to our derivation cohort had a sensitivity of 26%, specificity of 89%, PPV of 55%, and NPV of 69%. CONCLUSIONS: These data support use of a locally relevant, evidence-based risk algorithm to significantly reduce the number of untreated NG/CT cases in symptomatic Rwandan women. The risk algorithm could be a cost-effective way to target treatment to those at highest NG/CT risk. The algorithm could also aid in sexually transmitted infection risk and prevention communication between providers and clients.


Assuntos
Algoritmos , Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis , Gonorreia/diagnóstico , Neisseria gonorrhoeae , Adulto , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Feminino , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Modelos Logísticos , Programas de Rastreamento , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Ruanda/epidemiologia , Sensibilidade e Especificidade , Adulto Jovem
3.
Medicine (Baltimore) ; 100(13): e25265, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787610

RESUMO

RATIONALE: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. PATIENT CONCERNS: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. DIAGNOSIS: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. INTERVENTIONS: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. OUTCOMES: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. LESSONS: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.


Assuntos
Complemento C7/deficiência , Variação Genética/genética , Gonorreia/genética , Doenças da Deficiência Hereditária de Complemento/genética , Doenças da Deficiência Hereditária de Complemento/microbiologia , Neisseria gonorrhoeae , Complemento C7/genética , Feminino , Gonorreia/microbiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade
5.
BMC Infect Dis ; 21(1): 273, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736608

RESUMO

BACKGROUND: The emergence and spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae, nationally and internationally, is a serious threat to the management and control of gonorrhoea. Limited and conflicting data regarding the epidemiological drivers of gonococcal AMR internationally have been published. We examined the antimicrobial susceptibility/resistance of gonococcal isolates (n = 15,803) collected across 27 European Union/European Economic Area (EU/EEA) countries in 2009-2016, in conjunction to epidemiological and clinical data of the corresponding patients, to elucidate associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection. METHODS: In total, 15,803 N. gonorrhoeae isolates from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), 2009-2016, were examined. Associations between gonococcal susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection were investigated using univariate and multivariate logistic regression analysis. Statistical significance was determined by Pearson χ2-test or Fisher's exact test with two-tailed p-values of < 0.05 indicating significance. RESULTS: The overall gonococcal resistance from 2009 to 2016 was 51.7% (range during the years: 46.5-63.5%), 7.1% (4.5-13.2%), 4.3% (1.8-8.7%), and 0.2% (0.0-0.5%) to ciprofloxacin, azithromycin, cefixime, and ceftriaxone, respectively. The level of resistance combined with decreased susceptibility to ceftriaxone was 10.2% (5.7-15.5%). Resistance to cefixime and ciprofloxacin, and resistance combined with decreased susceptibility to ceftriaxone were positively associated with urogenital infections and heterosexual males, males with sexual orientation not reported and females (except for ciprofloxacin), i.e. when compared to men-who-have-sex-with-men (MSM). Azithromycin resistance was positively associated with heterosexual males, but no association was significant regarding anatomical site of infection. CONCLUSIONS: Overall, sexual orientation was the main variable associated with gonococcal AMR. Strongest positive associations were identified with heterosexual patients, particularly males, and not MSM. To provide evidence-based understanding and mitigate gonococcal AMR emergence and spread, associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection need to be further investigated in different geographic settings. In general, these insights will support identification of groups at increased risk and targeted public health actions such as intensified screening, 3-site testing using molecular diagnostics, sexual contact tracing, and surveillance of treatment failures.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Fatores Sexuais , Minorias Sexuais e de Gênero , Azitromicina/uso terapêutico , Cefixima/uso terapêutico , Ceftriaxona/uso terapêutico , Ciprofloxacina/uso terapêutico , União Europeia , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Heterossexualidade , Homossexualidade Masculina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação , Comportamento Sexual
6.
Nat Commun ; 12(1): 1799, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741965

RESUMO

Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.


