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Background Antimicrobial resistance (AMR) is a global threat to infectious disease control, particularly among recently hospitalized children. We sought to determine the prevalence and mitigating factors of resistance in enteric Escherichia coli among children discharged from health facilities in western Kenya. Methods Between June 2016 and November 2019, children aged 1 to 59 months were enrolled at the point of discharge from the hospital. E coli was isolated by microbiological culture from rectal swabs at baseline. β-Lactamases and macrolide resistance–conferring genes were detected by polymerase chain reaction. A modified Poisson regression model was used to assess the predictors mph (A) and CTX-M–type extended-spectrum β-lactamase (ESBL). Results Of the 238 children whose E coli isolates were tested, 91 (38.2%) and 109 (45.8%) had detectable CTX-M–type ESBL and mph (A) genes, respectively. Antibiotic treatment during hospitalization (adjusted prevalence ratio [aPR], 2.47; 95% CI, 1.12–5.43; P =.025), length of hospitalization (aPR, 1.42; 95% CI, 1.00–2.01; P =.052), and the practice of open defecation (aPR, 2.47; 95% CI, 1.40–4.36; P =.002) were independent predictors for CTX-M–type ESBL and mph (A) genes. Pneumococcal vaccination was associated with a 43% lower likelihood of CTX-M–type ESBL (aPR, 0.57; 95% CI,.38–.85; P =.005), while measles vaccination was associated with a 32% lower likelihood of mph (A) genes (aPR, 0.68; 95% CI,.49–.93; P =.017) in E coli isolates. Conclusions Among children discharged from the hospital, history of vaccination, shorter hospital stay, lack of in-hospital antibiotic exposure, and improved sanitation were associated with a lower likelihood of AMR genes. To mitigate the continued spread of AMR, AMR control programs should consider strategies beyond antimicrobial stewardship, including improvements in sanitation, increased vaccine coverage, and the development of novel vaccines. [ABSTRACT FROM AUTHOR]

Background The incidence of syphilis continues to increase in the United States, yet little is known about Treponema pallidum genomic epidemiology within American metropolitan areas. Methods We performed whole-genome sequencing and tprK deep sequencing of 28 T. pallidum– containing specimens, collected mostly from remnant Aptima swab specimens from 24 individuals from Seattle Sexual Health Clinic during 2021–2022. Results All 12 individuals infected with Nichols-lineage strains were men who have sex with men, while a specific SS14 cluster (mean, 0.33 single-nucleotide variant) included 1 man who has sex with women and 5 women. All T. pallidum strains sequenced were azithromycin resistant via 23S ribosomal RNA A2058G mutation. Identical T. pallidum genomic sequences were found in pharyngeal and rectal swab specimens taken concurrently from the same individuals. The tprK sequences were less variable between patient-matched specimens and between epidemiologically linked clusters. We detected a 528–base pair deletion in the tprK donor site locus, eliminating 9 donor sites, in T. pallidum genomes of 3 individuals with secondary syphilis, associated with diminution of TprK diversity. Conclusions We developed an end-to-end workflow for public health genomic surveillance of T. pallidum from remnant Aptima swab specimens. tprK sequencing may assist in linking cases beyond routine T. pallidum genome sequencing. T. pallidum strains with deletions in tprK donor sites currently circulate and are associated with diminished TprK antigenic diversity. [ABSTRACT FROM AUTHOR]

Background Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change. Methods We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status). Results From October–December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% from non-Hispanic Black persons, and 43.8% from symptomatic patients. MG prevalence was 16.6% (95% CI: 14.9–18.5%; site-specific range: 9.9–23.5%) and higher in St Louis (aPR: 1.9; 1.27–2.85), Greensboro (aPR: 1.8; 1.18–2.79), and Denver (aPR: 1.7; 1.12–2.44) than Seattle. Prevalence was highest in persons <18 years (30.4%) and declined 3% per each additional year of age (aPR:.97;.955–.982). MG was detected in 26.8%, 21.1%, 11.8%, and 15.4% of urethritis, vaginitis, cervicitis, and pelvic inflammatory disease (PID), respectively. It was present in 9% of asymptomatic males and 15.4% of asymptomatic females, and associated with male urethritis (aPR: 1.7; 1.22–2.50) and chlamydia (aPR: 1.7; 1.13–2.53). MRM prevalence was 59.1% (95% CI: 53.1–64.8%; site-specific range: 51.3–70.6%). MRMs were associated with vaginitis (aPR: 1.8; 1.14–2.85), cervicitis (aPR: 3.5; 1.69–7.30), and PID cervicitis (aPR: 1.8; 1.09–3.08). Conclusions MG infection is common in persons at high risk of sexually transmitted infections; testing symptomatic patients would facilitate appropriate therapy. Macrolide resistance is high and azithromycin should not be used without resistance testing. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae, the causative pathogen of gonorrhea, has been designated an urgent antimicrobial drug resistance threat by the Centers for Disease Control and Prevention (CDC) (1). Since the introduction of [...]

