Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 10.046
Filtrar
1.
Nat Commun ; 12(1): 1799, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33741965

RESUMEN

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.


Asunto(s)
Neisseria gonorrhoeae/efectos de los fármacos , Biosíntesis de Proteínas/efectos de los fármacos , Inhibidores de la Síntesis de la Proteína/farmacología , Ribosomas/efectos de los fármacos , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sitios de Unión/genética , Células CACO-2 , Femenino , Gonorrea/microbiología , Gonorrea/prevención & control , Humanos , Ratones , Neisseria gonorrhoeae/genética , Biosíntesis de Proteínas/genética , Inhibidores de la Síntesis de la Proteína/química , ARN Bacteriano/genética , ARN Bacteriano/metabolismo , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Ribosomas/genética , Ribosomas/metabolismo
3.
Medicine (Baltimore) ; 100(13): e25265, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33787610

RESUMEN

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.


Asunto(s)
Complemento C7/deficiencia , Variación Genética/genética , Gonorrea/genética , Enfermedades por Deficiencia de Complemento Hereditario/genética , Enfermedades por Deficiencia de Complemento Hereditario/microbiología , Neisseria gonorrhoeae , Complemento C7/genética , Femenino , Gonorrea/microbiología , Humanos , Japón , Masculino , Persona de Mediana Edad
4.
BMC Infect Dis ; 21(1): 273, 2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33736608

RESUMEN

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.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Gonorrea/microbiología , Neisseria gonorrhoeae/efectos de los fármacos , Factores Sexuales , Minorías Sexuales y de Género , Azitromicina/uso terapéutico , Cefixima/uso terapéutico , Ceftriaxona/uso terapéutico , Ciprofloxacino/uso terapéutico , Unión Europea , Femenino , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Heterosexualidad , Homosexualidad Masculina , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/aislamiento & purificación , Conducta Sexual
5.
Artículo en Inglés | MEDLINE | ID: mdl-33632090

RESUMEN

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.


Asunto(s)
Gentamicinas/uso terapéutico , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Femenino , Gentamicinas/farmacología , Gonorrea/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Nueva Gales del Sur , Factores Sexuales
6.
Phys Rev Lett ; 126(1): 018102, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33480767

RESUMEN

Dense cellular aggregates are common in biology, ranging from bacterial biofilms to organoids, cell spheroids, and tumors. Their dynamics, driven by intercellular forces, is intrinsically out of equilibrium. Motivated by bacterial colonies as a model system, we present a continuum theory to study dense, active, cellular aggregates. We describe the process of aggregate formation as an active phase separation phenomenon, while the merging of aggregates is rationalized as a coalescence of viscoelastic droplets where the key timescales are linked to the turnover of the active force. Our theory provides a general framework for studying the rheology and nonequilibrium dynamics of dense cellular aggregates.


Asunto(s)
Modelos Biológicos , Neisseria gonorrhoeae/citología , Fimbrias Bacterianas/fisiología
7.
BMC Infect Dis ; 21(1): 95, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33478403

RESUMEN

BACKGROUND: Recommendations for sexually transmitted infection (STI) screening vary significantly across countries. This study evaluated the prevalence of urogenital and extragenital infections with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) in patients visiting a French STI clinic in the Indian Ocean region to determine whether current STI screening practices should be updated. METHODS: This cross-sectional study examined all patients who visited the STI clinic between 2014 and 2015. Triplex polymerase chain reaction screening for CT, NG, and MG was performed on urine, vaginal, pharyngeal, and anal specimens (FTD Urethritis Basic Kit, Fast Track Diagnostics, Luxembourg). RESULTS: Of the 851 patients enrolled in the study, 367 were women (367/851, 43.2%) and 484 were men (484/851, 56.0%). Overall, 826 urogenital specimens (826/851, 97.1%), 606 pharyngeal specimens (606/851, 71.2%), and 127 anal specimens (127/851, 14.9%) were taken from enrolled patients. The prevalence of urogenital CT and MG was high in women ≤25 years (19/186, 10.21%; 5/186, 2.69%) and in men who have sex with women ≤30 years (16/212, 7.54%; 5/212, 2.36%). Among patients with urogenital CT infection, 13.7% (7/51) had urethritis. All patients with urogenital MG infection were asymptomatic. Men who have sex with men had a high prevalence of pharyngeal CT (2/45, 4.44%) and NG (3/44, 6.81%) and a high prevalence of anal CT (2/27, 7.41%), NG (2/27, 7.40%), and MG (1/27, 3.70%). After excluding patients with concomitant urogenital infection, extragenital infections with at least 1 of the 3 pathogens were found in 20 swabs (20/91, 21.9%) taken from 16 patients (16/81, 19.7%), all of them asymptomatic. CONCLUSIONS: Routine multisite screening for CT, NG, and MG should be performed to mitigate the transmission of STIs in high-risk sexually active populations.


