Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 37 Records) |
Query Trace: Cyr S[original query] |
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The management of gonorrhea in the era of emerging antimicrobial resistance: What primary care clinicians should know
Quilter LAS , St Cyr SB , Barbee LA . Med Clin North Am 2024 108 (2) 279-296 Gonorrhea rates continue to rise in the United States and Neisseria gonorrhoeae's propensity to develop resistance to all therapies used for treatment has complicated the management of gonorrhea. Ceftriaxone is the only remaining highly effective recommended regimen for gonococcal treatment and few new anti-gonococcal antimicrobials are being developed. The 2021 CDC STI Treatment Guidelines increased the dose of ceftriaxone to 500 mg (1 g if ≥ 150 kg) for uncomplicated infections. It is recommended that all clinicians should be aware of antimicrobial resistant gonorrhea and be able to appropriately manage any suspected gonorrhea treatment failure case. |
The impact of rapid drug susceptibility tests on gonorrhea burden and lifespan of antibiotic treatments: A modeling study among men who have sex with men in the United States
Yaesoubi R , Xi Q , Hsu K , Gift TL , St Cyr SB , Rönn MM , Salomon JA , Grad YH . Am J Epidemiol 2023 193 (1) 17-25 Rapid point-of-care tests that diagnose gonococcal infections and identify susceptibility to antibiotics enable individualized treatment. This could improve patient outcomes and slow the emergence and spread of resistance. However, little is known about the long-term impact of such diagnostics on the burden of gonorrhea and the effective lifespan of antibiotics. We used a mathematical model of gonorrhea transmission among men who have sex with men in the US to project the annual rate of reported gonorrhea cases and the effective lifespan of ceftriaxone, the recommended antibiotic for the first-line treatment of gonorrhea, as well as two previously recommended antibiotics, ciprofloxacin and tetracycline, when a rapid drug susceptibility test (DST) that reports susceptibility to ciprofloxacin and tetracycline is available. The use of a rapid DST with ≥50% sensitivity and ≥95% specificity, defined in terms of correct ascertainment of drug susceptibility and non-susceptibility status, could increase the combined effective lifespan of ciprofloxacin, tetracycline, and ceftriaxone by at least 2 years over 25 years of simulation. If test specificity is imperfect, however, the increase in the effective lifespan of antibiotics is accompanied by an increase in the rate of reported gonorrhea cases even under perfect sensitivity. |
Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin (preprint)
Joseph SJ , Thomas Iv JC , Schmerer MW , Cartee J , St Cyr S , Schlanger K , Kersh EN , Raphael BH , Gernert KM . bioRxiv 2021 2021.08.05.455198 Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the U.S. Here we analyze a global collection of ST-9363 genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009-2011 and again during the 2012-2013 time, facilitating the clonal expansion of this genogroup with AZMrs in the U.S. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the U.S. and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers.Competing Interest StatementThe authors have declared no competing interest. |
Mechanistic basis for decreased antimicrobial susceptibility in a clinical isolate of Neisseria gonorrhoeae possessing a mosaic-like mtr efflux pump locus (preprint)
Rouquette-Loughlin CE , Reimche JL , Balthazar JT , Dhulipala V , Gernert KM , Kersh EN , Pham CD , Pettus K , Abrams AJ , Trees DL , St Cyr S , Shafer WM . bioRxiv 2018 448712 Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae likely originating from commensal Neisseria sp. by transformation can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (Wadsworth et al. 2018. MBio. doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented herein provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials including antibiotics used in therapy of gonorrhea. |
Genomic analysis of 1710 surveillance-based Neisseria gonorrhoeae isolates from the USA in 2019 identifies predominant strain types and chromosomal antimicrobial-resistance determinants
Reimche JL , Clemons AA , Chivukula VL , Joseph SJ , Schmerer MW , Pham CD , Schlanger K , St Cyr SB , Kersh EN , Gernert KM . Microb Genom 2023 9 (5) This study characterized high-quality whole-genome sequences of a sentinel, surveillance-based collection of 1710 Neisseria gonorrhoeae (GC) isolates from 2019 collected in the USA as part of the Gonococcal Isolate Surveillance Project (GISP). It aims to provide a detailed report of strain diversity, phylogenetic relationships and resistance determinant profiles associated with reduced susceptibilities to antibiotics of concern. The 1710 isolates represented 164 multilocus sequence types and 21 predominant phylogenetic clades. Common genomic determinants defined most strains' phenotypic, reduced susceptibility to current and historic antibiotics (e.g. bla (TEM) plasmid for penicillin, tetM plasmid for tetracycline, gyrA for ciprofloxacin, 23S rRNA and/or mosaic mtr operon for azithromycin, and mosaic penA for cefixime and ceftriaxone). The most predominant phylogenetic clade accounted for 21 % of the isolates, included a majority of the isolates with low-level elevated MICs to azithromycin (2.0 µg ml(-1)), carried a mosaic mtr operon and variants in PorB, and showed expansion with respect to data previously reported from 2018. The second largest clade predominantly carried the GyrA S91F variant, was largely ciprofloxacin resistant (MIC ≥1.0 µg ml(-1)), and showed significant expansion with respect to 2018. Overall, a low proportion of isolates had medium- to high-level elevated MIC to azithromycin ((≥4.0 µg ml(-1)), based on C2611T or A2059G 23S rRNA variants). One isolate carried the penA 60.001 allele resulting in elevated MICs to cefixime and ceftriaxone of 1.0 µg ml(-1). This high-resolution snapshot of genetic profiles of 1710 GC sequences, through a comparison with 2018 data (1479 GC sequences) within the sentinel system, highlights change in proportions and expansion of select GC strains and the associated genetic mechanisms of resistance. The knowledge gained through molecular surveillance may support rapid identification of outbreaks of concern. Continued monitoring may inform public health responses to limit the development and spread of antibiotic-resistant gonorrhoea. |
Phylogenomic Comparison of Neisseria gonorrhoeae Causing Disseminated Gonococcal Infections and Uncomplicated Gonorrhea in Georgia, United States.
