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Associations Between Patterns of Sexual Initiation, Sexual Partnering, and Sexual Health Outcomes from Adolescence to Early Adulthood.

Thu, 09/19/2019 - 07:47
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Associations Between Patterns of Sexual Initiation, Sexual Partnering, and Sexual Health Outcomes from Adolescence to Early Adulthood.

Arch Sex Behav. 2018 08;47(6):1791-1810

Authors: Kahn NF, Halpern CT

Abstract
The goal of this study was to examine, in a nationally representative sample, relationships between various sexual initiation patterns, subsequent sexual partnerships, and related health outcomes from adolescence through early adulthood. Data were from a subset of 6587 respondents from the National Longitudinal Study of Adolescent to Adult Health. Bivariate analyses and adjusted logistic and ordinary least squares regression models were used to determine associations between membership in three sexual initiation classes, lifetime sexual partner counts, and multiple health outcomes, including lifetime sexually transmitted infection or disease (STI/STD) diagnosis, lifetime unintended pregnancy, and romantic relationship quality. Broadly, having fewer lifetime sexual partners was associated with lower odds of STI/STD diagnosis and unintended pregnancy, and better relationship quality; however, findings also indicated both within and between sexual initiation class differences in the relationship between lifetime sexual partners and all three health outcomes. In particular, results showed little variation in health outcomes by sexual partnering among those who postponed sexual activity, but members of the class characterized by early and atypical sexual initiation patterns who had fewer lifetime partners exhibited better health outcomes than most other initiation groups. These results show that while both sexual initiation and partnering patterns add important information for understanding sexual health from adolescence to early adulthood, partnering may be more relevant to these sexual health outcomes. Findings indicate a need for more comprehensive sexuality education focused on sexual risk reduction and promotion of relationship skills among adolescents and adults.

PMID: 29594701 [PubMed - indexed for MEDLINE]

Using genomics to understand antimicrobial resistance and transmission in Neisseria gonorrhoeae.

Sat, 09/14/2019 - 07:37
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Using genomics to understand antimicrobial resistance and transmission in Neisseria gonorrhoeae.

Microb Genom. 2019 02;5(2):

Authors: Sánchez-Busó L, Harris SR

Abstract
Gonorrhoea infections are on the increase and strains that are resistant to all antimicrobials used to treat the disease have been found worldwide. These observations encouraged the World Health Organization to include Neisseria gonorrhoeae on their list of high-priority organisms in need of new treatments. Fortunately, concurrent resistance to both antimicrobials used in dual therapy is still rare. The fight against antimicrobial resistance (AMR) must begin from an understanding of how it evolves and spreads in sexual networks. Genome-based analyses have allowed the study of the gonococcal population dynamics and transmission, giving a novel perspective on AMR gonorrhoea. Here, we will review past, present and future treatment options for gonorrhoea and explain how genomics is helping to increase our understanding of the changing AMR and transmission landscape. This article contains data hosted by Microreact.

PMID: 30698520 [PubMed - indexed for MEDLINE]

Enhanced molecular typing and macrolide and tetracycline-resistance mutations of Treponema pallidum in Barcelona.

Fri, 09/13/2019 - 07:36
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Enhanced molecular typing and macrolide and tetracycline-resistance mutations of Treponema pallidum in Barcelona.

Future Microbiol. 2019 Sep;14:1099-1108

Authors: Fernández-Naval C, Arando M, Espasa M, Antón A, Fernández-Huerta M, Silgado A, Jimenez I, Villatoro AM, González-López JJ, Serra-Pladevall J, Sulleiro E, Pumarola T, Vall-Mayans M, Esperalba J

Abstract
Aim: To describe the molecular types of Treponema pallidum and the proportion of macrolide and tetracycline resistance mutations in Barcelona. Materials & methods: Molecular type was determined using the Enhanced-CDC Typing system and antibiotic resistance was determined by sequencing the 23S and 16S rRNA genes. Results: A total of 183 patients were enrolled and 213 specimens (99 ulcers, 114 bloods) were collected. Sixty-two (70.5%) of 88 ulcers and 0 (0%) of bloods T. pallidum-DNA containing samples were fully typed. Up to 21 different strain types were identified (14d/g in 27.4%; 14f/g in 14.5%). Macrolide resistance mutations were present in 95% and tetracycline in 0%. Conclusion: Several different strains co-exist in Barcelona with a high proportion of macrolide resistance and absence of tetracycline resistance.

