Aporphine and amide alkaloids from Illigera parviflora.

Three undescribed alkaloids (+)-9-hydroxy-N-acetylnordicentrine (1), illigeparvinine (2), and deca-(2E,4Z)-2,4-dienoic acid 4-hydroxy-2-phenethyl amide (3), along with 19 known analogues (4-22), were isolated from the ethnic medicinal plant Illigera parviflora. Their structures were established using NMR, MS, and other spectroscopic analyses as well as X-ray diffraction. Moderate inhibition of human gastric carcinoma (MGC-803) and breast adenocarcinoma (T-47D) cell lines proliferation was observed for actinodaphnine (4) with IC50 values of 28.74 and 11.65 µM, respectively. These findings contribute new anticancer potential compounds and expand the chemical diversity known from the valuable traditional medicinal plant I. parviflora.

Treatment of maternal syphilis for preventing congenital syphilis: an observational study of adherence to treatment recommendation in Suzhou, China, 2019-2021.

BACKGROUND: China is one of the countries that set the goal to eliminate mother-to-child transmission (EMTCT) of syphilis by a target date. Active screening for syphilis among pregnant women, followed by effective treatment of maternal syphilis, is critical for achieving the goal. The China health authority issued national implementation protocols to guide EMTCT practice in health facilities. METHODS: Within a cohort of infants born to mothers infected with syphilis, we obtained the data of regimens used for treatment of maternal syphilis from the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis and Hepatitis B, and analysed the physician's treatment behaviour and its associated factors in a public hospital in Suzhou of China. RESULTS: A total of 450 pregnant women who were positive for treponemal or non-treponemal antibody, or had previous infection with syphilis were included into the study for analysis. Of them, 260 (57.8%) were positive for both treponemal and non-treponemal antibodies (syphilis seropositivity), and 353 (78.4%) were treated for syphilis according to the protocol in which 123 (34.8%) were treated with two courses. Non-adherence to treatment recommended by the protocol for maternal syphilis was significantly associated with antenatal visits in the third trimester (AOR 6.65, 95% CI 2.20-20.07, P =0.001), being positive only for a treponemal test (AOR 5.34, 95% CI 3.07-9.29, P <0.001) or having a syphilis infection before the pregnancy (AOR 2.05, 95% CI 1.14-3.69, P =0.017), whereas the uptake of treatment for two treatment courses was associated with attending antenatal care in 2020 or before (AOR 3.49, 95% CI 1.89-6.42, P <0.001), being positive for treponemal and non-treponemal tests (AOR 5.28, 95% CI 2.78-10.06, P <0.001) or having non-treponemal antibody titre of ≥1:8 (AOR 3.71, 95% CI 1.77-7.78, P =0.001). CONCLUSIONS: Implementation of the current recommendation to offer a universal treatment for syphilis among all pregnant women who are shown to be positive for a treponemal test alone is challenging in some clinical settings in China.

Associations of Chlamydia trachomatis serology with fertility-related and pregnancy adverse outcomes in women: a systematic review and meta-analysis of observational studies.

