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A multisite implementation of a real-time polymerase chain reaction assay to predict ciprofloxacin susceptibility in Neisseria gonorrhoeae.

Fri, 11/08/2019 - 08:24
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A multisite implementation of a real-time polymerase chain reaction assay to predict ciprofloxacin susceptibility in Neisseria gonorrhoeae.

Diagn Microbiol Infect Dis. 2019 Jul;94(3):213-217

Authors: Ellis O, Hemarajata P, Shahkolahi A, Masinde G, Buchs K, Humphries RM, Klausner JD

Abstract
There are no commercially available Food and Drug Administration-cleared rapid tests for Neisseria gonorrhoeae antimicrobial susceptibility testing. This study evaluated the performance of a laboratory-developed real-time polymerase chain reaction assay for genotyping the gyrA gene to determine antimicrobial susceptibility to ciprofloxacin. Validation and clinical performance of the gyrA assay were evaluated across 3 geographic locations (Los Angeles, San Francisco, Philadelphia). Following validation, clinical specimens were collected in Aptima Combo2® CT/NG transport medium from asymptomatic persons who tested positive for Neisseria gonorrhoeae and evaluated for assay percent reportable (i.e., proportion of N. gonorrhoeae-positive specimens that yielded a gyrA genotype). The percentage of gyrA genotyping results differed by laboratory and specimen type. The proportion of specimens that were reportable was best for urine/genital specimens (genotyped = 76.4% (95% confidence interval, 69.9-82%)) followed by rectal (genotyped = 67.2% (95% confidence interval, 63.4-70.6%)) and then pharyngeal specimens (genotyped = 36.1%, (95% confidence interval, 31.9-40.5%)). Overall, asymptomatic patients with N. gonorrhoeae yielded an interpretable genotype 57.2% (784/1370) of the time, of which 480 were wild-type gyrA, resulting in 61% (480/784) being potentially treatable with ciprofloxacin.

PMID: 30723007 [PubMed - indexed for MEDLINE]

Mycoplasma genitalium infection.

Thu, 11/07/2019 - 14:22
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Mycoplasma genitalium infection.

CMAJ. 2019 01 28;191(4):E103

Authors: Singh AE, Labbé AC, Auguste U

PMID: 30692107 [PubMed - indexed for MEDLINE]

A Brief History of Evolving Diagnostics and Therapy for Gonorrhea: Lessons Learned.

Thu, 11/07/2019 - 14:22
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A Brief History of Evolving Diagnostics and Therapy for Gonorrhea: Lessons Learned.

Clin Infect Dis. 2018 09 28;67(8):1294-1299

Authors: Hook EW, Kirkcaldy RD

Abstract
Progressively decreasing susceptibility of Neisseria gonorrhoeae to the antibiotics recommended for treatment has raised concerns about the public health threat of antibiotic resistant gonorrhea. This is not a new process, and the organism has reliably developed resistance to all modern antibiotics used for treatment since the dawn of the antibiotic era. The history of changing recommendations for gonorrhea therapy is complex, however, and has been influenced by diagnostic test methods and surveillance. Understanding the impact of these influences may provide insights into current approaches to address this reemerging public health challenge. We reviewed available methods for gonorrhea diagnosis, and public health recommendations for gonorrhea treatment. The literature review was supplemented by qualitative interviews with senior investigators whose research helped shape gonorrhea management strategies over the past 50 years. The process of development of antimicrobial resistance to the antibiotics widely used for treatment seems to be inexorable. Many currently voiced concerns are similar to those raised in the past. The public health threat of increasing antimicrobial resistance by N. gonorrhoeae has been amplified as a result of a smaller pipeline introducing new drugs for gonorrhea treatment. Improved methods for gonorrhea diagnosis have also repeatedly influenced appreciation of the burden of disease caused by N. gonorrhoeae. US Public Health Service leadership has also shaped and improved the management of this important public health problem.

PMID: 29659749 [PubMed - indexed for MEDLINE]

Launch of the BASHH guideline for the management of M. genitalium in adults.

Tue, 11/05/2019 - 08:18
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Launch of the BASHH guideline for the management of M. genitalium in adults.

