Treatment Of Gonococcal Infections Research Articles

Effect of C7-3-Peptide-Loaded Chitosan Nanoparticles Against Multi-Drug-Resistant Neisseria gonorrhoeae.

The emergence of Neisseria gonorrhoeae-resistant strains represents one of the most urgent global threats. In this regard, C7-3 peptide is one of the anti-virulence therapies that has demonstrated promising anti-gonococcal activity. Accordingly, this research aimed to formulate C7-3 peptide and its derivatives in chitosan nanoparticles. The peptide loaded chitosan nanoparticles were prepared using ion gelation method, and their physicochemical characteristics were investigated. The anti-gonococcal and antibiofilm activity of prepared NPs was assessed, and their cytotoxicity in human ovarian cells was evaluated. All prepared NPs were optimized for the smallest particle size of 136.9 to 168.3 nm. The EE% of C7-3, C7-3m1, and C7-3m2 CNPs reached 90.2, 92.5, and 91.8%, respectively. An in vitro release study demonstrated a continuous sustained-release pattern of C7-3 peptide from NPs. The SDS-PAGE assay confirmed the integrity of C7-3 peptide after the fabrication process. When comparing each peptide alone, the generated NPs demonstrated higher anti-gonococcal and anti-biofilm effectiveness against standard and resistant bacterial strains under anaerobic conditions. The cytotoxicity experiments revealed the cytocompatibility of NPs in HeLa cell lines. Given the advantages of enhanced anti-gonococcal activity of the C7-3 peptide and its derivatives when loaded with CNPs, as well as the antimicrobial properties of chitosan NPs, the reported NPs have great potential in the treatment of gonococcal infection.

Azithromycin Susceptibility Testing and Molecular Investigation of Neisseria gonorrhoeae Isolates Collected in Russia, 2020-2021.

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.

Intrauterine Devices in the Context of Gonococcal Infection, Chlamydial Infection, and Pelvic Inflammatory Disease: Not Mutually Exclusive.

The use of long-acting reversible contraception, namely, intrauterine device (IUDs) and the subdermal implant, has been recommended to address the high rate of the unintended pregnancy in the United States. IUDs are a safe, highly effective contraceptive method, suitable for most women. The underutilization of IUDs arises in part from the lack of translation of best practices in the clinical setting as well as fears and misperceptions about this contraceptive method held by health care providers and women. This article reviews screening and management of Neisseria gonorrhoeae and Chlamydia trachomatis infection and pelvic inflammatory disease (PID) in women who are using or want to use an IUD. An IUD may be inserted without prior screening for N gonorrhoeae or C trachomatis in women who are at low risk for sexually transmitted infections and asymptomatic. An in situ IUD may remain in the uterus during and after treatment for gonococcal infection, chlamydial infection, or PID. The risk of PID with an IUD in situ is less than 1%. Following IUD best practices, including their use in the context of sexually transmitted infections, can increase the availability of this method for suitable candidates and decrease the unintended pregnancy rate.

Biological microchip for assessing tetracycline-resistance in <i>Neisseria gonorrhoeae</i> clinical isolates in Russian Federation