PMID: 31512516 [PubMed - in process]

Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates in Yaoundé, Cameroon From 2009 to 2014.

Fri, 09/13/2019 - 07:36
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Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates in Yaoundé, Cameroon From 2009 to 2014.

Sex Transm Dis. 2018 12;45(12):e101-e103

Authors: Tayimetha CY, Unemo M

Abstract
We investigated the antimicrobial resistance in gonococci 2009 to 2014 in Yaoundé, Cameroon, and recommend revisions of the Cameroonian treatment guideline. We observed a high resistance to ciprofloxacin (17.6%) but no ceftriaxone resistance. Ceftriaxone should replace ciprofloxacin as the recommended first-line treatment for urethral/vaginal discharge. Enhanced resistance surveillance in Africa is essential.

PMID: 30234796 [PubMed - indexed for MEDLINE]

Proceedings of the 2017 International Forum on Gonococcal Infections and Resistance in Shenzhen, China.

Fri, 09/13/2019 - 07:36
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Proceedings of the 2017 International Forum on Gonococcal Infections and Resistance in Shenzhen, China.

Sex Transm Dis. 2018 10;45(10):e75-e79

Authors: Chen XS, key 2017 IFGIR contributors

Abstract
The 2017 International Forum on Gonococcal Infections and Resistance (2017 IFGIR) was held at Shenzhen, China from September 17, 2017, to September 19, 2017. The key objectives of the conference were to review and analyze the epidemiological profiles of gonococcal infections and antimicrobial resistance (AMR) at global, regional, and national levels; to share and discuss findings from ongoing and completed research studies; and to identify research needs to respond to the spread of gonococcal infections and AMR. The following contents were presented at the conference: global estimates of infections with Neisseria gonorrhoeae; global, regional and country status of gonococcal AMR; molecular techniques for predicting gonococcal AMR and the use of these technologies to enhance gonococcal AMR surveillance and clinical management; and updates on therapeutic approaches to gonococcal AMR.

PMID: 29664765 [PubMed - indexed for MEDLINE]

A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx.

Fri, 09/13/2019 - 07:36
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A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx.

Sex Transm Dis. 2018 10;45(10):677-683

Authors: Barbee LA, Nayak SU, Blumer JL, OʼRiordan MA, Gray W, Zenilman JM, Golden MR, Griffiss JM

Abstract
BACKGROUND: There are no fully oral recommended treatment regimens for gonorrhea. Inadequately treated pharyngeal gonococcal infections are a likely reservoir for transmission and development of antimicrobial resistance. We sought to determine an oral cefixime dosing regimen that would theoretically treat pharyngeal infections by gonococci with minimum inhibitory concentrations 0.5 μg/mL.
METHODS: We conducted an open-label, nonrandomized, phase I pharmacokinetic and safety study of cefixime in 25 healthy male and female volunteers divided into 4 dosing cohorts (cohort A, 400 mg; cohort B, 800 mg; cohort C, 1200 mg; and cohort D, 800 mg every 8 hours × 3 doses [total dose 2400 mg]) with a target serum concentration of at least 2.0 μg/mL for more than 20 hours. Cefixime concentrations from serum and pharyngeal fluid were determined with use of a validated liquid chromatography-tandem mass spectrometry assay. Safety measures included laboratories, physical examinations, and symptom diaries.
RESULTS: None of the single-dose regimens attained the target concentration; however, 50% of subjects in cohort D attained the target concentration. Variation in absorption and protein binding contributed to differences in concentrations. Pharyngeal fluid concentrations were negligible. The single-dose regimens were well tolerated; the multidose regimen resulted in mild to moderate gastrointestinal symptoms in 43% of subjects.
CONCLUSIONS: None of the dosing regimens achieved the target concentration. However, the proposed theoretical target was extrapolated from penicillin data; there are no empirically derived pharmacokinetic/pharmacodynamic criteria for pharyngeal gonorrhea. Under alternative cephalosporin-specific therapeutic goals, the multidose regimen may be effective, although the absence of cefixime in pharyngeal fluid is concerning. A clinical trial evaluating efficacy and defining pharmacokinetic/pharmacodynamic outcomes may be warranted.

