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1.
Aust J Gen Pract ; 53(7): 499-503, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38959520

ABSTRACT

BACKGROUND AND OBJECTIVES: There were 82.4 million new gonorrhoea cases worldwide in 2020. Dual treatment with ceftriaxone or cefixime and azithromycin or doxycycline is currently recommended for gonorrhoea in Indonesia. However, reduced susceptibility and resistance to cephalosporins and azithromycin are increasing. We evaluated the susceptibility pattern of Neisseria gonorrhoeae to cefixime, ceftriaxone, azithromycin and doxycycline. METHOD: N. gonorrhoeae isolates were obtained from 19 male participants with clinically and laboratory-confirmed gonorrhoea. Antibiotic susceptibility testing was conducted by disc diffusion and interpreted according to Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention criteria. RESULTS: Reduced susceptibility or resistance was observed against doxycycline in 19 isolates (100%), cefixime in six (31.6%), ceftriaxone in three (15.8%) and azithromycin in zero (0%) isolates. DISCUSSION: A dual treatment regimen with ceftriaxone and azithromycin can still be recommended as first-line therapy for gonorrhoea in Indonesia. Antibiotic susceptibility surveillance of N. gonorrhoeae should be routinely conducted.


Subject(s)
Anti-Bacterial Agents , Azithromycin , Ceftriaxone , Doxycycline , Gonorrhea , Microbial Sensitivity Tests , Neisseria gonorrhoeae , Humans , Indonesia , Neisseria gonorrhoeae/drug effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Gonorrhea/drug therapy , Male , Microbial Sensitivity Tests/methods , Azithromycin/therapeutic use , Doxycycline/therapeutic use , Ceftriaxone/therapeutic use , Ceftriaxone/pharmacology , Adult , Cefixime/therapeutic use , Cefixime/pharmacology , Primary Health Care/statistics & numerical data , Drug Resistance, Bacterial/drug effects , Drug Therapy, Combination/methods
2.
Article in English | MEDLINE | ID: mdl-38926917

ABSTRACT

Abstract: The Australian National Neisseria Network (NNN) comprises reference laboratories in each state and territory that report data on antimicrobial susceptibility testing to an agreed group of antimicrobial agents for the Australian Gonococcal Surveillance Programme (AGSP). The AGSP data are presented quarterly in tabulated form, as well as in the AGSP annual report. This report presents national gonococcal antimicrobial resistance surveillance data from 1 October to 31 December 2023.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Gonorrhea , Microbial Sensitivity Tests , Neisseria gonorrhoeae , Australia/epidemiology , Neisseria gonorrhoeae/drug effects , Humans , Gonorrhea/epidemiology , Gonorrhea/microbiology , Gonorrhea/drug therapy , Anti-Bacterial Agents/pharmacology , Population Surveillance
3.
Sex Health ; 212024 Jun.
Article in English | MEDLINE | ID: mdl-38935836

ABSTRACT

Background Gonorrhoea infections and antimicrobial resistance are rising in many countries, particularly among men who have sex with men, and an increasing proportion of infection is detected at extragenital sites. This study assessed trends in gonorrhoea diagnoses and antibiotic resistance at a sexual health service in New Zealand that followed national guidelines for specimen collection. Methods Routinely-collected data from Canterbury Health Laboratories of specimens taken at the Christchurch Sexual Health Service 2012-2022 were audited. Descriptive results included the number of patient testing events positive for gonorrhoea per year and site of infection (extragenital/urogenital). Annual test-positivity was calculated (number of positive patient testing events divided by total number of testing events) and the Cochran-Armitage Test for Trend was used to assess whether there was an association between test-positivity and year. Results Of 52,789 patient testing events, 1467 (2.8%) were positive for gonorrhoea (81% male). Half (49.3%) of people (57.9% of males, 12.2% of females) with a gonorrhoea infection had an extragenital infection in the absence of a urogenital infection. The number of extragenital infections increased at a faster rate than urogenital among males. Test-positivity increased from 1.3% in 2012 to 5.8% in 2022 (P Conclusions This study highlights the importance of extragenital sampling and maintaining bacterial culture methods for accurate diagnosis and treatment. The observation that gonorrhoea positivity rate and antimicrobial resistance rates are rising in New Zealand calls for urgent action.