Sex Transm Infect. 2019 06;95(4):237

Authors: Soni S, Horner PJ

PMID: 31097546 [PubMed - indexed for MEDLINE]

Syphilis in Pregnancy: The Reality in a Public Hospital.

Tue, 11/05/2019 - 08:18
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Syphilis in Pregnancy: The Reality in a Public Hospital.

Rev Bras Ginecol Obstet. 2019 Feb;41(2):90-96

Authors: Torres RG, Mendonça ALN, Montes GC, Manzan JJ, Ribeiro JU, Paschoini MC

Abstract
OBJECTIVE:  The present study assessed epidemiological and obstetrical data from pregnant women with syphilis at the Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (UFTM, in the Portuguese acronym), describing this disease during pregnancy and its vertical transmission for future healthcare actions.
METHODS:  Records from pregnant women who had been admitted to the Obstetrics Department of the Hospital de Clínicas of the UFTM and were diagnosed with syphilis between 2007 and 2016 were reviewed. A standardized form was used to collect epidemiological, obstetric data and outcomes of congenital infection. The present research has been authorized by the Ethics Committee of the institution.
RESULTS:  There were 268 women diagnosed with syphilis, with an average age of 23.6 years old. The majority of the patients were from Uberaba. Inadequate prenatal care was observed in 37.9% of the pregnant women. Only 34.2% of the patients completed the treatment according to the guidelines issued by the Ministry of Health of Brazil, and 19.8% of the partners of the patients underwent adequate syphilis treatment; 37 (13.8%) couples (patients and partners) underwent correct treatment. Regarding the obstetric outcomes, 4 (1.5%) patients had a miscarriage and 8 (3.4%) had fetal losses (from the fetal loss group, 7 had no adequate treatment); 61 (25.9%) patients had premature births - this prematurity has been significantly correlated to inadequate or incomplete treatment in 49 (27.9%) patients, compared with 12 (13.0%) patients with premature births and adequate treatment (p = 0.006). The average live newborn weight was 2,840 g; 25.3% had a birth weight < 2,500 g; 74.2% had congenital syphilis, a data with heavy correlation to inadequate or incomplete prenatal care, prematurity, and low birth weight.
CONCLUSION:  Public awareness policies on adequate prenatal care, intensification of serological screening, and early treatment of syphilis are needed, considering the rise of cases diagnosed during gestation and its potentially preventable deleterious consequences related to congenital transmission.

PMID: 30786305 [PubMed - indexed for MEDLINE]

The effectiveness of using entertainment education narratives to promote safer sexual behaviors of youth: A meta-analysis, 1985-2017.

Tue, 11/05/2019 - 08:18
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The effectiveness of using entertainment education narratives to promote safer sexual behaviors of youth: A meta-analysis, 1985-2017.

PLoS One. 2019;14(2):e0209969

Authors: Orozco-Olvera V, Shen F, Cluver L

Abstract
BACKGROUND: Risky sexual behaviors are associated with the transmission of sexually transmitted infections (STIs) and unwanted pregnancies, both major health concerns for youth worldwide. This review studies the effectiveness of narrated mass media programs in promoting safer sexual practices among youth in developed and developing countries.
METHODS: Electronic and manual searches were conducted to identify experimental and quasi-experimental studies with robust counterfactual designs published between 1985 and the first quarter of 2017. Effect sizes were meta-analyzed using mixed-effects models.
RESULTS: Eight experimental and two quasi-experimental studies met our inclusion criteria. The aggregated sample size was 23,476 participants, with a median of 902 participants per study. Entertainment education narratives had small but significant effects for three sexual behaviors. It reduced the number of sexual partners [standardized mean difference, (SMD) = 0.17, 95% confidence interval (CI) = 0.02-0.33, three effect sizes], reduced unprotected sex (SMD = 0.08, 95% CI = 0.03-0.12, nine effect sizes), and increased testing and management for STIs (SMD = 0.29, 95% CI = 0.11-0.46, two effect sizes). The interventions were not effective in reducing inter-generational sex, measured through the age-gap with sexual partners (SMD = 0.06, 95% CI = -0.06-0.19, four effect sizes). Entertainment education had medium-size effects on knowledge outcomes (SMD = 0.67, 95% CI = 0.32-1.02, seven effect sizes), where a time-decay relationship is observed. No effects were found on attitudes.
CONCLUSION: Although mass media entertainment had small effects in promoting safer sexual practices, its economies of scales over face-to-face interventions suggest its potential to be a cost-effective tool above an audience threshold. The use of study participants from the general youth population and the use of mostly effectiveness trials mitigate concerns regarding its scalability. The overall paucity of high-quality studies affirms the need for strengthening the evidence base of entertainment education. Future research should be undertaken to understand the moderator effects for different subgroups and intervention characteristics.

