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Yan Zhang,1 Li-Hua Hu,2,* Jia Huang,2 Ming-Qin Lu,2 Fan-Rong Zeng,2 Shao-Chun Chen1,3,* 1School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 2Zhejiang Provincial Institute of Dermatology, Deqing, People’s Republic of China; 3National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Hua Hu, Email dqhlhua@163.com Shao-Chun Chen, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email chensc@ncstdlc.orgObjective: This study aimed to assess the drug susceptibility of clinical isolates of Neisseria gonorrhoeae to spectinomycin, ceftriaxone and azithromycin. Moreover, the temporal trends in the minimum inhibitory concentration (MIC) of five antibiotics from Zhejiang, China, are also in the scope of this study.Methods: A total of 1710 gonococcal clinical strains were collected between 2007 and 2021 from health-care institutions in Zhejiang. The MICs of ceftriaxone, azithromycin, spectinomycin, penicillin and ciprofloxacin were assessed by agar dilution method on 1710 Neisseria gonorrhoeae isolates. Count data were expressed as strains and rates, and MICs distribution was elucidated using descriptive statistics.Results: The total resistance rates of gonococci to azithromycin, spectinomycin, penicillin and ciprofloxacin in this study were 19.3%, 0.3%, 75.4% and 99.7%, respectively.Conclusion: The in vitro results showed a high prevalence of resistance to ciprofloxacin and penicillin. Azithromycin resistance rate has exceeded 5%, suggested a high prevalence of resistance. Ceftriaxone and spectinomycin are suggested based on this study for the treatment of Neisseria gonorrhoeae in Zhejiang.Keywords: Neisseria gonorrhoeae, agar dilution method, ceftriaxone, spectinomycin

The continued emergence of Neisseria gonorrhoeae isolates which are resistant to first-line antibiotics has reinvigorated interest in alternative therapies such as expanded use of gentamicin (Gen). We hypothesized that expanded use of Gen promotes emergence of gonococci with clinical resistance to this aminoglycoside.

Background/purpose The evidence provided by syntheses of the preventative effects of gabexate mesilate against pancreatitis among patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) is limited and highly heterogeneous. To enhance the understanding of this topic, this study aimed to provide overview of gabexate mesilate on preventing post ERCP pancreatitis (PEP) by synthesizing all relevant randomized controlled trials (RCTs). Methods We searched three databases for relevant RCTs. Two authors independently extracted data of pancreatitis incidence after ERCP, abdominal pain within 48 hours, and hyperamylasemia for quality assessment and meta-analysis. Results Thirteen RCTs with 3718 patients undergoing ERCP met the eligibility criteria and were included. The results revealed that the use of gabexate mesilate led to lower PEP (Peto odds ratio: 0.66, 95% confidence interval [CI]: 0.49 to 0.89), especially in the subgroup of gabexate mesilate infusion starting more than 30 min (Risk ratio: 0.45, 95% CI: 0.29 to 0.72). Conclusion The present synthesis found that gabexate mesilate could be an option of prophylactic treatment of pancreatitis for patients undergoing ERCP, and reveals that it is favorable to administer it starting 30 min before the ERCP. This evidence may improve the clinical prevention of PEP.

We study the dynamics of Kuznetsov-Ma solitons (KMS) in the framework of vector nonlinear Schr\"odinger (Manakov) equations. Exact multi-parameter family of solutions for such KMSs is derived. This family of solutions includes the known results as well as the previously unknown solutions in the form of the non-degenerate KMSs. We present the existence diagram of such KMSs that follows from the exact solutions. These non-degenerate KMSs are formed by nonlinear superposition of two fundamental KMSs that have the same propagation period but different eigenvalues. We present the amplitude profiles of new solutions, their exact physical spectra, their link to ordinary vector solitons and offer easy ways of their excitation using numerical simulations., Comment: 15 pages, 14 figures

(1) Background: Our study investigated whether monocyte distribution width (MDW) could be used in emergency department (ED) settings as a predictor of prolonged length of stay (LOS) for patients with COVID-19. (2) Methods: A retrospective cohort study was conducted; patients presenting to the ED of an academic hospital with confirmed COVID-19 were enrolled. Multivariable logistic regression models were used to obtain the odds ratios (ORs) for predictors of an LOS of >14 days. A validation study for the association between MDW and cycle of threshold (Ct) value was performed. (3) Results: Fever > 38 °C (OR: 2.82, 95% CI, 1.13–7.02, p = 0.0259), tachypnea (OR: 4.76, 95% CI, 1.67–13.55, p = 0.0034), and MDW ≥ 21 (OR: 5.67, 95% CI, 1.19–27.10, p = 0.0269) were robust significant predictors of an LOS of >14 days. We developed a new scoring system in which patients were assigned 1 point for fever > 38 °C, 2 points for tachypnea > 20 breath/min, and 3 points for MDW ≥ 21. The optimal cutoff was a score of ≥2. MDW was negatively associated with Ct value (β: −0.32 per day, standard error = 0.12, p = 0.0099). (4) Conclusions: Elevated MDW was associated with a prolonged LOS.