PMID: 29624558 [PubMed - indexed for MEDLINE]

[¿Azitromicina como tratamiento contra Chlamydia trachomatis?]

Thu, 09/12/2019 - 07:34
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[¿Azitromicina como tratamiento contra Chlamydia trachomatis?]

Gac Med Mex. 2018;154(6):689-692

Authors: Maldonado-Calderón JL, López-Márquez FC, Ruiz-Flores P

Abstract
Azithromycin and doxycycline effectiveness has been demonstrated in the treatment of urogenital chlamydiasis, which has remained unchanged for a long time. Autoinoculation has been proposed as a method of reinfection and persistence of the disease in women and probably also owing to azithromycin pharmacokinetics in this tissue. With the new diagnostic methods and tests of cure, a difference has been demonstrated in favor of doxycycline in the treatment of rectal chlamydiasis Antimicrobial resistance has not played a relevant role since no treatment-resistant strains have been found in vivo. Nevertheless, azithromycin remains a first-choice drug, since it can be administered as a single dose, which favors therapeutic adherence.

PMID: 30532107 [PubMed - indexed for MEDLINE]

Making the Most of Point-of-care Testing for Sexually Transmitted Diseases.

Wed, 09/11/2019 - 10:32

Making the Most of Point-of-care Testing for Sexually Transmitted Diseases.

Clin Infect Dis. 2019 Aug 29;:

Authors: Van Der Pol B

PMID: 31504333 [PubMed - as supplied by publisher]

Potential for Point-of-Care Tests to Reduce Chlamydia-associated Burden in the United States: A Mathematical Modeling Analysis.

Wed, 09/11/2019 - 10:32

Potential for Point-of-Care Tests to Reduce Chlamydia-associated Burden in the United States: A Mathematical Modeling Analysis.

Clin Infect Dis. 2019 Aug 29;:

Authors: Rönn MM, Menzies NA, Gift TL, Chesson HW, Trikalinos TA, Bellerose M, Malyuta Y, Berruti A, Gaydos CA, Hsu KK, Salomon JA

Abstract
BACKGROUND: Point-of-care testing (POCT) assays for chlamydia are being developed. Their potential impact on the burden of chlamydial infection in the United States, in light of suboptimal screening coverage, remains unclear.
METHODS: Using a transmission model calibrated to data in the United States, we estimated the impact of POCT on chlamydia prevalence, incidence, and chlamydia-attributable pelvic inflammatory disease (PID) incidence, assuming status quo (Analysis 1) and improved (Analysis 2) screening frequencies. We tested the robustness of results to changes in POCT sensitivity, the proportion of patients getting treated immediately, the baseline proportion lost to follow-up (LTFU), and the average treatment delay.
RESULTS: In Analysis 1, high POCT sensitivity was needed to reduce the chlamydia-associated burden. With a POCT sensitivity of 90%, reductions from the baseline burden only occurred in scenarios in which over 60% of the screened individuals would get immediate treatment and the baseline LTFU proportion was 20%. With a POCT sensitivity of 99% (baseline LTFU 10%, 2-week treatment delay), if everyone were treated immediately, the prevalence reduction was estimated at 5.7% (95% credible interval [CrI] 3.9-8.2%). If only 30% of tested persons would wait for results, the prevalence reduction was only 1.6% (95% CrI 1.1-2.3). POCT with 99% sensitivity could avert up to 12 700 (95% CrI 5000-22 200) PID cases per year, if 100% were treated immediately (baseline LTFU 20% and 3-week treatment delay). In Analysis 2, when POCT was coupled with increasing screening coverage, reductions in the chlamydia burden could be realized with a POCT sensitivity of 90%.
CONCLUSIONS: POCT could improve chlamydia prevention efforts if test performance characteristics are significantly improved over currently available options.