Cartee JC , Joseph SJ , Weston E , Pham CD , Thomas JCth , Schlanger K , St Cyr SB , Farley MM , Moore AE , Tunali AK , Cloud C , Raphael BH . Open Forum Infect Dis 2022 9 (7) ofac247 Disseminated gonococcal infection (DGI) is a rare complication caused by the systemic dissemination of Neisseria gonorrhoeae to normally sterile anatomical sites. Little is known about the genetic diversity of DGI gonococcal strains and how they relate to other gonococcal strains causing uncomplicated mucosal infections. We used whole genome sequencing to characterize DGI isolates (n = 30) collected from a surveillance system in Georgia, United States, during 2017-2020 to understand phylogenetic clustering among DGI as well as uncomplicated uro- and extragenital gonococcal infection (UGI) isolates (n = 110) collected in Fulton County, Georgia, during 2017-2019. We also investigated the presence or absence of genetic markers related to antimicrobial resistance (AMR) as well as surveyed the genomes for putative virulence genetic factors associated with normal human-serum (NHS) resistance that might facilitate DGI. We found that DGI strains demonstrated significant genetic variability similar to the population structure of isolates causing UGI, with sporadic incidences of geographically clustered DGI strains. DGI isolates contained various AMR markers and genetic mechanisms associated with NHS resistance. DGI isolates had a higher frequency of the porB1A allele compared with UGI (67% vs 9%, P < .0001); however, no single NHS resistance marker was found in all DGI isolates. Continued DGI surveillance with genome-based characterization of DGI isolates is necessary to better understand specific factors that promote systemic dissemination. |
Management of Neisseria gonorrhoeae in the United States: Summary of evidence from the development of the 2020 gonorrhea treatment recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines
Barbee LA , St Cyr SB . Clin Infect Dis 2022 74 S95-s111 INTRODUCTION: Neisseria gonorrhoeae has developed resistance to all first-line recommended therapies, making gonococcal antimicrobial resistance a major public health concern given limited antibiotic options currently and an even smaller antimicrobial development pipeline. Since the release of the Centers for Disease Control and Prevention (CDC) 2015 STD Treatment Guidelines, azithromycin, part of the 2015 dual-drug treatment regimen, has had a rapid rise in resistance. The 2020 CDC Gonorrhea Treatment Recommendations and the 2021 Sexually Transmitted Infections (STI) Treatment Guidelines were developed weighing the priorities of treating the individual, protecting the population, and preventing antimicrobial resistance. METHODS: Gonorrhea subject matter experts (SME) generated 8 key questions and conducted a literature review of updated data from 2013 to 2019 on gonorrhea antimicrobial resistance, treatment failures, clinical trials, and other key topics. More than 2200 abstracts were assessed, and 248 clinically relevant articles were thoroughly reviewed. SMEs also evaluated N gonorrhoeae antimicrobial resistance data from the Gonococcal Isolate Surveillance Project (GISP). EVIDENCE: Although there have been reports of ceftriaxone treatment failures internationally, GISP data suggest that ceftriaxone minimal inhibitory concentrations (MICs) have remained stable in the United States, with < 0.1% exhibiting an "alert value" MIC (> 0.25 mcg/mL). However, GISP documented a rapid rise in the proportion of isolates with an elevated MIC (≥ 2.0 mcg/mL) to azithromycin-nearly 5% in 2018. At the same time, new pharmacokinetic/pharmacodynamic data are available, and there is greater recognition of the need for antimicrobial stewardship. SUMMARY: The 2021 CDC STI Treatment Guidelines now recommend 500mg ceftriaxone intramuscularly once for the treatment of uncomplicated gonorrhea at all anatomic sites. If coinfection with chlamydia has not been excluded, cotreatment with doxycycline 100mg twice daily for 7 days should be added. Few alternative therapies exist for persons with cephalosporin allergies; there are no recommended alternative therapies for N gonorrhoeae infection of the throat. |
Evaluating spatially adaptive guidelines for the treatment of gonorrhea to reduce the incidence of gonococcal infection and increase the effective lifespan of antibiotics
Yaesoubi R , Cohen T , Hsu K , Gift TL , St Cyr SB , Salomon JA , Grad YH . PLoS Comput Biol 2022 18 (2) e1009842 In the absence of point-of-care gonorrhea diagnostics that report antibiotic susceptibility, gonorrhea treatment is empiric and determined by standardized guidelines. These guidelines are informed by estimates of resistance prevalence from national surveillance systems. We examined whether guidelines informed by local, rather than national, surveillance data could reduce the incidence of gonorrhea and increase the effective lifespan of antibiotics used in treatment guidelines. We used a transmission dynamic model of gonorrhea among men who have sex with men (MSM) in 16 U.S. metropolitan areas to determine whether spatially adaptive treatment guidelines based on local estimates of resistance prevalence can extend the effective lifespan of hypothetical antibiotics. The rate of gonorrhea cases in these metropolitan areas was 5,548 cases per 100,000 MSM in 2017. Under the current strategy of updating the treatment guideline when the prevalence of resistance exceeds 5%, we showed that spatially adaptive guidelines could reduce the annual rate of gonorrhea cases by 200 cases (95% uncertainty interval: 169, 232) per 100,000 MSM population while extending the use of a first-line antibiotic by 0.75 (0.55, 0.95) years. One potential strategy to reduce the incidence of gonorrhea while extending the effective lifespan of antibiotics is to inform treatment guidelines based on local, rather than national, resistance prevalence. |
Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin.