BACKGROUND: Chlamydia trachomatis (CT) infection has an increased risk for fertility-related and pregnancy adverse outcomes partly due to mechanisms related to a pro-inflammatory response to CT-, or cHSP60-induced delayed hypersensitivity. This study aimed to assess the evidence on the association between CT serology and adverse outcomes. METHODS: PubMed/Medline, Embase and Web of Science databases were searched for observational studies on the association of CT-specific antibodies (e. g. IgG, IgA, IgM, etc.) with infertility, tubal factor infertility (TFIF), ectopic pregnancy (EP), spontaneous abortion (SA), or preterm labor (PL) that were published from database inception to 31 August 2022. Pooled adjusted odds ratios or relative risks with corresponding 95% confidence intervals were calculated using a random effects model. This study was registered with PROSPERO (CRD42022368366). FINDINGS: We identified 128 studies that met the inclusion criteria, comprising 87 case-control, 34 cross-sectional and 7 cohort studies, for a total of 167 records involving 128,625 women participants included into the meta-analyses. Based on the adjusted estimates, it was found that CT-specific IgG was significantly associated with TFIF (pooled adjusted OR = 2.09, 95% CI 1.33-3.27, I2 = 63.8%) or EP (pooled adjusted OR = 3.00, 95% CI 1.66-5.40, I2 = 93.0%). Analyses of the unadjusted estimates indicated significant associations between CT-specific IgG and infertility, TFIF, EP or SA (four pooled unadjusted ORs ranging between 1.60 and 5.14, I2 ranging between 40% and 83%); IgA and infertility, TFIF, EP (three pooled unadjusted ORs ranging between 3.64 and 4.91, I2 ranging between 0% and 74%); IgM and TFIF (pooled unadjusted OR = 5.70, 95% CI 1.58-20.56, I2 = 56%); or cHSP60 and TFIF (pooled unadjusted OR = 7.83, 95% CI 5.42-11.31, I2 = 49%). INTERPRETATION: A broad range of CT-specific antibodies have been studied in association with fertility-related and pregnancy adverse outcomes. However, our study identified a low- or moderate-quality evidence for an association of CT serology with the outcomes. There are substantial research gaps in relation to the clinical implications of CT serological biomarkers. FUNDING: The work was supported by the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021).

An evaluation of a multiplex PCR assay for the detection of Treponema pallidum, HSV-1, and HSV-2.

Multiplex PCR can utilize limited clinical material and is more cost-effective and expected to be used for the detection of Treponema pallidum, herpes simplex virus type 1 and 2 (HSV-1,2). We established a multiplex TP-HSV1-HSV2 Polymerase Chain Reaction (multiplex PCR) targeting the conserved regions of the PolA gene of TP and the UL42 gene of HSV1 and HSV2 to test skin lesions of 115 patients suspected of having TP and HSV1/2 infections. The laboratory sensitivities for all 3 pathogens were 300 copies/mL. The overall clinical sensitivity and specificity in secretion samples for TP were 91.7% and 100%, for HSV1 100% and 98%, and for HSV2 89.7% and 100%, respectively. The method appears superior in patients suspected of early TP infection but negative for nontreponemal antibody testing, and the method is also useful for the differential diagnosis of new skin lesions on genital, perianal, and oral sites of patients with a history of previous syphilis.

Using pooled urogenital, anorectal and oropharyngeal specimens to detect Chlamydia trachomatis and Neisseria gonorrhoeae among men who have sex with men in China: a multisite diagnostic accuracy study.

OBJECTIVES: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at both urogenital and extragenital sites has been recommended in many countries. Testing of the infections using pooled specimens from urogenital and extragenital sites offer the opportunity to shorten the testing time and reduce the testing cost. Ex-ante pooling is placing the original single-site specimens in a tube with transport media, while ex-post pooling is making a pool of the transport media from both anorectal and oropharyngeal specimens and the urine. This study aimed to conduct a multisite performance evaluation of two pool-specimen approaches (ex-ante and ex-post) in detection of CT and NG using the Cobas 4800 platform among men who have sex with men (MSM) in China. DESIGN: Diagnostic accuracy study. SETTING, PARTICIPANTS AND OUTCOME MEASURES: Participants were recruited from MSM communities at six cities in China. Two oropharyngeal and anorectal swabs collected by clinical staff and 20 mL first-void urine collected by the participant himself were used for evaluating sensitivity and specificity. RESULTS: A total of 1311 specimens were collected from 437 participants in six cities. The sensitivities of ex-ante pooling approach as compared with single-specimen approach (reference standard) were 98.7% (95% CI, 92.7% to 100.0%) for detection of CT and 89.7% (95% CI, 75.8% to 97.1%) for NG, and the specificities were 99.5% (95% CI, 98.0% to 99.9%) and 98.7% (95% CI, 97.1% to 99.6%), respectively. The sensitivities of ex-post pooling approach were 98.7% (95% CI, 92.7% to 100.0%) for CT and 100.0% (95% CI, 91.0% to 100.0%) for NG, and the specificities were 100.0% (95% CI, 99.0% to 100.0%) and 100.0% (95% CI, 99.1% to 100.0%), respectively. CONCLUSIONS: The ex-ante and ex-post pooling approaches show good sensitivity and specificity in detecting urogenital and extragenital CT and/or NG, indicating that these approaches can be used in epidemiological surveillance and clinical management of CT and NG infections, particularly among MSM population.