PMID: 31504314 [PubMed - as supplied by publisher]

Identification of Novel Neisseria gonorrhoeae Lineages Harboring Resistance Plasmids in Coastal Kenya.

Wed, 09/11/2019 - 10:32
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Identification of Novel Neisseria gonorrhoeae Lineages Harboring Resistance Plasmids in Coastal Kenya.

J Infect Dis. 2018 07 24;218(5):801-808

Authors: Cehovin A, Harrison OB, Lewis SB, Ward PN, Ngetsa C, Graham SM, Sanders EJ, Maiden MCJ, Tang CM

Abstract
Background: Africa has the highest incidence of gonorrhea in the world. However, little is known about gonococcal populations in this continent or mechanisms of antimicrobial resistance (AMR).
Methods: Whole-genome sequence data were analyzed from 103 Neisseria gonorrhoeae isolates from 73 patients, mainly men who have sex with men, from coastal Kenya. We annotated loci, defined the core genome, defined mechanisms of AMR, and performed phylogenetic analysis. For patients with multiple episodes of gonorrhea, we determined whether infections occurred with related strains.
Results: We identified 3 clusters of isolates that are phylogenetically distinct from isolates found elsewhere. Plasmids were virtually ubiquitous: pTetM and pblaTEM were found in 97%, and 55% of isolates, respectively. This was associated with high doxycycline use for undiagnosed sexually transmitted infections. Twenty-three percent of multiple episodes of gonorrhea in the same individual were caused by a related strain, suggesting inadequate treatment or reinfection.
Conclusions: The prevalence of plasmid-mediated AMR in Kenyan gonococci contrasts with that in wealthy countries, where AMR is largely chromosomally mediated. Antimicrobials have a profound effect on the maintenance of lineages harboring plasmids. Doxycycline can select for tetracycline and penicillin resistance, through plasmid cooperation. Understanding the mechanisms of AMR in high-risk groups is required to inform treatment strategies.

PMID: 29701830 [PubMed - indexed for MEDLINE]

Putative vaccine candidates and drug targets identified by reverse vaccinology and subtractive genomics approaches to control Haemophilus ducreyi, the causative agent of chancroid.

Sat, 09/07/2019 - 07:24
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Putative vaccine candidates and drug targets identified by reverse vaccinology and subtractive genomics approaches to control Haemophilus ducreyi, the causative agent of chancroid.

J R Soc Interface. 2018 05;15(142):

Authors: de Sarom A, Kumar Jaiswal A, Tiwari S, de Castro Oliveira L, Barh D, Azevedo V, Jose Oliveira C, de Castro Soares S

Abstract
Chancroid is a sexually transmitted infection (STI) caused by the Gram-negative bacterium Haemophilus ducreyi The control of chancroid is difficult and the only current available treatment is antibiotic therapy; however, antibiotic resistance has been reported in endemic areas. Owing to recent outbreaks of STIs worldwide, it is important to keep searching for new treatment strategies and preventive measures. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine and drug targets against 28 strains of H. ducreyi We identified 847 non-host homologous proteins, being 332 exposed/secreted/membrane and 515 cytoplasmic proteins. We also checked their essentiality, functionality and virulence. Altogether, we predicted 13 candidate vaccine targets and three drug targets, where two vaccines (A01_1275, ABC transporter substrate-binding protein; and A01_0690, Probable transmembrane protein) and three drug targets (A01_0698, Purine nucleoside phosphorylase; A01_0702, Transcription termination factor; and A01_0677, Fructose-bisphosphate aldolase class II) are harboured by pathogenicity islands. Finally, we applied a molecular docking approach to analyse each drug target and selected ZINC77257029, ZINC43552589 and ZINC67912117 as promising molecules with favourable interactions with the target active site residues. Altogether, the targets identified here may be used in future strategies to control chancroid worldwide.

PMID: 29792307 [PubMed - indexed for MEDLINE]

Impact of Deployment on Reproductive Health in U.S. Active-Duty Servicewomen and Veterans.

Thu, 09/05/2019 - 10:21
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Impact of Deployment on Reproductive Health in U.S. Active-Duty Servicewomen and Veterans.

