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Antibiotic-resistant gonorrheal infections are an urgent health concern. The MtrCDE system confers multidrug resistance to Neisseria gonorrhoeae, an obligate human pathogen, and the causative agent of the sexually-transmitted infection gonorrhea. The inner membrane pump MtrD effluxes a variety of hydrophobic and amphiphilic substrates and thereby confers resistance to a multitude of antibiotics. Using a combination of free and directed Molecular Dynamics (MD) simulations, we analyzed the interactions of MtrD with Azithromycin, an MtrD substrate and one of the last remaining courses of treatment for multidrug resistant gonorrhea. We also simulated the interactions between MtrD and Streptomycin, a non-substrate of MtrD. Using targeted MD (TMD) techniques and known conformations of MtrD homologues, we guided MtrD through the conformational changes of a putative transport cycle by applying small forces to α-carbons of the protein backbone; forces were not applied to Azithromycin or to Streptomycin. In our TMD experiments, we observed the transport of Azithromycin (in three possible protonation states) and the rejection of Streptomycin. To supplement our findings, we then demonstrate the spontaneous diffusion of Azithromycin through the periplasmic cleft in long time-scale, unbiased MD simulations. Our findings support the hypothesis that the transition from Binding to Extrusion is an energy requiring step in the transport process. Our data also suggest that multiple binding modes, and potentially multiple residue contact pathways, exist within the periplasmic cleft of MtrD, even for bulky substrates. To our knowledge, this is the first computational demonstration of substrate transport, and non-substrate rejection, by MtrD.

Background: Gonorrhoea is a sexually transmitted infection that is commonly related to male infertility. The infection affects sperm transport through the urinary tract and subsequent damage of the testicular tubes. The infection also impair sperm production as the infection is rarely asymptomatic and can be difficult to diagnose, it is possible that its contribution to male infertility is underestimated. Infection of the genitals results in a purulent (pus-like) discharge from the genitals which may be foul smelling, inflammation, redness, swelling, dysuria, and a burning sensation during urination. As with Chlamydia, it is possible to have a Gonorrhea infection without noticeable symptoms, and which can cause permanent scarring and blockage in the sperm production duct. Gonorrhoea is a bacterial infection and is treatable with antibiotics. Laboratory studies reveal that N. gonorrhoeae infection can impair motility, viability and spermatogenesis; increase anti-sperm antibodies are associated with a decrease in semen parameters as a result of the production of anti-sperm antibodies in the genital tract. Aim: The study aimed at reviewing the possible role of gonorrhoea in male infertility. Method: Research publications such as Pubmed, Scopus, Medline etc. Results: over 115 journals of international repute were obtained, out of which 50 were found to be closely relevant such as; the implication of N. gonorrheae in male infertility, complication of N. gonorrhea infection, N. gonorrhea e and male infertility and were reviewed. Conclusion: N. gonorrhoae was found implicative in male infertility and the need for comprehensive modern laboratory methods for the diagnosis of the infection and also to included routine laboratory tests.

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 Neisseri...

The three species Neisseria meningitidis , Neisseria gonorrheae , and Neisseria lactamica are often regarded as highly recombining bacteria. N . meningitidis has been considered a paradigmatic case of the “semiclonal model” or of “epidemic clonality,” demonstrating occasional bouts of clonal propagation in an otherwise recombining species. In this model, occasional clonality generates linkage disequilibrium in the short term. In the long run, however, the effects of clonality are countered by recombination. We show that many data are at odds with this proposal and that N . meningitidis fits the criteria that we have proposed for predominant clonal evolution (PCE). We point out that ( i ) the proposed way to distinguish epidemic clonality from PCE may be faulty and ( ii ) the evidence of deep phylogenies by microarrays and whole-genome sequencing is at odds with the predictions of the semiclonal model. Last, we revisit the species status of N . meningitidis , N . gonorrheae , and N . lactamica in the light of the PCE model.

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.