Joseph SJ , Thomas Iv JC , Schmerer MW , Cartee J , St Cyr S , Schlanger K , Kersh EN , Raphael BH , Gernert KM . Genome Biol Evol 2021 14 (1) Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 core-genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the U.S. Here we analyze a global collection of ST-9363 core-genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 core-genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 core-genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009-2011 and again during the 2012-2013 time, facilitating the clonal expansion of this core-genogroup with AZMrs in the U.S. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the U.S. and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young core-genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers. |
Antimicrobial susceptibility of urogenital and extragenital neisseria gonorrhoeae isolates among men who have sex with men - SURRG and eGISP, 2018-2019
Quilter LAS , St Cyr SB , Hong J , Asbel L , Bautista I , Carter B , Casimir Y , Denny M , Ervin M , Gomez R , Harvey A , Holderman JL , Johnson K , Kohn RP , Learner ER , Mauk K , Menza T , Mettenbrink C , Nettleton WD , Nicosia KR , Pham CD , Ried C , Schlanger K , Schneider A , Soge OO , Tabidze I , Taylor SN , Tilghman W , Toler C , Weinstock H , Torrone EA . Sex Transm Dis 2021 48 S111-S117 BACKGROUND: We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through CDC's enhanced Gonococcal Isolate Surveillance Project (eGISP) and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). METHODS: During January 1, 2018-December 31, 2019, 12 eGISP and 8 SURRG sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in STD clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs) and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. RESULTS: Participating clinics collected 3,974 urethral, 1,553 rectal, and 1,049 pharyngeal isolates from 5,456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared to anogenital isolates (p < 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥0.125 μg/ml) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (p < 0.05). CONCLUSIONS: Based on data collected from multi-jurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of N. gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time. |
Strengthening the U.S. Response to Resistant Gonorrhea (SURRG): An overview of a multi-site program to enhance local response capacity for antibiotic-resistant Neisseria gonorrhoeae
Schlanger K , Learner ER , Pham CD , Mauk K , Golden M , Wendel KA , Amsterdam L , McNeil CJ , Johnson K , Nguyen TQ , Holderman JL , Hasty GL , St Cyr SB , Town K , Nash EE , Kirkcaldy RD . Sex Transm Dis 2021 48 S97-S103 BACKGROUND: In 2016, CDC initiated Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) in multiple jurisdictions to enhance antibiotic resistant gonorrhea rapid detection and response infrastructure and evaluate the impact of key strategies. METHODS: Eight jurisdictions were funded to establish or enhance local gonococcal culture specimen collection in STD and community clinics, conduct rapid antimicrobial susceptibility testing (AST) in local laboratories, modify systems for enhanced data collection and rapid communication of results, and initiate enhanced partner services among patients with gonorrhea demonstrating elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime or azithromycin. RESULTS: Grantees incorporated genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018-2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% (3,412) and 8.9% (4,883) of local reported cases in 2018 and 2019 respectively). Of isolates that underwent AST, 11% demonstrated elevated azithromycin MICs; fewer than 0.5% demonstrated elevated ceftriaxone or cefixime MICs. Among patients whose infections demonstrated elevated MICs, 81.7% were interviewed for partner elicitation; however, limited new cases were identified among partners and contacts. CONCLUSIONS: As a public health model to build capacity to slow the spread of emerging resistance, SURRG successfully expanded culture collection, implemented rapid AST, and implemented an enhanced partner services investigation approach in participating jurisdictions. Findings from SURRG may enhance preparedness efforts and inform a longer-term, comprehensive, and evidence-based public health response to emerging gonococcal resistance. Continued development of innovative approaches to address emerging resistance is needed. |
Demographic and epidemiological characteristics associated with reduced antimicrobial susceptibility to Neisseria gonorrhoeae in the United States, Strengthening the U.S. Response to Resistant Gonorrhea (SURRG), 2018-2019
Gieseker K , Learner ER , Mauk K , Barbee LA , McNeil CJ , Hasty GL , Black JM , Johnson K , Quyen Nguyen T , Shrestha D , Pham CD , St Cyr S , Schlanger K , Kirkcaldy RD . Sex Transm Dis 2021 48 S118-S123 BACKGROUND: Jurisdictions participating in Strengthening the United States Response to Resistant Gonorrhea (SURRG) implemented specimen collection for culture and antimicrobial susceptibility testing (AST) from a sample of persons of all genders (at multiple anatomic sites) attending STD clinics and community clinics. We describe the percentage and characteristics of patients whose isolates demonstrated reduced susceptibility (RS) to azithromycin, ceftriaxone, or cefixime. METHODS: We included patients from clinics that participated in SURRG whose isolates underwent AST by Etest. We defined RS as azithromycin minimum inhibitory concentrations (MICs) ≥2 μg/ml (AZM-RS), ceftriaxone MICs ≥0.125 μg/ml (CRO-RS), or cefixime MICs ≥0.25 μg/ml (CFX-RS). Patients with repeated infections appeared >1 time in the data. We calculated the frequency and percentage of patients with an isolate demonstrating RS by epidemiological characteristics. RESULTS: During 2018-2019, 10,013 patients from eight jurisdictions provided 10,735 isolates. Among 10,013 patients, 11.0% (n = 1,099) had ≥1 isolate with AZM-RS (range by jurisdiction 2.5%-18.0%). Approximately 11.3% of 8,771 of patients visiting STD clinics and approximately 8.8% of 1,242 patients visiting community clinics had an AZM-RS isolate. Nearly 6% of 1,013 females had an AZM-RS isolate; among males, the percent of patients with an AZM-RS isolate was 17.7% among 4,177 men who have sex only with men and 6.1% among 3,581 men who have sex only with women. Few (0.4%) patients had isolates with CFX-RS (n = 40) or CRO-RS (n = 43). CONCLUSIONS: Although infections with reduced cephalosporin susceptibility were rare, AZM-RS infections were prevalent in this sample of patients in multiple jurisdictions and across gender and gender of sex partner categories. |