Assuntos
Neisseria gonorrhoeae/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Ribossomos/efeitos dos fármacos , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação/genética , Células CACO-2 , Feminino , Gonorreia/microbiologia , Gonorreia/prevenção & controle , Humanos , Camundongos , Neisseria gonorrhoeae/genética , Biossíntese de Proteínas/genética , Inibidores da Síntese de Proteínas/química , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Ribossomos/genética , Ribossomos/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-33632090

RESUMO

Abstract: The key issues with Neisseria gonorrhoeae infections, in Australia and elsewhere, are coincident increases in disease rates and in antimicrobial resistance (AMR), although these factors have not been shown to be correlated. Despite advances in diagnosis, control of this disease remains elusive, and incidence in Australia continues to increase. Of the Australian jurisdictions, New South Wales (NSW) has the highest N. gonorrhoeae notifications, and over the five-year period 2015-2019, notifications in NSW have increased above the national average (by 116% versus 85%, respectively). Gonococcal disease control is reliant on effective antibiotic regimens. However, escalating AMR in N. gonorrhoeae is a global health priority, as the collateral injury of untreated infections has substantive impacts on sexual and newborn health. Currently, our first-line therapy for gonorrhoea is also our last line, with no ideal alternative identified. Despite some limitations, gentamicin is licensed and readily available in Australia, and is proposed for treatment of resistant N. gonorrhoeae in national guidelines; however, supportive published microbiological data are lacking. Analysis of gonococcal resistance patterns within Australia for the period 1991-2019, including 35,000 clinical isolates from NSW, illustrates the establishment and spread of population-level resistance to all contemporaneous therapies. An analysis of gentamicin susceptibility on 2,768 N. gonorrhoeae clinical isolates from NSW, for the period 2015-2020, demonstrates that the median minimum inhibitory concentration (MIC) for gentamicin in NSW has remained low, at 4.0 mg/L, and resistance was not detected in any isolate. There has been no demonstration of MIC drift over time (p = 0.91, Kruskal-Wallis test), nor differences in MIC distributions according to patients' sex or site of specimen collection. This is the first large-scale evaluation of gentamicin susceptibility in N. gonorrhoeae in Australia. No gentamicin resistance was detected in clinical isolates, 2015-2020, hence this is likely to be an available treatment option for resistant gonococcal infections in NSW.


Assuntos
Gentamicinas/uso terapêutico , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Gentamicinas/farmacologia , Gonorreia/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , New South Wales , Fatores Sexuais
10.
BMC Infect Dis ; 20(1): 809, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153450

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an emerging global health threat. Surveillance of AMR in N. gonorrhoeae in the Western Pacific Region is important, as resistant strains have typically emerged from this region. There are sparse data regarding antibiotic susceptibility of N. gonorrhoeae from Vietnam. This study aimed to provide updated data on antibiotic susceptibilities in N. gonorrhoeae isolates from Hanoi, Vietnam. METHODS: From 2017 to 2019, 409 N. gonorrhoeae clinical isolates were collected at the National Hospital for Venereology and Dermatology in Hanoi, Vietnam. Antibiotic susceptibility testing was performed by disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) protocol. The zone diameters of inhibition were recorded and interpreted according to standard CLSI criteria, except for azithromycin, due to the absence of CLSI interpretation. Categorical variables were analyzed by Chi-square and Fisher's exact tests. Linear regression was used to evaluate zones of inhibition by year. RESULTS: Among the 409 isolates, no isolates were susceptible to penicillin, 98.3% were resistant to ciprofloxacin, and all isolates were susceptible to spectinomycin. There were 122/407 (30.0%) isolates resistant to azithromycin and there was an association between resistance and year (p <  0.01), ranging from 15.3% of isolates in 2017 to 46.7% of the isolates in 2018. Resistance to cefixime was found in 13/406 (3.2%) of isolates and there was no association by year (p = 0.30). Resistance to ceftriaxone occurred in 3/408 (0.7%) of isolates. Linear regression indicated the zone of inhibition diameters decreased by 0.83 mm each year for ceftriaxone (95% CI: - 1.3, - 0.4; p <  0.01) and decreased by 0.83 mm each year (95% CI: - 1.33, - 0.33; p <  0.01) for azithromycin; the association was not significant for cefixime (p = 0.07). CONCLUSIONS: We found decreasing susceptibility of N. gonorrhoeae to ceftriaxone and azithromycin, as well as a high prevalence of resistance to azithromycin, among isolates in Hanoi, Vietnam from 2017 to 2019. The trends of decreasing susceptibility to first-line treatments are concerning and highlight the urgency of addressing antimicrobial resistance in N. gonorrhoeae. Expanded surveillance efforts within the Western Pacific Region are critical to monitoring trends and informing treatment guidelines.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Feminino , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Laboratórios , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria gonorrhoeae/isolamento & purificação , Vietnã/epidemiologia , Adulto Jovem
11.
Nat Commun ; 11(1): 5374, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097713