Background Resistant Neisseria gonorrheae (NG) is a growing concern in California, nationally, and globally. Since 1987, California has participated in the Gonococcal Isolate Surveillance Project (GISP), a Centers for Disease Control and Prevention-funded project to monitor trends in antimicrobial susceptibility in sentinel STD clinic sites throughout the United States. We sought to describe trends in California NG susceptibility to ceftriaxone (CRO) and azithromycin (AZI), recommended therapy for NG, for 2005–2016. Methods Per GISP protocol, cultures are collected from the first 25 men presenting with NG urethritis each month at GISP clinic sites in California, and antimicrobial susceptibility testing (AST) is performed via agar dilution at GISP regional laboratories. Reduced susceptibility (RS) to CRO was defined as minimum inhibitory concentration (MIC) ≥0.125 µg/ml and AZI MIC ≥2 µg/ml. Demographics and MIC trends over time were examined. Results Between 2005 and 2016, there were 9,692 NG isolates submitted in California GISP clinics. There were 24 (0.25%) isolates with RS to CRO and 92 (0.96%) isolates with RS to AZI. There was a higher proportion of isolates from men who have sex with men with RS to AZI (but not CRO) compared with men who have sex with women (chi-squared P-values: AZI = 0.0015; CRO = 0.70). In 2016, the percent of isolates demonstrating RS to AZI increased to 3.69% (n = 32), compared with 0.69% of isolates with RS to AZI in 2005–2015 (chi-squared P-value < .0001); there was no significant difference in the percent of isolates with RS to CRO in 2016 compared with prior years (Figure 1). Figures 2 and 3 demonstrate the distribution of AZI MICs and CRO MICs, respectively, from 2005–2016. There have been no isolates to date in California GISP with RS to both ceftriaxone and azithromycin. Conclusion Gonococcal surveillance data demonstrate an increase in the proportion of isolates with decreased susceptibility to azithromycin in 2016 in California compared with prior years. Although there has never been a documented treatment failure to the recommended therapy of CRO and AZI in California, clinicians should remain vigilant for treatment failures given these concerning increases. Disclosures All authors: No reported disclosures.

Background Most of Neisseria gonorrhoeae strains isolated from Thai patients are resistant to ciprofloxacin and ciprofloxacin is no longer recommended for therapy of gonococcal infection in Thailand. Sitafloxacin is a new generation of fluoroquinolones that contains in vitro activities against many bacteria that are resistant to ciprofloxacin. Sitafloxacin has a high concentration in urine. The objective of the study was to determine in vitro activity of sitafloxacin against ciprofloxacin-resistant N.gonorrheae. Methods Antimicrobial susceptibility tests for 52 strains of Neisseria gonorrhoeae isolated from patients attended Bangrak Hospital in Bangkok were performed. The tested antibiotics were ceftriaxone, cefixime, ciprofloxacin, and sitafloxacin. The minimum inhibitory concentrations (MICs) and inhibition zone diameters were determined by standard agar dilution and disk diffusion method, respectively, according to the Clinical and Laboratory Standards Institute (CLSI) 2013. Results All 52 N.gonorrheae isolates were susceptible to ceftriaxone (MIC < 0.025 mg/l, zone diameter > 35mm) and cefixime (MIC < 0.025 mg/l, zone diameter > 31mm). All N. gonorrheae isolates were resistant to ciprofloxacin (MIC > 1 mg/l, zone diameter < 27 mm). The inhibition zone diameters of sitafloxacin (5 microgram disk) against 52 isolates of N. gonorrhoeae were > 41 mm in 35 isolates (67%) and between 28 and 40 mm in 17 isolates (33%). If the cut-off value of inhibition zone diameter of resistance to ciprofloxacin ( Conclusion Sitafloxacin seems to be active against ciprofloxacin-resistant N. gonorrheae. A clinical study on therapy of gonococcal urethritis due to ciprofloxacin-resistant N. gonorrheae should be considered. Disclosures All authors: No reported disclosures.