A total of 399 Neisseria gonorrhoeae clinical isolates collected in different regions of the Russian Federation in 20152017 were analyzed for tetracycline susceptibility and genetic markers of resistance. Drug susceptibility testing was performed by serial dilution method in agar and minimum inhibitory concentration (MIC) was measured according to the Russian “Guidelines for microbial susceptibility testing for antibacterial agents No. 4.2.1890-04”. Tetracycline resistance determinants were studied by using hydrogel microarray with immobilized oligonucleotide probes able to identify a series of chromosomal mutations and detect plasmid tetM gene. Different resistance determinants were found in 193 isolates (48.4%). Mutation in codon 57 in the rpsJ gene (41.2%) was most common that decreases tetracycline affinity to ribosome 30S subunit, mainly due to Val57Met substitution both as a point mutation as well as in combination with others. Mutations in the rpsJ gene were found in strains with the intermediate tetracycline susceptibility. Mutations in the porB gene (lower tetracycline influx) held the se cond place in prevalence pattern (23.1%); the Gly120Lys substitution usually led to emergence of tetracycline resistance either as a point mutation or in combination with other substitutions. Substitutions of Gly120 for other residues (Asp, Asn, and Thr) and Ala121 for Asp, Asn, and Gly had much less effect on resistance level. The –35 delA deletion in the promoter region of mtrR gene (increased expression of MtrC-MtrD-MtrE efflux pump) was observed in 11.3% strains. The tetM gene was found in 27 strains including 17 American and 10 Dutch type tetM determinants. Evolutionary tree was constructed for the tetM genes with the estimation of their homology with similar genes in genera Streptococcus, Enterococcus and Mycoplasma. Mutations in chromosomal genes resulted in increase of tetracycline MIC up to 2–4 mg/L; 4 mg/L MIC was observed in case of simultaneous presence of several mutations. Strains bearing tetM gene-containing plasmid showed extremely high resistance level: MIC ≥ 8 mg/L (64 mg/L for the two samples). Thus, long-lasting withdrawal of tetracycline use for treatment of gonococcal infections in Russia (since 2003) resulted in decreased percentage of resistant strains (including strains with intermediate susceptibility) from 75% down to 45.4%. However, currently tetracycline resistance in Russia remains elevated that is explained by the presence of different resistance determinants in the half of isolates under study.

Management of cephalosporin resistance in Neisseria gonorrhoeae

Gonorrhea is a sexually transmitted disease caused by Neisseria gonorrhoeae, and substantially harms human health and socioeconomic development. Due to inappropriate treatment and the presence of drug resistance genes in patients, antibiotic resistance has emerged in Neisseria gonorrhoeae, such as resistance to penicillin, tetracycline, ciprofloxacin, or other antibiotics. Currently, extended-spectrum cephalosporins (ESCs)are the first-line treatment of gonococcal infection. With the wide use of ESCs, the sensitivity of Neisseria gonorrhoeae to ESCs has been decreasing gradually, and there have been reports on cases of treatment failure in clinical practice. In order to control gonorrhea and deal with drug resistance in Neisseria gonorrhoeae, combined therapy, alternative therapy and new drugs have been developed in clinic. Key words: Neisseria gonorrhoeae; Cephalosporins; Drug resistance; Therapeutic uses; Drug substitution

Community-based sexually transmitted infection screening and increased detection of pharyngeal and urogenital Chlamydia trachomatis and Neisseria gonorrhoeae infections in female sex workers in Hong Kong.

Female sex workers (FSWs) are vulnerable to sexually transmitted infections (STIs) and are one of the key populations being infected most by Chlamydia trachomatis and Neisseria gonorrhoeae infections. In Hong Kong, limited data on the burden of chlamydial and gonococcal infections exist because regular screenings are not offered. This study aimed to investigate the prevalence of C. trachomatis and N. gonorrhoeae in FSWs and to assess predictors associated with unprotected fellatio. A cross-sectional study was conduct on 340 FSWs attending a community organization for HIV/STI screening, and a questionnaire addressing sociodemographic and behavioral characteristics was administered to all FSWs. The prevalence of syphilis infection was 2.1%, and none was tested positive for HIV. The positivity for pharyngeal C. trachomatis and N. gonorrhoeae was 3.2% and 4.4%, respectively, whereas that for urogenital chlamydial and gonococcal infection was 10.6% and 0.9%, respectively. Of 313 FSWs offering fellatio, having unprotected fellatio with clients was significantly associated with the perceived low risk of contracting STI via fellatio (adjusted odds ratio [OR], 1.88), working in clubs (adjusted OR, 11.14), working on streets (adjusted OR, 3.28), recently started working in the sex industry for 1 year or less (adjusted OR, 3.05), and reporting group sex in the previous year (adjusted OR, 11.03). The prevalence of HIV and syphilis infection remains low. This study reveals a relatively high prevalence of N. gonorrhoeae detected mostly in the pharynx. Offering pharyngeal screening for STI would facilitate early diagnosis and treatment of gonococcal infection in FSWs in Hong Kong.