RESUMO

The emergence of resistance to azithromycin complicates treatment of Neisseria gonorrhoeae, the etiologic agent of gonorrhea. Substantial azithromycin resistance remains unexplained after accounting for known resistance mutations. Bacterial genome-wide association studies (GWAS) can identify novel resistance genes but must control for genetic confounders while maintaining power. Here, we show that compared to single-locus GWAS, conducting GWAS conditioned on known resistance mutations reduces the number of false positives and identifies a G70D mutation in the RplD 50S ribosomal protein L4 as significantly associated with increased azithromycin resistance (p-value = 1.08 × 10-11). We experimentally confirm our GWAS results and demonstrate that RplD G70D and other macrolide binding site mutations are prevalent (present in 5.42% of 4850 isolates) and widespread (identified in 21/65 countries across two decades). Overall, our findings demonstrate the utility of conditional associations for improving the performance of microbial GWAS and advance our understanding of the genetic basis of macrolide resistance.


Assuntos
Farmacorresistência Bacteriana/genética , Genoma Bacteriano , Estudo de Associação Genômica Ampla , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Antibacterianos/farmacologia , Azitromicina/farmacologia , Sítios de Ligação/genética , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Humanos , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Mutação/efeitos dos fármacos , RNA Ribossômico 23S/genética
12.
BMC Infect Dis ; 20(1): 795, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109139

RESUMO

BACKGROUND: Some patients who test positive for sexually transmitted infections (STIs) fail to return for results and treatment. To target improvement actions, we need to find out who these patients are. This study aimed to explore factors associated with failure to return within 30 days (FTR30) after testing among patients with positive results in a free STI testing centre in Paris. METHODS: All patients with at least one positive result between October 2016 and May 2017 and who completed a self-administered questionnaire were included in this cross-sectional study (n = 214). The questionnaire included sociodemographic factors, sexual behaviour and history of testing. Factors associated with FTR30 were assessed using logistic regression models. RESULTS: More than two-thirds of patients were men (72%), and the median age of patients was 27 years. Most patients were born in metropolitan France (56%) or in sub-Saharan Africa (22%). Men who had sex with men represented 36% of the study population. The FTR30 rate was 14% (95% CI [10-19%]). In multivariate analysis, previous HIV testing in younger persons (aOR: 3.36, 95% CI [1.27-8.84]), being accompanied by another person at the pretest consultation (aOR: 3.45, 95% CI [1.36-8.91]), and lower self-perceived risk of HIV infection (aOR: 2.79, 95% CI [1.07-7.30]) were associated with a higher FTR30. Testing for chlamydia/gonorrhoea without presumptive treatment was associated with a lower FTR30 (aOR: 0.21, 95% CI [0.07-0.59]). CONCLUSIONS: These factors that affect failure to return are related to the patient's representations and involvement in the STI screening process. Increasing health literacy and patient empowerment could help to decrease failure to return after being tested positive for HIV/STI. TRIAL REGISTRATION: Not applicable.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HIV/isolamento & purificação , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Pacientes Desistentes do Tratamento , Adulto , Chlamydia/isolamento & purificação , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Estudos Transversais , Feminino , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Gonorreia/microbiologia , Infecções por HIV/virologia , Homossexualidade Masculina , Humanos , Modelos Logísticos , Masculino , Neisseria gonorrhoeae/isolamento & purificação , Paris/epidemiologia , Assunção de Riscos , Comportamento Sexual , Minorias Sexuais e de Gênero , Inquéritos e Questionários , Adulto Jovem
13.
BMC Infect Dis ; 20(1): 703, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977759

RESUMO

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 ß-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.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Neisseria gonorrhoeae/genética , Penicilinas/uso terapêutico , Plasmídeos/genética , Resistência a Tetraciclina/genética , Tetraciclina/uso terapêutico , DNA Bacteriano/genética , Feminino , Genótipo , Gonorreia/microbiologia , Humanos , Quênia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação , Sequenciamento Completo do Genoma , beta-Lactamases/genética
15.
BMC Infect Dis ; 20(1): 486, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641070