Asunto(s)
Chlamydia trachomatis/aislamiento & purificación , Mycoplasma genitalium/aislamiento & purificación , Neisseria gonorrhoeae/aislamiento & purificación , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/microbiología , Adolescente , Adulto , Anciano , Canal Anal/microbiología , Estudios Transversales , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Faringe/microbiología , Prevalencia , Reunión/epidemiología , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/transmisión , Sistema Urogenital/microbiología , Adulto Joven
9.
BMC Infect Dis ; 20(1): 809, 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33153450

RESUMEN

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.


Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Ceftriaxona/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Gonorrea/epidemiología , Gonorrea/microbiología , Humanos , Laboratorios , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neisseria gonorrhoeae/aislamiento & purificación , Vietnam/epidemiología , Adulto Joven
10.
Nat Commun ; 11(1): 5374, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33097713

RESUMEN

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.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Genoma Bacteriano , Estudio de Asociación del Genoma Completo , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Antibacterianos/farmacología , Azitromicina/farmacología , Sitios de Unión/genética , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Humanos , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Mutación/efectos de los fármacos , ARN Ribosómico 23S/genética
11.
BMC Infect Dis ; 20(1): 795, 2020 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-33109139

RESUMEN

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.


Asunto(s)
Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , VIH/aislamiento & purificación , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Pacientes Desistentes del Tratamiento , Adulto , Chlamydia/aislamiento & purificación , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/microbiología , Estudios Transversales , Femenino , Gonorrea/diagnóstico , Gonorrea/epidemiología , Gonorrea/microbiología , Infecciones por VIH/virología , Homosexualidad Masculina , Humanos , Modelos Logísticos , Masculino , Neisseria gonorrhoeae/aislamiento & purificación , Paris/epidemiología , Asunción de Riesgos , Conducta Sexual , Minorías Sexuales y de Género , Encuestas y Cuestionarios , Adulto Joven
12.
Int J Nanomedicine ; 15: 7877-7887, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33116506

RESUMEN

Purpose: The emergence of Neisseria gonorrhoeae strains that are resistant to the most commonly used antibiotics represents a great concern for global public health. This challenges the effectiveness of clinical treatment regimens and demands the development of alternative antigonococcal agent. In this regard, chitosan nanoparticles (CNPs) are known to have antimicrobial activity against a wide range of pathogens. Thus, they have become a potential candidate for combatting this era of multi-drug resistance. This study aims to formulate CNPs, characterize their physicochemical properties, and examine their antimicrobial activity against gonococcus. Materials and Methods: The ionic gelation method was used to prepare CNPs of different concentrations. Characterization for their particle size (PZ), polydispersity index (PDI), and zeta potential (ZP) was performed. The anti-microbial activity of CNPs was investigated against 13 WHO N. gonorrhoeae reference strains, using the broth dilution method. Cytotoxicity of CNPs and their effect on bacterial adhesion to HeLa cells were investigated. Results: The average PZ and ZP of the prepared NPs were increased when the concentration of chitosan was increased from 1 to 5 mg/mL and found to be in the range of 193 nm ± 1.9 to 530 nm ± 13.3, and 14 mV ± 0.5 to 20 mV ± 1, respectively. Transmission electron microscopes (TEM) images revealed spherical NPs, and the NPs had a low PDI value of ≤0.27. The formed CNPs produced antibacterial activity against all tested strains, including those resistant to multiple antibiotics, with a minimum inhibitory concentration (MIC90) of 0.16 to 0.31 mg/mL and a minimum bactericidal concentration (MBC) of 0.31 to 0.61 mg/mL. Of note, at all MIC90 and MBC, the CNPs had no significant cytotoxic effect on HeLa cells and reduced bacterial adhesion to these cells at MBC doses. Conclusion: The present work findings suggest the potential of the CNPs for the treatment of gonorrhoea.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Quitosano/química , Quitosano/farmacología , Nanopartículas/química , Neisseria gonorrhoeae/efectos de los fármacos , Antibacterianos/toxicidad , Adhesión Bacteriana/efectos de los fármacos , Quitosano/toxicidad , Células HeLa , Humanos , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/fisiología , Tamaño de la Partícula
13.
BMC Infect Dis ; 20(1): 703, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32977759