Background: The current testing approach to diagnose Chlamydia trachomatis (CT) infection relies on nucleic acid amplification tests (NAATs). These tests are highly sensitive, but do not distinguish between active infection and residual bacterial nucleic acid which may remain after resolution of infection, or via cross-contamination. Better methods to assess the viability of CT detected in clinical samples would be useful in determining the relevance of CT detection in a variety of clinical settings. The goal of this study was to test viability PCR (vPCR) as a method to distinguish viable bacteria from non-viable CT. Methods: The vPCR relies on a propidium monoazide dye (PMAxx), which intercalates into accessible DNA from dead organisms and prevents their detection in a PCR assay for the CT ompA gene. We used digital PCR to quantify absolute genome copy numbers from samples. We validated the vPCR approach using laboratory stocks of CT with known viability. Then, we tested total DNA, viable CT DNA, and culture results from 18 clinical vaginal specimens and 25 rectal clinical specimens, all of which had tested positive by NAAT. Results: In laboratory stocks of CT, vPCR using defined ratios of heat-killed to live bacteria tracked closely with expected results. In vaginal clinical specimens, vPCR and total DNA results were correlated, though total DNA genomes outnumbered viable genomes by 2.2–52.6-fold more copies. As expected, vPCR detected more total genomes than culture results. Both vPCR and total DNA correlated with culture results (Spearman correlation R = 0.8425 for total DNA and 0.8056 for vPCR). Ten rectal NAAT positive specimens were negative by total DNA PCR, vPCR, and were negative or inconclusive by culture. Of the 6 rectal specimens that were culture positive, all were total DNA and vPCR positive. vPCR additionally detected viable bacterial DNA in 8 specimens which were NAAT + and culture negative, though levels were very low (mean 1,357 copies/ml) Conclusions: vPCR is a fast and easy method to assess viability in clinical specimens and is more correlated with culture results than total DNA PCR. Inconsistent ratios between total DNA and vPCR results suggest that the amount of dead bacteria varies considerably in clinical specimens. Results from rectal specimens suggest that many NAAT positive specimens do not in fact represent live replicating bacteria, and likely result in significant overuse of unnecessary antibiotics. [ABSTRACT FROM AUTHOR]

Background Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Methods Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. Results A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL. Conclusions Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials. [ABSTRACT FROM AUTHOR]

Nisseria gonorrhoeae is a sexually transmitted pathogen that has progressively developed resistance to the antimicrobial agents recommended for treatment (1). Third-generation cephalosporins are among the last class of antimicrobial agents [...]

Background There is conflicting evidence on whether prior azithromycin (AZM) exposure is associated with reduced susceptibility to AZM (AZMRS) among persons infected with Neisseria gonorrhoeae (NG). Methods The study population included Public Health–Seattle and King County Sexual Health Clinic (SHC) patients with culture-positive NG infection at ≥1 anatomic site whose isolates were tested for AZM susceptibility in 2012–2019. We used multivariate logistic regression to examine the association of time since last AZM prescription from the SHC in ≤12 months with subsequent diagnosis with AZMRS NG (minimum inhibitory concentration [MIC], ≥2.0 µg/mL) and used linear regression to assess the association between the number of AZM prescriptions in ≤12 months and AZM MIC level, controlling for demographic, behavioral, and clinical characteristics. Results A total of 2155 unique patients had 2828 incident NG infections, 156 (6%) of which were caused by AZMRS NG. AZMRS NG was strongly associated with receipt of AZM from the SHC in the prior 29 days (adjusted odds ratio, 6.76; 95% confidence interval [CI], 1.76 to 25.90) but not with receipt of AZM in the prior 30–365 days. Log AZM MIC level was not associated with the number of AZM prescriptions within ≤12 months (adjusted correlation, 0.0004; 95% CI, –.04 to.037) but was associated with number of prescriptions within <30 days (adjusted coefficient, 0.56; 95% CI,.13 to.98). Conclusions Recent individual-level AZM treatment is associated with subsequent AZMRS gonococcal infections. The long half-life and persistence of subtherapeutic levels of AZM may result in selection of resistant NG strains in persons with recent AZM use. [ABSTRACT FROM AUTHOR]