Implementation and evaluation of gradient strip antimicrobial susceptibility testing in US public health laboratories to respond to resistant gonorrhea
Raphael BH , Pham CD , Sharpe S , Mauk K , Harvey A , Khubbar M , Triplett L , Soge OO , Denny M , Palavecino EL , Finney R , Olsen A , Carlson J , St Cyr SB , Schlanger K , Kersh EN . Sex Transm Dis 2021 48 S157-S160 BACKGROUND: Gradient strip antimicrobial susceptibility testing (AST) using Etest® is conducted by local public health jurisdictions participating in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) program to inform public health responses to resistant gonorrhea. Proficiency testing results across the participating laboratories were analyzed and a comparison of Etest® with the agar dilution method was conducted. METHODS: Laboratories participating in SURRG performed Etest® for azithromycin (AZM), cefixime (CFX), and ceftriaxone (CRO). Concurrence between minimum inhibitory concentrations (MICs) obtained with Etest® versus the agar dilution method using corresponding isolates was defined as +/- 1 double dilution. Specific levels of reduced susceptibility were termed "alerts" and included isolates with the following MICs: ≥ 2.0 μg/ml (AZM), ≥ 0.25 μg/ml (CFX), and ≥ 0.125 μg/ml (CRO). Categorical (alert/non-alert) agreement was calculated for MICs determined using Etest® and agar dilution methods. RESULTS: SURRG laboratories had high proficiency testing scores (≥98%) and low levels of inter-laboratory variations in MICs. The overall concurrence of MICs (essential agreement) determined using agar dilution and Etest® was 96% (CRO), 96% (CFX), and 95% (AZM). Depending on the antibiotic tested, between 27-66% of isolates with alert MICs determined by Etest® also had alert MICs using the reference agar dilution methodology, however most of these alert MICs were detected at threshold levels. CONCLUSIONS: This study demonstrates that MICs produced by SURRG laboratories using Etest® have a high level of concurrence with agar dilution. Although confirmation of specific alert MICs varied, Etest® facilities rapid detection and response to emerging resistant gonorrhea. |
Test of cure return rate and test positivity, Strengthening the U.S Response to Resistant Gonorrhea (SURRG), United States, 2018-2019
Schlanger K , Mauk K , Learner ER , Schillinger JA , Nishiyama M , Kohn R , Thibault C , Hermus H , Dewater J , Pabon V , Black J , St Cyr S , Pham CR , Kirkcaldy RD . Sex Transm Dis 2021 48 S167-S173 BACKGROUND: Reduced antibiotic susceptibility (RS) in Neisseria gonorrhoeae (GC) may increase treatment failure. Conducting tests-of-cure (TOC) for patients with RS-GC may facilitate identification of treatment failures. METHODS: We examined 2018-2019 data from eight jurisdictions participating in CDC's Strengthening U.S. Response to Resistant Gonorrhea project. Jurisdictions collected GC isolates and epidemiological data from patients and performed antimicrobial susceptibility testing. Minimum inhibitory concentrations of ceftriaxone ≥0.125 μg/mL, cefixime ≥0.250 μg/mL, or azithromycin ≥2.0 μg/mL were defined as RS. Patients with RS-infections were asked to return for a TOC 8-10 days post-treatment. We calculated a weighted TOC return rate and described time to TOC and suspected reasons for any positive TOC results. RESULTS: Overall, 1,165 patients were diagnosed with RS-infections. Over half returned for TOC (weighted TOC: 61% [95% confidence interval: 50.1%-72.6%], range by jurisdiction: 32%-80%). TOC rates were higher among asymptomatic (68%) than symptomatic patients (53%, p = 0.001), and MSM (62%) compared to MSW (50%; p < 0.001). Median time between treatment and TOC was 12 days (interquartile range: 9-16). Of the 31 (4.5%) TOC patients with positive results, 13 (42%) were suspected due to reinfection and 11 (36%) due to false positive results. There were no treatment failures suspected to be due to RS-GC. CONCLUSIONS: Most patients with a RS-infection returned for a TOC, though return rates varied by jurisdiction and patient characteristics. TOC can identify and facilitate treatment of reinfections, but false positive TOC results may complicate interpretation and clinical management. |
Exploring and comparing the structure of sexual networks affected by Neisseria gonorrhoeae using sexual partner services investigation and genomic data.
Town K , Learner ER , Chivukula VL , Mauk K , Reimche JL , Schmerer MW , Black J , Pathela P , Bhattacharyya S , Kerani RP , Gieseker KE , Fukuda A , Sankaran M , McNeil CJ , Spicknall IH , Raphael BH , St Cyr SB , Bernstein K , Kersh EN , Kirkcaldy RD , Schlanger K , Gernert KM . Sex Transm Dis 2021 48 S131-S136 BACKGROUND: Sexual networks are difficult to construct due to incomplete sexual partner data. The proximity of people within a network may be inferred from genetically similar infections. We explored genomic data combined with partner services investigation (PSI) data to extend our understanding of sexual networks affected by Neisseria gonorrhoeae (NG). METHODS: We used 2017-2019 PSI and whole-genome sequencing (WGS) data from eight jurisdictions participating in CDC's Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. Clusters were identified from sexual contacts and through genetically similar NG isolates. Sexual mixing patterns were characterized by describing the clusters by the individual's gender and gender of their sex partners. RESULTS: Our study included 4,627 diagnoses of NG infection (81% sequenced), 2,455 people received a PSI, 393 people were negative contacts of cases, and 495 contacts with unknown NG status. We identified 823 distinct clusters using PSI data combined with WGS data. Of cases that were not linked to any other case using PSI data, 37% were linked when using WGS data. Overall, 40% of PSI cases were allocated to a larger cluster when PSI and WGS data were combined compared with PSI data alone. Mixed clusters containing women, men who report sex with women, and men who report sex with men were common when using the WGS data either alone or in combination with the PSI data. CONCLUSIONS: Combining PSI and WGS data improves our understanding of sexual network connectivity. |
Phylogenomic analysis reveals persistence of gonococcal strains with reduced-susceptibility to extended-spectrum cephalosporins and mosaic penA-34.