Semin Reprod Med. 2018 11;36(6):361-370

Authors: Gawron LM, Mohanty AF, Kaiser JE, Gundlapalli AV

Abstract
Reproductive-age women are a fast-growing component of active-duty military personnel who experience deployment and combat more frequently than previous service-era women Veterans. With the expansion of the number of women and their roles, the United States Departments of Defense and Veterans Affairs have prioritized development and integration of reproductive services into their health systems. Thus, understanding associations between deployments or combat exposures and short- or long-term adverse reproductive health outcomes is imperative for policy and programmatic development. Servicewomen and women Veterans may access reproductive services across civilian and military or Veteran systems and providers, increasing the need for awareness and communication regarding deployment experiences with a broad array of providers. An example is the high prevalence of military sexual trauma reported by women Veterans and the associated mental health diagnoses that may lead to a lifetime of high risk-coping behaviors that increase reproductive health risks, such as sexually transmitted infections, unintended pregnancies, and others. Care coordination models that integrate reproductive healthcare needs, especially during vulnerable times such as at the time of military separation and in the immediate postdeployment phase, may identify risk factors for early intervention with the potential to mitigate lifelong risks.

PMID: 31003251 [PubMed - indexed for MEDLINE]

Neisseria Gonorrhoae and their antimicrobial susceptibility patterns among symptomatic patients from Gondar town, north West Ethiopia.

Wed, 09/04/2019 - 07:19
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Neisseria Gonorrhoae and their antimicrobial susceptibility patterns among symptomatic patients from Gondar town, north West Ethiopia.

Antimicrob Resist Infect Control. 2018;7:85

Authors: Yeshanew AG, Geremew RA

Abstract
Background: Neisseria gonorrhoeae, the causative agent of gonorrhoea, is a Gram negative, coffee-bean shaped facultative intracellular diplococcus bacterium, the classical sexually transmitted bacteria. Nowadays, N. gonorrhoeae has developed high-level resistance to all traditional antimicrobials used for the treatment of gonorrhoea and makes the treatment complicated. So, the aim of this study was to determine magnitude and antimicrobial resistance patterns of N. gonorrhoeae.
Methods: A cross sectional study was conducted between April and August 2016 among STI clinic clients in Gondar town hospitals and health centers. Urethral swab and cervical swab specimens were inoculated to Thayer Martin media (OXOID, UK) plates. Observation of Gram-negative intracellular diplococcic was a presumptive diagnosis of gonococcal infection. Finally, antimicrobial susceptibility was assessed by using a modified Kirby-Bauer disk diffusion test, with results indicating susceptible, intermediate or resistant. Data were entered and analyzed using SPSS version 20.
Results: The overall prevalence of laboratory confirmed N. gonorrhoeae was 25(20.8%). The isolated N. gonorrhoeae was resistant 100% to tetracycline, penicillin and 80% percent was multidrug resistant.
Conclusion: Prevalence and drug resistance of N. gonorrhoeae were high in the study area. A large study is needed in order to know the magnitude in the community as well as to increase awareness of both regional health bureaus and the Ministry of Health about the treatment guide-lines.

PMID: 30026943 [PubMed - indexed for MEDLINE]

Empiric antimicrobial treatment for asymptomatic sexual contacts of sexually transmitted infection in the era of antimicrobial resistance: time to rethink?

Tue, 09/03/2019 - 07:17
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Empiric antimicrobial treatment for asymptomatic sexual contacts of sexually transmitted infection in the era of antimicrobial resistance: time to rethink?

Int J STD AIDS. 2019 02;30(2):137-139

Authors: Pearce E, Chan DJ, Smith DE

Abstract
Prudent prescribing of antimicrobials is essential in ameliorating the public health problem of antimicrobial resistance. This retrospective audit assesses whether empiric antimicrobial treatment for asymptomatic sexual contacts of sexually transmitted infection is appropriate based on laboratory confirmation.

PMID: 30293504 [PubMed - indexed for MEDLINE]

Diagnosing sexually transmitted infections in resource-constrained settings: challenges and ways forward.

Sat, 08/31/2019 - 07:11
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Diagnosing sexually transmitted infections in resource-constrained settings: challenges and ways forward.