Subject(s)
Gonorrhea , Humans , Gonorrhea/diagnosis , Gonorrhea/epidemiology , New Zealand/epidemiology , Male , Female , Neisseria gonorrhoeae/isolation & purification , Sexual Health/statistics & numerical data , Anti-Bacterial Agents/therapeutic use , Adult , Drug Resistance, Bacterial
4.
Int J Mol Sci ; 25(11)2024 May 26.
Article in English | MEDLINE | ID: mdl-38891969

ABSTRACT

The increasing problem of antimicrobial resistance in N. gonorrhoeae necessitates the development of molecular typing schemes that are suitable for rapid and mass screening. The objective of this study was to design and validate a mini-MLST scheme for N. gonorrhoeae based on global pathogen population data. Using sequences of seven housekeeping genes of 21,402 isolates with known MLSTs from the PubMLST database, we identified eighteen informative polymorphisms and obtained mini-MLST nucleotide profiles to predict MLSTs of isolates. We proposed a new MLST grouping system for N. gonorrhoeae based on mini-MLST profiles. Phylogenetic analysis revealed that MLST genogroups are a stable characteristic of the N. gonorrhoeae global population. The proposed grouping system has been shown to bring together isolates with similar antimicrobial susceptibility, as demonstrated by the characteristics of major genogroups. Established MLST prediction algorithms based on nucleotide profiles are now publicly available. The mini-MLST scheme was evaluated using a MLST detection/prediction method based on the original hydrogel DNA microarray. The results confirmed a high predictive ability up to the MLST genogroup. The proposed holistic approach to gonococcal population analysis can be used for the continuous surveillance of known and emerging resistant N. gonorrhoeae isolates.


Subject(s)
Gonorrhea , Multilocus Sequence Typing , Neisseria gonorrhoeae , Phylogeny , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/classification , Multilocus Sequence Typing/methods , Gonorrhea/microbiology , Gonorrhea/diagnosis , Humans , Bacterial Typing Techniques/methods
5.
Afr J Reprod Health ; 28(4): 90-110, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38904761

ABSTRACT

Despite significant research on the prevalence of STIs in South African men who have sex with men (MSM), recent data on the prevalence and risk factors for curable STI infections among this key populations are limited. This study determined the prevalence of and risk factors associated with Neisseria gonorrhoeae and Chlamydia trachomatis infections among MSM. The sample consisted of 200 MSM resident in Durban. Data were collected using a self-administered questionnaire, and urine samples were collected and tested for N. gonorrhoeae and C. trachomatis. The prevalence of N. gonorrhoeae and C. trachomatis were 3.0% and 6.0%, respectively. Younger age was significantly associated with testing positive for C. trachomatis (p=0.037). Being between the ages of 30-39 years old reduced the risk of acquiring C. trachomatis infection (OR: 0.10, 95% CI: 0.0120-0.7564, p=0.026). In addition, being circumcised reduced the risk of contracting C. trachomatis (adjusted OR: 0.01, 95% CI: 0.0005-0.3516, p=0.01). However, having between 2-4 sex partners increased the risk of testing positive for C. trachomatis (adjusted OR: 107.45, 95% CI: 1.3467-8573.3130, p=0.036). The following factors were significantly associated (p<0.05) with testing positive for N. gonorrhoeae infection: cohabiting with sex partner, engaging in group sex, and drug use. Fear and stigma were the main barriers to accessing health care in the studied population. This study provided evidence of high rates of C. trachomatis infection among MSM resident in Durban. Based on the results, South African MSM, especially the young MSM population, should be given priority when delivering intervention programs to prevent STIs.


Malgré des recherches importantes sur la prévalence des IST chez les hommes sud-africains ayant des rapports sexuels avec des hommes (HSH), les données récentes sur la prévalence et les facteurs de risque d'infections IST curables parmi ces populations clés sont limitées. Cette étude a déterminé la prévalence et les facteurs de risque associés aux infections à Neisseria gonorrhoeae et à Chlamydia trachomatis chez les HARSAH. L'échantillon était composé de 200 HSH résidant à Durban. Les données ont été collectées à l'aide d'un questionnaire auto-administré et des échantillons d'urine ont été collectés et testés pour N. gonorrhoeae et C. trachomatis. La prévalence de N. gonorrhoeae et de C. trachomatis était respectivement de 3,0 % et 6,0 %. Un âge plus jeune était significativement associé à un test positif pour C. trachomatis (p = 0,037). Le fait d'être âgé de 30 à 39 ans réduisait le risque de contracter une infection à C. trachomatis (OR : 0,10, IC à 95 % : 0,0120-0,7564, p = 0,026). De plus, être circoncis réduisait le risque de contracter C. trachomatis (OR ajusté : 0,01, IC à 95 % : 0,0005-0,3516, p=0,01). Cependant, avoir entre 2 et 4 partenaires sexuels augmentait le risque d'être testé positif pour C. trachomatis (OR ajusté : 107,45, IC à 95 % : 1,3467-8573,3130, p=0,036). Les facteurs suivants étaient significativement associés (p < 0,05) au test positif pour l'infection à N. gonorrhoeae : cohabitation avec un partenaire sexuel, participation à des relations sexuelles en groupe et consommation de drogues. La peur et la stigmatisation étaient les principaux obstacles à l'accès aux soins de santé dans la population étudiée. Cette étude a mis en évidence des taux élevés d'infection à C. trachomatis parmi les HSH résidant à Durban. Sur la base des résultats, les HSH sud-africains, en particulier la jeune population HSH, devraient être prioritaires lors de la mise en œuvre de programmes d'intervention visant à prévenir les IST.