PMID: 30753185 [PubMed - indexed for MEDLINE]

Sexual Risk Behavior Among Youth With Bipolar Disorder: Identifying Demographic and Clinical Risk Factors.

Sat, 11/02/2019 - 06:12
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Sexual Risk Behavior Among Youth With Bipolar Disorder: Identifying Demographic and Clinical Risk Factors.

J Am Acad Child Adolesc Psychiatry. 2018 02;57(2):118-124

Authors: Krantz M, Goldstein T, Rooks B, Merranko J, Liao F, Gill MK, Diler R, Hafeman D, Ryan N, Goldstein B, Yen S, Hower H, Hunt J, Keller M, Strober M, Axelson D, Birmaher B

Abstract
OBJECTIVE: This study aims to document rates of sexual activity among youth with bipolar spectrum disorder (BD) and to examine demographic and clinical factors associated with first sexual activity and sexual risk behavior during follow-up.
METHOD: The sample was drawn from the Course and Outcome of Bipolar Youth (COBY) study of 413 youth 7 to 17 years at baseline who met criteria for bipolar spectrum disorder according to the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Psychiatric symptoms during follow-up were assessed using the Adolescent Longitudinal Interview Follow-Up Evaluation (ALIFE). Sexual behavior and level of sexual risk (e.g., unprotected sex, multiple partners, and/or partners with known sexually transmitted infections) were assessed by trained evaluators using the ALIFE Psychosocial Functioning Scale. Analyses were conducted in relation to first sexual behavior during follow-up and then to subsequent sexual behaviors (mean 9.7 years, standard deviation 3.2).
RESULTS: Sexually active COBY youth (n = 292 of 413; 71%) were more likely females, using substances, and not living with both parents. Consistent with findings among healthy youth, earlier first sexual activity in the sample was significantly associated with low socioeconomic status, female sex, comorbid disruptive behavior disorder, and substance use. As with healthy youth, sexual risk behavior during follow-up was significantly associated with non-Caucasian race, low socioeconomic status, substance use, and history of sexual abuse. Of those COBY youth who were sexually active, 11% reported sexual assault or abuse, 36% reported becoming pregnant (or the significant other becoming pregnant), and 15% reported having at least 1 abortion (or the significant other having an abortion) during follow-up. Hypomanic symptoms during follow-up were temporally associated with the greatest risk for sexual risk behavior.
CONCLUSION: Demographic and clinical factors could help identify youth with bipolar spectrum disorder at significantly greatest risk for sexual activity and sexual risk behavior. Attending to sexual risk behaviors in this population is warranted.

PMID: 29413144 [PubMed - indexed for MEDLINE]

C4BP-IgM protein as a novel therapeutic approach to treat Neisseria gonorrhoeae infections.

Wed, 10/30/2019 - 06:06

C4BP-IgM protein as a novel therapeutic approach to treat Neisseria gonorrhoeae infections.

JCI Insight. 2019 Oct 29;:

Authors: Bettoni S, Shaughnessy J, Maziarz K, Ermert D, Gulati S, Zheng B, Mörgelin M, Jacobsson S, Riesbeck K, Unemo M, Ram S, Blom AM