Introduction Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (N. gonorrhoeae) becomes a grave public health problem in the world. A strengthened Antimicrobial Resistance Surveillance Program is needed to track the trend of AMR development. However, the lack of a proper antimicrobial susceptibility test (AST) method is a barrier to expand the AMR surveillance in China. Traditional agar dilution (AD) method is laborious and E-test strips have no approval license for clinical use. Herein, a Chinese group modified the microdilution (MD) method for clinical ASTs. The objective of this study is to compare the MD method with the AD method for N. gonorrhoeae AST. Materials and methods A total of 166 clinical isolates were tested for antimicrobial susceptibility of ceftriaxone, spectinomycin, azithromycin, ciprofloxacin, tetracycline, and penicillin using MD and AD method simultaneously. Results of MD method were read manually or automatically. Rates of essential agreement (EA), category agreement (CA), minor error, and very major error were compared. Results The total EAs (compared with results read manually) of penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, and azithromycin were 90.4%, 97.0%, 85.5%, 100.0%, 94%, and 72.3%; and CAs were 82.5%, 94.0%, 100%, 100%, 95.2%, and 94%, respectively. Conclusion We conclude that the MD method might be an alternative for clinical AST of N. gonorrhoeae in China. In particular, MD method has the potency of accurate differentiation of isolates resistant to ceftriaxone or azithromycin, which were empirically recommended for gonococcal treatment, but its quality remained suboptimal, and further improvement is needed for clinical use.

Global dissemination of the Neisseria gonorrhoeae ceftriaxone-resistant FC428 clone jeopardizes the currently recommended ceftriaxone-based first-line therapies. Ceftriaxone resistance in the FC428 clone has been associated with the presence of its mosaic penA allele 60.001. Here we investigated the contribution penA allele 60.001 to ceftriaxone resistance and its impact on biological fitness. Gonococcal isolates expressing penA allele 60.001 and mosaic penA allele 10.001, which is widespread in the Asia-Pacific region and associated with reduced susceptibility to ceftriaxone and cefixime, were genetic engineered to exchange their penA alleles. Subsequent antimicrobial susceptibility analyses showed that mutants containing penA 60.001 displayed 8- to 16-fold higher ceftriaxone and cefixime minimal inhibitory concentrations (MICs) compared with otherwise isogenic mutants containing penA 10.001. Further analysis of biological fitness showed that in vitro liquid growth of single strains and in the competition was identical between the isogenic penA allele exchange mutants. However, in the presence of high concentrations of palmitic acid or lithocholic acid, the penA 60.001-containing mutants grew better than the isogenic penA 10.001-containing mutants when grown as single strains. In contrast, the penA 10.001 mutants outcompeted the penA 60.001 mutants when grown in competition at slightly lower palmitic acid or lithocholic acid concentrations. Finally, the penA 60.001 mutants were outcompeted by their penA 10.001 counterparts for in vivo colonization and survival in a mouse vaginal tract infection model. In conclusion, penA allele 60.001 is essential for ceftriaxone resistance of the FC428 clone, while its impact on biological fitness is dependent on the specific growth conditions.

We reveal a new class of \textit{non-degenerate} Akhmediev breather (AB) solutions of Manakov equations that only exist in the focusing case. Based on exact solutions, we present the existence diagram of such excitations on the frequency-wavenumber plane. Conventional single-frequency modulation instability leads to simultaneous excitation of three ABs with two of them being non-degenerate., Comment: 6 pages, 3 figures

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

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.

We report a recent (2018) gonorrhoeal urethritis caused by a multidrug-resistant Neisseria gonorrhoeae strain in China. The isolated N. gonorrhoeae strain from a male and female pair expressed high...

Purpose Gentamicin is a promising antimicrobial for the treatment of gonorrhea. The study aimed to evaluate gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates in China. Methods In this study, the agar dilution method was used to determine the MICs of 470 isolates collected in 2016 to four effective antimicrobials (gentamicin, azithromycin, ceftriaxone, and spectinomycin). Results Gentamicin MICs ranged from 1 to 8 mg/L. No isolate was resistant to gentamicin. Of seven isolates simultaneously resistant to azithromycin and ceftriaxone, 6 isolates demonstrated MICs of 4 mg/L or less to gentamicin. No cross relationships were found between MICs of gentamicinand susceptibility profiles of azithromycin, ceftriaxone, and spectinomycin. Conclusion The in vitro results suggest that gentamicin can be a promising treatment option for gonococcal infections in China. Clinical trials to evaluate the therapeutic efficacy of gentamicin are required.