Background The prevalence of pharyngeal chlamydia is low, but its incidence and duration are unknown. A high incidence or duration may support the role of pharyngeal chlamydia in sustaining chlamydia transmission. Methods From March 2016 to December 2018, we enrolled men who have sex with men (MSM) in a 48-week cohort study in Seattle, Washington. Participants self-collected pharyngeal specimens weekly. We tested specimens using nucleic acid amplification testing at the conclusion of the study. In primary analyses, we defined incident pharyngeal chlamydia as >2 consecutive weeks of a positive pharyngeal specimen. In sensitivity analyses, we defined incident chlamydia as >1 week of a positive specimen. We estimated duration of pharyngeal chlamydia, censoring at loss to follow-up, receipt of antibiotics, or end of study. Results A total of 140 participants contributed 70.5 person-years (PY); 1.4% had pharyngeal chlamydia at enrollment. In primary analyses, there were 8 pharyngeal chlamydia cases among 6 MSM (incidence = 11.4 per 100 PY; 95% confidence interval [CI]: 6.0–21.9). In sensitivity analysis, there were 19 cases among 16 MSM (incidence = 27.1 per 100 PY; 95% CI: 18.5–39.8). The median duration was 6.0 weeks (95% CI: 2.0–undefined) in primary analysis and 2.0 weeks (95% CI: 1.1–6.0) in sensitivity analysis. Duration was shorter for those with a history of chlamydia compared with those without (3.6 vs 8.7 weeks; P =.02). Conclusions Pharyngeal chlamydia has a low incidence and duration relative to other extragenital sexually transmitted infections. Its contribution to population-level transmission remains unclear. [ABSTRACT FROM AUTHOR]

Most archived Neisseria gonorrhoeae samples collected from 2008 to 2012 from Kenyan women had tet (M)-encoding high-level tetracycline resistance; this could reduce the efficacy of doxycycline postexposure prophylaxis against N. gonorrhoeae. Using archived Neisseria gonorrhoeae samples from 2008 to 2012, the prevalence of tet (M) genemediating high-level tetracycline resistance in N. gonorrhoeae was 96% among 50 Kenyan women. Determining the local and national prevalence of gonococcal tetracycline resistance and surveillance of gonococcal antimicrobial resistance can inform the implementation of doxycycline postexposure prophylaxis for STI prevention. [ABSTRACT FROM AUTHOR]

Background The duration of rectal gonococcal and chlamydial infection remains unknown. This basic epidemiologic parameter is needed to understand transmission dynamics. Methods We conducted a prospective, longitudinal, observational cohort study of 140 men who have sex with men (MSM) at risk of gonorrhea and chlamydia acquisition. For 48 weeks, enrolled men collected rectal swabs (Aptima multi-test kit) at home and responded to an electronic survey about sexual behavior and health conditions weekly. Swabs remained untested until participants completed the study. We used Kaplan-Meier estimates to determine the median duration of infection, censoring infections for treatment, loss to follow-up, and end-of-study. We used log-rank test to compare duration of infection by human immunodeficiency virus (HIV) status, history of infection with gonorrhea or chlamydia, and coinfection with the other pathogen. Results 140 enrolled MSM contributed 70.5 person-years of follow-up. Eighteen men had 20 incident rectal gonococcal infections, which persisted for 2–23 weeks; 30% were censored for treatment. The estimated median duration of rectal gonorrhea was 9 weeks (95% confidence interval [CI]: 3–12 weeks). Twenty-four men experienced 32 rectal chlamydial infections, persisting between 2 and 42 weeks; 60% were censored. The estimated duration of rectal chlamydia was 13 weeks (95% CI: 6 weeks–undefined). There were no differences in the duration of rectal gonorrhea or chlamydia by HIV status, history of chlamydia/gonorrhea, or coinfection. Conclusions On average, rectal gonorrhea and chlamydial infections last 2–3 months, although some infections persisted for 6–11 months. Further understanding into predictors of persistence is needed. [ABSTRACT FROM AUTHOR]