Thomas 4th JC , Joseph SJ , Cartee JC , Pham CD , Schmerer MW , Schlanger K , St Cyr SB , Kersh EN , Raphael BH . Nat Commun 2021 12 (1) 3801 The recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935-1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally. |
Genomic analysis of the predominant strains and antimicrobial resistance determinants within 1479 Neisseria gonorrhoeae isolates from the U.S. Gonococcal Isolate Surveillance Project in 2018.
Reimche JL , Chivukula VL , Schmerer MW , Joseph SJ , Pham CD , Schlanger K , St Cyr SB , Weinstock HS , Raphael BH , Kersh EN , Gernert KM . Sex Transm Dis 2021 48 S78-S87 BACKGROUND: The prevalence of Neisseria gonorrhoeae (GC) isolates with elevated minimum inhibitory concentrations (MICs) to various antibiotics continues to rise in the U.S. and globally. Genomic analysis provides a powerful tool for surveillance of circulating strains, antimicrobial resistance determinants, and understanding of transmission through a population. METHODS: GC isolates collected from the U.S. Gonococcal Isolate Surveillance Project (GISP) in 2018 (n=1479) were sequenced and characterized. Whole genome sequencing was used to identify sequence types, antimicrobial resistance profiles, and phylogenetic relationships across demographic and geographic populations. RESULTS: Genetic characterization identified that (1) 80% of the GC isolates were represented in 33 multilocus sequence types, (2) isolates clustered in 23 major phylogenetic clusters with select phenotypic and demographic prevalence, and (3) common antimicrobial resistance determinants associated with low-level or high-level decreased susceptibility or resistance to relevant antibiotics. CONCLUSIONS: Characterization of this 2018 GISP genomic dataset, which is the largest U.S. whole genome sequence data set to date, sets the basis for future prospective studies, and establishes a genomic baseline of GC populations for local and national monitoring. |
Sustained Transmission of Neisseria gonorrhoeae with High-Level Resistance to Azithromycin, Indianapolis, Indiana 2017-2018.
Holderman JL , Thomas JC , Schlanger K , Black JM , Town K , Cyr SB , Pham CD , Kirkcaldy RD . Clin Infect Dis 2021 73 (5) 808-815 BACKGROUND: Since 2014, Neisseria gonorrhoeae (Ng) azithromycin (AZM) susceptibility has declined in the United States, but high-level azithromycin resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 Ng isolates with HL-AZMR identified in Indianapolis over 13 months. METHODS: Ng culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) by Etest . AZM minimum inhibitory concentrations 256 g/ml were classified as HL-AZMR. Local disease intervention specialists interviewed patients whose isolates demonstrated HL-AZMR and conducted partner services. Relatedness of isolates was investigated by genomic analyses. RESULTS: During 2017-2018, 1,016 Ng isolates collected at the Bell Flower Clinic underwent AST. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin-susceptible. Of the 12 men, nine were white and reported male sex partners. Nine of the men were able to be re-tested; all were cured with 250mg ceftriaxone plus 1g azithromycin. Two men named each other as partners; no other partners in common were reported. Genomic analysis demonstrated close relatedness of the HL-AZMR isolates and a novel combination of a mosaic-mtrR promoter along with 23S rRNA mutations that appear to have emerged from circulating strains. CONCLUSIONS: The close genetic relatedness with limited epidemiological linkages between patients highlights the challenges of gonorrhea partner investigations and suggests undetected local transmission. Local AST, rapid public health action, and epidemiologic investigations combined with genomic analysis provides a multi-pronged approach to understanding an STD outbreak. |
Sustained Transmission of Neisseria gonorrhoeae with High-Level Resistance to Azithromycin, in Indianapolis, Indiana, 2017-2018.