Subject(s)
Chlamydia Infections , Chlamydia trachomatis , Gonorrhea , Homosexuality, Male , Neisseria gonorrhoeae , Humans , Male , Gonorrhea/epidemiology , Chlamydia Infections/epidemiology , South Africa/epidemiology , Adult , Prevalence , Risk Factors , Homosexuality, Male/statistics & numerical data , Neisseria gonorrhoeae/isolation & purification , Chlamydia trachomatis/isolation & purification , Young Adult , Sexual Partners , Sexual Behavior , Cross-Sectional Studies , Surveys and Questionnaires , Adolescent
6.
Curr Microbiol ; 81(8): 221, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874629

ABSTRACT

Schaalia turicensis is facultative anaerobic Gram-positive bacillus that commonly inhabits the oropharynx, gastrointestinal, and genitourinary tract of healthy individuals. This organism has been co-isolated with Neisseria gonorrhoeae from 15-year-old Thai male patient with gonococcal urethritis in Bangkok, Thailand. In this study, we characterized the class 1 integron in S. turicensis isolate using whole-genome sequencing and bioinformatics analysis. Sequencing analysis confirmed the presence of an imperfect class 1 integron located on chromosome and a novel 24.5-kb-long composite transposon, named Tn7083. The transposon Tn7083 carried genes encoding chloramphenicol resistance (cmx), sulfonamide resistance (sul1), and aminoglycoside resistance [aph(6)-Id (strB), aph(3'')-Ib (strA), aph(3')-Ia].


Subject(s)
Anti-Bacterial Agents , Genome, Bacterial , Gonorrhea , Urethritis , Humans , Male , Thailand , Urethritis/microbiology , Gonorrhea/microbiology , Anti-Bacterial Agents/pharmacology , Adolescent , Whole Genome Sequencing , Microbial Sensitivity Tests , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/isolation & purification , Neisseria gonorrhoeae/classification , Neisseria gonorrhoeae/drug effects , DNA Transposable Elements/genetics , Drug Resistance, Bacterial/genetics
7.
P R Health Sci J ; 43(2): 68-72, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38860959

ABSTRACT

OBJECTIVE: Monitoring the susceptibility patterns of Neisseria gonorrhoeae is essential for the continuing compliance with current treatment recommendations. Puerto Rico conducts susceptibility tests on N. gonorrhoeae; however, trends on antimicrobial resistance in the island have not been reported since the mid 80's. METHODS: We performed a secondary analysis of a national data repository on the antimicrobial susceptibility of N. gonorrhoeae isolates between 2012 and 2017; a period of time when the CDC recommended a single dose of ceftriaxone and azithromycin for the treatment of uncomplicated gonorrhea. Data on susceptibility to eight antibiotics using the standard disk diffusion method was obtained for 30.0% (84/276) of the samples collected from the Sexually Transmitted Disease clinics in Puerto Rico. We also performed patient demographic analyses linked to resistance. RESULTS: Rates of resistance to ceftriaxone and azithromycin were 0% and 4.0% (2/50), respectively. The percentage of isolates resistant to antimicrobials no longer recommended in Puerto Rico, such as tetracycline, ciprofloxacin, and penicillin, was 86.0% (43/50), 76.0% (38/50), and 38.0% (19/50), respectively. Prevalence of resistant N. gonorrhoeae was higher among men who have sex with men, MSM (79%, 37/47). DISCUSSION: Lack of resistance to ceftriaxone and slow emergence of azithromycin resistance was identified from 2012-2017. It is imperative to continue the surveillance for emerging patterns of resistance, especially for ceftriaxone, as it is part of the current treatment guidelines. Therefore, protocols for culture based surveillance, including sample transport and processing, should be strengthened to ensure quality assured epidemiology of gonococcal resistance in Puerto Rico.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Gonorrhea , Microbial Sensitivity Tests , Neisseria gonorrhoeae , Puerto Rico , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/isolation & purification , Humans , Male , Gonorrhea/drug therapy , Gonorrhea/microbiology , Gonorrhea/epidemiology , Female , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Adult , Young Adult , Azithromycin/pharmacology , Azithromycin/administration & dosage , Ceftriaxone/pharmacology , Adolescent , Middle Aged
8.
Emerg Infect Dis ; 30(7): 1493-1495, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38916864

ABSTRACT

To determine antimicrobial susceptibility of Neisseria gonorrhoeae, we analyzed phenotypes and genomes of 72 isolates collected in Cambodia in 2023. Of those, 9/72 (12.5%) were extensively drug resistant, a 3-fold increase from 2022. Genomic analysis confirmed expansion of newly emerging resistant clones and ongoing resistance emergence across new phylogenetic backbones.