BackgroundAntimicrobial resistance to Neisseria gonorrhoeae has emerged for each of the antibiotics recommended as first-line therapies following their introduction into clinical practice. To improve rational and effective clinical antibiotic treatment, we analyzed the prescription patterns of antibiotics and their therapeutic effect in the treatment of uncomplicated gonorrhea in China.MethodsWe obtained data from a follow-up multicenter surveillance program. Multinomial logistic regression analyses were conducted to explore the associations between demographic/clinical variables with the levels of sensitivity to ceftriaxone and prescription of high-dose ceftriaxone.ResultsIn this study, 1686 patients infected with N. gonorrhoeae were recruited in a surveillance network during 1 January 2013 through 31 December 2017 in 7 hospitals distributed in 5 provinces. The prevalence of isolates with decreased susceptibility to ceftriaxone was 9.8% (131/1333), fluctuating between 5.6% and 12.1%. Injectable ceftriaxone was chosen as the first-line treatment among 83.1% of patients, and most of them (72.7% [1018/1401]) received >1000 mg dosage. Patients who were previously infected with gonorrhea or other sexually transmitted infections (adjusted odds ratio [AOR], 1.618 [95% confidence interval {CI}, 1.11–2.358]; AOR, 2.08 [95% CI, 1.41–3.069]) or who already used antibiotics for this infection (AOR, 1.599 [95% CI, 1.041–2.454]) were associated with a higher prescribed ceftriaxone dosage. All of the patients recruited in this study were cured regardless of the isolates’ susceptibility to ceftriaxone or the dosage of ceftriaxone they received.ConclusionsNo ceftriaxone treatment failure for uncomplicated gonorrhea was reported in China; however, high-dose ceftriaxone was widely used in China. Its impacts need further study.

Background: Tracking the spread of the Neisseria gonorrhoeae strains with decreased susceptibility or resistance to cephalosporins is a major priority for global surveillance programmes. Whole-genome sequencing (WGS) has been widely used by increasing countries in North America, Europe, and Pacific to determine the decreased susceptible or resistance determinants of Neisseria gonorrhoeae, track the spread of these determinants throughout the gonococcal population at national or regional level. However, no studies to date have examined the genomic epidemiology of gonorrhea in Asia where the antimicrobial resistant strains of Neisseria gonorrhoeae appears to have emerged before disseminating the strains globally. Methods: We obtained clinical isolates and data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) from 2012 to 2013. We sequenced the genomes of 435 clinical isolates of Neisseria gonorrhoeae, including 112 (25.6%) isolates with decreased susceptibility to ceftriaxone (Cfx-DS). We assessed the association between antimicrobial resistance genotype and phenotype. We also compared our data with the whole genome data of the isolates from the USA and the UK in the GenBank. Findings: The most prevalent MLST STs in our gonococcal population were MLST ST7827 (n = 74), followed by ST7365 (n = 58), ST1600 (n = 38), ST7367 (n = 35), and ST7363 (n = 29). MLST ST1901 which was reported as the predominant ST in the US was not found in our population. A total of 2512 strains, including additional 2077 published NG strains, were further included for phylogenetic analysis. It generated two distinct lineages - lineage 1 and lineage 2. Analysis of MLST ST1901 in the database indicate that most of MLST ST1901 isolates in the lineage2.6 were Cfx-DS isolates while all isolates in the lineage 2.1 were sensitive to ceftriaxone (77/110 vs. 0/13; p

Background Neisseria gonorrhoeae resistance to azithromycin has become a significant public health concern globally, and high-level azithromycin-resistant (HL-AzmR) isolates have emerged frequently. However, high-level azithromycin resistance is considered to be caused by mutated alleles of 23S rRNA gene at position 2059, and identification of HL-AzmR isolates mainly relies on agar dilution method or E-test method. This study aimed to assess the accuracy of the molecular assays targeting the mutation A2059G for identifying HL-AzmR isolates and thereby determine the association between the mutation and high-level azithromycin resistance. Methods Two researchers independently searched six databases to identify studies published from the launch of each database to October 15, 2017. The fixed effects model was used to estimate the pooled sensitivity rate, specificity rate, positive predictive value (PPV), and negative predictive value (NPV). Summary receiver operating characteristic curves were generated, and the area under the curve (AUC) was determined to estimate the overall performance of the assays. The Deeks' test was conducted to evaluate potential publication bias. Results Ten relevant studies were included in the meta-analysis to assess the synthetic accuracy of the molecular assays. The molecular assays had the synthetic sensitivity rate of 97.8% and the synthetic specificity rate of 99.1%. And the aggregated PPV and NPV were 96.4% and 99.5%, respectively. AUC was 0.99, suggesting a close relation existing between the mutation A2059G and high-level azithromycin resistance. This indicated that the molecular assays targeting the mutation A2059G have relatively high overall accuracy for identifying HL-AzmR N. gonor-rhoeae isolates. Publication bias was statistically significant. Conclusion The mutation A2059G is the critical factor causing high-level azithromycin resistance. Hence, molecular methods are recommended to be put into clinical practice by commercialization, which will assist clinicians to prescribe more precisely.