Holderman JL , Thomas JC , Schlanger K , Black JM , Town K , Cyr SB , Pham CD , Kirkcaldy RD . Clin Infect Dis 2021 73 (5) 808-815 BACKGROUND: Since 2014, Neisseria gonorrhoeae (Ng) azithromycin (AZM) susceptibility has declined in the United States, but high-level azithromycin resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 Ng isolates with HL-AZMR identified in Indianapolis over 13 months. METHODS: Ng culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) by Etest ®. AZM minimum inhibitory concentrations ≥256 µg/ml were classified as HL-AZMR. Local disease intervention specialists interviewed patients whose isolates demonstrated HL-AZMR and conducted partner services. Relatedness of isolates was investigated by genomic analyses. RESULTS: During 2017-2018, 1,016 Ng isolates collected at the Bell Flower Clinic underwent AST. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin-susceptible. Of the 12 men, nine were white and reported male sex partners. Nine of the men were able to be re-tested; all were cured with 250 mg ceftriaxone plus 1g azithromycin. Two men named each other as partners; no other partners in common were reported. Genomic analysis demonstrated close relatedness of the HL-AZMR isolates and a novel combination of a mosaic-mtrR promoter along with 23S rRNA mutations that appear to have emerged from circulating strains. CONCLUSIONS: The close genetic relatedness with limited epidemiological linkages between patients highlights the challenges of gonorrhea partner investigations and suggests undetected local transmission. Local AST, rapid public health action, and epidemiologic investigations combined with genomic analysis provides a multi-pronged approach to understanding an STD outbreak. |
Sexually transmitted infections among US women and men: Prevalence and incidence estimates, 2018
Kreisel KM , Spicknall IH , Gargano JW , Lewis FM , Lewis RM , Markowitz LE , Roberts H , Satcher Johnson A , Song R , St Cyr SB , Weston EJ , Torrone EA , Weinstock HS . Sex Transm Dis 2021 48 (4) 208-214 BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States (US) were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the US for eight STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by gender and age group. Primary estimates are represented by medians and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1=66.6, Q3=68.7) million prevalent and 26.2 (Q1=24.0, Q3=28.7) million incident STIs in the US. Chlamydia, trichomoniasis, genital herpes, and HPV comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15-24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the US is high. Almost half of incident STIs occurred in persons aged 15-24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts. |
Estimates of the prevalence and incidence of chlamydia and gonorrhea among US men and women, 2018
Kreisel KM , Weston EJ , St Cyr SB , Spicknall IH . Sex Transm Dis 2021 48 (4) 222-231 BACKGROUND: The most recent prevalence and incidence estimates for chlamydia and gonorrhea, the two most reported nationally notifiable conditions in the United States (US), were for 2008. We present updated estimates for the number of prevalent and incident chlamydial and gonococcal infections for 2018. METHODS: We estimated chlamydial prevalence directly from the 2015-2018 cycles of the National Health and Nutrition Examination Survey (NHANES) and chlamydial incidence using a mathematical model primarily informed by NHANES and case report data. Total and antimicrobial resistant (AMR) gonococcal prevalence and incidence were estimated using mathematical models primarily informed by case report and Gonococcal Isolate Surveillance Program data. Estimates were calculated for the total population, all women, and all men aged 15-39 years, stratified by age group. Primary estimates represent medians and uncertainty intervals represent the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each infection. RESULTS: Among persons aged 15-39 years in the US in 2018, we estimate 2.35 (Q1=2.20, Q3=2.51) million prevalent and 3.98 (Q1=3.77, Q3=4.22) million incident chlamydial infections, and an estimated 209,000 (Q1=183,000, Q3=241,000) prevalent and 1.57 (Q1=1.44, Q3=1.72) million incident gonococcal infections. Of all gonococcal infections, there were 107,000 (Q1=94,000, Q3=124,000) prevalent and 804,000 (Q1=738,000, Q3=883,000) incident infections demonstrating AMR or elevated minimum inhibitory concentrations (MICs) to selected antibiotics. CONCLUSIONS: Chlamydia and gonorrhea were very common in the US in 2018. Estimates show that more than 800,000 newly acquired gonococcal infections in 2018 demonstrated resistance or elevated MICs to currently or previously recommended antibiotics. |
Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020
St Cyr S , Barbee L , Workowski KA , Bachmann LH , Pham C , Schlanger K , Torrone E , Weinstock H , Kersh EN , Thorpe P . MMWR Morb Mortal Wkly Rep 2020 69 (50) 1911-1916 Sexually transmitted infections (STIs) caused by the bacteria Neisseria gonorrhoeae (gonococcal infections) have increased 63% since 2014 and are a cause of sequelae including pelvic inflammatory disease, ectopic pregnancy, and infertility and can facilitate transmission of human immunodeficiency virus (HIV) (1,2). Effective treatment can prevent complications and transmission, but N. gonorrhoeae's ability to acquire antimicrobial resistance influences treatment recommendations and complicates control (3). In 2010, CDC recommended a single 250 mg intramuscular (IM) dose of ceftriaxone and a single 1 g oral dose of azithromycin for treatment of uncomplicated gonococcal infections of the cervix, urethra, and rectum as a strategy for preventing ceftriaxone resistance and treating possible coinfection with Chlamydia trachomatis (4). Increasing concern for antimicrobial stewardship and the potential impact of dual therapy on commensal organisms and concurrent pathogens (3), in conjunction with the continued low incidence of ceftriaxone resistance and the increased incidence of azithromycin resistance, has led to reevaluation of this recommendation. This report, which updates previous guidelines (5), recommends a single 500 mg IM dose of ceftriaxone for treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydial infection has not been excluded, concurrent treatment with doxycycline (100 mg orally twice a day for 7 days) is recommended. Continuing to monitor for emergence of ceftriaxone resistance through surveillance and health care providers' reporting of treatment failures is essential to ensuring continued efficacy of recommended regimens. |
Notes from the field: First case in the United States of Neisseria gonorrhoeae harboring emerging mosaic penA60 allele, conferring reduced susceptibility to cefixime and ceftriaxone
Picker MA , Knoblock RJ , Hansen H , Bautista I , Griego R , Barber L , Bendik W , Lam K , Adelman E , Qiu-Shultz Z , Raphael BH , Pham CD , Kersh EN , Weinstock H , St Cyr SB . MMWR Morb Mortal Wkly Rep 2020 69 (49) 1876-1877 In November 2019, the Southern Nevada Public Health Laboratory of the Southern Nevada Health District (SNHD) identified a male urethral gonococcal isolate later demonstrating reduced susceptibility to cefixime (minimum inhibitory concentration [MIC] = 2.0 μg/mL) and ceftriaxone (MIC = 1.0 μg/mL) but susceptible to azithromycin (MIC = 0.25 μg/mL). Molecular testing by CDC in the United States revealed the emerging mosaic penA60 allele, first identified in Japan in 2016 (1), which confers reduced susceptibility to cephalosporins and increases the risk for treatment failure. The penA60 allele has been identified in China (2), Canada (3,4), Denmark (5), Australia (6), France (7), and the United Kingdom (8). The Nevada case is the first identified case of a Neisseria gonorrhoeae isolate harboring the mosaic penA60 allele reported in the United States. |
Atypical Mutation in Neisseria gonorrhoeae 23S rRNA Associated with High-Level Azithromycin Resistance.