Subject(s)
Anti-Bacterial Agents , Gonorrhea , Microbial Sensitivity Tests , Neisseria gonorrhoeae , World Health Organization , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/genetics , Cambodia/epidemiology , Humans , Gonorrhea/microbiology , Gonorrhea/epidemiology , Gonorrhea/drug therapy , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Phylogeny , Male , Female , Adult
9.
J Infect Public Health ; 17(7): 102447, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38824739

ABSTRACT

BACKGROUND: Current clinical care for common bacterial STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG)) involves empiric antimicrobial therapy when clients are symptomatic, or if asymptomatic, waiting for laboratory testing and recall if indicated. Near-to-patient testing (NPT) can improve pathogen-specific prescribing and reduce unnecessary or inappropriate antibiotic use in treating sexually transmitted infections (STI) by providing same-day delivery of results and treatment. METHODS: We compared the economic cost of NPT to current clinic practice for managing clients with suspected proctitis, non-gonococcal urethritis (NGU), or as an STI contact, from a health provider's perspective. With a microsimulation of 1000 clients, we calculated the cost per client tested and per STI- and pathogen- detected for each testing strategy. Sensitivity analyses were conducted to assess the robustness of the main outcomes. Costs are reported as Australian dollars (2023). RESULTS: In the standard care arm, cost per client tested for proctitis, NGU in men who have sex with men (MSM) and heterosexual men were the highest at $247.96 (95% Prediction Interval (PI): 246.77-249.15), $204.23 (95% PI: 202.70-205.75) and $195.01 (95% PI: 193.81-196.21) respectively. Comparatively, in the NPT arm, it costs $162.36 (95% PI: 161.43-163.28), $158.39 (95% PI: 157.62-159.15) and $149.17 (95% PI: 148.62-149.73), respectively. Using NPT resulted in cost savings of 34.52%, 22.45% and 23.51%, respectively. Among all the testing strategies, substantial difference in cost per client tested between the standard care arm and the NPT arm was observed for contacts of CT or NG, varying from 27.37% to 35.28%. CONCLUSION: We found that NPT is cost-saving compared with standard clinical care for individuals with STI symptoms and sexual contacts of CT, NG, and MG.


Subject(s)
Sexually Transmitted Diseases , Humans , Male , Female , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/economics , Sexually Transmitted Diseases/drug therapy , Gonorrhea/diagnosis , Gonorrhea/economics , Gonorrhea/drug therapy , Australia , Adult , Cost-Benefit Analysis , Chlamydia Infections/diagnosis , Chlamydia Infections/economics , Chlamydia Infections/drug therapy , Chlamydia trachomatis , Neisseria gonorrhoeae/isolation & purification , Mycoplasma genitalium , Mass Screening/economics , Mass Screening/methods , Mycoplasma Infections/diagnosis , Mycoplasma Infections/drug therapy , Mycoplasma Infections/economics , Urethritis/diagnosis , Urethritis/economics , Urethritis/drug therapy , Urethritis/microbiology
10.
Expert Opin Ther Pat ; 34(6): 511-524, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38856987

ABSTRACT

INTRODUCTION: Neisseria gonorrhoeae is a common sexually transmitted disease connected with extensive drug resistance to many antibiotics. Presently, only expanded spectrum cephalosporins (ceftriaxone and cefixime) and azithromycin remain useful for its management. AREAS COVERED: New chemotypes for the classical antibiotic drug target gyrase/topoisomerase IV afforded inhibitors with potent binding to these enzymes, with an inhibition mechanism distinct from that of fluoroquinolones, and thus less prone to mutations. The α-carbonic anhydrase from the genome of this bacterium (NgCAα) was also validated as an antibacterial target. EXPERT OPINION: By exploiting different subunits from the gyrase/topoisomerase IV as well as new chemotypes, two new antibiotics reached Phase II/III clinical trials, zoliflodacin and gepotidacin. They possess a novel inhibition mechanism, binding in distinct parts of the enzyme compared to the fluoroquinolones. Other chemotypes with inhibitory activity in these enzymes were also reported. NgCAα inhibitors belonging to a variety of classes were obtained, with several sulfonamides showing MIC values in the range of 0.25-4 µg/mL and significant activity in animal models of this infection. Acetazolamide and similar CA inhibitors might thus be repurposed as antiinfectives. The scientific/patent literature has been searched for on PubMed, ScienceDirect, Espacenet, and PatentGuru, from 2016 to 2024.