ObjectivesChina has a high burden of gonorrhea, but an imbalanced male-to-female (M/F) ratio of reported cases. Therefore, the prevalence of gonorrhea in China may be underestimated due to inadequate testing of potentially infected females. The objective of this study is to investigate the cause of this imbalanced M/F ratio and develop strategies to enhance gonorrhea surveillance, particularly among females.MethodsThe national center for STD control (NCSTDC) of China CDC collected data in Zhongshan city over the year 2018 from the National Notifiable Disease Report System (NNDRS) and the Hospital and Laboratory Information Systems (HIS and LIS) that obtains information from 24 hospitals.ResultsAnalysis of 1,542 reported cases of gonorrhea and the case distribution among different hospitals showed that most of the female cases (80.31%) were reported by gynecological clinics. The M/F ratio of reported cases varied between different hospitals and was dependent on the intensity of testing of females by their gynecological clinics.ConclusionsThis study showed a significant correlation between M/F ratios and the relative contribution of female gonorrhea testing, especially in gynecology clinics. Enhancing gonorrhea testing among females should be advocated to improve surveillance in China.

Introduction Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (N. gonorrhoeae) becomes a grave public health problem in the world. A strengthened Antimicrobial Resistance Surveillance Program is needed to track the trend of AMR development. However, the lack of a proper antimicrobial susceptibility test (AST) method is a barrier to expand the AMR surveillance in China. Traditional agar dilution (AD) method is laborious and E-test strips have no approval license for clinical use. Herein, a Chinese group modified the microdilution (MD) method for clinical ASTs. The objective of this study is to compare the MD method with the AD method for N. gonorrhoeae AST. Materials and Methods A total of 166 clinical isolates were tested for antimicrobial susceptibility of ceftriaxone, spectinomycin, azithromycin, ciprofloxacin, tetracycline, and penicillin using MD and AD method simultaneously. Results of MD method were read manually or automatically. Rates of essential agreement (EA), category agreement (CA), minor error, and very major error were compared. Results The total EAs (compared with results read manually) of penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, and azithromycin were 90.4%, 97.0%, 85.5%, 100.0%, 94%, and 72.3%; and CAs were 82.5%, 94.0%, 100%, 100%, 95.2%, and 94%, respectively. Conclusion We conclude that the MD method might be an alternative for clinical AST of N. gonorrhoeae in China. In particular, MD method has the potency of accurate differentiation of isolates resistant to ceftriaxone or azithromycin, which were empirically recommended for gonococcal treatment, but its quality remained suboptimal, and further improvement is needed for clinical use.

Objectives The development and emergence of antimicrobial resistance in Neisseria gonorrhoeae (NG) have become a major public-health problem worldwide. This study aimed to analyse the antimicrobial susceptibility and molecular characteristics of NG isolates in Shenzhen, China. Methods A total of 1282 NG isolates were consecutively collected between 2010 and 2017. Patient demographic information was also collected. MICs of ceftriaxone, spectinomycin, ciprofloxacin, azithromycin and penicillin were determined by agar dilution. Isolates were genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). Results Among the isolates, 97.4% were resistant to ciprofloxacin and 68.2% to penicillin. Moreover, 5.0% showed decreased susceptibility to ceftriaxone (CROD) and 17.3% were resistant to azithromycin (AZM-R); 1.3% were simultaneously CROD and AZM-R. All isolates were susceptible to spectinomycin. Increasing ceftriaxone MICs were found from 2010 to 2017. A total of 427 sequence types (STs) and 68 genogroups were identified from 724 isolates. ST5061, ST3741 and ST1766 were observed across the study years. ST14638 (n = 3) was predominant among 32 CROD isolates. Prevalent STs were ST5061 (n = 6), ST1866 (n = 5) and ST11133 (n = 5) among 96 AZM-R isolates. Conclusions A high prevalence of isolates resistant to ciprofloxacin and penicillin was found in this study. Azithromycin, one antimicrobial of dual antimicrobial therapy recommended by the WHO, showed a high prevalence of resistance. The other, ceftriaxone, can be used continuously in this region owing to lower resistance levels. However, the emergence of CROD and decreasing susceptibility to ceftriaxone indicate that continuous antimicrobial resistance surveillance is essential.