A Nationwide Survey on Detection of Chlamydia trachomatis in Health Facilities in China.

BACKGROUND: This study evaluated the clinical laboratory capacity for the diagnosis of Chlamydia trachomatis (CT) in China to provide recommendations to improve the diagnostic capacity and quality of this clinically important sexually transmitted disease. METHODS: An electronic questionnaire-based cross-sectional, survey study was conducted by the National Center for STD Control among different types of healthcare facilities in China from July to December 2021. RESULTS: The surveyed laboratory facilities were located in 332 cities in 31 provinces in China. A total of 4640 records from clinical laboratories were included in the data set for the final analysis. Less than half of the laboratories (41.6% [1931 of 4640]) performed the CT diagnostic test; of these, 721 laboratories (15.5% [721 of 4640]) carried out nucleic acid amplification test (NAAT) methods, and 1318 laboratories (28.4% [1318 of 4640]) performed antigen-based immunochromatographic assays. Most laboratories were equipped with biological safety cabinets (93.7% [4348 of 4640]), 49.2% (2283 of 4640) were equipped with fully automated nucleic acid extractors, and 55.2% (2560 of 4640) were equipped with polymerase chain reaction amplification instruments. The laboratories from Southern China or third-class hospitals (i.e., the highest rated hospitals) had the highest proportion using NAATs to diagnose CT among the surveyed health facilities. CONCLUSIONS: Advancing laboratories to use NAAT to detect CT should be phased step-by-step by different areas and levels of hospitals according to the current situation.

Knowledge on Chlamydia trachomatis and Acceptance to Testing for It Among Young Students in China.

BACKGROUND: Actively screening for Chlamydia trachomatis (CT) is important for young people because of a high prevalence of asymptomatic infection in this population. This study aimed to investigate knowledge on CT and preference to the screening services for CT among young students in China. METHODS: From June to July 2022, a web-based questionnaire survey was conducted to collect information on sociodemographic characteristics, sexual behaviors, knowledge of CT, previous testing for CT, and preference to platform of testing for CT among Chinese young students. An online home-based self-sampling test (HBSST) service was offered free of charge if the participant was willing to be tested for CT. Statistical analyses included descriptive analysis, χ 2 test, and multivariable logistic regression. RESULTS: Of 520 participants, 419 (80.6%) were aged between 16 and 24 years, 235 (45.2%) reported having sexual experience in the past, and 27 (5.2%) being tested before for CT. Slightly higher than 10% (57/520) of students were knowledgeable about CT. About one-third (36.9%) expressed their willingness to have a testing for CT but majority of them (63.1%) preferred to a free testing. Having sexual experience was significantly associated with the willingness to take the HBSST service (adjusted odds ratio, 2.96; 95% confidence interval, 1.92-4.58). A total of 139 (26.7%) participants requested the HBSST service online and 43.2% (60/139) returned the specimen for testing, in which 2 positives (3.3%) were found. CONCLUSIONS: The knowledge on CT and the previous uptake or current willingness to have a testing for CT was low among Chinese young students.

Performance evaluation of eight treponemal antibody tests in China.