Abstract
Gonorrhea is a sexually transmitted infection with 87 million new cases per year globally. Increasing antibiotic resistance has severely limited treatment options. A mechanism that Neisseria gonorrhoeae uses to evade complement attack is binding of the complement inhibitor C4b-binding protein (C4BP). We screened 107 PorB1a and 83 PorB1b clinical isolates randomly selected from a Swedish strain collection over the last 10 years and noted that 96/107 (89.7%) PorB1a and 16/83 (19.3%) PorB1b bound C4BP; C4BP binding significantly correlated with the ability to evade complement-dependent killing (r = 0.78; p<0.0001). We designed two chimeric proteins that fused C4BP domains to the backbone of immunoglobulins IgG or IgM (C4BP-IgG; C4BP-IgM) with the aim of enhancing complement activation and killing of gonococci. Both proteins bound gonococci (Kd C4BP-IgM = 2.4 nM; Kd C4BP-IgG 981 nM), but only hexameric C4BP-IgM efficiently out-competed heptameric C4BP from bacterial surface resulting in enhanced complement deposition and bacterial killing. Furthermore, C4BP-IgM significantly attenuated the duration and burden of colonization of two C4BP-binding gonococcal isolates, but not a C4BP non-binding strain in the mouse vaginal colonization model using human factor H/C4BP transgenic mice. Our pre-clinical data present C4BP-IgM as an adjunctive to conventional antimicrobials for the treatment of gonorrhea.

PMID: 31661468 [PubMed - as supplied by publisher]

Sexually Transmitted Infections in Pregnancy and Reproductive Health: Proceedings of the STAR Sexually Transmitted Infection Clinical Trial Group Programmatic Meeting.

Tue, 10/29/2019 - 15:05
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Sexually Transmitted Infections in Pregnancy and Reproductive Health: Proceedings of the STAR Sexually Transmitted Infection Clinical Trial Group Programmatic Meeting.

Sex Transm Dis. 2019 Oct 22;:

Authors: Wynn A, Bristow CC, Cristillo AD, Murphy SM, van den Broek N, Muzny C, Kallapur S, Cohen C, Ingalls RR, Wiesenfeld H, Litch JA, Morris SR, Klausner JD

Abstract
The goal of the STAR Sexually Transmitted Infection Clinical Trial Group (STI CTG) Programmatic meeting on STIs in Pregnancy and Reproductive Health in April 2018 was to review the latest research and develop recommendations to improve prevention and management of STIs during pregnancy. Experts from academia, government, non-profit and industry discussed the burden of STIs during pregnancy, the impact of STIs on adverse pregnancy and birth outcomes, interventions that work to reduce STIs in pregnancy, and the evidence, policy, and technology needed to improve STI care during pregnancy. Key points of the meeting are as follows: (i) Alternative treatments and therapies for use during pregnancy are needed; (ii) Further research into the relationship between the vaginal microbiome and STIs during pregnancy should be supported; (iii) More research to determine whether STI tests function equally well in pregnant as non-pregnant women is needed; (iv) Development of new lower cost, rapid point-of-care testing assays could allow for expanded STI screening globally; (v) Policies should be implemented that create standard screening and treatment practices globally; (vi) Federal funding should be increased for STI testing and treatment initiatives supported by the Centers for Disease Control and Prevention (CDC), the Centers of Excellence in STI Treatment, public STD clinics, and the President's Emergency Plan for AIDS Relief (PEPFAR).

PMID: 31658242 [PubMed - as supplied by publisher]

Non-standard treatment for uncomplicated Chlamydia trachomatis urogenital infections: a systematic review.

Tue, 10/29/2019 - 15:05
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Non-standard treatment for uncomplicated Chlamydia trachomatis urogenital infections: a systematic review.