Antimicrobial resistance monitoring in Neisseria gonorrhoeae and strategic use of funds from the Global Fund to set up a systematic Moroccan gonococcal antimicrobial surveillance programme

ObjectivesThe aims of this study were to assess antimicrobial resistance in Neisseria gonorrhoeae infections and update the treatment in the national guidelines for the syndromic management of sexually transmitted infections...

Gonococcal Infections

Gonococcal Infections

Gonococcal Infections

Gonococcal Infections

Multidrug Resistance inNeisseria gonorrhoeae

Gonorrhea, caused by Neisseria gonorrhoeae is the second most prevalent bacterial sexually transmitted infection. The disease causes serious reproductive complications such as pelvic inflammatory disease, ectopic pregnancy, and infertility, and can facilitate human immunodeficiency virus transmission. Numerous antimicrobial agents have been used for the treatment of gonorrhea since sulfanilamides were introduced in 1936. Unfortunately, N. gonorrhoeae readily develops resistance to antimicrobial agents. Strains with decreased susceptibility to oral third generation cephalosporin (cefixime) are currently emerging. The US Centers for Disease Control and Prevention (CDC) no longer recommends cefixime at any dose as a first-line regimen for treatment of gonococcal infections, but recommends combination therapy with ceftriaxone 250 mg intramuscularly and either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days as the most reliably effective treatment for uncomplicated gonorrhea.

Cephalosporins of the third generation for the treatment of gonorrhea

The article presents the data on antibiotic resistance and N. gonorrhoeae mechanisms for developing resistance to antimicrobial drugs belonging to different pharmacologic groups and applied for causal treatment of gonorrhea. The article proves the key problem related to the treatment of gonococcal infection in Russia lies in the prevalence of strains being resistant to most of the antibacterial drugs that used to be applied in the clinical practice on a broad scale and efficiently. So, cephalosporins of the third generation are presently the only drug type that N. gonorrhoeae remains sensitive to. Their application ensures the maximum efficacy against the gonococcal infection. According to the presentday international recommendations complying with the WHO criteria as well as accumulated experience, cefixime, a drug belonging to cephalosporins of the third generation, can be a drug of choice for the antibacterial therapy of gonorrhea along with ceftriaxon.

Successful Treatment of Uncomplicated Gonococcal Urethritis in HIV-Infected Patients with Single-Dose Oral Cefpodoxime

Fluoroquinolones are no longer recommended for the treatment of gonococcal infections in the United States. Cephalosporins - ceftriaxone and cefixime - are the treatment of choice, as suggested by the Centers for Disease Control and Prevention (USA). There are limited data on the efficacy of cefpodoxime for the treatment of uncomplicated gonococcal infections. Two cases of HIV-infected homosexual men who were successfully treated with cefpodoxime for urethritis caused by Neisseria gonorrhoeae are described in the present study.

Trends of sexually transmitted diseases and antimicrobial resistance in Neisseria gonorrhoeae

Sexually transmitted diseases (STDs), especially HIV infection, gonococcal infection and genital chlamydial infections are increasing all over the world. UNAIDS recently reported that the number of HIV/AIDS patients had been increasing and the highest prevalence was found in African countries, followed by Caribbean, Asian and Eastern European countries. HIV infection has also been gradually increasing in Japan. In non-HIV STDs, genital chlamydial infections are increasing worldwide also. On the contrary, gonococcal infections have been decreasing in many countries except Asian countries. N. gonorrhoeae has been changing in its infecting sites. The pharynx is the most important infecting site, because gonococcal infection in the pharynx may be one of the causes of the wide spread of N. gonorrhoeae. Antimicrobial-resistant N. gonorrhoeae has wide distribution throughout the world. For example, penicillin-resistant N. gonorrhoeae is prevalent in various part of the world, and fluoroquinolone-resistant N. gonorrhoeae is prevalent mainly in Asia. In addition to penicillin, tetracycline and fluoroquinolone resistance, N. gonorrhoeae acquired resistance to almost all of the cephalosporins except for ceftriaxone and cefodizime in Japan. Although there is no resistant strain to ceftriaxone, cefodizime and spectinomycin, 1.0 g single dose of ceftriaxone is considered to be the most suitable regimen for the treatment of gonococcal infection including the pharyngeal infection, because of the 100% elimination rate of N. gonorrhoeae from the urethra, cervix and pharynx obtained in a recent study.

