Search Results (36)

Background: There is an urgent need for novel treatment options for Neisseria gonorrhoeae. Methenamine is an interesting urinary antiseptic with a very low propensity to induce antimicrobial resistance. Methods: We assessed the MICs of methenamine-hippurate for 18 N. gonorrhoeae isolates. We then assessed the in vivo efficacy of methenamine-hippurate against N. gonorrhoeae using the Galleria mellonella infection model. Results: We found that all the gonococcal isolates had a methenamine-hippurate MIC of 300 mg/L. This MIC was not higher in isolates with higher ceftriaxone MICs. No toxicity of methenamine at the doses tested was found, and doses as low as 200 mg/kg were effective in the G. mellonella model. Conclusions: Further studies in mice and humans are required to assess if methenamine-hippurate could be used to treat gonococcal urethritis alone or in combination with other agents such as ceftriaxone. Full article

Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of N. gonorrhoeae infection are required as resistance to current antibiotics is widespread. Toxin–antitoxin (TA) systems modulate bacterial physiology by interfering with vital cellular processes; type II TA systems, where both toxin and antitoxin are proteins, are the best-studied. Bioinformatics analysis revealed genes encoding an uncharacterized type II HicAB TA system in the N. gonorrhoeae strain FA1090 chromosome, which were also present in >83% of the other gonococcal genome sequences examined. Gonococcal HicA overproduction inhibited bacterial growth in Escherichia coli, an effect that could be counteracted by the co-expression of HicB. Kill/rescue assays showed that this effect was bacteriostatic rather than bactericidal. The site-directed mutagenesis of key histidine and glycine residues (Gly22, His24, His29) abolished HicA-mediated growth arrest. N. gonorrhoeae FA1090∆hicAB and complemented derivatives that expressed IPTG-inducible hicA, hicB, or hicAB, respectively, grew as wild type, except for IPTG-induced FA1090∆hicAB::hicA. RT-PCR demonstrated that hicAB are transcribed in vitro under the culture conditions used. The deletion of hicAB had no effect on biofilm formation. Our study describes the first characterization of a HicAB TA system in N. gonorrhoeae. Full article

Background/Objectives: Neisseria gonorrhoeae is the third most common sexually transmitted infection (STI), which may become untreatable soon if resistance continues to drastically increase. Due to increases in resistance to recommended antibiotics, alternative sources of novel compounds to combat this threat are being explored. Interestingly, marine sponges have proven to produce a plethora of bioactive compounds that display anticancer, antiviral, antifungal, and antibacterial activity. Methods: In this study, the extracts of the sponge collected from Saint Thomas, US Virgin Islands were examined to determine their antibacterial activity against E. coli, S. aureus, and N. gonorrhoeae. Results: The ethyl acetate sponge extracts significantly inhibited growth of N. gonorrhoeae, while none inhibited S. aureus and E. coli. The bioassay-guided purification of the ethyl acetate extract resulted in the isolation of 6-desmethyl-6-ethylspongosoritin A (1) and plakortone B (2). To determine if the pure sponge metabolite could improve the efficacy of ceftriaxone against a high-level ceftriaxone (HTX)-resistant gonococcal strain, an antibiotic checkerboard assay was done by combining various concentrations of either precursor fractions or the purified compound 2 with ceftriaxone. Plakortone B (2) and ceftriaxone acted in synergy against gonococcal strains and inhibited growth by increasing membrane permeability when exposed for 4 h and 24 h. Conclusions: This suggests that marine sponges may serve as a source for novel bioactive compounds against antibiotic-resistant strains of N. gonorrhoeae, as well as improve the efficacy of currently prescribed antibiotics. Full article