Background Ceftriaxone resistance in Neisseria gonorrhoeae has become an imminent threat to effective control of gonorrhoea globally. In recent years, the ceftriaxone-resistant FC428 clone has shown international dissemination. After our first report of the FC428 clone in China in 2016, we now describe another six cases of FC428-related ceftriaxone-resistant N. gonorrhoeae isolates from 2017 and 2018. Objectives To identify the phenotypic and molecular characteristics of newly reported ceftriaxone-resistant isolates in China and to investigate the relationship between these isolates and FC428 clones reported globally. Methods Antimicrobial susceptibility to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, ciprofloxacin and tetracycline was determined by the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST), MLST and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed for genotyping and SNPs extracted from whole-genome sequences were used for phylogenetic analysis. Results All isolates were resistant to ceftriaxone, cefixime, penicillin, tetracycline and ciprofloxacin, but were susceptible to azithromycin and spectinomycin. NG-MAST, MLST and NG-STAR genotyping showed that all isolates shared identical or similar STs ( Conclusions The newly reported cases in China were related to the internationally spreading FC428 clone. These isolates might have played a central role in international transmission of the FC428 clone. High ceftriaxone doses (1–2 g) still provide effective therapy.

In 2016, we identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in China. The strain genotype was identical to the resistant clone FC428 that originated in Japan. Enhanced international collaborative surveillance programs are crucial to track the transmission of the ceftriaxone-resistant clones.

(1) Background: Sepsis is a life-threatening condition, and most patients with sepsis first present to the emergency department (ED) where early identification of sepsis is challenging due to the unavailability of an effective diagnostic model. (2) Methods: In this retrospective study, patients aged ≥20 years who presented to the ED of an academic hospital with systemic inflammatory response syndrome (SIRS) were included. The SIRS, sequential organ failure assessment (SOFA), and quick SOFA (qSOFA) scores were obtained for all patients. Routine complete blood cell testing in conjugation with the examination of new inflammatory biomarkers, namely monocyte distribution width (MDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), was performed at the ED. Propensity score matching was performed between patients with and without sepsis. Logistic regression was used for constructing models for early sepsis prediction. (3) Results: We included 296 patients with sepsis and 1184 without sepsis. A SIRS score of &gt, 2, a SOFA score of &gt, 2, and a qSOFA score of &gt, 1 showed low sensitivity, moderate specificity, and limited diagnostic accuracy for predicting early sepsis infection (c-statistics of 0.660, 0.576, and 0.536, respectively). MDW &gt, 20, PLR &gt, 9, and PLR &gt, 210 showed higher sensitivity and moderate specificity. When we combined these biomarkers and scoring systems, we observed a significant improvement in diagnostic performance (c-statistics of 0.796 for a SIRS score of &gt, 2, 0.761 for a SOFA score of &gt, 2, and 0.757 for a qSOFA score of &gt, 1), (4) Conclusions: The new biomarkers MDW, NLR, and PLR can be used for the early detection of sepsis in the current sepsis scoring systems.

Cephalosporin-resistant Neisseria gonorrhoeae is a major public health concern. N. gonorrhoeae of multiantigen sequence type G1407 and multilocus sequence type 1901 is an internationally spreading cephalosporin-resistant clone. We detected 4 cases of infection with this clone in China and analyzed resistance determinants by using N. gonorrhoeae sequence typing for antimicrobial resistance.

Background Antimicrobial resistance (AMR) to N. gonorrhoeae has emerged for each of the antibiotics following their introduction into clinical practice recommended as first-line therapies. To improve rational and effective clinical antibiotic treatment, we analyzed the prescription patterns of antibiotics and its therapeutic effect in the treatment of uncomplicated gonorrhea in China. Methods We obtained data from a follow-up multicenter-surveillance program. Multinomial logistic regression analyses were conducted to explore the associations between demographic/clinical variables with the levels of sensitivity to ceftriaxone and prescription of high-dose ceftriaxone. Results In this study, 1686 patients infected with N. gonorrhoeae were recruited in a surveillance network during the period of 1 January 2013 through 31 December 2017 in 7 hospitals distributed in 5 provinces. The prevalence of isolates with decreased susceptibility to ceftriaxone was 9.8% (131/1333), fluctuating between 5.6%∼12.1%. Injectable ceftriaxone was chosen as the first-line treatment among 83.1% patients, and most of them (72.7%,1018/1401) received more than 1000 mg dosage. Patients who were infected with gonorrhea or infected with other STDs before (AOR 1.611 95%CI [1.103–2.352]; AOR 2.329 95%CI [1.553–3.494]) or who used already antibiotics for this infection (AOR 1.597, 95%CI [1.04–2.452]) were associated with higher prescribed ceftriaxone dosage prescribed. All of the patients recruited in this study were cured regardless of the isolates’ susceptibility to ceftriaxone or the dosage of ceftriaxone they received. Conclusion No ceftriaxone failure treatment for uncomplicated gonorrhea were reported in China, however, high-dose ceftriaxone were widely used in China, its impacts needs further studies. Disclosure No significant relationships.