RESUMEN

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.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Neisseria gonorrhoeae/genética , Penicilinas/uso terapéutico , Plásmidos/genética , Resistencia a la Tetraciclina/genética , Tetraciclina/uso terapéutico , ADN Bacteriano/genética , Femenino , Genotipo , Gonorrea/microbiología , Humanos , Kenia/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/aislamiento & purificación , Secuenciación Completa del Genoma , beta-Lactamasas/genética
14.
Artículo en Alemán | MEDLINE | ID: mdl-32930821

RESUMEN

In February 2019, the fourth expert meeting on rapid diagnostic tests (RDTs) for sexually transmitted infections (STI) was held at the Robert Koch Institute (RKI) in Berlin. Novel technical developments and new aspects of RDT applications were discussed by representatives from the German STI Society (DSTIG); RKI; the Paul Ehrlich Institute; national reference centers for HIV, HBV, and HCV; and reference laboratories for Chlamydia, gonococci, and Treponema pallidum.As a result of this meeting, we present a revision of the joint statement on STI diagnostics with RDTs from 2017. The Regulation (EU) 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices became effective in May 2017 and includes more stringent regulatory requirements for RDTs, mainly concerning conformity of manufacturing processes and performance characteristics of class D in vitro diagnostics (detection of HIV, HBV, HCV, and T. pallidum). Some RDTs for HIV, HCV, and T. pallidum have been evaluated in clinical studies and/or were WHO prequalified and may be used in low-threshold services. Among them are some HIV RDTs available and approved for self-testing. In addition, some HBV RDTs based on detection of HBs antigen (HBsAg) received WHO prequalification. However, false negative results may occur in samples with low HBsAg levels, as for instance in HIV-coinfected patients receiving antiretroviral therapy. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), antigen-based RDTs still do not allow reliable detection of infection. Only PCR-based CT/NG RDTs possess sufficient diagnostic accuracy to be used as point-of-care tests. Rapid PCR tests for NG, however, do not provide any information about antimicrobial resistance.


Asunto(s)
Chlamydia , Infecciones por VIH/diagnóstico , Hepatitis C/diagnóstico , Enfermedades de Transmisión Sexual/diagnóstico , Berlin , Alemania , Virus de la Hepatitis B , Humanos , Neisseria gonorrhoeae , Treponema pallidum
15.
PLoS One ; 15(9): e0238745, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32886722