Background and Objectives: Neisseria gonorrhoeae and Chlamydia trachomatis can cause similar clinical syndromes and may coexist in infections. In emergency medicine, empirical treatment targeting both pathogens is often employed, potentially contributing to antibiotic resistance. Gonococcal resistance has emerged against first-line antimicrobials, necessitating prior testing for fluoroquinolone susceptibility. Certest Biotec developed two molecular diagnostic products for simultaneous detection: VIASURE C. trachomatis & N. gonorrhoeae Real-Time PCR Detection Kit and VIASURE Neisseria gonorrhoeae Ciprofloxacin-Resistant Real-Time PCR Detection Kit. To evaluate these products, clinical performance assessments were conducted at the Clinical Microbiology Laboratory of Miguel Servet University Hospital in Zaragoza, Spain. Results and Conclusions: Both VIASURE assays under study demonstrated high clinical sensitivity and specificity compared to reference molecular assays and Sanger sequencing. These kits offer an accurate diagnosis, facilitating appropriate treatment choices while addressing concerns about emerging antibiotic resistance. Methods: A total of 540 clinical samples from 540 patients already characterized as positive or negative for CT and NG by a molecular assay and by antibiotic susceptibility testing for ciprofloxacin using a concentration gradient diffusion method were used for the clinical evaluation. In cases where sensitivity results were unavailable, conventional PCR and Sanger sequencing were employed. Full article

Neisseria gonorrhoeae (NG) has developed resistance to nearly all antibiotics used for its treatment. However, very limited data are available regarding the antimicrobial resistance of NG isolates among MSM in Poland. The aim of this study was to evaluate the susceptibility of Neisseria gonorrhoeae isolates in this key population. We investigated the antimicrobial susceptibility of NG isolates to six antimicrobials (ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin). Minimum inhibitory concentrations (MICs; mg/L) were determined using Etests on gonococcal isolates. One hundred high-risk MSM were included in the study (25 HIV-positive and 75 HIV-negative using pre-exposure prophylaxis for HIV). The rate of NG infection was 28%. All NG isolates were susceptible to cefixime and ceftriaxone. Susceptibility to azithromycin was found in 69.2% (18/26) of the NG isolates and resistance in 30.8% (8/26) of NG isolates. Susceptibility to tetracycline was found in 50% (13/26) of the isolates and resistance in 50% (13/26) of the isolates. We observed gonorrhea to be more prevalent in patients with a higher number of oral sexual contacts. Increasing azithromycin resistance is especially concerning for future treatment options, especially if ceftriaxone/cefixime resistance starts to develop and for people with beta-lactam antibiotics allergies. Doxy-PEP might lose its partial efficacy for NG soon. Full article

A new Italian intersociety position statement on the prevention of ophthalmia neonatorum was published in 2023. In this document, attention was paid to the indications for the screening of gonococcal and chlamydial infections during pregnancy according to the international and national guidelines for the prevention of sexually transmitted infections (STIs). We conducted an observational retrospective study to assess whether the current guidelines for the prevention of STIs are being followed correctly. From February to August 2022, 2507 women nearing childbirth were enrolled. Among them, 42.4% received a swab for Chlamydia and only 0.5% for gonococcus. Concerning the geographical area of origin, most of the screened women came from Western Europe. None of the women who received gonococcal swabs and only 105 women out of 1062 screened for Chlamydia were under 25 years of age. Overall, only seven swabs were positive for Chlamydia, while none were positive for gonococcus. Concerning the age, geographical area of origin, and medical history of the women with a positive screening for Chlamydia, all were over 25 years old, six were from Western Europe, one was from South America, and none had other STIs. Although monocentric in nature, this study shows that the guidelines are not being followed correctly. Full article