JUSTIFICATIVA: Adolescentes e jovens constituem o grupo mais vulnerável às Doenças Sexualmente Transmissíveis (DST), que estão entre as infecções mais prevalentes no mundo e representam um sério impacto na saúde reprodutiva deste grupo etário. OBJETIVO: Estimar a prevalência, identificar os fatores de risco para a infecção por N. gonorrhoeae e a co-positividade com C. trachomatis em adolescentes e jovens sexualmente ativas residentes em uma cidade de médio porte do estado de Goiás e descrever o perfil sócio demográfico e comportamental da população atendida no Programa de Saúde da Família (PSF). METODOLOGIA: A investigação foi delineada como um estudo de prevalência em 651 adolescentes e jovens, não grávidas, de 15 a 24 anos, cadastradas no Programa de Saúde da Família (PSF) em Inhumas, Goiás. Foram excluídas adolescentes grávidas ou no puerpério, em uso de antibióticos ou menstruadas. O diagnóstico da infecção gonocócica e da infecção por C. trachomatis foi realizado empregando a Reação de Cadeia de Polimerase (PCR) em amostras endocervicais utilizando o kit Amplicor Roche para N. gonorrhoeae e C. trachomatis. Os dados sócio-demográficos e de comportamento sexual foram obtidos através de questionário, na forma de entrevista. Análise univariada foi realizada para identificar potenciais fatores de risco associados à infecção. Amostras de swab endocervical foram colhidas de 322 pacientes sexualmente ativas para a detecção do DNA da N. gonorrhoeae e da C. trachomatis. RESULTADOS: A média de idade das 428 adolescentes e jovens sexualmente ativas foi de 18,6 (dp=2,7), sendo 64,3% solteiras. O uso inconsistente de preservativo foi observado em 78,0% das meninas e 11,9 % nunca o usaram. A sexarca ocorreu antes dos quinze anos em 23,4%. A gravidez ocorreu antes dos 20 anos em 90% delas e em 23,5% antes dos 15 anos. A prevalência de N. gonorrhoeae foi de 3,4% (IC 95%1,8 - 6,2) em 322 pacientes das quais foram obtidas amostras de swab endocervical. A co-infecção com clamídia foi 27,3%. A análise univariada mostrou que o fator de risco associado à infecção por N. gonorrhoeae foi o não uso de preservativos. CONCLUSÕES: As jovens e adolescentes do presente estudo apresentaram vários comportamentos considerados de risco para DST e aquelas que referiram não usar preservativos apresentaram um risco maior de estarem infectados pelo gonococo. BACKGROUND: Adolescents and youth are the group most vulnerable to sexually transmitted diseases (STDs), which are among the most prevalent infections in the world and represent a serious impact on reproductive health in this age group. OBJECTIVE: To estimate the prevalence and identify risk factors for infection by N. gonorrhoeae and co-positivity with C. trachomatis in sexually active adolescents and young adults living in a midsize city of Goias and describe the socio-demographic and behavioral profile of the population seen at the Family Health Program (PSF). METHODOLOGY: The study was designed as a prevalence study in 651 adolescents and young adults, not pregnant, 15 to 24 years were enrolled in the Family Health Program (FHP) in Inhumas, Goiás were excluded pregnant or postpartum teens in antibiotics or menstruating. The diagnosis of gonococcal infection and infection by C. trachomatis was performed using the Polymerase Chain Reaction (PCR) in endocervical specimens using the Roche Amplicor kit for N. gonorrhoeae and C. trachomatis. The socio-demographic and sexual behavior were obtained through a questionnaire as an interview. Univariate analysis was performed to identify potential risk factors associated with infection. Endocervical swab samples were collected from 322 sexually active patients to dtect the DNA of N. gonorrhoeae and C. trachomatis. RESULTS: The mean age of 428 sexually active adolescents and young adults was 18.6 (SD = 2.7), with 64.3% single. Inconsistent use of condoms was observed in 78.0% of girls and 11.9% never used it. The first sexual intercourse occurred before the age of fifteen in 23.4%. Pregnancy before age 20 occurred in 90% and 23.5% of them before age 15. The prevalence of N. gonorrhoeae was 3.4% (95% CI 1.8 to 6.2) in 322 patients from whom samples were collected endocervical swab. Co-infection with chlamydia was 27.3%. Univariate analysis showed that the risk factor associated with infection by N.gonorrhoeae was not using condoms. CONCLUSIONS: Young women and adolescents in this study exhibited various behaviors considered at risk for STDs and those who reported not using condoms had a higher risk of being infected by the gonococcus. WORDS - KEY: Neisseria gonorrhoeae; Adolescents Prevalence; STD; PCR.