A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan.

We compared the susceptibilities of 100 Neisseria gonorrhoeae isolates obtained from January to June 2000 to a variety of antimicrobial agents, including various cephems, with the susceptibilities of 55 isolates obtained from May to December 1995. In 11 of the 15 cephems tested, the MIC50 (minimum inhibitory concentration for 50% of isolates) ratios, calculated by dividing the MIC50 for isolates from 2000 by that for isolates from 1995, showed 4-fold to 16-fold differences. The MIC90 ratios of cefodizime and cefditoren showed only a 1-fold and 2-fold difference, respectively. However, the MIC90 ratios of the remaining 13 cephems showed 4-fold to 64-fold differences. We selected the most favorable antibiotic regimens for the single-dose treatment of gonorrhea in Japan according to the antigonococcal activity and pharmacokinetics, based on the criterion (therapeutic time) proposed by Moran and Levine i.e., the regimen should produce a concentration in the serum or plasma at least four times that of the MIC90 value for at least 10 h. Of the 20 single-dose regimens evaluated, only ceftriaxone 1 g intravenously and cefodizime 1 g intravenously were found to have a therapeutic time of more than 10 h for the isolates from 2000. Our results indicated that the susceptibilities of the isolates from 2000 to all the cephems tested, except for cefditoren and cefodizime, decreased remarkably in comparison with the susceptibilities of the isolates from 1995, while parenteral ceftriaxone 1 g and cefodizime 1 g appeared to be the most favorable single-dose regimens for the treatment of gonococcal infections in Japan.

Emerging antimicrobial resistance, plasmid profile and pulsed-field gel electrophoresis pattern of the endonuclease-digested genomic DNA of Neisseria gonorrhoeae.

Resistant gonococci are very prevalent in many countries, particularly in Asia. This study was conducted to determine the trend of resistance, the effect of decreasing the ciprofloxacin susceptibilities of gonococci on the prevalence of penicillinase-producing N. gonorrhoeae (PPNG), and to compare the epidemiology of strains with the previous studies. A total of 602 strains of gonococci were isolated from prostitutes in 1997-1999. Antimicrobial susceptibility was tested by NCCLS disk diffusion and agar dilution methods. For epidemiologic analysis, plasmid analysis and pulsed-field gel electrophoresis (PFGE) were performed. The proportion of PPNG remained high (79%), and the strains with decreased susceptibility to ciprofloxacin increased significantly from 67% in 1997 to 84% in 1999. Compared to our previous study, the PFGE patterns were similar, while the proportion of strain with the 3.2-MDa plasmid markedly decreased. In conclusion, a rapid increase in ciprofloxacin-nonsusceptible strains may suggest difficulties in the treatment of gonococcal infections in the near future with the drug. The recent decrease of PPNG with the 3.2-MDa plasmid may suggest that there is an epidemiological change in gonococcal infections, and the prevalence of related PFGE patterns suggests the dissemination of a few clones among the high risk populations.

Importance of drug resistance in gonococci: from mechanisms to monitoring

Neisseria gonorrhoeae isolates continue to develop an impressive arsenal of resistance mechanisms to antimicrobial agents, including resistance to some of the antibiotics presently recommended for the treatment of gonococcal infections.

Azithromycin and erythromycin resistant Neisseria gonorrhoeae following treatment with azithromycin.