In this study, the performance of 8 commercially available treponemal antibody tests was evaluated. Higher specificity was achieved in the automated chemiluminescence immunoassays(CIA assays) than enzyme-linked immunosorbent (ELISA) assays, but no significant differences were found in terms of the sensitivity levels. The levels of test sensitivity did not differ by HIV status and TRUST titer but did differ by clinical stage. The results of WB-IgG revealed that the level of antibodies against the 4 antigens showed an upward trend with the development of the clinical stages of syphilis, reaching a peak in tertiary syphilis and then decreasing. The present results supported the good performance of CIA tests used in the blood source screening of syphilis, which reduced the waste of plasma. The reaction intensities of anti-TP17 and TP47 antibodies in past treated syphilis samples were considerably weak and were expected to be used for monitoring the therapeutic effect of syphilis.

Increased Risk of Sexually Transmitted Infections in Men Who Have Sex With Men Taking Preexposure Prophylaxis: A Meta-analysis.

BACKGROUND: Men who have sex with men (MSM) are a priority population for preexposure prophylaxis (PrEP) for HIV prevention. We summarized the surveillance data from the studies of MSM taking PrEP versus before taking PrEP to investigate the possible increased risk of sexually transmitted infections (STIs). METHODS: Two researchers independently searched 5 databases from January 2012 to April 2022 to identify relevant studies reporting the incidence density of syphilis, gonorrhea, and chlamydia infection. Subgroup analyses based on the type and location of research were conducted. The publication bias was detected by Egger's publication bias plot. RESULTS: Twenty studies met the inclusion criteria for the meta-analysis. The pooled estimate of incidence density of syphilis was 9.53 per 100 person-years (PY), whereas 36.48 per 100 PY for chlamydial infection and 34.79 per 100 PY for gonorrhea, higher than the MSM before taking PrEP. The results of the subgroup analysis showed that the incidence density tended to be lower in prospective studies than in retrospective studies and lower in North American studies than in other regions' studies. CONCLUSIONS: The high incidence of STIs in the MSM taking PrEP needs to be increasingly appreciated, and more effective prevention method for STIs is valuable among MSM alongside HIV prevention uptake.

Impact of Alternative Growth Supplements on Antimicrobial Susceptibility Testing of Neisseria gonorrhoeae.

Purpose: The accurate detection of antibiotic susceptibility of Neisseria gonorrhoeae (N. gonorrhoeae) is of great importance for the treatment of patients with gonorrhea as well as to hinder the progress of drug resistance. To promote the application of gonococcal antibiotic susceptibility monitoring in primary hospitals and remote medical institutions, this study evaluated the effect of alternative growth supplements on the antibiotic susceptibility testing of N. gonorrhoeae isolates. Methods: We divided the antimicrobial-containing media into three groups by adding different growth supplements (sterile defibrinated sheep blood, bovine hemoglobin, and Vitox). We tested the antimicrobial susceptibility of 80 N. gonorrhoeae isolates in different groups against eight antibiotics. Nonparametric signed-rank tests were utilized to compare the minimum inhibitory concentration (MIC) results of each group. Taking the MIC results of Vitox group as expected, the essential agreement (EA) and category agreement (CA) of the other two groups were calculated. Results: For the group using sheep blood as growth supplements, the EA values and CA values of each antibiotic were above 90.00% and minor error rates were less than 7.00%. No very major error and major error were observed. For the group using hemoglobin as growth supplements, the EA values of the susceptibility results of zoliflodacin, penicillin, and ceftriaxone were lower than 90.00%. The overall MIC results of using hemoglobin as a growth supplement were higher than those of sheep blood and Vitox in the susceptibility testing of these three antibiotics. Conclusion: Compared with the expected results, sheep blood may be considered for the use as an alternative material for N. gonorrhoeae antibiotics susceptibility surveillance, while hemoglobin may not be suitable for supplement to antimicrobial-containing medium.

In Vitro Study of the Interaction of Gentamicin with Ceftriaxone and Azithromycin against Neisseria gonorrhoeae Using Agar Dilution Method.

