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Background Neisseria gonorrheae and Chlamydia trachomatis are associated with mucosal inflammation and human immunodeficiency virus 1 (HIV-1) transmission. We assessed levels of inflammatory cytokines in men who have sex with men (MSM) with and without rectal gonorrhea and/or chlamydia in Lima, Peru. Methods We screened 605 MSM reporting condomless receptive anal intercourse for rectal N. gonorrheae / C. trachomatis using nucleic acid testing. We identified 101 cases of gonorrhea and/or chlamydia and randomly selected 50 N. gonorrheae / C. trachomatis positive cases and matched 52 negative controls. We measured levels of IL-1β, IL-6, IL-8, and TNF-α in rectal secretions. Tests for HIV-1, rectal N. gonorrheae / C. trachomatis , and mucosal cytokines were repeated after 3 and 6 months. Cytokine levels in cases and uninfected controls were compared using Wilcoxon rank-sum tests and linear regression. Results MSM with gonorrhea/chlamydia had elevated levels of all cytokines in rectal mucosa compared with matched controls (all P values <.001). Following antibiotic treatment there were no significant differences in cytokine levels at 3- or 6-month follow-up evaluations (all P values >.05). Discussion Rectal gonorrhea/chlamydia infection is associated with transient mucosal inflammation and cytokine recruitment. Our data provide proof of concept for rectal sexually transmitted infection screening as an HIV prevention strategy for MSM. Clinical Trials Registration. NCT03010020. [ABSTRACT FROM AUTHOR]

Background: Neisseria gonorrhoeae is a gram negative diplococci which causess a sexually transmitted infection. N. gonorrhoeae is an obligate human pathogen that causes infection to the mucussecreting epithelial cells both in male and female. In 2017, the centre of disease control and World Health Organization published the list of global priority pathogens with denting therapeutic options, including antibiotic-resistant N. gonorrhoeae. During the covid-19 pandemic, excessive use of antibiotics led to raise of drug resistance. The infection is widespread and intractable. If this happens, more people will be left with an incurable infection which may cause serious health problems. Results: We characterized zoliflodacin thoroughly. Here is discussed the clinical trials and side effects on human health by searching different keywords like “zoliflodacin”, “covid-19”, “clinical trials” from different data sources like Pub-Med, Google-Scholar, and Science-Direct. Zoliflodacin targets antibiotic-resistant N. gonorrhoeae. Zoliflodacin is mainly known based on its therapeutic effects against N. gonorrhoeae. It acts by inhibiting bacterial type 2 topoisomerase with binding site in bacterial gyrase. Zoliflodacin is effective in treating gonococcal urogenital and rectal infection. Conclusion: Antibiotic is the only option to treat N. gonorrhoeae. There is no vaccine available to treat gonorrhea. The new drug, zoliflodacin, specifically targets antibiotic-resistant gonorrhea and its is why researchers have studied this antibiotic from different point of views. In this study, we elaborate the discovery of zoliflodacin, its mechanism of action, the current clinical trials, and the effectiveness of zoliflodacin. [ABSTRACT FROM AUTHOR]

Background: Neisseria gonorrhoeae is a gram negative diplococci which causess a sexually transmitted infection. N. gonorrhoeae is an obligate human pathogen that causes infection to the mucus-secreting epithelial cells both in male and female. In 2017, the centre of disease control and World Health Organization published the list of global priority pathogens with denting therapeutic options, including antibiotic-resistant N. gonorrhoeae. During the covid-19 pandemic, excessive use of antibiotics led to raise of drug resistance. The infection is widespread and intractable. If this happens, more people will be left with an incurable infection which may cause serious health problems. Results: We characterized zoliflodacin thoroughly. Here is discussed the clinical trials and side effects on human health by searching different keywords like “zoliflodacin”, “covid-19”, “clinical trials” from different data sources like Pub-Med, Google-Scholar, and Science-Direct. Zoliflodacin targets antibiotic-resistant N. gonorrhoeae. Zoliflodacin is mainly known based on its therapeutic effects against N. gonorrhoeae. It acts by inhibiting bacterial type 2 topoisomerase with binding site in bacterial gyrase. Zoliflodacin is effective in treating gonococcal urogenital and rectal infection. Conclusion: Antibiotic is the only option to treat N. gonorrhoeae. There is no vaccine available to treat gonorrhea. The new drug, zoliflodacin, specifically targets antibiotic-resistant gonorrhea and its is why researchers have studied this antibiotic from different point of views. In this study, we elaborate the discovery of zoliflodacin, its mechanism of action, the current clinical trials, and the effectiveness of zoliflodacin.