Subject(s)
Anti-Bacterial Agents , Drug Repositioning , Drug Resistance, Bacterial , Gonorrhea , Neisseria gonorrhoeae , Patents as Topic , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/enzymology , Anti-Bacterial Agents/pharmacology , Humans , Animals , Gonorrhea/drug therapy , Gonorrhea/microbiology , Topoisomerase II Inhibitors/pharmacology , Oxazolidinones/pharmacology , Microbial Sensitivity Tests , DNA Topoisomerase IV/antagonists & inhibitors , DNA Topoisomerase IV/metabolism , DNA Gyrase/metabolism , Morpholines , Isoxazoles , Spiro Compounds , Heterocyclic Compounds, 3-Ring , Barbiturates , Acenaphthenes
12.
Sci Rep ; 14(1): 10496, 2024 05 07.
Article in English | MEDLINE | ID: mdl-38714714

ABSTRACT

The use of self-collected specimens as an alternative to healthcare worker-collected specimens for diagnostic testing has gained increasing attention in recent years. This systematic review aimed to assess the diagnostic accuracy of self-collected specimens compared to healthcare worker-collected specimens across different sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), human papillomavirus (HPV), Mycoplasma genitalium (MG), Neisseria gonorrhoea (NG), Treponema pallidum and Trichomonas vaginalis (TV) in females. A rigorous process was followed to screen for studies in various electronic databases. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. There were no studies on syphilis that met the criteria for inclusion in the review. A total of six studies for chlamydia, five studies for HPV, four studies for MG, and seven studies for gonorrhoea and trichomoniasis were included in the review. However, not all studies were included in the sub-group meta-analysis. The analysis revealed that self-collected specimens demonstrated comparable diagnostic accuracy to healthcare worker-collected specimens across most STIs. This indicates that the diagnostic accuracy of self-collected specimens can provide accurate results and enhance access to diagnostic testing, potentially improving healthcare service delivery. Future research should further explore the diagnostic accuracy of self-collected specimens in larger and more diverse populations.


Subject(s)
Health Personnel , Sexually Transmitted Diseases , Specimen Handling , Humans , Female , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/microbiology , Specimen Handling/methods , Neisseria gonorrhoeae/isolation & purification , Gonorrhea/diagnosis , Chlamydia trachomatis/isolation & purification
13.
Expert Rev Anti Infect Ther ; 22(6): 373-377, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781483

ABSTRACT

INTRODUCTION: Neonatal ocular prophylaxis with 0.5% erythromycin ophthalmic ointment is mandated by law in many U.S. states despite its lack of efficacy in preventing chlamydial ophthalmia and the low incidence of gonococcal ophthalmia today. The current shortage of 0.5% erythromycin ophthalmic ointment is bringing into question what alternatives exist for neonatal ocular prophylaxis for the prevention of gonococcal ophthalmia. Providers in states with mandates are concerned with the implications of administering intramuscular ceftriaxone to every newborn. Azithromycin eye drops are being considered as an alternative. AREAS COVERED: This article discusses 1% azithromycin eye drops as an alternative to 0.5% erythromycin ophthalmic ointment. Clinical experience, side effects, resistance, logistics, pharmacokinetics, and pharmacodynamics are considered. EXPERT OPINION: Azithromycin eye drops are not an appropriate alternative to 0.5% erythromycin ophthalmic ointment for ocular prophylaxis. Prenatal screening and treatment of pregnant women is the most effective way to prevent neonatal ophthalmia. Mandates for universal prophylaxis should be withdrawn to avoid unnecessary medication administration, healthcare costs, and potential harm.


Subject(s)
Anti-Bacterial Agents , Azithromycin , Erythromycin , Gonorrhea , Ophthalmia Neonatorum , Ophthalmic Solutions , Humans , Azithromycin/administration & dosage , Azithromycin/pharmacokinetics , Ophthalmic Solutions/administration & dosage , Anti-Bacterial Agents/administration & dosage , United States , Gonorrhea/drug therapy , Gonorrhea/prevention & control , Infant, Newborn , Female , Ophthalmia Neonatorum/prevention & control , Ophthalmia Neonatorum/drug therapy , Pregnancy , Erythromycin/administration & dosage , Antibiotic Prophylaxis/methods , Neisseria gonorrhoeae/drug effects
14.
Int J Infect Dis ; 145: 107082, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38703812