The susceptibility to gentamicin of N. gonorrhoeae isolates collected in three Chinese provinces and the correlation among the MICs of gentamicin, azithromycin, and ceftriaxone were investigated in this study. The effects of combinations from those three antibiotics were also in the scope of this study to determine the efficacy of gentamicin as a combination therapeutic drug. The agar dilution method was used to measure the minimum inhibitory concentrations (MICs) of ceftriaxone, azithromycin and gentamicin on N. gonorrhoeae isolates. The synergy between these three antimicrobials were determined using the agar dilution checkerboard method. Subgroup studies were conducted to explore differences between azithromycin- and ceftriaxone-sensitive and resistant isolates. A total of 139 (36.60%) and 233 (61.30%) isolates demonstrated full susceptibility and intermediate susceptibility to gentamicin, respectively. The correlation analysis showed that the MICs of ceftriaxone and azithromycin weakly correlated with the value of gentamicin. The overall results of the three antibiotic combinations revealed indifferent effects. Combination therapy established a significant reduction on the MIC value. Most of the N. gonorrhoeae isolates tested in this study demonstrated a certain degree of susceptibility to gentamicin. Overall, antimicrobial combinations of gentamicin with ceftriaxone or azithromycin demonstrate indifferent effects.

Diagnosis of Neisseria Gonorrhoeae by Loop-Mediated Isothermal Amplification: Systematic Review and Meta-Analysis.

Neisseria gonorrhoeae (gonococci) is the pathogen of gonorrhea. At present, there is no robust statistical analysis targeting the detection accuracy for N.gonorrhoeae of loop-mediated isothermal amplification (LAMP). We performed a full search of five databases for studies using the LAMP method to detect N.gonorrhoeae in this study. Nine datasets derived from eight studies satisfying the inclusion requirement were collected for this study. The pooled sensitivity rate and specificity were calculated as 98.53 and 99.49%. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 66.0, 0.04 and 1863.8. After plotting the summary receiver operating characteristic (sROC), the area under the curve (AUC) and Q* index was calculated as 0.99 and 0.9774. Subgroup analyses based on the type of samples, location, and gold standard did not find sources of significant heterogeneity. In conclusion, the LAMP method could be an effective and convenient method with high accuracy for the clinical detection of N.gonorrhoeae. Moreover, the confirmation of this finding needs more high-quality studies with regional data and large samples.

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Tetracycline Antibiotics from 9 Provinces in China Since 2020.

Purpose: The increasing drug resistance of Neisseria gonorrhoeae has become a serious public health concern. This study investigated N. gonorrhoeae isolates susceptibility to tetracycline antibiotics and the correlation between minimum inhibitory concentrations (MICs) of different antibiotics. The presence of resistance determinants in N. gonorrhoeae strains displaying different levels of tigecycline resistance was also compared. Methods: The minimum inhibitory concentrations (MICs) of tetracycline, minocycline, tigecycline, eravacycline, omadacycline on 412 N. gonorrhoeae isolates were measured by the agar dilution method. The MICs of ceftriaxone and azithromycin were also measured to determine the correlations between antibiotics by the value of the correlation coefficient R. The presence of resistance determinants was identified through polymerase chain reaction (PCR) and sequencing. Results: The MIC90 was 64mg/L for tetracycline, 64mg/L for minocycline, 0.5mg/L for tigecycline, 0.5mg/L for eravacycline, 4mg/L for omadacycline, 0.25 mg/L for ceftriaxone, and 1mg/L for azithromycin. The MIC90 and mode of tigecycline and eravacycline were much lower than those of tetracycline and minocycline. A poor correlation between omadacycline, eravacycline and tetracycline susceptibility was observed. Minocycline has a strong correlation with tetracycline. PorB1 typing, TetM-encoding plasmid, and mtrR promoter adenine deletion were significantly correlated with tigecycline MIC > 0.25mg/L. Conclusion: This study suggested that tigecycline and eravacycline had better in vitro activity and might be alternative antibiotics against resistant N. gonorrhoeae infections. Nevertheless, further in vitro experiments and clinical studies are needed for verification.