Neisseria gonorrheae , the causative agent of genitourinary infections, has been associated with asymptomatic or recurrent infections and has the potential to form biofilms and induce inflammation and cell transformation. Herein, we aimed to use computational analysis to predict novel associations between chronic inflammation caused by gonorrhea infection and neoplastic transformation. Prioritization and gene enrichment strategies based on virulence and resistance genes utilizing essential genes from the DEG and PANTHER databases, respectively, were performed. Using the STRING database, protein‒protein interaction networks were constructed with 55 nodes of bacterial proteins and 72 nodes of proteins involved in the host immune response. MCODE and cytoHubba were used to identify 12 bacterial hub proteins (murA, murB, murC, murD, murE, purN, purL, thyA, uvrB, kdsB, lpxC, and ftsH) and 19 human hub proteins, of which TNF, STAT3 and AKT1 had high significance. The PPI networks are based on the connectivity degree (K), betweenness centrality (BC), and closeness centrality (CC) values. Hub genes are vital for cell survival and growth, and their significance as potential drug targets is discussed. This computational study provides a comprehensive understanding of inflammation and carcinogenesis pathways that are activated during gonorrhea infection. • Hub genes are therapeutic targets for treating N. gonorrheae infection-induced neoplastic cell transformation. • Prioritized host and bacterial hub genes are potential drug targets against inflammation-induced cell transformation. • N. g onorrheae hub genes involved in nucleotide biosynthesis, DNA repair, lipid A biosynthesis and cell wall formation are significant. • Prioritized host hub genes, including AKT1, PIK3CA, TNF, TLR2, TLR6, and STAT3, are significant. [ABSTRACT FROM AUTHOR]

Abstract Gonorrheal infections are the second most prevalent sexually transmitted diseases STDs in the USA populations after Chlamydia. These infections have now become an urgent problem to address because Neisseria gonorrhoeae is capable of developing resistance to multiple antibiotic classes. Infection with these antibiotic-resistant strains has become the major public health concern. Although extensive researches are ongoing to control its transmission and to develop the productive treatments against this pathogen, no effective vaccine could develop till now. The present study will effectively contribute to the future designing of USA specific epitope-based vaccines. Through computational approaches, this study has highlighted putative epitopes from Neisseria gonorrhoeae which restrict maximally to the frequent HLA alleles in the USA populations. Antigenic and non-allergenic nature of predicted epitopes was verified using vexijen and AllerTOP tools respectively. Total seven epitopes, four from class-I and three from class-II were antigenic as well as non-allergenic. These epitopes showed USA population coverage of 99.3% with no allergenic response. Still, additional studies are needed to validate the immunogenic properties of the predicted epitopes which are likely vaccine target for gonorrhoea in the USA populations. Graphical abstract Image 1 Highlights • Epitopes of N. Gonorrhea from dd-alanine ligase, type IV pilin protein and competence lipoprotein were predicted. • 4 class I and 3 class II epitopes gave 99.3% population coverage for USA population with no allergenic response. • Future wet lab studies are needed to predict immunogenic properties of these epitope. [ABSTRACT FROM AUTHOR]

Bacterial infections are associated with infertility in men. This study was aimed to investigate microdeletions on Yq chromosome in semen infected with bacteria by using bacteriological, biochemical, and serological assays. The investigation showed that 107 of 300 (84.80%) semen samples collected from infertile men with primary or secondary infertility were infected with different species of bacteria. Chlamydia trachomatis and Neisseria gonorrheae were the most frequently diagnosed bacteria in the infected semen samples. The percentages of infections of semen samples with C. trachomatis and N. gonorrhea were 42.31% and 35.28% respectively. Genomic DNA from each semen sample infected with predominant bacteria was analyzed for AZF deletions by using multiplex PCR. Different patterns of AZF microdeletions were obtained. It can be concluded that sexually transmitted bacteria may contribute in microdeletions of Yq chromosome by indirectly producing reactive oxygen species and causing gene defect in AZF regions.

Three different real-time PCR assays were evaluated as confirmatory tests for Neisseria gonorrhoeae after initial screening using the COBAS AMPLICOR Chlamydia trachomatis and N. gonorrhoeae duplex assay. The target genes used for the confirmation were the gyr, cppB and 16S rRNA genes. Analytical specificity was determined by testing 60 strains belonging to different bacterial species and/or serogroups. The primers chosen from the 16S rRNA gene for confirmation of N. gonorrhoeae were highly specific, showed no cross-reactivity with other bacteria included in the study, and had an analytical sensitivity of 1 CFU. Of 192 clinical specimens that were positive for N. gonorrhoeae according to the COBAS AMPLICOR assay, 42 were confirmed as positive using the 16S rRNA gene target, 26 were confirmed using the cppB target, and 30 were confirmed using the gyr target. It was concluded that the real-time PCR assay targeting the 16S rRNA gene is a useful confirmatory assay to complement the COBAS AMPLICOR screening test for N. gonorrhoeae. [ABSTRACT FROM AUTHOR]