RESUMO

BACKGROUND: Asymptomatic screening for gonorrhoea in heterosexual men is currently not recommended in many countries including Australia, given the prevalence is relatively low in the heterosexual population. We aimed to determine the proportion of urethral gonorrhoea cases among heterosexual men attending a sexual health clinic that was asymptomatic and symptomatic, the time since last sexual contact to the onset of symptoms and the time to clinic presentation following the onset of symptoms. METHODS: This was a cross-sectional study that included heterosexual men aged 16 years or above attending the Melbourne Sexual Health Centre (MSHC) in Australia between August 2017 and August 2018. Gonorrhoea cases were diagnosed by nucleic acid amplification testing (NAAT) and/or culture. Descriptive analyses were conducted for all gonorrhoea cases including demographic characteristics, recent sexual practices, reported urethral symptoms and duration, sexual contact with a person diagnosed with gonorrhoea, investigations performed and laboratory results. RESULTS: There were 116 confirmed cases of urethral gonorrhoea in heterosexual men over the study period of which 6.0% (95% CI: 2.7-12.1%) were asymptomatic. Typical urethral discharge was present in 80.2% (95% CI: 71.9-86.5%) of men. The mean time between last sexual contact and the onset of symptoms was 7.0 days, and between the onset of symptoms to presentation to the clinic was 5.6 days. CONCLUSIONS: A small proportion of heterosexual men with urethral gonorrhoea do not have any symptoms. Heterosexual men with urethral symptoms usually seek for healthcare within a week, prompting rapid healthcare-seeking behaviour.


Assuntos
Infecções Assintomáticas/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Heterossexualidade , Neisseria gonorrhoeae/genética , Saúde Sexual , Doenças Uretrais/diagnóstico , Doenças Uretrais/epidemiologia , Adolescente , Adulto , Austrália/epidemiologia , Estudos Transversais , Gonorreia/microbiologia , Gonorreia/fisiopatologia , Humanos , Masculino , Técnicas de Amplificação de Ácido Nucleico/métodos , Prevalência , Doenças Uretrais/microbiologia , Adulto Jovem
16.
BMC Infect Dis ; 20(1): 514, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677988

RESUMO

BACKGROUND: Worldwide, an increase in antimicrobial resistance (AMR) of Neisseria gonorrhoeae has been observed. Until now, no protocol for an external quality assessment (EQA) has been available for Germany. The German gonococcal resistance network (GORENET) performed an EQA of primary laboratories in Germany in order to assess quality of antibiotic susceptibility testing, to gain information about laboratory procedures and to assess the impact of these procedures on test results. METHODS: Laboratories assessed drug susceptibility to cefixime, ceftriaxone, azithromycin, penicillin and ciprofloxacin for five N. gonorrhoeae strains, using their standard laboratory protocols. Minimal inhibitory concentrations (MICs) were compared to World Health Organisation (WHO) consensus results (or, if not available, reference laboratory results), while deviation by +/- one doubling dilution was accepted. Data on laboratory procedures were collected via a standardised questionnaire. Generalized linear models and conditional inference trees (CTREE) were used to assess relationships between laboratory procedures and testing outcomes. RESULTS: Twenty-one primary laboratories participated in the EQA in June 2018. 96% of ciprofloxacin MICs were reported within accepted deviations, as well as 88% for cefixime, 85% for ceftriaxone, 79% for penicillin and 70% for azithromycin. The use of interpretation standards and general laboratory procedures like agar base, incubation settings or the use of control strains strongly differed between laboratories. In statistical analysis, incubation time of cultures < 24 h was associated with correct measurements. Additionally, a 5% CO2 concentration was associated with correct results regarding azithromycin compared to 3%. CTREE analysis showed that incubation time, humidity and CO2 concentration had the greatest influence on the average deviation from consensus results. CONCLUSIONS: In conclusion, we report the development of a protocol for N. gonorrhoeae antimicrobial susceptibility testing in Germany. While testing results were in accordance with the expected consensus results in 70-96%, depending on the antibiotic agent, laboratory methodology was heterogeneous and may significantly affect the testing quality. We therefore recommend the development of a standard operating procedure (SOP) for N. gonorrhoeae susceptibility testing in Germany.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia/tratamento farmacológico , Laboratórios/normas , Ensaio de Proficiência Laboratorial , Neisseria gonorrhoeae/efeitos dos fármacos , Antibacterianos/farmacologia , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Cefixima/farmacologia , Cefixima/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Alemanha , Gonorreia/microbiologia , Humanos , Ensaio de Proficiência Laboratorial/métodos , Testes de Sensibilidade Microbiana , Penicilinas/farmacologia , Penicilinas/uso terapêutico , Controle de Qualidade , Padrões de Referência , Inquéritos e Questionários
17.
BMC Infect Dis ; 20(1): 419, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546213