ABSTRACT

OBJECTIVES: Antimicrobial resistance poses a considerable threat in high-antimicrobial-consumption populations, such as men who have sex with men (MSM) taking HIV pre-exposure prophylaxis. While the ResistAZM trial found no increase in macrolide resistance genes in MSM with gonorrhea after azithromycin treatment, the MORDOR trial observed an increase in these genes after mass azithromycin distribution. We hypothesized that this could be due to saturation of the resistome. To test this hypothesis, we compared the abundance of macrolide resistance determinants in anorectal samples between the baselines of the two trials. METHODS: Shotgun metagenome reads from the anorectal baseline samples from the ResistAZM (n = 42) and MORDOR (n = 30) trials were analyzed using AMRPlusPlus. Nonhost reads were mapped to the MEGARes database to detect antibiotic resistance genes (ARG). Antimicrobial resistance (AMR) was normalized using cumulative sum scaling, and ARG abundance was estimated. RESULTS: Macrolide, lincosamides, and streptogramins determinants were approximately 10-fold more abundant in the ResistAZM than the MORDOR samples (P ≤ 0.001). CONCLUSION: The findings are compatible with our hypothesis. Thus, in populations with high-antimicrobial use, the relationship between antimicrobial consumption and AMR may be diminished due to saturation. These findings are vital for future studies investigating the resistogencity of novel interventions, such as doxycycline post-exposure prophylaxis, in populations with high preceding consumption of antimicrobials.


Subject(s)
Anti-Bacterial Agents , Azithromycin , Drug Resistance, Bacterial , Humans , Male , Anti-Bacterial Agents/pharmacology , Azithromycin/pharmacology , Drug Resistance, Bacterial/genetics , Gonorrhea/microbiology , Gonorrhea/drug therapy , Homosexuality, Male , Macrolides/pharmacology , Lincosamides/pharmacology , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/genetics , Streptogramins/pharmacology , HIV Infections/drug therapy , Adult , Pre-Exposure Prophylaxis , Metagenome
15.
PLoS One ; 19(5): e0302785, 2024.
Article in English | MEDLINE | ID: mdl-38768150

ABSTRACT

INTRODUCTION: The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the oropharynx and rectum for men who have sex with men (MSM), and because at-home self-collected swabs for these infections are not licensed by Health Canada or the United States Food and Drug Administration, decreased accessed to in-person care during and since the COVID19 pandemic potentially means missed case findings. OBJECTIVES: To evaluate the performance of at-home self-collected pharyngeal and rectal swabs for gonorrhea and chlamydia nucleic acid amplification testing. METHODOLOGY: All persons who contacted our Sexual Health Clinic and who had a clinical indication to complete oral and/or rectal swabs for gonorrhea and chlamydia were invited to complete at-home swabs in advance of their scheduled appointments. We mailed swabs and instructions to those who consented. Participants brought these swabs to their scheduled in clinic appointments, where we repeated the same swabs. All matching swabs were sent to the laboratory for analysis to determine concordance. RESULTS: From September 8, 2022 to July 18, 2023, we enrolled 296 eligible participants who provided 1184 swabs. For analysis, cancelled specimens and specimens with invalid results were excluded, leaving 1032 swabs for comparison. We identified 66 STI diagnoses in 47 unique participants. Overall accuracy was high (exceeding 99%), except for rectal chlamydia, which was 96.0%. While the performance of self-swabs for chlamydia was lower compared to gonorrhea, at-home swabs identified six chlamydia infections that were missed by in-clinic collected swabs (two pharyngeal, four rectal). Removing these six cases as "false positives" increased overall accuracy for chlamydia detection to 99.7% (pharyngeal) and 97.8% (rectal). CONCLUSION: Self-collected at-home swabs had good performance acceptable for gonorrhea and chlamydia nucleic acid amplification testing.


Subject(s)
Chlamydia Infections , Chlamydia trachomatis , Gonorrhea , Neisseria gonorrhoeae , Pharynx , Rectum , Specimen Handling , Humans , Chlamydia trachomatis/isolation & purification , Chlamydia trachomatis/genetics , Chlamydia Infections/diagnosis , Chlamydia Infections/microbiology , Gonorrhea/diagnosis , Gonorrhea/microbiology , Male , Neisseria gonorrhoeae/isolation & purification , Neisseria gonorrhoeae/genetics , Rectum/microbiology , Pharynx/microbiology , Specimen Handling/methods , Adult , Female , Nucleic Acid Amplification Techniques/methods , Homosexuality, Male , Middle Aged , Self Care , Young Adult
16.
J Med Chem ; 67(11): 9613-9627, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38776401

ABSTRACT

The development of antibacterial drugs with new mechanisms of action is crucial in combating the rise of antibiotic-resistant infections. Bacterial carbonic anhydrases (CAs, EC 4.2.1.1) have been validated as promising antibacterial targets against pathogens such as Helicobacter pylori, Neisseria gonorrhoeae, and vancomycin-resistant enterococci. A multitarget strategy is proposed to design penicillin-based CA inhibitor hybrids for tackling resistance by targeting multiple bacterial pathways, thereby resensitizing drug-resistant strains to clinical antibiotics. The sulfonamide derivatives potently inhibited the CAs from N. gonorrhoeae and Escherichia coli with KI values in the range of 7.1-617.2 nM. Computational simulations with the main penicillin-binding protein (PBP) of N. gonorrhoeae indicated that these hybrid derivatives maintained the mechanism of action of the lead ß-lactams. A subset of derivatives showed potent PBP-related antigonococcal effects against multidrug-resistant N. gonorrhoeae strains, with several compounds significantly outperforming both the lead ß-lactam and CA inhibitor drugs (MIC values in the range 0.25 to 0.5 µg/mL).