Background Ceftriaxone has been used to treat gonorrhea in China for more than one decade, but an increasing level of decreased susceptibility or clinical resistance to ceftriaxone has been found. Moreover, the international spread ceftriaxone-resistant clones has been recognized as a threat to effective control of gonorrhea. We now describe an imported ceftriaxone-resistant N. gonorrhoeae strain isolated in China, 2016. Methods The isolate was collected in 2016. The antimicrobial susceptibility to ceftriaxone (CRO), cefixime (CFM), azithromycin (AZM), spectinomycin (SPT) and ciprofloxacin (CIP) was determined using the agar dilution method in reference lab at National Center for STD Control. A combination of molecular epidemiological methods including N. gonorrhoeae multiantigen sequence typing (NG-MAST), multi-locus sequence typing (MLST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) was used to determine characteristics and resistant determinants of this isolate. Results The strain was resistant to CRO (MIC 0.5 mg/L), CFM (MIC 1 mg/L), TET (4 mg/L) and CIP (≥32 mg/L), but susceptible to AZM (0.25 mg/L) and SPT (16 mg/L). The MLST type was ST1903, and NG-MAST type was ST3435. The NG-STAR type was ST233, which contains a type 60 mosaic penA allele, –35A Del in the mtrR promoter, G120K-A121D in PorB, L421P in PonA, S91F-D95A in GyrA, S87R in ParC, and wild-type 23srRNA. Conclusion We identified a ceftriaxone-resistant N. gonorrhoeae strain which has sustainably transmitted worldwide for more than 3 years. The epidemiological and molecular typing data drew an integral transmission chain of this clone from Japan to China, and then disseminated globally. These findings indicate an imported risk of resistant clones in China and also call for an enhanced global gonococcal antimicrobial surveillance to track the emergence and dissemination of resistant strains for timely control the spread. Disclosure No significant relationships.

Purpose: Artificial neural networks (ANNs) are one type of artificial intelligence. Here, we use an ANN-based machine learning algorithm to automatically predict visual outcomes after ranibizumab treatment in diabetic macular edema. Methods: Patient data were used to optimize ANNs for regression calculation. The target was established as the final visual acuity at 52, 78, or 104 weeks. The input baseline variables were sex, age, diabetes type or condition, systemic diseases, eye status and treatment time tables. Three groups were randomly devised to build, test and demonstrate the accuracy of the algorithms. Results: At 52, 78 and 104 weeks, 512, 483 and 464 eyes were included, respectively. For the training group, testing group and validation group, the respective correlation coefficients were 0.75, 0.77 and 0.70 (52 weeks), 0.79, 0.80 and 0.55 (78 weeks), and 0.83, 0.47 and 0.81 (104 weeks), while the mean standard errors of final visual acuity were 6.50, 6.11 and 6.40 (52 weeks), 5.91, 5.83 and 7.59, (78 weeks), and 5.39, 8.70 and 6.81 (104 weeks). Conclusions: Machine learning had good correlation coefficients for predicating prognosis with ranibizumab with just baseline characteristics. These models could be the useful clinical tools for prediction of success of the treatments.