Pham CD , Nash E , Liu H , Schmerer MW , Sharpe S , Woods G , Roland B , Schlanger K , St Cyr SB , Carlson J , Sellers K , Olsen A , Sanon R , Hardin H , Soge OO , Raphael BH , Kersh EN . Antimicrob Agents Chemother 2020 65 (2) A2059G mutation in the 23S rRNA gene is the only reported mechanism conferring high-level azithromycin resistance (HL-AZMR) in Neisseria gonorrhoea Through U.S. gonococcal antimicrobial resistance surveillance projects, we identified four HL-AZMR gonococcal isolates lacking this mutational genotype. Genetic analysis revealed an A2058G mutation of 23S rRNA alleles in all four isolates. In vitro selected gonococcal strains with homozygous A2058G recapitulated the HL-AZMR phenotype. Taken together, we postulate that A2058G mutation confers HL-AZMR in N. gonorrhoeae. |
Azithromycin susceptibility of Neisseria gonorrhoeae in the USA in 2017: a genomic analysis of surveillance data.
Gernert KM , Seby S , Schmerer MW , Thomas JCth , Pham CD , Cyr SS , Schlanger K , Weinstock H , Shafer WM , Raphael BH , Kersh EN . Lancet Microbe 2020 1 (4) e154-e164 BACKGROUND: The number of cases of gonorrhoea in the USA and worldwide caused by Neisseria gonorrhoeae is increasing (555 608 reported US cases in 2017, and 87 million cases worldwide in 2016). Many countries report declining in vitro susceptibility of azithromycin, which is a concern because azithromycin and ceftriaxone are the recommended dual treatment in many countries. We aimed to identify strain types associated with decreased susceptibility to azithromycin. METHODS: We did a genomic analysis of N gonorrhoeae isolates obtained by the US Gonococcal Isolate Surveillance Project. Isolates were whole-genome sequenced based on decreased susceptibility to azithromycin (minimal inhibitory concentration [MIC] ≥2 μg/mL, using agar dilution antibiotic susceptibility testing) and geographical representation. Bioinformatic analyses established genomic diversity, strain population dynamics, and antimicrobial resistance profiles. FINDINGS: 410 isolates were sorted into more than 20 unique phylogenetic clades. One predominant persistent clade (consisting of 97 isolates) included the most isolates with azithromycin MICs of 2 μg/mL or higher (61 of 97 [63%] vs 59 of 311 [19%]; p<0·0001) and carried a mosaic mtr (multiple transferable resistance) locus (68 of 97 [70%] vs two of 313 [1%]; p<0·0001). Of the remaining 313 isolates, 57 (18%) had decreased susceptibility to azithromycin (MIC ≥4 μg/mL), which was attributed to 23S rRNA variants (56 of 57 [98%]) and formed phylogenetically diverse clades, showing various levels of clonal expansion. INTERPRETATION: Reduced azithromycin susceptibility was associated with expanding and persistent clades harbouring two well described resistance mechanisms, mosaic mtr locus and 23S rRNA variants. Understanding the role of recombination, particularly within the mtr locus, on the fitness and expansion of strains with decreased susceptibility has important implications for the public health response to minimise gonorrhoea transmission. FUNDING: US Centers for Disease Control and Prevention (CDC), CDC Combating Antibiotic Resistant Bacteria initiative, Oak Ridge Institute for Science Education, US Department of Energy/CDC/Emory University, National Institutes of Health, and Biomedical Laboratory Research and Development Service of the US Department of Veterans Affairs. |
A Culture Collection of 50 Neisseria gonorrhoeae Isolates.