J Int AIDS Soc. 2019 Aug;22 Suppl 6:e25343

Authors: Wi TE, Ndowa FJ, Ferreyra C, Kelly-Cirino C, Taylor MM, Toskin I, Kiarie J, Santesso N, Unemo M

Abstract
INTRODUCTION: Sexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings.
METHODS: We prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.
RESULTS AND DISCUSSIONS: The diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions.
CONCLUSIONS: The WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

PMID: 31468679 [PubMed - in process]

Substance Use Treatment Patient and Provider Perspectives on Accessing Sexual and Reproductive Health Services: Barriers, Facilitators, and the Need for Integration of Care.

Thu, 08/29/2019 - 07:07
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Substance Use Treatment Patient and Provider Perspectives on Accessing Sexual and Reproductive Health Services: Barriers, Facilitators, and the Need for Integration of Care.

Subst Use Misuse. 2019 Aug 27;:1-13

Authors: MacAfee LK, Harfmann RF, Cannon LM, Minadeo L, Kolenic G, Kusunoki Y, Dalton VK

Abstract
Background: Women with substance use disorders have high rates of adverse sexual and reproductive health (SRH) outcomes, including unintended pregnancy, sexually transmitted infections, and contraceptive nonuse. Little research has explored barriers and facilitators to accessing SRH services experienced by women with substance use disorders. Objectives: To investigate barriers and facilitators to accessing SRH services experienced by women with substance use disorders. To assess perspectives on integration of SRH services into substance use treatment. Methods: Twenty-nine semi-structured interviews were conducted with female patients (N = 17) and providers (N = 12) at four substance use treatment facilities in Michigan between October 2015 and January 2016. Respondents were asked about experiences accessing SRH services and perspectives on integration of SRH services into substance use treatment. Data were analyzed using the constant comparative method. Results: Patients and providers discussed barriers to accessing SRH services, including competing priorities, structural barriers, lack of knowledge on SRH services and substance use, fear of Child Protective Services and law enforcement, and stigma. Facilitators included reprioritization of SRH, accessible transportation, insurance coverage and funding for SRH services, and education and training on SRH. Finally, participants expressed support for integration of SRH services into substance use treatment. Conclusions/Importance: Understanding the barriers to accessing SRH services is essential to reducing the adverse SRH outcomes experienced by women with substance use disorders. Substance use treatment is a critical time to offer SRH services. Integration of care is a potential model for improving the SRH of women with substance use disorders.

PMID: 31455128 [PubMed - as supplied by publisher]

Self-derived structure-disrupting peptides targeting methionine aminopeptidase in pathogenic bacteria: a new strategy to generate antimicrobial peptides.

Tue, 08/27/2019 - 06:17
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Self-derived structure-disrupting peptides targeting methionine aminopeptidase in pathogenic bacteria: a new strategy to generate antimicrobial peptides.

FASEB J. 2019 02;33(2):2095-2104

Authors: Zhan J, Jia H, Semchenko EA, Bian Y, Zhou AM, Li Z, Yang Y, Wang J, Sarkar S, Totsika M, Blanchard H, Jen FE, Ye Q, Haselhorst T, Jennings MP, Seib KL, Zhou Y

Abstract
Bacterial infection is one of the leading causes of death in young, elderly, and immune-compromised patients. The rapid spread of multi-drug-resistant (MDR) bacteria is a global health emergency and there is a lack of new drugs to control MDR pathogens. We describe a heretofore-unexplored discovery pathway for novel antibiotics that is based on self-targeting, structure-disrupting peptides. We show that a helical peptide, KFF- EcH3, derived from the Escherichia coli methionine aminopeptidase can disrupt secondary and tertiary structure of this essential enzyme, thereby killing the bacterium (including MDR strains). Significantly, no detectable resistance developed against this peptide. Based on a computational analysis, our study predicted that peptide KFF- EcH3 has the strongest interaction with the structural core of the methionine aminopeptidase. We further used our approach to identify peptide KFF- NgH1 to target the same enzyme from Neisseria gonorrhoeae. This peptide inhibited bacterial growth and was able to treat a gonococcal infection in a human cervical epithelial cell model. These findings present an exciting new paradigm in antibiotic discovery using self-derived peptides that can be developed to target the structures of any essential bacterial proteins.-Zhan, J., Jia, H., Semchenko, E. A., Bian, Y., Zhou, A. M., Li, Z., Yang, Y., Wang, J., Sarkar, S., Totsika, M., Blanchard, H., Jen, F. E.-C., Ye, Q., Haselhorst, T., Jennings, M. P., Seib, K. L., Zhou, Y. Self-derived structure-disrupting peptides targeting methionine aminopeptidase in pathogenic bacteria: a new strategy to generate antimicrobial peptides.