RESUMO

BACKGROUND: Four new variants of Chlamydia trachomatis (nvCTs), detected in several countries, cause false-negative or equivocal results using the Aptima Combo 2 assay (AC2; Hologic). We evaluated the clinical sensitivity and specificity, as well as the analytical inclusivity and exclusivity of the updated AC2 for the detection of CT and Neisseria gonorrhoeae (NG) on the automated Panther system (Hologic). METHODS: We examined 1004 clinical AC2 samples and 225 analytical samples spiked with phenotypically and/or genetically diverse NG and CT strains, and other potentially cross-reacting microbial species. The clinical AC2 samples included CT wild type (WT)-positive (n = 488), all four described AC2 diagnostic-escape nvCTs (n = 170), NG-positive (n = 214), and CT/NG-negative (n = 202) specimens. RESULTS: All nvCT-positive samples (100%) and 486 (99.6%) of the CT WT-positive samples were positive in the updated AC2. All NG-positive, CT/NG-negative, Trichomonas vaginalis (TV)-positive, bacterial vaginosis-positive, and Candida-positive AC2 specimens gave correct results. The clinical sensitivity and specificity of the updated AC2 for CT detection was 99.7 and 100%, respectively, and for NG detection was 100% for both. Examining spiked samples, the analytical inclusivity and exclusivity were 100%, i.e., in clinically relevant concentrations of spiked microbe. CONCLUSIONS: The updated AC2, including two CT targets and one NG target, showed a high sensitivity, specificity, inclusivity and exclusivity for the detection of CT WT, nvCTs, and NG. The updated AC2 on the fully automated Panther system offers a simple, rapid, high-throughput, sensitive, and specific diagnosis of CT and NG, which can easily be combined with detection of Mycoplasma genitalium and TV.


Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Análise de Sequência de RNA/métodos , Candida/genética , Candidíase/diagnóstico , Candidíase/microbiologia , Infecções por Chlamydia/microbiologia , Reações Cruzadas , Feminino , Gonorreia/diagnóstico , Gonorreia/microbiologia , Humanos , Neisseria gonorrhoeae/genética , RNA Bacteriano/genética , RNA Ribossômico 23S/genética , Sensibilidade e Especificidade , Tricomoníase/diagnóstico , Tricomoníase/parasitologia , Trichomonas vaginalis/genética
18.
Lancet Infect Dis ; 20(8): 976-982, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32530426