RESUMEN

BACKGROUND: Men who have sex with men (MSM) and transgender women (TGW) are at risk for sexually transmitted infections (STIs), including those of the oropharynx. We estimated the prevalence and factors associated with oral sex practices and characterized oropharyngeal STIs among a cohort of MSM and TGW in Nigeria. METHODS: From 2013 to 2018, TRUST/RV368 recruited MSM and TGW into HIV/STI diagnosis and treatment at community-based clinics in Nigeria. Participants who completed HIV testing and oral sex questions at enrollment were selected. Cross-sectional analyses with bivariate and multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs). Oropharyngeal swab testing for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) began in 2014 and for those with diagnostic results at enrollment, the unadjusted association of oral sex practices with oropharyngeal STIs was conducted. RESULTS: A total of 1342 participants had a median age of 25 years (interquartile range: 22-29), 58% were living with HIV, and 69% reported oral sex practices. Factors associated with increased odds of engaging in oral sex included living with HIV (adjusted [a]OR: 1.4, 95% CI: 1.1-1.8), self-identifying as a woman (aOR:1.8, 95% CI: 1.1-2.8), mobile phone ownership (aOR:2.3, 95% CI: 1.3-3.9), receptive anal sex (aOR:1.7, 95% CI:1.3-2.3) and multiple male sexual partners (2 to 4 vs. ≤1, aOR:1.5, 95% CI: 1.0-2.2; 5+ vs ≤1, aOR:2.9, 95% CI:1.9-4.3). Oropharyngeal STI prevalence was 7% (52/752) and higher among those who engaged in oral sex compared to those who did not (unadjusted OR: 2.5, 95% CI:1.2-5.3). CONCLUSIONS: Oral sex was common and associated with an increased odds of oropharyngeal STIs among MSM and TGW from Nigeria. In the absence of screening and treatment guidelines, condoms continue to be the mainstay for oral STI prevention. A pre-exposure prophylaxis for bacterial STIs would complement current prevention strategies to curb transmission.


Asunto(s)
Infecciones por VIH/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Conducta Sexual/estadística & datos numéricos , Personas Transgénero/estadística & datos numéricos , Adolescente , Adulto , Chlamydia trachomatis/fisiología , Estudios de Cohortes , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/microbiología , Humanos , Masculino , Persona de Mediana Edad , Neisseria gonorrhoeae/fisiología , Nigeria , Riesgo , Adulto Joven
17.
PLoS One ; 15(9): e0237424, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32870912

RESUMEN

BACKGROUND: There is a need for a rapid diagnostic point of care test to detect Neisseria gonorrhoeae (NG) infection to prevent incorrect, lack or excess of treatment resulting from current syndromic management in low-resource settings. An assay to identify NG antimicrobial resistance (AMR) is also highly desirable to facilitate antibiotic stewardship. Here we describe the development of two target product profiles (TPPs): one for a test for etiological diagnosis of NG and Chlamydia trachomatis (CT) (TPP1) and one for the detection of NG AMR/susceptibility (TPP2). METHODS: Draft TPPs were initially developed based on a landscape analysis of existing diagnostics and expert input. TPPs were refined via an online Delphi survey with two rounds of input from 68 respondents. TPP characteristics on which <75% of non-industry respondents agreed were further discussed and revised by an expert working group. RESULTS: The need for a test to identify NG in patients with urethral or vaginal discharge was identified as a minimal requirement of TPP1, with a test that can diagnose NG in asymptomatic patients as the optimal requirement. A sensitivity of 80% was considered acceptable, either in context of syndromic management or screening high-risk populations. For TPP2, the agreed minimal requirement was for a test to be used at level 2 healthcare facilities and above, with an optimal requirement of level 1 or above. A lateral flow format was preferred for TPP1, while it was considered likely that TPP2 would require a molecular format. A total of 31 test characteristics were included in TPP1 and 27 in TPP2. CONCLUSIONS: Following the working group revisions, TPPs were posted online for public feedback for two months, and are now finalized. The final TPPs are currently guiding the development of new diagnostics that meet the defined characteristics to reach the market within two years.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Farmacorresistencia Bacteriana , Gonorrea/diagnóstico , Pruebas en el Punto de Atención , Chlamydia trachomatis/aislamiento & purificación , Pruebas Diagnósticas de Rutina , Humanos , Neisseria gonorrhoeae/aislamiento & purificación
18.
Rev Panam Salud Publica ; 44, sept. 2020
Artículo en Español | PAHO-IRIS | ID: phr-52321