A pre-treatment and a 3-week post-treatment isolate of Neisseria gonorrhoeae from a 13-year-old boy treated with azithromycin in a single 1 g oral dose were characterized microbiologically. Both isolates were of the same serovar/auxotype (1B6/non-requiring) and had similar antibiograms apart from erythromycin and azithromycin: the pre- and post-treatment MICs (minimum inhibitory concentrations) were: 1 mg/L and 32 mg/L to erythromycin and 0.125 mg/L and 3 mg/L to azithromycin. The finding that both isolates were 1B6/NR, had similar antibiograms (other than azithromycin and erythromycin), and no other 1B6/NR isolates were resistant to erythromycin supports the view that macrolide resistance developed following treatment. A high overall level of azithromycin susceptibility was confirmed by testing 67 clinical isolates: MIC90 0.5 mg/L (range 0.023-0.75 mg/L). We conclude that the long half-life of azithromycin which is beneficial in treating chlamydial infection may result in increased selective pressure for resistance in gonococci. This report also highlights the importance of antibiotic susceptibility surveillance of gonococci and stresses the need for appropriate treatment of gonococcal infection, particularly when it is prescribed outwith departments of genitourinary medicine.

Comparative Trial of Azithromycin and Ciprofloxacin in the Treatment of Gonorrhea

This single-blind (investigator) comparative study was designed to determine the efficacy and tolerability of 1 g of azithromycin vs 500 mg of ciprofloxacin both given as a single oral dose in patients with gonorrhea, who were constantly on the move. One hundred eight patients (59 men and 49 women) with clinically suspected gonococcal infection, confirmed by Gram-stain and culture, were enrolled. Data of 50 patients treated with azithromycin and 51 with ciprofloxacin were evaluable for efficacy and tolerability at the end of the study. After 2 weeks clinical and microbiological cure rates were 96.0% (48 out of 50) for the patients treated with azithromycin and 92.15% (47 out of 51) for the patients treated with ciprofloxacin (p>0.05). Adverse reactions were reported in 5 patients treated with azithromycin and 6 with ciprofloxacin. In conclusion, 1 g azithromycin is at least as clinically and microbiologically effective and well tolerated as 500 mg of ciprofloxacin in the treatment of gonococcal infections. The drug is particularly useful for sailors and people constantly on the move.

Ciprofloxacin in the treatment of gonorrhoea and non-gonococcal urethritis.

The treatment of gonococcal infections by quinolones is reviewed. Acrosoxacin is effective, but side effects are relatively common. Ciprofloxacin is effective in single dosage against urogenital gonococcal infections, and probably also against rectal and pharyngeal infections. It is effective against infections by penicillinase-producing Neisseria gonorrhoeae. In vitro, ciprofloxacin is active against Chlamydia trachomatis, and preliminary results indicate that this drug may be of value in the treatment of non-gonococcal urethritis and chlamydial infection. No major side effects of ciprofloxacin therapy in patients with these infections have been reported.

Treatment of Uncomplicated Infections due to Neisseria gonorrhoeae

GONORRHEA remains the most frequently reported infectious disease in the United States. Antimicrobial resistance in the gonococcus continues to evolve, and coinfection withChlamydia trachomatisis a serious problem. Therefore, the periodic review of current therapies for gonorrhea to ensure effective treatment must be a major objective of the National Gonorrhea Control Program in the United States. In the past five years, the number of potentially useful antimicrobial agents for the treatment of gonococcal infections has proliferated: these include second- and third-generation cephalosporins, regimens combining the β-lactamase inhibitors clavulanic acid and sulbactam with penicillin and amoxicillin, and the quinolones. This article reviews (1) recent trends in gonococcal antimicrobial resistance and in vitro susceptibility to established and experimental regimens; (2) coinfection due toC trachomatisandNeisseria gonorrhoeaewithin the past five years; (3) therapy for incubating syphilis and gonorrhea; (4) prophylaxis of sexual partners exposed to resistant organisms; and (5)