BMJ Open. 2018 12 04;8(12):e023808

Authors: Krahn J, Louette A, Caine V, Ha S, Wong T, Lau TTY, Singh AE

Abstract
OBJECTIVES: To review the literature for non-standard treatment options for uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults.
DESIGN: Systematic review.
DATA SOURCES: Ovid MEDLINE/PubMed, Ovid EMBASE, Cochrane Trials & Systematic Review Databases, CINAHL Plus with Full Text, Web of Science Core Collection, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and Health Canada Trials Database were searched for studies in English or French from 1 January 2006 to 6 August 2017. Keywords included CT, anti-infective or anti-bacterial agents, therapy/pharmacotherapy/management.
REVIEW METHODS: Included were primary research studies. Outcome measures included clinical or microbiological cure, treatment failure and adverse events. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed for risk of bias using the Revised Cochrane Risk of Bias V.2.0 tool for randomised and the Newcastle-Ottawa Quality Assessment Scale for non-randomised studies.
FUNDING SOURCE: Public Health Agency of Canada.
RESULTS: Of the 6899 records identified through the database search, 11 studies were included. One randomised controlled trial reported that delayed release doxycycline was non-inferior to azithromycin. Two studies examined higher doses of azithromycin but reported no additional benefit. One study looked at a 5-day azithromycin treatment regimen and reported a high cure rate. Two studies reported efficacy of sitafloxacin, and a single study supports the use of levofloxacin. Two phase 2 studies reported efficacy of single-dose rifalazil in both men and women. Only one retrospective study was identified that examined treatment in pregnant women and reported that efficacy with single-dose azithromycin exceeded that of amoxicillin and erythromycin. A single study examining the efficacy of a beta-lactam antibiotic was stopped early due to high treatment failures.
CONCLUSIONS: The paucity of existing data highlights the need for further adequately powered studies to evaluate rifalazil, delayed release doxycycline, levofloxacin and other agents for the treatment of uncomplicated CT infections.
PROSPERO REGISTRATION NUMBER: CRD42017073096.

PMID: 30518587 [PubMed - indexed for MEDLINE]

Direct-qPCR Assay for Coupled Identification and Antimicrobial Susceptibility Testing of Neisseria gonorrhoeae.

Tue, 10/29/2019 - 15:05
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Direct-qPCR Assay for Coupled Identification and Antimicrobial Susceptibility Testing of Neisseria gonorrhoeae.

ACS Infect Dis. 2018 09 14;4(9):1377-1384

Authors: Chen L, Shin DJ, Zheng S, Melendez JH, Gaydos CA, Wang TH

Abstract
Multidrug-resistant gonorrhea has become an urgent issue for global public health. As the causative agent of gonorrhea, Neisseria gonorrhoeae, has been progressively developing resistance to nearly all prescribed antimicrobial drugs, monitoring its antimicrobial resistance on a broader scale has become a crucial agenda for effective antibiotic stewardship. Unfortunately, gold standard antimicrobial susceptibility testing (AST) relies on time and labor-intensive phenotypic assays, which lag behind the current diagnostic workflow for N. gonorrhoeae identification based on nucleic acid amplification tests (NAAT). Newer assay technologies based on NAAT can rapidly identify N. gonorrhoeae from clinical specimen but fundamentally lack the capacity to provide phenotypic AST information. Herein, we propose a direct-quantitative PCR (direct-qPCR) assay that enables pathogen-specific identification and phenotypic AST via quantitative measurement of N. gonorrhoeae growth directly from a liquid medium without any sample preprocessing. The assay has an analytical sensitivity of 102 CFU/mL and is highly specific to N. gonorrhoeae in the presence of urogenital flora and clinical swab eluent. We tested seven N. gonorrhoeae strains against three antibiotic agents, penicillin, tetracycline, and ciprofloxacin, and achieved 95.2% category agreement and 85.7% essential agreement with the FDA-approved E-test. The assay presented in this work has the unique ability to identify N. gonorrhoeae and provide phenotypic AST directly from the liquid medium with cell densities as low as 102 CFU/mL, demonstrating an accelerated, sensitive, and scalable workflow for performing both identification and AST of  N. gonorrhoeae.

PMID: 29999304 [PubMed - indexed for MEDLINE]

Trends in Antimicrobial Resistance Patterns in Neisseria Gonorrhoeae in Australia and New Zealand: A Meta-analysis and Systematic Review.

Mon, 10/28/2019 - 15:03
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Trends in Antimicrobial Resistance Patterns in Neisseria Gonorrhoeae in Australia and New Zealand: A Meta-analysis and Systematic Review.