Background Gonorrhea remains one of the most common sexually transmitted diseases worldwide. Successful treatment has been hampered by emerging resistance to each of the antibiotics recommended as first-line therapies. We retrospectively analyzed the susceptibility of gonorrhea to azithromycin and ceftriaxone using data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) in order to provide evidence for updating the treatment recommendations in China. Methods and findings In this study, we included 3,849 isolates collected from patients with a confirmed positive Neisseria gonorrhoeae (N. gonorrhoeae) culture at clinic visits during the period of 1 January 2013 through 31 December 2016 in 7 provinces. Antimicrobial susceptibility testing of gonorrhea isolates using agar dilution was conducted to determine minimum inhibitory concentration (MIC). Resistance to azithromycin (RTA) was defined as MIC ≥ 1.0 mg/l, and decreased susceptibility to ceftriaxone (DSC) was defined as MIC ≥ 0.125 mg/l. The prevalence of isolates with RTA was 18.6% (710/3,827; 95% CI 17.4%–19.8%). The percentage of patients with DSC fluctuated between 9.7% and 12.2% over this period. The overall prevalence of isolates with both RTA and DSC was 2.3% (87/3,827; 95% CI 1.9%–2.8%) and it increased from 1.9% in 2013 to 3.3% in 2016 (chi-squared test for trend, P = 0.03). Study limitations include the retrospective study design and potential biases in the sample, which may overrepresent men with symptomatic infection, coastal residents, and people reporting as heterosexual. Conclusions To our knowledge, this is the first national study on susceptibility of N. gonorrhoeae to azithromycin and ceftriaxone in China. Our findings indicate high rates of RTA and DSC from 2013 to 2016. Although dual therapy with azithromycin and ceftriaxone has been recommended by WHO and many countries to treat gonorrhea, reevaluation of this therapy is needed prior to its introduction in China., In an observational study using data from the China Gonococcal Resistance Surveillance Programme, Yueping Yin estimate rates of reduced susceptibility to WHO-recommended antibiotics for Neisseria gonorrhoeae., Author summary Why was this study done? Antimicrobial resistance in Neisseria gonorrhoeae (N. gonorrhoeae) is a global threat in the control of this infection. China has one of the biggest antimicrobial consumption rates globally. However, China has limited data on antimicrobial resistance in gonorrhea. Systematic and timely collection and analysis of data on antimicrobial susceptibility of N. gonorrhoeae will inform the development of Chinese treatment guidelines and clinical practice standards. What did the researchers do and find? Minimum inhibitory concentrations (MICs) of azithromycin and ceftriaxone were determined for 3,849 clinical isolates from patients with gonorrhea who provided samples during the time period 2013 to 2016 in 7 provinces in China. Following the Clinical and Laboratory Standards Institute criteria, MIC values were used to define isolates as resistant to azithromycin and/or with decreased susceptibility to ceftriaxone. High prevalence of resistance to azithromycin (18.6%) and decreased susceptibility to ceftriaxone (10.8%) were found in our study population. The prevalence of concomitant resistance to azithromycin and decreased susceptibility to ceftriaxone increased from 1.9% in 2013 to 3.3% in 2016. What do these findings mean? N. gonorrhoeae strains resistant to azithromycin and/or with decreased susceptibility to ceftriaxone are prevalent in China, posing a challenge for gonorrhea control. The results can be used to inform national recommendations for N. gonorrhoeae treatment in China.

OBJECTIVES: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. This is the first nationwide study performed within the China Gonococcal Antimicrobial Susceptibility Programme (China-GASP) regarding AMR including ceftriaxone genetic resistance determinants and molecular epidemiology of gonococci in China. METHODS: Gonococcal isolates (n = 1257) from consecutive patients were collected at 11 sentinel sites distributed across China during 2012-13. Susceptibility to ceftriaxone spectinomycin ciprofloxacin and tetracycline was determined using the agar dilution method. Ceftriaxone resistance determinants penA and penB were examined using sequencing. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed for molecular epidemiology. RESULTS: Among isolates 0.2% were resistant to spectinomycin 4.4% to ceftriaxone 42.9% to tetracyclines (high-level resistance) and 99.8% to ciprofloxacin. Among 890 sequenced isolates 16 (1.8%) possessed a penA mosaic allele; 4 of these isolates belonged to the MDR internationally spread NG-MAST genogroup G1407 (first description in China). Non-mosaic penA alleles with an A501T mutation and an A102D alteration in porB1b were statistically associated with decreased susceptibility/resistance to ceftriaxone. NG-MAST G10339 G1424 and G1053 were associated with decreased susceptibility/resistance to ceftriaxone. CONCLUSIONS: In China ceftriaxone and spectinomycin can continue to be recommended for gonorrhoea treatment with the possible exception of Hainan and Sichuan provinces where ceftriaxone resistance exceeded 5% and AMR surveillance needs to be strengthened. Molecular approaches including genotyping and AMR determinant analysis can be valuable to supplement and enhance conventional surveillance of gonococcal AMR in China. (c) The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions please e-mail: journals.permissions@oup.com.