Background: Children who have been discharged from hospital in sub-Saharan Africa remain at substantial risk of mortality in the post-discharge period. Antimicrobial resistance (AMR) may be an important factor. We sought to determine the prevalence and risk factors associated with AMR in commensal Escherichia coli(E. coli) from Kenyan children at the time of discharge. Methodology/Principle findings: Fecal samples were collected from 406 children aged 1–59 months in western Kenya at the time of discharge from hospital and cultured for E. coli. Susceptibility to ampicillin, ceftriaxone, cefotaxime, ceftazidime, cefoxitin, imipenem, ciprofloxacin, gentamicin, combined amoxicillin/clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin, and chloramphenicol was determined by disc diffusion according to guidelines from the Clinical and Laboratory Standards Institute (CLSI). Poisson regression was used to determine associations between participant characteristics and the presence of extended-spectrum beta-lactamases (ESBL) producing E. coli. Non-susceptibility to ampicillin (95%), gentamicin (44%), ceftriaxone (46%), and the presence of ESBL (44%) was high. Receipt of antibiotics during the hospitalization was associated with the presence of ESBL (= 2.23; 95% CI: 1.29–3.83) as was being hospitalized within the prior year (aPR = 1.32 [1.07–1.69]). Open defecation (aPR = 2.02; 95% CI: 1.39–2.94), having a toilet shared with other households (1.49; 95% CI: 1.17–1.89), and being female (1.42; 95% CI: 1.15–1.76) were associated with carriage of ESBL E. coli Conclusions/Significance: AMR is common among isolates of E. coli from children at hospital discharge in Kenya, including nearly half having detectable ESBL. Author summary: Children who have been hospitalized in sub-Saharan Africa remain at a high risk of death and morbidity for at least 6 months following discharge. These children may harbor AMR in commensal bacteria following hospitalization, which may be associated with poor outcomes. There are limited data describing AMR and risk factors that are associated with AMR carriage at hospital discharge. In this cross-sectional study of Kenyan children under 5 years of age discharged from hospitals, we found AMR to be high. Children who received antibiotics in the hospital, had limited access to improved sanitation, and who were female had the highest prevalence of ESBL-producing E. coli. [ABSTRACT FROM AUTHOR]

Background: Some evidence suggests that oropharyngeal commensal Neisseria spp. act as a reservoir of antimicrobial resistance (AMR) leading to AMR Neisseria gonorrhoeae (Ng) through horizontal gene transfer. However, commensal Neisseria spp. are rarely cultured, there are limited data on their AMR profiles, and how often AMR in commensal Neisseria spp. leads to AMR Ng is unknown. Methods: From 2019-2022, we cultured commensal Neisseria spp. using de-identified remnant pharyngeal specimens collected from male patients presenting to the municipal Sexual Health Clinic (SHC) and eight clinics in King County, WA who met clinical criteria for gonorrhea culture. Ng and Neisseria meningitidis (Nm) were confirmed by API NH and excluded from the study. Commensal Neisseria species confirmation was performed with the Bruker MALDI Biotyper and minimum inhibitory concentrations (MICs) for azithromycin (AZM), cefixime (CFX) and ceftriaxone (CRO) were determined by Etest. We defined cefixime resistance (CFXR) and ceftriaxone resistance (CROR) as MIC ≥0.5 µg/ml, azithromycin resistance (AZMR) as MIC ≥2 µg/ml, and high-level AZMR (HL-AZMR) as MIC≥256 µg/ml. Results: We speciated 715 oropharyngeal non-Ng, non-Nm Neisseria spp. belonging to 10 different species by MALDI Biotyper, N. subflava (66.9%), N. macacae (9.5%), N. flavescens (9.5%), N. mucosa (5%), N. oralis (2.4%), N. perflava (2.1%), N. lactamica (1.4%), N. cinerea (1.1%), N. sicca (1.1%), and N. elongata (1%). Etest performed on 415 isolates of commensal Neisseria spp. showed high levels of AZMR (95%), CFXR (22%), and CROR (12%). The MIC ranges, MIC50, and MIC90 for the three antimicrobials were AZM 0.064 -- >256, 128, and >256; CFX < 0.016 -- 2µg/ml, 0.25 µg/ml, and 1 µg/ml; CRO 0.002 -- 2µg/ml, 0.125 µg/ml, and 0.5 µg/ml, respectively. HL-AZMR predominated among the commensal Neisseria spp. Conclusion: Oropharyngeal commensal Neisseria spp. from male patients attending sexual health clinics in Seattle, WA, demonstrated high levels of macrolide and cephalosporin resistance suggesting that they harbor AMR determinants that can be transferred to Ng. However, given the rarity of CRO and CFX resistant Ng, transfer of AMR determinants from Neisseria spp. to Ng is likely a very rare event. [ABSTRACT FROM AUTHOR]