The antimicrobial resistance of Neisseria gonorrhoeae (NG) is an increasing public health concern, highlighted by the fact that gonococcus is considered as a ‘high’-priority pathogen by the WHO for research and development of new therapeutic options. According to the data of the European Centre for Disease Prevention and Control (ECDC) in 2022, the rate of NG infections is the highest recorded since European surveillance of sexually transmitted infections began in 2009. We report a brief description of a patient infected with two different isolates of drug-resistant N. gonorrhoeae. N. gonorrhoeae cultures were positive from oropharyngeal and urethral swabs and isolates had different antimicrobial susceptibility. We investigated the antimicrobial susceptibility of these isolates to six antimicrobials (ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin), and minimum inhibitory concentrations (MICs; mg/L) were determined using Etest on gonococcal isolates. Oropharyngeal isolate was resistant to azithromycin while urethral was resistant to penicillin, ciprofloxacin, and tetracycline. Two different and phylogenetically distinct sequence types of NG isolates were identified. Understanding the dynamics and drivers of resistance spread can provide an improved rationale for antibiotic management, and the level of NG resistance should be monitored closely. Full article

Mycoplasma genitalium (M. genitalium) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance remain limited. This is the first study from Croatia that aimed to assess the prevalence and trends of resistance in M. genitalium strains isolated from male individuals by detecting macrolide and fluoroquinolone resistance genes. The study also aimed to explore the factors associated with resistance and changes in resistance patterns over time. Urine samples collected from male individuals in the Zagreb County and northwest region of Croatia between 2018 and 2023 were tested for M. genitalium with the use of molecular methods. Positive samples were subjected to DNA extraction and multiplex tandem polymerase chain reaction (MT-PCR) targeting genetic mutations associated with macrolide (23S rRNA gene) and fluoroquinolone (parC gene) resistance. Of the 8073 urine samples tested from 6480 male individuals (and following the exclusion of repeated specimens), we found that the prevalence of M. genitalium infection was 2.2%. Macrolide resistance was observed in 60.4% of strains, while fluoroquinolone resistance was found in 19.2%. Co-resistance to both antibiotics was present in 18.2% of cases. A statistically significant increase in fluoroquinolone resistance was noted over the study period (p = 0.010), but this was not evident for azithromycin resistance (p = 0.165). There were no statistically significant differences in resistance patterns between age groups, whereas re-testing of patients revealed dynamic changes in resistance profiles over time. The high burden of macrolide resistance and increasing fluoroquinolone resistance underscore the urgent need for comprehensive resistance testing and surveillance programs. The implementation of resistance-guided treatment strategies, along with enhanced access to molecular diagnostics, is pivotal for effectively managing M. genitalium infections. Full article

Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, poses a significant global public health threat. Infection in women can be asymptomatic and may result in severe reproductive complications. Escalating antibiotic resistance underscores the need for an effective vaccine. Approaches being explored include subunit vaccines and outer membrane vesicles (OMVs), but an ideal candidate remains elusive. Meningococcal OMV-based vaccines have been associated with reduced rates of gonorrhea in retrospective epidemiologic studies, and with accelerated gonococcal clearance in mouse vaginal colonization models. Cross-protection is attributed to shared antigens and possibly cross-reactive, bactericidal antibodies. Using a Candidate Antigen Selection Strategy (CASS) based on the gonococcal transcriptome during human mucosal infection, we identified new potential vaccine targets that, when used to immunize mice, induced the production of antibodies with bactericidal activity against N. gonorrhoeae strains. The current study determined antigen recognition by human sera from N. gonorrhoeae-infected subjects, evaluated their potential as a multi-antigen (combination) vaccine in mice and examined the impact of different adjuvants (Alum or Alum+MPLA) on functional antibody responses to N. gonorrhoeae. Our results indicated that a stronger Th1 immune response component induced by Alum+MPLA led to antibodies with improved bactericidal activity. In conclusion, a combination of CASS-derived antigens may be promising for developing effective gonococcal vaccines. Full article