Antibiotics (Basel). 2019 Oct 23;8(4):

Authors: Fletcher-Lartey S, Dronavalli M, Alexander K, Ghosh S, Boonwaat L, Thomas J, Robinson A, Patel Z, Forssman B, Pal N

Abstract
(1) Background: The widespread development of resistance among Neisseria gonorrhoeae (NG) clinical isolates has been reported by surveillance systems around the world. This meta-analysis estimated the changes in susceptibility patterns among antibiotics under surveillance in Australia and New Zealand. (2) Methods: Articles published in English from 1980-2018, from Australia or New Zealand, that met the selection criteria were included. The meta-analysis was carried out using the R statistical software. (3) Results: In Australia, there has been decreasing susceptibility of gonococcal isolates to selected antimicrobials over time. Azithromycin (Odds Ratio (OR): 0.73; 95% Confidence Interval (CI) 0.64-0.82) and ceftriaxone (OR: 0.69; 95% CI 0.59-0.80) showed decreasing levels of susceptibility each year. Western Australia (OR: 0.76; 95% CI 0.60-0.96) and Victoria (OR: 0.74; 95% CI 0.60-0.90) also had decreasing levels of susceptibility to ceftriaxone over time compared with other states and territories. (4) Conclusions: The results highlight the need for the development of new approaches for managing cases of gonorrhoea. Improved antimicrobial stewardship, enhanced surveillance and contact tracing are needed to identify and respond to changes in antibiotic resistance in a timely manner. Increasing awareness and public health follow-up of cases can help to interrupt the cycle of infection and limit transmission.

PMID: 31652729 [PubMed]

Macrophage-Neisseria gonorrhoeae Interactions: A Better Understanding of Pathogen Mechanisms of Immunomodulation.

Mon, 10/28/2019 - 15:03
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Macrophage-Neisseria gonorrhoeae Interactions: A Better Understanding of Pathogen Mechanisms of Immunomodulation.

Front Immunol. 2018;9:3044

Authors: Escobar A, Rodas PI, Acuña-Castillo C

Abstract
Neisseria gonorrhoeae is a significant health problem worldwide due to multi-drug resistance issues and absence of an effective vaccine. Patients infected with N. gonorrhoeae have not shown a better immune response in successive infections. This might be explained by the fact that N. gonorrhoeae possesses several mechanisms to evade the innate and adaptative immune responses at different levels. Macrophages are a key cellular component in the innate immune response against microorganisms. The current information suggests that gonococcus can hijack the host response by mechanisms that involve the control of macrophages activity. In this mini review, we intend to condense the recent knowledge on the macrophage-N. gonorrhoeae interactions with a focus on strategies developed by gonococcus to evade or to exploit immune response to establish a successful infection. Finally, we discuss the opportunities and challenges of therapeutics for controlling immune manipulation by N. gonorrhoeae.

PMID: 30627130 [PubMed - indexed for MEDLINE]

Antimicrobial resistance prediction and phylogenetic analysis of Neisseria gonorrhoeae isolates using the Oxford Nanopore MinION sequencer.

Mon, 10/28/2019 - 15:03
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Antimicrobial resistance prediction and phylogenetic analysis of Neisseria gonorrhoeae isolates using the Oxford Nanopore MinION sequencer.

Sci Rep. 2018 12 04;8(1):17596

Authors: Golparian D, Donà V, Sánchez-Busó L, Foerster S, Harris S, Endimiani A, Low N, Unemo M

Abstract
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is common, compromising gonorrhoea treatment internationally. Rapid characterisation of AMR strains could ensure appropriate and personalised treatment, and support identification and investigation of gonorrhoea outbreaks in nearly real-time. Whole-genome sequencing is ideal for investigation of emergence and dissemination of AMR determinants, predicting AMR, in the gonococcal population and spread of AMR strains in the human population. The novel, rapid and revolutionary long-read sequencer MinION is a small hand-held device that generates bacterial genomes within one day. However, accuracy of MinION reads has been suboptimal for many objectives and the MinION has not been evaluated for gonococci. In this first MinION study for gonococci, we show that MinION-derived sequences analysed with existing open-access, web-based sequence analysis tools are not sufficiently accurate to identify key gonococcal AMR determinants. Nevertheless, using an in house-developed CLC Genomics Workbench including de novo assembly and optimised BLAST algorithms, we show that 2D ONT-derived sequences can be used for accurate prediction of decreased susceptibility or resistance to recommended antimicrobials in gonococcal isolates. We also show that the 2D ONT-derived sequences are useful for rapid phylogenomic-based molecular epidemiological investigations, and, in hybrid assemblies with Illumina sequences, for producing contiguous assemblies and finished reference genomes.