RESUMO

BACKGROUND: WHO recommends that men who have sex with men (MSM) receive gonorrhoea and chlamydia testing, but many evidence-based preventive services are unaffordable. The pay-it-forward strategy offers an individual a gift (eg, a test for sexually transmitted diseases) and then asks whether they would like to give a gift (eg, a future test) to another person. This study examined the effectiveness of a pay-it-forward programme to increase gonorrhoea and chlamydia testing among MSM in China. METHODS: We did a randomised controlled superiority trial at three HIV testing sites run by MSM community-based organisations in Guangzhou and Beijing, China. We included MSM aged 16 years or older who were seeking HIV testing and met indications for gonorrhoea and chlamydia testing. Restricted randomisation was done using computer-generated permuted blocks. 30 groups were randomised into three arms (1:1:1): a pay-it-forward arm in which men were offered free gonorrhoea and chlamydia testing and then asked whether they would like to donate for testing of prospective participants, a pay-what-you-want arm in which men were offered free testing and given the option to pay any desired amount for the test, and a standard-of-care arm in which testing was offered at ¥150 (US$22). There was no masking to arm assignment. The primary outcome was gonorrhoea and chlamydia test uptake ascertained by administrative records. We used generalised estimating equations to estimate intervention effects with one-sided 95% CIs and a prespecified superiority margin of 20%. The trial is registered with ClinicalTrials.gov, NCT03741725. FINDINGS: Between Dec 8, 2018, and Jan 19, 2019, 301 men were recruited and included in the analysis. 101 were randomly assigned to the pay-it-forward group, 100 to the pay-what-you-want group, and 100 to the standard-of-care group. Test uptake for gonorrhoea and chlamydia was 56% (57 of 101 participants) in the pay-it-forward arm, 46% (46 of 100 participants) in the pay-what-you-want arm, and 18% (18 of 100 participants) in the standard-of-care arm. The estimated difference in test uptake between the pay-it-forward and standard-of-care group was 38·4% (95% CI lower bound 28·4%). Among men in the pay-it-forward arm, 54 of 57 (95%) chose to donate to support testing for others. INTERPRETATION: The pay-it-forward strategy can increase gonorrhoea and chlamydia testing uptake among Chinese MSM and could be a useful tool for scaling up preventive services that carry a mandatory fee. FUNDING: US National Institute of Health; Special Programme for Research and Training in Tropical Diseases, sponsored by UNICEF, UNDP, World Bank, and WHO; the National Key Research and Development Program of China; Doris Duke Charitable Foundation; and Social Entrepreneurship to Spur Health.


Assuntos
Infecções por Chlamydia/epidemiologia , Gonorreia/epidemiologia , Homossexualidade Masculina , Reembolso de Seguro de Saúde , Doenças Sexualmente Transmissíveis/epidemiologia , Adulto , China/epidemiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Testes Diagnósticos de Rotina , Gonorreia/diagnóstico , Gonorreia/microbiologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doenças Sexualmente Transmissíveis/diagnóstico , Doenças Sexualmente Transmissíveis/microbiologia , Fatores Socioeconômicos , Adulto Jovem
19.
PLoS One ; 15(6): e0233753, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479537

RESUMO

BACKGROUND: Neisseria gonorrhoeae (gonococcus) is the etiologic agent for the sexually transmitted Infection gonorrhea, a disease with a significant global public health impact. The treatment regimen for gonorrhea has been changed frequently over the past few decades due to the organism's propensity for developing antibiotic resistance. This study investigated antimicrobial susceptibility patterns of quinolones, third-generation cephalosporin, and other relevant antimicrobials found in N. gonorrhoeae isolated from men presenting with urethral discharge at selected healthcare facilities in Addis Ababa, Ethiopia, with the aim of revising the national treatment regimen based on the information generated from this study. METHODS: A total of 599 male patients presenting with urethral discharge were included in the current study. Urethral discharge specimens were cultured on Modified Thayer Martín media and suspected gonococcal colonies were confirmed using Oxidase and Superoxol tests followed by identification through a commercial kit (API-NHR). Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method using ciprofloxacin (5µg), ceftriaxone (30µg), cefixime (5µg), cefoxitin (30 µg), penicillin (10µg) and spectinomycin (100 µg) on enriched GC agar. Minimum Inhibitory Concentration (MIC) was also carried out using concentration gradient strips (E-tests) of the same antimicrobial agents. RESULTS: The prevalence of gonococcal isolates in the current study was 69%. Out of the 361 gonococcal isolates, close to 68% were fluoroquinolone non-susceptible, with 60% resistant and 7% having an intermediate status. However, all tested isolates were susceptible to ceftriaxone. In addition, all of the isolates have shown reduced non-susceptibility to spectinomycin and cefoxitin. CONCLUSION: The prevalence of gonococcal isolates in men presenting with urethral discharge at selected healthcare facilities in Addis Ababa, Ethiopia was found to be high. The high level of fluoroquinolone resistance observed in gonococcal isolates recovered in this study necessitates revision of the national syndromic treatment guideline.


Assuntos
Resistência Microbiana a Medicamentos , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Antibacterianos/farmacologia , Líquidos Corporais/microbiologia , Cefalosporinas/farmacologia , Gonorreia/patologia , Humanos , Masculino , Neisseria gonorrhoeae/patogenicidade , Uretra/microbiologia , Uretra/patologia
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