Subject(s)
Anti-Bacterial Agents , Carbonic Anhydrase Inhibitors , Carbonic Anhydrases , Microbial Sensitivity Tests , Neisseria gonorrhoeae , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/enzymology , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Carbonic Anhydrases/metabolism , Penicillins/pharmacology , Penicillins/chemistry , Drug Resistance, Multiple, Bacterial/drug effects , Structure-Activity Relationship , Humans , Sulfonamides/pharmacology , Sulfonamides/chemistry , Sulfonamides/chemical synthesis , Molecular Structure , Escherichia coli/drug effects , Escherichia coli/enzymology
17.
Front Cell Infect Microbiol ; 14: 1407863, 2024.
Article in English | MEDLINE | ID: mdl-38808060

ABSTRACT

The genus Neisseria, which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic Neisseria species are closely related but cause quite different diseases, meningococcal sepsis and meningitis (Neisseria meningitidis) and sexually transmitted gonorrhea (Neisseria gonorrhoeae). Although obvious differences in bacterial niches and mechanisms for transmission exists, pathogenic Neisseria have high levels of conservation at the levels of nucleotide sequences, gene content and synteny. Species of Neisseria express broad-spectrum O-linked protein glycosylation where the glycoproteins are largely transmembrane proteins or lipoproteins localized on the cell surface or in the periplasm. There are diverse functions among the identified glycoproteins, for example type IV biogenesis proteins, proteins involved in antimicrobial resistance, as well as surface proteins that have been suggested as vaccine candidates. The most abundant glycoprotein, PilE, is the major subunit of pili which are an important colonization factor. The glycans attached can vary extensively due to phase variation of protein glycosylation (pgl) genes and polymorphic pgl gene content. The exact roles of glycosylation in Neisseria remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to evade the human immune system. In addition, pathogenic and commensal Neisseria appear to have significant glycosylation differences. Here, the current knowledge and implications of protein glycosylation genes, glycan diversity, glycoproteins and immunogenicity in pathogenic Neisseria are summarized and discussed.


Subject(s)
Neisseria gonorrhoeae , Neisseria meningitidis , Humans , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Glycoproteins/metabolism , Glycoproteins/genetics , Glycosylation , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/metabolism , Neisseria gonorrhoeae/pathogenicity , Neisseria gonorrhoeae/immunology , Neisseria meningitidis/genetics , Neisseria meningitidis/metabolism , Polysaccharides/metabolism , Meningitis, Meningococcal/microbiology , Gonorrhea/microbiology
18.
Front Cell Infect Microbiol ; 14: 1384611, 2024.
Article in English | MEDLINE | ID: mdl-38808065

ABSTRACT

Neisseria gonorrhoeae (Ng) is a uniquely adapted human pathogen and the etiological agent of gonorrhea, a sexually transmitted disease. Ng has developed numerous mechanisms to avoid and actively suppress innate and adaptive immune responses. Ng successfully colonizes and establishes topologically distinct colonies in human macrophages and avoids phagocytic killing. During colonization, Ng manipulates the actin cytoskeleton to invade and create an intracellular niche supportive of bacterial replication. The cellular reservoir(s) supporting bacterial replication and persistence in gonorrhea infections are poorly defined. The manner in which gonococci colonize macrophages points to this innate immune phagocyte as a strong candidate for a cellular niche during natural infection. Here we investigate whether nutrients availability and immunological polarization alter macrophage colonization by Ng. Differentiation of macrophages in pro-inflammatory (M1-like) and tolerogenic (M2-like) phenotypes prior to infection reveals that Ng can invade macrophages in all activation states, albeit with lower efficiency in M1-like macrophages. These results suggest that during natural infection, bacteria could invade and grow within macrophages regardless of the nutrients availability and the macrophage immune activation status.