PMID: 30514867 [PubMed - indexed for MEDLINE]

Australian Gonococcal Surveillance Programme, 1 January to 31 March 2018

Thu, 10/24/2019 - 08:54
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Australian Gonococcal Surveillance Programme, 1 January to 31 March 2018

Commun Dis Intell (2018). 2019 Jun 17;43:

Authors: Lahra MM, Enriquez RP

PMID: 31203584 [PubMed - indexed for MEDLINE]

Australian Gonococcal Surveillance Programme, 1 July to 30 September 2018

Thu, 10/24/2019 - 08:54
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Australian Gonococcal Surveillance Programme, 1 July to 30 September 2018

Commun Dis Intell (2018). 2019 May 15;43:

Authors: Lahra MM, Enriquez RP, George CRR, The National Neisseria Network

PMID: 31091404 [PubMed - indexed for MEDLINE]

Microbiological Analysis from a Phase 2 Randomized Study in Adults Evaluating Single Oral Doses of Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria gonorrhoeae.

Thu, 10/24/2019 - 08:54
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Microbiological Analysis from a Phase 2 Randomized Study in Adults Evaluating Single Oral Doses of Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria gonorrhoeae.

Antimicrob Agents Chemother. 2018 12;62(12):

Authors: Scangarella-Oman NE, Hossain M, Dixon PB, Ingraham K, Min S, Tiffany CA, Perry CR, Raychaudhuri A, Dumont EF, Huang J, Hook EW, Miller LA

Abstract
We evaluated microbiological correlates for the successful treatment of Neisseria gonorrhoeae isolates from a phase 2 study of gepotidacin, a novel triazaacenaphthylene antibacterial, for therapy of uncomplicated urogenital gonorrhea. Culture, susceptibility testing, genotypic characterization, and frequency of resistance (FoR) were performed for selected isolates. Microbiological success was defined as culture-confirmed eradication of N. gonorrhoeae Against 69 baseline urogenital isolates, gepotidacin MICs ranged from ≤0.06 to 1 µg/ml (MIC90 = 0.5 µg/ml). For gepotidacin, the ratio of the area under the free-drug concentration-time curve to the MIC (fAUC/MIC) was associated with therapeutic success. Success was 100% (61/61) at fAUC/MICs of ≥48 and decreased to 63% (5/8) for fAUC/MICs of ≤25. All 3 isolates from microbiological failures were ciprofloxacin resistant, had a baseline gepotidacin MIC of 1 µg/ml, and carried a preexisting ParC D86N mutation, a critical residue for gepotidacin binding. In a test-of-cure analysis, the resistance to gepotidacin emerged in 2 isolates (MICs increased ≥32-fold) with additional GyrA A92T mutations, also implicated in gepotidacin binding. Test-of-cure isolates had the same sequence type as the corresponding baseline isolates. For 5 selected baseline isolates, all carrying a ParC D86N mutation, the in vitro FoR to gepotidacin was low (10-9 to 10-10); the resistant mutants had the same A92T mutation as the 2 isolates in which resistance emerged. Five participants with isolates harboring the ParC D86N mutation were treatment successes. In summary, fAUC/MICs of ≥48 predicted 100% microbiological success, including 3 isolates with the ParC D86N mutation (fAUC/MICs ≥ 97). Pharmacokinetic/pharmacodynamic determinations may help to evaluate new therapies for gonorrhea; further study of gepotidacin is warranted. (This study has been registered at ClinicalTrials.gov under identifier NCT02294682.).

PMID: 30249694 [PubMed - indexed for MEDLINE]

Two cases of multidrug-resistant genitourinary Mycoplasma genitalium infection successfully eradicated with minocycline.

Wed, 10/23/2019 - 08:52
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Two cases of multidrug-resistant genitourinary Mycoplasma genitalium infection successfully eradicated with minocycline.