Liu H , Vidyaprakash E , Schmerer MW , Pham DC , St Cyr S , Kersh EN . Microbiol Resour Announc 2020 9 (40) A culture collection of 50 Neisseria gonorrhoeae isolates is available from the CDC & FDA Antibiotic Resistance Isolate Bank. Associated data include antibiotic susceptibility information for azithromycin, cefixime, cefpodoxime, ceftriaxone, tetracycline, ciprofloxacin, penicillin, and spectinomycin and linked whole-genome sequences. |
Childhood obesity evidence base project: A systematic review and meta-analysis of a new taxonomy of intervention components to improve weight status in children 2-5 years of age, 2005-2019
Scott-Sheldon LAJ , Hedges LV , Cyr C , Young-Hyman D , Khan LK , Magnus M , King H , Arteaga S , Cawley J , Economos CD , Haire-Joshu D , Hunter CM , Lee BY , Kumanyika SK , Ritchie LD , Robinson TN , Schwartz MB . Child Obes 2020 16 S221-s248 Objective: To evaluate the efficacy of childhood obesity interventions and conduct a taxonomy of intervention components that are most effective in changing obesity-related health outcomes in children 2-5 years of age. Methods: Comprehensive searches located 51 studies from 18,335 unique records. Eligible studies: (1) assessed children aged 2-5, living in the United States; (2) evaluated an intervention to improve weight status; (3) identified a same-aged comparison group; (4) measured BMI; and (5) were available between January 2005 and August 2019. Coders extracted study, sample, and intervention characteristics. Effect sizes [ESs; and 95% confidence intervals (CIs)] were calculated by using random-effects models. Meta-regression was used to determine which intervention components explain variability in ESs. Results: Included were 51 studies evaluating 58 interventions (N = 29,085; mean age = 4 years; 50% girls). Relative to controls, children receiving an intervention had a lower BMI at the end of the intervention (g = 0.10, 95% CI = 0.02-0.18; k = 55) and at the last follow-up (g = 0.17, 95% CI = 0.04-0.30; k = 14; range = 18-143 weeks). Three intervention components moderated efficacy: engage caregivers in praise/encouragement for positive health-related behavior; provide education about the importance of screen time reduction to caregivers; and engage pediatricians/health care providers. Conclusions: Early childhood obesity interventions are effective in reducing BMI in preschool children. Our findings suggest that facilitating caregiver education about the importance of screen time reduction may be an important strategy in reducing early childhood obesity. |
Childhood obesity evidence base project: A rationale for taxonomic versus conventional meta-analysis
Hedges LV , Saul JA , Cyr C , Magnus M , Scott-Sheldon LAJ , Young-Hyman D , Khan LK . Child Obes 2020 16 S21-s26 Introduction: There is a great need for analytic techniques that allow for the synthesis of learning across seemingly idiosyncratic interventions. Objectives: The primary objective of this paper is to introduce taxonomic meta-analysis and explain how it is different from conventional meta-analysis. Results: Conventional meta-analysis has previously been used to examine the effectiveness of childhood obesity prevention interventions. However, these tend to examine narrowly defined sections of obesity prevention initiatives, and as such, do not allow the field to draw conclusions across settings, participants, or subjects. Compared with conventional meta-analysis, taxonomic meta-analysis widens the aperture of what can be examined to synthesize evidence across interventions with diverse topics, goals, research designs, and settings. A component approach is employed to examine interventions at the level of their essential features or activities to identify the concrete aspects of interventions that are used (intervention components), characteristics of the intended populations (target population or intended recipient characteristics), and facets of the environments in which they operate (contextual elements), and the relationship of these components to effect size. In addition, compared with conventional meta-analysis methods, taxonomic meta-analyses can include the results of natural experiments, policy initiatives, program implementation efforts and highly controlled experiments (as examples) regardless of the design of the report being analyzed as long as the intended outcome is the same. It also characterizes the domain of interventions that have been studied. Conclusion: Taxonomic meta-analysis can be a powerful tool for summarizing the evidence that exists and for generating hypotheses that are worthy of more rigorous testing. |
Childhood obesity evidence base project: Methods for taxonomy development for application in taxonomic meta-analysis
King H , Magnus M , Hedges LV , Cyr C , Young-Hyman D , Kettel Khan L , Scott-Sheldon LAJ , Saul JA , Arteaga S , Cawley J , Economos CD , Haire-Joshu D , Hunter CM , Lee BY , Kumanyika SK , Ritchie LD , Robinson TN , Schwartz MB . Child Obes 2020 16 S27-s220 Meta-analysis has been used to examine the effectiveness of childhood obesity prevention efforts, yet traditional conventional meta-analytic methods restrict the kinds of studies included, and either narrowly define mechanisms and agents of change, or examine the effectiveness of whole interventions as opposed to the specific actions that comprise interventions. Taxonomic meta-analytic methods widen the aperture of what can be included in a meta-analysis data set, allowing for inclusion of many types of interventions and study designs. The National Collaborative on Childhood Obesity Research Childhood Obesity Evidence Base (COEB) project focuses on interventions intended to prevent childhood obesity in children 2-5 years old who have an outcome measure of BMI. The COEB created taxonomies, anchored in the Social Ecological Model, which catalog specific outcomes, intervention components, intended recipients, and contexts of policies, initiatives, and interventions conducted at the individual, interpersonal, organizational, community, and societal level. Taxonomies were created by discovery from the literature itself using grounded theory. This article describes the process used for a novel taxonomic meta-analysis of childhood obesity prevention studies between the years 2010 and 2019. This method can be applied to other areas of research, including obesity prevention in additional populations. |
Utility of MALDI-TOF MS for differentiation of Neisseria gonorrhoeae isolates with dissimilar azithromycin susceptibility profiles
Pham CD , Pettus K , Nash EE , Liu H , St Cyr SB , Schlanger K , Papp J , Gartin J , Dorji T , Akullo K , Kersh EN . J Antimicrob Chemother 2020 75 (11) 3202-3208 BACKGROUND: Antibiotic-resistant gonorrhoea has been a chronic public health burden since the mid-1930s. Recent emergence of isolates resistant to the current recommended antibiotics for gonorrhoea further magnifies the threat of untreatable gonorrhoea. The lack of new, effective antibiotics highlights the need for better understanding of the population structure of Neisseria gonorrhoeae in order to provide greater insight on how to curtail the spread of antimicrobial-resistant N. gonorrhoeae. OBJECTIVES: To explore a potential application of MALDI-TOF MS to differentiate N. gonorrhoeae displaying different levels of susceptibility to the antibiotic azithromycin. METHODS: We conducted MALDI-TOF MS using the Bruker Biotyper on 392 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project (GISP) and/or the Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. The MALDI-TOF MS spectra were visually analysed to assess the presence of distinctive peak(s). Statistical analysis was performed to assess the relationship between gonococcal isolates with the distinct protein peak and antibiotic susceptibility. RESULTS: In this study, we were able to differentiate N. gonorrhoeae isolates into two distinct subpopulations using MALDI-TOF MS. Isolates were distinguished by the presence or absence of a spectral peak at 11 300 Da. Notably, these two groups exhibited different levels of susceptibility to azithromycin. CONCLUSIONS: We have shown that in addition to its ability to identify N. gonorrhoeae, MALDI-TOF MS could also be used to differentiate gonococcal isolates with different levels of susceptibility to azithromycin. |
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