Subject(s)
Macrophages , Neisseria gonorrhoeae , Nutrients , Neisseria gonorrhoeae/immunology , Macrophages/microbiology , Macrophages/immunology , Humans , Gonorrhea/microbiology , Gonorrhea/immunology , Macrophage Activation , Host-Pathogen Interactions/immunology
19.
Forensic Sci Int ; 360: 112070, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38810590

ABSTRACT

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are the most common bacterial sexually transmitted infections (STIs) worldwide. These STIs are frequently asymptomatic, which often delays diagnosis and treatment with the risk of serious long-term complications. Current French recommendations call for targeted screening of populations considered to be at risk, including victims of sexual assault. However, no recent data on the prevalence of these STIs in this population are available in France. The aim of this study was therefore to determine the prevalence of CT/NG infections among victims of sexual assault attending three Clinical Forensic Units (CFUs). METHODS: We retrospectively reviewed the forensic records of patients aged over 12 years reporting a sexual assault and referred between January 1, 2020 and December 31, 2021 to the CFU of Montpellier, Angers or Saint-Denis de La Réunion. Patients who had been screened for CT and NG infections were included. RESULTS: 341 alleged victims of sexual assault (324 women, 17 men, median age = 23 years) were screened for CT/NG STIs during the inclusion period (Montpellier, n=196; Angers, n=63; Saint-Denis, n=82). The median time between the sexual assault and the examination was 1 day. CT and NG were detected in 28 patients (8.2 %) and 8 patients (2.3 %) respectively, with no men tested positive. Positive results concerned genital samples, except for two CT-positive anorectal samples and one NG-positive oropharyngeal sample. Two patients (0.6 %) were co-infected with CT/NG. The overall prevalence of CT/NG STIs was 10.0 % and was higher in the 18-24 age group, reaching 13.2 % for CT. CONCLUSIONS: This multicenter study confirms the high prevalence of CT/NG STIs in victims of sexual assault, and the vulnerability of the youngest age groups to these infections. Systematic screening for CT/NG STIs at the time of the forensic examination is the key to early diagnosis and effective treatment to prevent transmission and subsequent complications in these patients.


Subject(s)
Chlamydia Infections , Chlamydia trachomatis , Crime Victims , Gonorrhea , Neisseria gonorrhoeae , Humans , Female , France/epidemiology , Male , Gonorrhea/epidemiology , Gonorrhea/diagnosis , Chlamydia Infections/epidemiology , Chlamydia Infections/diagnosis , Retrospective Studies , Adult , Prevalence , Crime Victims/statistics & numerical data , Young Adult , Chlamydia trachomatis/isolation & purification , Adolescent , Neisseria gonorrhoeae/isolation & purification , Sex Offenses/statistics & numerical data , Middle Aged , Child , Forensic Medicine
20.
Sex Transm Dis ; 51(6): 388-392, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38733972

ABSTRACT

BACKGROUND: Standard-of-care nucleic acid amplification tests (routine NAATs) for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) can take several days to result and therefore delay treatment. Rapid point-of-care GC/CT NAAT (rapid NAAT) could reduce the time to treatment and therefore onward transmission. This study evaluated the incremental cost per infectious day averted and overall cost of implementation associated with rapid compared with routine NAAT. METHODS: Prospective sexually transmitted infection (STI) treatment data from men who have sex with men and transgender women in San Diego who received rapid NAAT between November 2018 and February 2021 were evaluated. Historical time from testing to treatment for routine NAAT was abstracted from the literature. Costs per test for rapid and routine NAAT were calculated using a micro-costing approach. The incremental cost per infectious day averted comparing rapid to routine NAAT and the costs of rapid GC/CT NAAT implementation in San Diego Public Health STI clinics were calculated. RESULTS: Overall, 2333 individuals underwent rapid NAAT with a median time from sample collection to treatment of 2 days compared with 7 to 14 days for routine NAAT equating to a reduction of 5 to 12 days. The cost of rapid and routine GC/CT NAAT was $57.86 and $18.38 per test, respectively, with a cost-effectiveness of between $2.43 and $5.82 per infectious day averted. The incremental cost of rapid NAAT improved when at least 2000 tests were performed annually. CONCLUSIONS: Although rapid GC/CT NAAT is more expensive than routine testing, the reduction of infectious days between testing and treatment may reduce transmission and provide improved STI treatment services to patients.


Subject(s)
Chlamydia Infections , Chlamydia trachomatis , Gonorrhea , Homosexuality, Male , Neisseria gonorrhoeae , Nucleic Acid Amplification Techniques , Humans , Male , Gonorrhea/diagnosis , Gonorrhea/economics , Chlamydia Infections/diagnosis , Chlamydia Infections/economics , Nucleic Acid Amplification Techniques/economics , Neisseria gonorrhoeae/isolation & purification , Chlamydia trachomatis/isolation & purification , Adult , California/epidemiology , Cost-Benefit Analysis , Prospective Studies , Female , Point-of-Care Testing/economics , Transgender Persons
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