The potential for enhanced diagnosis and control of gonococcal infection through the application of advances in molecular medicine is now being realized. However, the introduction of diagnostic nucleic acid amplification assays (NAATs) revealed some significant limitations of these applications. Resolution of some, but not all, of these problems has led to recommendations for refined testing algorithms and a better recognition and acceptance of the limitations of NAATs. Resource restriction has limited the use of diagnostic NAATs, especially in less-developed countries where disease rates are highest. However, NAATs have also proved useful in public health approaches to gonorrhea control in all settings. Additional applications including molecular typing of gonococci to identify and interrupt gonococcal transmission chains and definition of antimicrobial resistance patterns in the gonococcus have been proposed. These approaches, especially those for antimicrobial resistance determination, have been less successful for a number of reasons, including their cost and other unresolved issues. [ABSTRACT FROM AUTHOR]

Frequently, encountered gynaecologic infections and pathogens involved are presented. A review is given of bartholinitis, vulvovaginitis-bacterial vaginosis, candidiasis, trichomoniasis cervicitis and pelvic inflammatory disease: Neisseria gonorrhoeae, Chlamydia trachomatis and herpes simplex virus 2. Of each infection a thorough description of clinical symptoms and diagnostic criteria is followed by up-to-date treatment advices. For vulvovaginitis, cervicitis and pelvic inflammatory disease antifungal and antimicrobial agents, route of administration, the required daily dosage and time of administration are presented in an overview table. [ABSTRACT FROM AUTHOR]

The Centers for Disease Control and the World Health Organization have issued a list of priority pathogens for which there are dwindling therapeutic options, including antibiotic-resistant Neisseria gonorrheae , for which novel oral agents are urgently needed. Zoliflodacin, the first in a new class of antibacterial agents called the spiropyrimidinetriones, is being developed for the treatment of gonorrhea. It has a unique mode of inhibition against bacterial type II topoisomerases with binding sites in bacterial gyrase that are distinct from those of the fluoroquinolones. Zoliflodacin is bactericidal, with a low frequency of resistance and potent antibacterial activity against N. gonorrheae , including multi-drug-resistant strains (MICs ranging from ≤0.002 to 0.25 μg/mL). Although being developed for the treatment of gonorrhea, zoliflodacin also has activity against Gram-positive, fastidious Gram-negative, and atypical pathogens. A hollow-fiber infection model using S. aureus showed that that pharmacokinetic/pharmacodynamic index of f AUC/MIC best correlated with efficacy in in vivo neutropenic thigh models in mice. This data and unbound exposure magnitudes derived from the thigh models were subsequently utilized in a surrogate pathogen approach to establish dose ranges for clinical development with N. gonorrheae. In preclinical studies, a wide safety margin supported progression to phase 1 studies in healthy volunteers, which showed linear pharmacokinetics, good oral bioavailability, and no significant safety findings. In a phase 2 study, zoliflodacin was effective in treating gonococcal urogenital and rectal infections. In partnership with the Global Antibiotic Research Development Program (GARDP), zoliflodacin is currently being studied in a global phase 3 clinical trial. Zoliflodacin represents a promising new oral therapy for drug-resistant infections caused by N. gonorrheae .

In this review, the epidemiology, diagnosis, and treatment of pelvic inflammatory disease (PID) are discussed from a USA perspective and the difficulties that USA adolescents face in recognizing and seeking care for PID and other sexually transmitted infections (STIs) are emphasized. Females aged 15-24 years have the highest incidence of cervical infection with Chlamydia trachomatis and Neisseria gonorrheae , the principal causes of PID. PID is common in this age group. However, the incidence of PID in the USA is not known, because it is not a reportable disease, and because clinicians vary in the criteria used for the diagnosis. The Centers for Disease Control and Prevention (CDC) recommended the following diagnostic criteria that include lower abdominal or pelvic pain and at least one of the following: adnexal tenderness or cervical motion tenderness or uterine tenderness. Because PID can have serious sequelae, the criteria emphasize sensitivity (few false-negatives) at the expense of specificity (some false-positives). Patients who have PID are usually treated in the outpatient setting, following the CDC's Guidelines for the Treatment of Sexually Transmitted Diseases 2015. They receive one dose of an intramuscular cephalosporin, together with 2 weeks of oral doxy cycline, and sometimes oral metronidazole. Improvement should usually be evident in 3 days. The USA does not offer comprehensive sex education for adolescents in public or private schools. Adolescents are unlikely to recognize the symptoms of PID and seek medical treatment. Confidentiality is important to adolescents, and low cost or free sources of confidential care are uncommon, making it unlikely that an adolescent would seek care even if she suspected an STI. The CDC has concluded that screening programs for chlamydia and gonorrhea infection help prevent PID; however, the lack of appropriate sources of care makes adolescents' participation in screening programs unlikely., Competing Interests: Disclosure The authors report no conflicts of interest in this work.