PMID: 30260702 [PubMed - indexed for MEDLINE]

Mycoplasma genitalium macrolide resistance update: Rate among a 2016-2017 cohort of patients in Barcelona, Spain.

Mon, 08/26/2019 - 06:15
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Mycoplasma genitalium macrolide resistance update: Rate among a 2016-2017 cohort of patients in Barcelona, Spain.

Enferm Infecc Microbiol Clin. 2019 Aug 21;:

Authors: Fernández-Huerta M, Vall M, Fernández-Naval C, Barberá MJ, Arando M, López L, Andreu A, Pumarola T, Serra-Pladevall J, Esperalba J, Espasa M

Abstract
INTRODUCTION: Mycoplasma genitalium is a major cause of urethritis and other genital syndromes. Antibiotic resistance, especially to macrolides, is increasing at an alarming rate worldwide. The aim of this study was to estimate the rate of macrolide resistance in M. genitalium among a 2016-2017 cohort of patients in Barcelona, Spain; and to compare this estimate with previous data from 2013 to 2014 in this region.
METHODS: The study was conducted retrospectively with M. genitalium-positive samples collected between December 2016 and February 2017 at the Hospital Vall d'Hebron Microbiology Department. Genotypic markers of macrolide resistance were primarily detected using the ResistancePlus® MG molecular assay (SpeeDx). Mutations were then confirmed by sequencing.
RESULTS: Macrolide resistance-mediating mutations were detected in 30/83 infections (36.1% [95% CI, 25.9%-47.4%]). This resistance was more frequent among men who have sex with men (55.0% [95% CI, 38.5%-70.7%]) compared to heterosexual men (27.3% [95% CI, 10.7%-50.2%]) and women (9.5% [95% CI, 1.3%-30.4%]), p<0.001. Additionally, macrolide resistance did not significantly increase in this cohort when compared with previous investigations.
CONCLUSION: Despite the current notable rate of macrolide resistance in M. genitalium, resistance did not significantly increase between 2013-2014 and 2016-2017 in our region. Nevertheless, strict local surveillance and the implementation of rapid diagnostic tests that combine the detection of the bacterium and resistance-mediating mutations may facilitate the optimization of antibiotic administration and reduce the transmission of resistance in M. genitalium.

PMID: 31445815 [PubMed - as supplied by publisher]

Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections.

Sat, 08/24/2019 - 06:11
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Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections.

Int J Nanomedicine. 2019;14:5957-5976

Authors: Vanić Ž, Rukavina Z, Manner S, Fallarero A, Uzelac L, Kralj M, Amidžić Klarić D, Bogdanov A, Raffai T, Virok DP, Filipović-Grčić J, Škalko-Basnet N

Abstract
Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects.
Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections.
Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells.
Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control.
Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

PMID: 31440052 [PubMed - in process]

Neisseria gonorrhoeae host adaptation and pathogenesis.

Sat, 08/24/2019 - 06:11
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Neisseria gonorrhoeae host adaptation and pathogenesis.

Nat Rev Microbiol. 2018 04;16(4):226-240

Authors: Quillin SJ, Seifert HS

Abstract
The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N. gonorrhoeae has retained features that are common in commensals, but it has also developed unique features that are crucial to its pathogenesis. The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N. gonorrhoeae infection. This knowledge will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics. In this Review, we discuss sex-related symptomatic gonorrhoeal disease and provide an overview of the bacterial factors that are important for the different stages of pathogenesis, including transmission, colonization and immune evasion, and we discuss the problem of antibiotic resistance.

PMID: 29430011 [PubMed - indexed for MEDLINE]

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