Int J STD AIDS. 2019 04;30(5):512-514

Authors: Glaser AM, Geisler WM, Ratliff AE, Xiao L, Waites KB, Gaisa M

Abstract
Mycoplasma genitalium (MG) infection is a sexually transmitted infection that causes up to 25% of nongonococcal urethritis (NGU). MG strains carrying genetic markers of antimicrobial resistance that may affect treatment outcomes are increasingly recognized as a public health concern. We present two cases of persistent MG NGU with strains carrying both macrolide and quinolone resistance-associated mutations that were eradicated successfully by an extended course of minocycline.

PMID: 30999836 [PubMed - indexed for MEDLINE]

In vitro activity of the novel triazaacenaphthylene gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae.

Wed, 10/23/2019 - 08:52
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In vitro activity of the novel triazaacenaphthylene gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae.

J Antimicrob Chemother. 2018 08 01;73(8):2072-2077

Authors: Jacobsson S, Golparian D, Scangarella-Oman N, Unemo M

Abstract
Objectives: Increased antimicrobial resistance surveillance and new effective antimicrobials are crucial to maintain treatable gonorrhoea. We examined the in vitro activity of gepotidacin, a novel triazaacenaphthylene, and the effect of efflux pump inactivation on clinical Neisseria gonorrhoeae isolates and international reference strains (n = 252) and compared gepotidacin with antimicrobials currently or previously recommended for gonorrhoea treatment.
Methods: MICs (mg/L) were determined by agar dilution (gepotidacin) or by Etest (seven other antimicrobials). The gyrA and parC genes were sequenced and the impact of inactivation of the MtrCDE, MacAB and NorM efflux pumps on gepotidacin MICs was examined.
Results: Gepotidacin showed potent in vitro activity against all gonococcal isolates (n = 252; MIC ≤4 mg/L). The modal MIC, MIC50, MIC90 and MIC range of gepotidacin were 0.5, 0.5, 1 and 0.032-4 mg/L, respectively. Inactivation of the MtrCDE efflux pump, but not MacAB or NorM, decreased the gepotidacin MICs for most strains. No significant cross-resistance between gepotidacin and any other antimicrobials, including the fluoroquinolone ciprofloxacin, was identified. However, the ParC D86N mutation (possibly together with additional antimicrobial resistance mutation), which is associated with fluoroquinolone resistance, was associated with increased gepotidacin MICs.
Conclusions: Gepotidacin demonstrated high in vitro activity against gonococcal strains, indicating that gepotidacin could potentially be an effective option for gonorrhoea treatment, particularly in a dual antimicrobial therapy regimen and for patients with resistance or allergy to extended-spectrum cephalosporins. Nevertheless, elucidating in vitro and in vivo resistance emergence and mechanisms in detail, together with further gonorrhoea clinical studies, ideally also including chlamydia and Mycoplasma genitalium are essential.

PMID: 29796611 [PubMed - indexed for MEDLINE]

Novel Chlamydia species isolated from snakes are temperature-sensitive and exhibit decreased susceptibility to azithromycin.

Wed, 10/23/2019 - 08:52
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Novel Chlamydia species isolated from snakes are temperature-sensitive and exhibit decreased susceptibility to azithromycin.

Sci Rep. 2018 04 04;8(1):5660

Authors: Staub E, Marti H, Biondi R, Levi A, Donati M, Leonard CA, Ley SD, Pillonel T, Greub G, Seth-Smith HMB, Borel N

Abstract
Chlamydia species have recently been recognized as emerging pathogens in snakes. However, isolation of novel snake chlamydiae is critical and their growth characteristics are largely unknown. In this study, two novel chlamydial species are described: Chlamydia serpentis and Chlamydia poikilothermis, isolated after attempts on 23 cloacal and choanal swabs from 18 PCR-positive captive snakes originating from different Swiss snake collections. Isolation success, growth curve and infectivity rates over a 48-hour time period were dependent on temperature (37 °C for C. serpentis, 28 °C for C. poikilothermis). C. serpentis and C. poikilothermis were sensitive to tetracycline and moxifloxacin during evaluation by in vitro antibiotic susceptibility assay but intermediate to resistant (2-4 μg/ml) to azithromycin. Whole genome sequencing of the isolates provided proof of the novel species status, and gives insights into the evolution of these branches of genus Chlamydia.

PMID: 29618824 [PubMed - indexed for MEDLINE]

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