RESUMEN

[RESUMEN]. Objetivo. Medir desigualdades sociales en la resistencia antimicrobiana de la Neisseria gonorrhoeae en Colombia. Métodos. Estudio ecológico utilizando un multipanel de datos desagregado a nivel subnacional de los aislamientos en la N. gonorrhoeae como proxy de resistencia antimicrobiana (RAM) entre 2009 y 2018. Se llevó a cabo una caracterización sociodemográfica, un análisis de la sensibilidad antimicrobiana de aislamientos de N. gonorrhoeae, y una medición de desigualdades en la RAM para la N. gonorrhoeae mediante el índice de desigualdad de la pendiente, el índice de desigualdad relativo y el índice de concentración. Resultados. Los hallazgos indican resistencia antimicrobiana de aislamientos de N. gonorrhoeae a penicilina (50,7%) y tetraciclina (67,3%); y la existencia de desigualdades absolutas y relativas durante el período analizado. Las barreras de acceso a servicios de salud, no haber recibido información de prevención de las infecciones de transmisión sexual, necesidades básicas insatisfechas y analfabetismo explicaron las desigualdades en la RAM de la N. gonorrhoeae. Conclusiones. Seis recomendaciones emergen para contener en gran medida la RAM en la N. gonorrhoeae: i) aumentar conciencia sobre la salud sexual y reproductiva segura; ii) repensar cómo entregar mensajes claves con enfoque de equidad; iii) mejorar los sistemas de información, prescripción y cadena de medicamentos; iv) crear coaliciones para mejorar la respuesta y compartir objetivos con el sector privado; v) mejorar la disponibilidad y desagregación de los datos; y vi) apoyar investigaciones en desigualdades en RAM.


[ABSTRACT]. Objective. Measure social inequalities in antimicrobial resistance in Neisseria gonorrhoeae in Colombia. Methods. Ecological study using a multi-panel of data, disaggregated at the subnational level, and using isolations of N. gonorrhoeae as a proxy for antimicrobial resistance (AMR) between 2009 and 2018. A sociodemographic characterization, an analysis of the antimicrobial sensitivity of isolations of N. gonorrhoeae, and a measurement of inequalities in AMR in N. gonorrhoeae were conducted using the slope index of inequality, the relative inequality index, and the concentration index. Results. The findings indicate antimicrobial resistance to penicillin (50.7%) and tetracycline (67.3%) in isolations of N. gonorrhoeae, and the existence of absolute and relative inequalities during the study period. Access barriers to health services, not having received information on the prevention of sexually transmitted infections, basic unmet needs, and illiteracy explained the inequalities in AMR in N. gonorrhoeae. Conclusions. Six recommendations emerged with a view to largely containing AMR in N. gonorrhoeae: i) increase awareness of safe sexual and reproductive health; ii) rethink how to deliver key messages with an equity approach; iii) improve information, prescription, and drug chain systems; iv) form coalitions to improve response and share objectives with the private sector; v) improve the availability and disaggregation of data; and vi) support research on inequalities in AMR.


[RESUMO]. Objetivo. Medir as desigualdades sociais na resistência antimicrobiana de Neisseria gonorrhoeae na Colômbia. Métodos. Estudo ecológico que utilizou um painel múltiplo de dados desagregados ao nível subnacional de isolados de N. gonorrhoeae como substituto para a resistência antimicrobiana (RAM) entre 2009 e 2018. Realizamos uma caracterização sociodemográfica, uma análise da sensibilidade antimicrobiana dos isolados de N. gonorrhoeae e uma medição das desigualdades na RAM para N. gonorrhoeae utilizando o índice absoluto de desigualdade, o índice relativo de desigualdade e o índice de concentração. Resultados. Os resultados indicam a existência de resistência antimicrobiana nos isolados de N. gonorrhoeae à penicilina (50,7%) e à tetraciclina (67,3%), bem como desigualdades absolutas e relativas durante o período analisado. Os obstáculos no acesso aos serviços de saúde, a falta de informações sobre a prevenção de infecções sexualmente transmissíveis, a existência de necessidades básicas não satisfeitas e o analfabetismo explicam as desigualdades na RAM de N. gonorrhoeae. Conclusões. Podem ser feitas seis recomendações para conter em grande medida a RAM de N. gonorrhoeae: i) aumentar a conscientização sobre a saúde sexual e reprodutiva segura, ii) repensar a forma de transmitir as mensagens principais, com foco na equidade, iii) melhorar os sistemas de informação, prescrição e a cadeia de medicamentos, iv) criar coalisões para melhorar a capacidade de resposta e compartilhar objetivos com o setor privado, v) melhorar a disponibilidade e a desagregação de dados e vi) apoiar a pesquisa sobre as desigualdades na RAM.