Sexually transmitted infections (STIs) constitute one of the leading causes of disease burden worldwide, leading to considerable morbidity, mortality, health expenditures, and stigma. Of note are the most common bacterial STIs, chlamydial and gonococcal infections, whose etiological agents are Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), respectively. Despite being usually asymptomatic, in some cases these infections can be associated with long-term severe complications, such as pelvic inflammatory disease, chronic pelvic pain, infertility, ectopic pregnancy, and increased risk of other STIs acquisition. As the symptoms, when present, are usually similar in both infections, and in most of the cases these infections co-occur, the dual-test strategy, searching for both pathogens, should be preferred. In line with this, herein we focus on the main aspects of CT and NG infections, the clinical symptoms as well as the appropriate state-of-the-art diagnostic tests and treatment. Cost-effective strategies for controlling CT and NG infections worldwide are addressed. The treatment for both infections is based on antibiotics. However, the continuing global rise in the incidence of these infections, concomitantly with the increased risk of antibiotics resistance, leads to difficulties in their control, particularly in the case of NG infections. We also discuss the potential mechanism of tumorigenesis related to CT infections. The molecular bases of CT and NG infections are addressed, as they should provide clues for control or eradication, through the development of new drugs and/or effective vaccines against these pathogens. Full article

The goal of this work was to determine the factors affecting the emergence of azithromycin-resistant Neisseria gonorrhoeae isolates in Russia, where azithromycin was never recommended for the treatment of gonococcal infections. Clinical N. gonorrhoeae isolates collected in 2018–2021 (428 isolates) were analyzed. No azithromycin-resistant isolates were found in 2018–2019, but in 2020–2021, a significant increase in the ratio of azithromycin-resistant isolates was observed: 16.8% and 9.3%, respectively. A hydrogel DNA microarray was developed for the analysis of resistance determinants: mutations in the genes encoding the mtrCDE efflux system and in all four copies of the 23S rRNA gene (position 2611). A majority of the azithromycin-resistant Russian isolates belonged to the NG-MAST G12302 genogroup, and the resistance was associated with the presence of a mosaic structure of the mtrR gene promoter region with the −35 delA deletion, an Ala86Thr mutation in the mtrR gene, and a mosaic structure of the mtrD gene. A comparative phylogenetic study of modern Russian and European N. gonorrhoeae populations allowed us to conclude that the emergence of azithromycin resistance in Russia in 2020 was the result of the appearance and spread of European N. gonorrhoeae strains belonging to the G12302 genogroup due to possible cross-border transfer. Full article

The aim of this work was to study the resistance to macrolides (azithromycin) in the modern Russian population of N. gonorrhoeae with the analysis of genetic resistance determinants. Azithromycin is not used to treat gonococcal infection in Russia. However, among 162 isolates collected in 2020–2021, 22 isolates (13.6%) were phenotypically resistant to azithromycin. Mutations in 23S rRNA genes were found only in two isolates; erm and mefA genes were absent. Azithromycin resistance was shown to be predominantly associated with mutations in the mtrR and mtrD genes of the MtrCDE efflux pump and their mosaic alleles which may have formed due to a horizontal transfer from N. meningitidis. A total of 30 types of mtrR alleles and 10 types of mtrD alleles were identified including mosaic variants. Matching between the mtrR and mtrD alleles was revealed to indicate the cooperative molecular evolution of these genes. A link between the mtrR and mtrD alleles and NG-MAST types was found only for NG-MAST 228 and 807, typical of N. gonorrhoeae in Russia. The high level of resistance to azithromycin in Russia may be related to the spread of multiple transferable resistance to antimicrobials regardless of their use in the treatment of gonococcal infection. Full article