Chlamydia trachomatis (CT) and Neisseria gonorrheae (GC) are presented together, not because of their similarities in disease presentation, but because of the current trend in screening samples for both simultaneously. Historically, these organisms were identified using very different laboratory methods: CT by tissue culture and GC by growth in specialized bacterial medium. However, over the past decade a revolutionary change has taken place in the approach used to detect these two sexually transmitted infections (STIs). In many instances, molecular testing, either nucleic acid hybridization or nucleic acid amplification, has replaced culture and immunoassays.

Diagnosing Neisseria gonorrheae using nucleic acid amplification tests (NAATs) might increase the sensitivity, compared to cultivation. However, using NAATs has also been problematic mainly due to the close genetic relationships between different Neisseria species, resulting in false positive diagnoses. This study was conducted to clinically validate a previously published real-time polymerase chain reaction (PCR) method targeting the porA pseudogene in N. gonorrheae in comparison to culture techniques.In total, 360 samples, urethra (n = 109), rectum (n = 84), pharynx (n = 119), and cervix (n = 48) from 185 males and 57 females, were analyzed using porA pseudogene PCR and cultivation. Sequencing of the entire porA pseudogene and the 16S rRNA gene were used to resolve discrepant results.Of the 360 samples, 37 were positive by both culture and PCR, however, the PCR identified 15 additional confirmed positive samples. The PCR method showed a sensitivity, specificity, positive predictive value, and negative predictive value of 100% in a preselected population. The preselected population had a true gonorrhea prevalence of 17.4%.The present porA pseudogene real-time PCR comprises a valuable supplement to the traditional culture techniques for diagnosis of N. gonorrheae, especially for samples from extragenital sites such as pharynx and rectum.

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.

Introduction Data regarding extra-genital Neisseria gonorrheae (NG) and Chlamydia trachomatis (CT) in men who have sex with men (MSM), and transwomen (TW) in Latin America is limited. We determined the prevalence of pharyngeal, rectal, and urethral NG and CT among MSM, and TW and associated risk factors and behaviours. Methods We used data from the Expedited Partner Therapy Screening Study of men who have sex with men (MSM) and transgender women (TW) in Lima, Peru. Participants completed a CASI survey regarding socio-demographic data, sexual risk behaviours, and STD symptoms. Anal and pharyngeal swabs and urine specimens collected by the study physician were tested for CT and NG using NAAT (Aptima GenProbe). Results We screened 834 participants (551-gay identified men, 264 heterosexual/bisexual men and 19 TW) for CT and NG between October 2012 and July 2014. The median age of participants was 27 years (range 18–70). CT prevalence was 3.5% in urine, 4.5% in pharyngeal and 15.6% in rectal specimens. NG prevalence was 2.7% in urine, 9.4% in pharyngeal and 8.3% in rectal specimens. Approximately 75% of participants with rectal infections reported no symptoms in the previous 30 days. More than 92% of extra-genital CT infections and 83% of extra-genital NG infections were identified in participants with negative urine test results. Younger age was strongly associated with increased prevalence of both pharyngeal NG (p = 0.054) and rectal CT (p = 0.008) and NG infections (p = 0.002). Receptive anal intercourse was associated with higher prevalence of rectal CT infection (p = 0.012). Pharyngeal NG (p = 0.005) was more frequent in participants reporting multiple partners. Conclusion Extragenital CT and NG infection is highly prevalent, usually asymptomatic and in a majority of cases, associated with negative urine tests among MSM and TW in Peru. Routine screening at multiple anatomic sites using NAAT should be performed.

Canals and cysts are not rare embryonic malformations of the male genitoperineal median raphe. These patients usually consult dermatovenereologists . They normally remain asymptomatic for a long period, but secondary infections, caused by Neisseria gonorrheae , may occur. Surgical excision is the treatment of choice.