Asunto(s)
Farmacorresistencia Microbiana , Neisseria gonorrhoeae , Disparidades en el Estado de Salud , Salud Sexual y Reproductiva , Sistemas de Salud , Colombia , Farmacorresistencia Microbiana , Disparidades en el Estado de Salud , Salud Sexual y Reproductiva , Sistemas de Salud , Farmacorresistencia Microbiana , Disparidades en el Estado de Salud , Salud Sexual y Reproductiva , Sistemas de Salud , Colombia
19.
Nat Commun ; 11(1): 4126, 2020 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-32807804

RESUMEN

Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and antibiotic resistance. In contrast with the trend of increasing resistance, clinical isolates that have reverted to susceptibility regularly appear, prompting questions about which pressures compete with antibiotics to shape gonococcal evolution. Here, we used genome-wide association to identify loss-of-function (LOF) mutations in the efflux pump mtrCDE operon as a mechanism of increased antibiotic susceptibility and demonstrate that these mutations are overrepresented in cervical relative to urethral isolates. This enrichment holds true for LOF mutations in another efflux pump, farAB, and in urogenitally-adapted versus typical N. meningitidis, providing evidence for a model in which expression of these pumps in the female urogenital tract incurs a fitness cost for pathogenic Neisseria. Overall, our findings highlight the impact of integrating microbial population genomics with host metadata and demonstrate how host environmental pressures can lead to increased antibiotic susceptibility.


Asunto(s)
Proteínas Bacterianas/metabolismo , Cuello del Útero/microbiología , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Animales , Proteínas Bacterianas/genética , Farmacorresistencia Microbiana/genética , Femenino , Regulación Bacteriana de la Expresión Génica , Estudio de Asociación del Genoma Completo , Humanos , Pruebas de Sensibilidad Microbiana , Mutación/genética , Neisseria gonorrhoeae/metabolismo , Operón/genética , Regiones Promotoras Genéticas/genética
20.
BMC Public Health ; 20(1): 1239, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32795362

RESUMEN

BACKGROUND: Repeat Chlamydia trachomatis (CT) infections are common. To better understand the characteristics of patients frequently infected with CT at our sexually transmitted infection (STI) care services, we assessed the differences between patients repeatedly infected with CT and those who repeatedly tested negative. METHODS: In this cross-sectional analysis of cohort data, we assessed individuals tested for CT at different STI care providers between 2011 and mid-2018 in Southwest Limburg, the Netherlands (n = 17,616). Patients with ≥2 repeat CT infections in the study period were categorized as "patients with repeat CT infections." Multivariable logistic regression analyses were performed for the binary outcome measure: patients with repeat CT infections versus patients who repeatedly tested negative (reference group). Additional analyses were performed for only the STI clinic population. RESULTS: Patients aged < 25 years (OR: 1.83; 95%CI:1.38-2.43), co-infected with HIV (OR: 2.07; 95%CI: 1.02-4.22) or co-infected with Neisseria gonorrhoeae (NG) (OR: 5.04; 95%CI: 3.33-7.63) had more repeat CT infections. In additional analyses among exclusively STI clinic visitors, patients with urogenital symptoms (OR: 2.17; 95%CI: 1.41-3.35), and patients notified for STIs (OR: 4.55; 95%CI: 3.17-6.54) had more frequent repeat CT infections. CONCLUSIONS: Patients aged < 25 years and patients coinfected with HIV or NG had more frequent repeat CT infections, accounting for ~ 20% of the diagnosed CT infections. These patients are likely at the highest risk for transmitting and acquiring CT. Therefore, testing and retesting this group remains important to enhance CT control.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis/aislamiento & purificación , Tamizaje Masivo/estadística & datos numéricos , Adolescente , Adulto , Estudios de Cohortes , Coinfección , Estudios Transversales , Femenino , Gonorrea/epidemiología , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neisseria gonorrhoeae , Países Bajos/epidemiología , Factores de Riesgo , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...