We determined the prevalence and reported risk factors associated with sexually transmitted and reproductive tract infections (STI/RTIs) among patients who presented with genital symptoms in STI/outpatient department (OPD) clinics in two regional referral hospitals and six health centres in six regions in Tanzania. Methods: The patients were consecutively recruited, and the data collection was conducted in eight health care facilities from 2014 to 2016. Genital swabs were collected for the detection of the aetiological pathogens of STI/RTIs. Results: A total of 1243 participants were recruited in the study; the majority (1073, 86%) were women. The overall median age was 27.8. The prevalence of Neisseria gonorrhoeae was 25.7% (319/1243), with proportions of 50.9 and 21.5% for men and women, respectively, of Chlamydia trachomatis 12.9% (160/1241) and Mycoplasma genitalium 4.7% (53/1134). Unmarried men were more often likely to be infected with gonococcal infections as compared to their women counterparts (57.9 vs. 24.1%) p < 0.001. The majority presented with genital discharge syndrome (GDS) 93.6% (1163/1243), genital ulcer disease (GUD) 13.0% (162/1243) and GDS + GUD 9.6% (119/1243). GDS was more common in the health centres, 96.1% (1195/1243), vs. the regional referral hospitals, 92.2% (1146/1243) (p = 0.01), but those reported to the regional referral hospitals were more likely to be infected with N. gonorrhoeae (OR = 2.5) and C. trachomatis (OR = 2.1) than those from the health centres (p < 0.001). The prevalence of bacterial vaginosis (BV) and vaginal candidiasis (VC) was 24.1 and 10.4%, respectively. Interestingly, unmarried and BV-positive women were less likely to be infected with VC (p = 0.03), though VC was strongly inversely associated with an N. gonorrhoeae infection (p < 0.001). High proportions of N. gonorrhoeae (51.1%) and C. trachomatis (23.3%) were found in the Dodoma and Dar es Salaam regions, respectively. M. genitalium (7.6%) was found to be the highest in Mwanza. Conclusion: We reported a high prevalence of STI/RTIs. The findings suggest that these infections are common and prevalent in STI/OPD clinics in six regions of Tanzania. We recommend surveillance to be conducted regularly to elucidate the true burden of emerging and classical STI/RTIs by employing modern and advanced laboratory techniques for the detection and monitoring of STI/RTIs in low- and high-risk populations, including the community settings. Full article

Neisseria gonorrhoeae is one of the most frequent etiologic agents of STDs (sexually transmitted diseases). Untreated asymptomatic gonococcal infection in women can lead to spreading of the infection in the sexually active population and could lead to late consequences, such as sterility or ectopic pregnancies. One important issue about N. gonorrhoeae is its increasing resistance to antibiotics. This paper summarized the newest molecular antimicrobial resistance (AMR) detection assays for Neisseria gonorrhoeae connected with the latest therapeutic antimicrobials and gonococcal vaccine candidates. The assays used to detect AMR varied from the classical minimal inhibitory concentration (MIC) detection to whole-genome sequencing. New drugs against multi drug resistant (MDR) N. gonorrhoeae have been proposed and were evaluated in vivo and in vitro as being efficient in decreasing the N. gonorrhoeae burden. In addition, anti-N. gonorrhoeae vaccine candidates are being researched, which have been assessed by multiple techniques. With the efforts of many researchers who are studying the detection of antimicrobial resistance in this bacterium and identifying new drugs and new vaccine candidates against it, there is hope in reducing the gonorrhea burden worldwide. Full article

Neisseria gonorrhoeae (gonococcus) and Neisseria meningitidis (meningococcus) are important global pathogens which cause the sexually transmitted diseases gonorrhea and meningitis, respectively, as well as sepsis. We prepared a review according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), with the aims of (a) evaluating the data on the MenB vaccination as protection against sexually transmitted infections by N. gonorrhoeae and (b) to briefly comment on the data of ongoing studies of new vaccines. We evaluated existing evidence on the effect of 4CMenB, a multi-component vaccine, on invasive diseases caused by different meningococcal serogroups and on gonorrhea. Non-B meningococcal serogroups showed that the 4CMenB vaccine could potentially offer some level of protection against non-B meningococcal serogroups and N. gonorrhoeae. The assessment of the potential protection conferred by 4CMenB is further challenged by the fact that further studies are still needed to fully understand natural immune responses against gonococcal infections. A further limitation could be the potential differences between the protection mechanisms against N. gonorrhoeae, which causes local infections, and the protection mechanisms against N. meningitidis, which causes systemic infections. Full article