To determine a rapid and reliable protocol for the differentiation of Mima polymorpha, M. polymorpha var. oxidans, Herellea, Bacterium antitratum, Neisseria gonorrheae , and other related members of the genus Neisseria , reference cultures were examined on a variety of microbiological media. The media were selected because of the typical morphological and biochemical characteristics exhibited by the test organisms and were those media which would be readily available in a microbiology facility. After compiling data obtained from 21,714 observations, an inclusive protocol is presented which has proven to be quite adequate for the identification of these particular gram-negative bacteria.

The frequencies of positive endocervical Neisseria gonorrheae cultures in women using a conventional or a copper-bearing-type IUD were compared. 155 women who wanted to use IUDs were randomly assigned to 1 of 2 IUD groups. These women received either a conventional-type (Dalkon shield) or a copper-bearing device (copper T-200). The women were later brought back for an examination after wearing the device for 1-18 months. An endocervical culture was performed for each woman for the detection of Neisseria gonorrheae. There was no significant differe nce in the frequency of positive cultures in the 2 IUD groups. There were 5 positive gonococcal cultures (8.1%) in the conventional IUD group and there were 7 positive gonococcal cultures (7.5%) in the copper IUD group. The findings suggest that the increased concentration of copper in the endocervical mucus does not affect this organism.

Liberated or not, no woman is flattered by the notion that women are the only carriers of covert gonorrheal infection. Nor is she pleased by the thoroughness with which public health agencies trace female contacts of infected men, as contrasted with their laissez-faire in tracking down male contacts of infected women. Her pride is not readily placated by the plausible explanation that because gonorrhea in men is always floridly overt, infected men will seek medical attention of their own accord. How valid is this explanation? Can men be exonerated from harboring covert gonorrheal infection? Studies in the Norfolk Venereal Disease Clinic 1,2 demonstrated that about 10% of men exposed to infected women harbored Neisseria gonorrheae in their urethras without manifesting any symptoms. In 8.3%, the organisms persisted from 8 to 56 days after exposure. None would have known that he was a reservoir of infectious organisms—a danger to himself and

Inflammation of the mouth is a relatively common clinical condition among children, particularly of the outpatient class. In a number of cases the stomatitis is due to some known condition such as trauma, avitaminosis, metallic poisons, thrush, certain uncommon bacterial infections (Corynebacterium diphtheriae or Neisseria gonorrheae) and that which accompanies the exanthems. However, there remains a clinically common group about the cause of which there has been considerable doubt. Uncertainty as to the etiology of this condition has led to a variety of names, over thirty synonyms in all being applied to it. Some of these are descriptive, e. g. catarrhal, aphthous, membranous or ulcerative, while some are based on the etiology, e. g. "Vincent's" or "fusospirochetal." Although fusospirochetal organisms are frequently encountered in this disease, many authors have questioned their causal relationship. These organisms are not recoverable from all cases presenting a similar clinical appearance, while on the other

It is a pleasure to review a book of such true excellence. Blair, Lennette, and Truant are to be congratulated for a superb job of assembling material covering the identification and isolation of bacteria, fungi, parasites, and viruses in a single volume. Usually manuals of this type are of interest only to the clinical laboratory worker. In this instance I feel this volume is a "must" for any internist whose subspecialty interest is infectious diseases. Large medical centers have microbiology laboratories staffed by well-trained individuals whose primary interest is clinical microbiology. But some hospital laboratories may not have kept abreast of the great progress that has occurred in the last decade. Improvements in transportation of specimens, isolation of Neisseria gonorrheae and N meningitidis , and identification of members of the family Enterobacteriaceae are examples. Consultation with this manual will allow the internist to review his hospital's microbiological methods with authority. One

To the Editor:— The article by Dr. W. R. Lang on "Experiences in a Vaginitis Clinic" inThe Journalof Dec. 3, 1960, p. 1814, makes no mention of Neisseria gonorrheae as the causative organism in any of the many hundreds of cases of vaginitis in adults. Unless gonorrhea cases were excluded from the series without mention in the article, it is indeed most unusual if N. gonorrheae were not identified by appropriate cultural methods in any of these cases.