Introduction Gonococcal infections have been a major sexually transmitted disease (STD) since 1980s’and also a serious public health problem in China. A national surveillance report showed that the number of reported gonorrhoea cases were 1 00 245 in 2015. Resistant gonococcal infections are the obstacle in control work of the disease, which not only affect the treatment as well as the development of complications, but also facilitate the further transmission. The WHO has been drafted a global action plan to control the spread and impact of antimicrobial resistance in Neisseria Gonorrhoeae. This report will to analysis the susceptibility trends of NG to ciprofloxacin, spectinomycin, and ceftriaxone from 2005 to 2013 in China including PPNG and TRNG rate. Methods The production of β-lactamase was determined by paper acidometric testing method. Antimicrobial susceptibility testing was performed for tetracycline, ciprofloxacin, spectinomycin, and ceftriaxone using the agar dilution method. Establishment of quality control standards and system, which provide regular examination of participant laboratories through sending quality control strains, as well as through field supervision in China. Results About 11625 NG isolates were collected from patients with uncomplicated gonorrhoea in 2005–2013. A total of 4565 (39.27%) PPNG were and 4807 (41.21%) TRNG were identified, with an increase from 28.09% in 2005 to 39.15% in 2013. A total of 11 178 (96.16%) ciprofloxacin-resistant strains were identified and the rate of ciprofloxacin-resistant strains keep stable from 2005 to 2013. All of isolates were susceptible to spectinomycin and ceftriaxone from 2005–2013, but a total of 4325 (36.79) ceftriaxone-intermediate strains were identified. Conclusion Antimicrobial susceptibility of NG isolated in China from 2005 to 2013 was characterised by high rate of PPNG, TRNG, and ciprofloxacin -resistant strains. Results of the study illustrate that spectinomycin and ceftriaxone can be considered as the choice drugs for empirical treatment of infection in China.

OBJECTIVE This study aimed to gain information on the antimicrobial susceptibility and molecular epidemiological typing of Neisseria gonorrhoeae (NG) isolates in China in 2012. METHODS A total of 244 NG isolates were consecutively recovered from patients with uncomplicated gonorrhea attending sexually transmitted disease clinics in 3 Chinese cities-Guangzhou, Nanjing, and Tianjin-in 2012. Neisseria gonorrhoeae susceptibilities to penicillin and tetracycline were examined by detecting penicillinase-producing NG (PPNG) and high-level tetracycline-resistant NG, and NG susceptibilities to ciprofloxacin, spectinomycin, ceftriaxone, and cefixime were determined using an agar dilution method. Neisseria gonorrhoeae isolates were typed by multiple-locus variable number tandem repeat analysis. We conducted a χ analysis to compare clusters with Bonferroni correction and Kruskal-Wallis test. RESULTS Neisseria gonorrhoeae isolates gathered from the 3 cities differed significantly in the prevalence of tetracycline-resistant NG (P < 0.001) and NG treated with ceftriaxone with a minimum inhibitory concentration of 0.125 mg/L or higher (P < 0.001). The analysis of the combination of the 7 variable number of tandem repeats loci for all of the 244 isolates yielded 110 multiple-locus variable number tandem repeat analysis types falling into 5 clusters. Cluster III was associated with PPNG, whereas cluster II was associated with non-PPNG (P < 0.05) and NG treated with ceftriaxone with a minimum inhibitory concentration of 0.125 mg/L or higher (P < 0.05). CONCLUSIONS Antimicrobials that can be used with confidence to treat NG infection currently in China include ceftriaxone and spectinomycin, but not penicillin, tetracycline, ciprofloxacin, and cefixime. Moreover, some of the resulting clusters were associated with PPNG and NG with decreased ceftriaxone susceptibility.

In order to develop more effective therapeutic vaccines against cancers with high-risk human papillomavirus (HPV) infection, it is crucial to enhance the immunogenicity, eliminate the oncogenicity of oncoproteins, and take a combination of E7- and E6-containing vaccines. It has been shown recently that PE(ΔIII)-E7-KDEL3 (E7), a fusion protein containing the HPV16 oncoprotein E7 and the translocation domain of Pseudomonas aeruginosa exotoxin A, is effective against TC-1 tumor cells inoculated in mice, therefore, we engineered PE(ΔIII)-E6-CRL-KDEL3 (E6), the de-oncogenic versions of the E7 and E6 fusion proteins [i.e. PE(ΔIII)-E7(d)-KDEL3, E7(d), and PE(ΔIII)-E6(d)-CRL-KDEL3, E6(d)] and tested the immunoefficacies of these fusion proteins as mono- and bivalent vaccines. Results indicated that the E7(d) get higher immunogenicity than its wild type and the E6 fusion proteins augmented the immunogenicity and antitumor effects of their E7 counterparts. Furthermore, the bivalent vaccine system E7(d) plus E6(d), in the presence of cisplatin, showed the best tumoristatic and tumoricidal effects against established tumors in vivo. Therefore, it can be concluded that this novel therapeutic vaccine system, upon further optimization, may shed new light on clinical management of HPV-related carcinomas.

A 65-year-old female developed elevated intraocular pressure (IOP) with angle closure in the right eye. The fundus examination revealed vitreo-retinal hemorrhage that had occurred after neodymium-doped yttrium aluminum garnet (Nd:YAG) laser iridotomy. The retinal hemorrhage resolved spontaneously. This is a rare complication that occurs when the IOP is lowered rapidly. Ocular decompression retinopathy (ODR) was identified. We reviewed several cases of ODR that were treated by various interventions. We also discuss the possible pathogenesis, prognosis, and treatment strategy.