High Prevalence of Rectal Chlamydia trachomatis Infection With the Same Genotype as Urogenital Infection in Female Outpatients in Sexually Transmitted Disease Clinics in China.

BACKGROUND: Little is known about rectal Chlamydia trachomatis (CT) infection in outpatients attending sexually transmitted disease (STD) clinics in China. In this study, we aimed to explore the clinical and epidemiologic features of rectal CT infection in this population. METHODS: A cross-sectional study was conducted among patients attending STD clinics in Tianjin and Guangxi provinces of China from June 2018 to August 2020. Bivariate and multivariate logistic regression analysis were developed to explore the association of different risk factors for urogenital and rectal CT infection. RESULTS: The prevalence of urogenital and rectal CT was 11.2% (154/1374) and 4.9% (68/1377), respectively. The rectal CT prevalence among female and male patients was 7.8% (60/767) and 1.3% (8/610), respectively. The most common genotype in urogenital CT-positive samples was genotype E (29.9%), while the most common genotype among rectal CT-positive samples was genotype J (23.4%). More than 85% (52/60) of women infected with rectal CT were co-infected with urogenital CT. About 90.0% (36/40) of women shared similar genotypes between rectal and urogenital samples. Females and patients infected with urogenital CT were deemed to be at an increased risk for rectal CT infection. A high proportion of rectal CT infection had concurrent urogenital CT infection, especially in women, and most of the co-infections were shared among the same genotypes. CONCLUSIONS: It would be prudent to encourage awareness and introduce detection tests and treatment strategies for rectal CT infection particularly in female patients visiting STD clinics in China.

A Multiplex Molecular Assay for Detection of Six penA Codons To Predict Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae.

The emerging cephalosporin-resistant Neisseria gonorrhoeae poses an urgent threat to the continued efficacy of the last-line monotherapy for gonorrhea. Consequently, high-throughput, accurate, and reasonable molecular assays are urgently needed for strengthening antimicrobial-resistance surveillance in N. gonorrhoeae. In this study, we designed a high-throughput multiplex method that incorporates high-resolution melting technology and is based on a 6-codon assay (among the most parsimonious assays) developed following comprehensive and systematic reviews. The results showed that our method can precisely distinguish specific single-nucleotide polymorphisms in resistance-associated genes with a specificity and sensitivity of 100% and a detection limit as low as 10 copies per reaction. This method can be directly applied to clinical samples without cumbersome culture and successfully predicted all cephalosporin-resistant isolates (sensitivity: 100%). The method presented here represents a technique for rapid testing of antimicrobial resistance and will serve as a valuable tool for tailor-made antimicrobial therapy and for monitoring the transmission of cephalosporin-resistant strains.

Evaluation of the Accuracy of Various Disks and Strips for Rapid Culture-Based Gonococcal Antimicrobial Susceptibility Screening Tests in China.

PURPOSE: Neisseria gonorrhoeae, resistant to the first-line treatment option ceftriaxone, is widespread in China from 2016. Nowadays, diverse reagents of disks and strips for rapid gonococcal antimicrobial susceptibility tests used in clinics are culture-based disks diffusion and gradient strips methods. This study aimed to evaluate the accuracy, quality, and availability of almost all disks and strips acquired in the Chinese market and serve as a reference for clinical selection. METHODS: We tested the performance of 15 commercial disks and 9 commercial gradient strips acquired in China, compared with traditional agar dilution method. The overall performance was evaluated by the categorical agreement. The reagent accuracy of gradient strips was assessed by the essential agreement. RESULTS: A total of 167 gonococcal isolates were used to evaluate antimicrobial disks from three brands. The overall categorical agreements were 71.7% to 81.8% for ceftriaxone, less than 58% for cefixime, 100% for spectinomycin, over 98% for ciprofloxacin, below 70.5% for penicillin, and 73.3% to 81.8% for tetracycline. A total of 81 isolates were tested for different gradient strips. Categorical agreements were over 96% for ceftriaxone, 86.2% for azithromycin, 62.3% to 67.1% for penicillin, 41.9% to 67.5% for tetracycline, and 95% for ciprofloxacin. Essential agreements were 57.7% to 87.3% for ceftriaxone, 70% for azithromycin, 64.9% to 68.4% for penicillin, 51.8% to 71.2% for tetracycline, and 91.3% for ciprofloxacin. CONCLUSION: Rapid test reagents of disks and strips based on gonococcal culture have suboptimal performance. Disk diffusion for spectinomycin or ciprofloxacin can be recommended for clinical individualized prescription. The gradient strips are of great value to identify ceftriaxone-resistant gonococcal strains. Furthermore, abundant improvements are required for many reagents to further optimize their accuracy till the fulfillment of molecular detection.

Antimicrobial Susceptibility of Ertapenem in Neisseria gonorrhoeae Isolates Collected Within the China Gonococcal Resistance Surveillance Programme (China-GRSP) 2018.

PURPOSE: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on Neisseria gonorrhoeae collected from eight Chinese provinces in 2018. METHODS: The MICs of ertapenem on 503 Neisseria gonorrhoeae isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected. RESULTS: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤0.008 mg/L to 0.5 mg/L. The corresponding MIC50 and MIC90 were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of r = 0.487 (P <0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low (r = -0.12, P = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥0.25 mg/L for ertapenem. CONCLUSION: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections.

The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in Neisseria gonorrhoeae: A Systematic Review and Meta-Analysis.

BACKGROUND: Neisseria gonorrhoeae (N. gonorrhoeae) is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of N. gonorrhoeae has become a serious public health problem. The accuracy of molecular detection for detecting moderate-level azithromycin resistance is not well-established. We summarized the data from studies of the N. gonorrhoeae 23S rRNA mutation at position 2611 with azithromycin resistance to determine the relationship between the mutation and resistance. METHODS AND FINDINGS: In this systematic review and meta-analysis, two researchers independently searched six databases for studies with data for the azithromycin minimum inhibitory concentrations (MICs) and the 23S rRNA mutation C2611T of each N. gonorrhoeae isolate. Since the breakpoint of moderate-level resistance to azithromycin (ML-AzmR) was not determined, we divided the moderate level into two groups according to the range of MICs (moderate resistance limited to 2-128 mg/L or 4-128 mg/L) for data extraction. A random-effects model was used to calculate the pooled sensitivity rate, the specificity rate, the pooled positive likelihood ratio (PLR), the negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR). Meta-regression analyses by detection method, isolates sampling (a random sample or not), location, and sample size were performed to explore the possible causes of heterogeneity. The potential publication bias of the included studies was conducted by the Deeks' test. We included 20 studies in our study: 20 studies have data of N. gonorrhoeae with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of N. gonorrhoeae with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2-128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6-74%), the pooled specificity rate was 98.7% (95% CI, 98.2-99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4-128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9-94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1-96.6%), and the DOR ranged from 41.9 to 364.1 (mean, 123.6). CONCLUSION: Through this meta-analysis, we found that the C2611T mutation of 23S rRNA is valuable for the molecular diagnostic of moderate-level azithromycin resistance (ML-AzmR) in N. gonorrhoeae, especially when the moderate level is set at 4-128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.

Performance of point-of-care tests for the detection of chlamydia trachomatis infections: A systematic review and meta-analysis.

BACKGROUND: Chlamydia trachomatis (CT) is one of the most prevalent bacterial sexually transmitted infections (STIs) globally but has been inadequately detected for intervention. Introduction of point-of-care tests (POCTs) for CT is critical for filling the intervention gaps. We conducted a systematical review and meta-analysis on diagnostic performance of POCTs for CT to assist in guiding the application of these assays in CT screening and detection. METHODS: We searched PubMed/Medline and Embase databases, from January 2004 to May 2021, for studies reporting the performance of POCTs for identifying CT using specimens collected from urethral, vaginal, cervical, anorectal, or pharyngeal site or of urine. Two investigators independently screened and extracted data for controlling the quality of data extraction. Any discrepancies in study selection and data extraction were resolved through consensus. We only included studies with sufficient data to estimate sensitivity and specificity, and used laboratory-based nucleic acid amplification test (NAAT) as the reference standard. The main outcomes were pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs). Summary estimates were calculated using a random-effects model and summary receiver operator curves (SROCs) were generated using the Moses-Littenberg method. STATA 14.0 and Meta-DiSc 1.4 were used for statistical analysis. The study protocol is registered with PROSPERO, number CRD42019140544. FINDINGS: Of 3,038 records identified, 39 studies (42,336 specimens) were included in the study, including 14 studies on evaluation of antigen detection (AD)-based and 25 on NAAT-based POCTs. The overall pooled sensitivity, specificity and DOR were 56% (95% CI 45%-67%), 99% (95% CI 98%-99%) and 86 (95% CI 46-163), respectively, for AD-based POCTs and corresponding values for NAAT-based POCTs were 94% (95% CI 91%-96%), 99% (95% CI 99%-99%) and 1,933(95% CI 1,018-3,669), respectively. The pooled sensitivity of AD-based POCTs varied across the types of specimens, indicating 46% for cervical swabs (95% CI 37%-56%; range 22.7%-71.4%), 52% for vaginal swabs (95% CI 34%-70%; range 17.1%-86.8%) and 57% for male urine (95% CI 36%-75%; range 20.0%-82.6%). For NAAT-based POCTs, the pooled sensitivity was 94% (95% CI 90%-96%) for cervical swabs, 94% (95% CI 86%-98%) for vaginal swabs, 95% (95% CI 91%-97%) for urine specimens and 93% (95% CI 87%-96%) for anorectal swabs. INTERPRETATION: NAAT-based POCTs for CT have a significantly better performance particularly in sensitivity for diagnosing the infection with CT than the AD-based POCTs. Screening strategy with AD-based POCTs may potentially result in a substantial under-detection of the infections.

Rectal Mycoplasma genitalium in Patients Attending Sexually Transmitted Disease Clinics in China: An Infection That Cannot Be Ignored.

BACKGROUND: Previous studies have investigated rectal Mycoplasma genitalium (MG) in men who have sex with men (MSM), while little is known about the prevalence of rectal MG infection in individuals attending sexually transmitted disease (STD) clinics in China. We aimed to estimate the prevalence of rectal MG infection in this population and identified the potential risk factors for rectal MG infection. METHODS: A cross-sectional study was conducted among individuals attending STD clinics located in China from June 2018 to August 2020. Univariate and multivariate logistic regression analyses were conducted to explore the association of different risk factors for rectal MG infection. RESULTS: A total of 1,382 patients were included in the final analyses. A total of 30 of 1377 rectal swabs (2.2%) and 77 of 1374 urogenital samples (5.6%) were positive for MG. In Guangxi, 18 of 47 patients (38.3%) infected with urogenital MG and 5 of 19 patients (26.3%) infected with rectal MG received the recommended treatment. Factors found to be significantly associated with rectal MG infection included: male (adjusted odds ratio (AOR) 0.232, [95% CI: 0.072-0.745]) compared to female, homosexual or bisexual (AOR 40.427, [95% CI: 3.880-421.196]) compared to heterosexual, and those infected with urogenital MG (AOR 7.215, [95% CI: 2.898-17.965]) compared to those who did not get infected with urogenital MG. CONCLUSION: Rectal MG infection should be thought of not only in MSM population but also in STD clinic patients, especially females who have urogenital MG infection. Appropriate strategy for rectal MG screening and treatment needs to be developed for these patients in China.