Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19.

BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

Mechanism of benzoxazinoids affecting the growth and development of Fusarium oxysporum f. sp. fabae.

Continuous cropping of faba bean (Vicia faba L.) has led to a high incidence of wilt disease. The implementation of an intercropping system involving wheat and faba bean can effectively control the propagation of faba bean wilt disease. To investigate the mechanisms of wheat in mitigating faba bean wilt disease in a wheat-faba bean intercropping system. A comprehensive investigation was conducted to assess the temporal variations in Fusarium oxysporum f. sp. fabae (FOF) on the chemotaxis of benzoxazinoids (BXs) and wheat root through indoor culture tests. The effects of BXs on FOF mycelial growth, spore germination, spore production, and electrical conductivity were examined. The influence of BXs on the ultrastructure of FOF was investigated through transmission electron microscopy. Eukaryotic mRNA sequencing was utilized to analyze the differentially expressed genes in FOF upon treatment with BXs. FOF exhibited a significant positive chemotactic effect on BXs in wheat roots and root secretions. BXs possessed the potential to exert significant allelopathic effects on the mycelial growth, spore germination, and sporulation of FOF. In addition, BXs demonstrated a remarkable ability to disrupt the structural integrity and stability of the membrane and cell wall of the FOF mycelia. BXs possessed the capability of posing threats to the integrity and stability of the cell membrane and cell wall. This ultimately resulted in physiological dysfunction, effectively inhibiting the regular growth and developmental processes of the FOF.

Benzoxazinoids secreted by wheat root weaken the pathogenicity of Fusarium oxysporum f. sp. fabae by inhibiting linoleic acid and nucleotide metabolisms.

KEY MESSAGE: The regulatory action of BXs secreted by wheat on the pathogenicity of FOF causing Fusarium wilt in faba bean were analyzed. DIMBOA and MBOA weakened the pathogenicity of FOF. A large number of pathogenic bacteria in continuous cropping soil infect faba bean plants, leading to the occurrence of wilt disease, which restricts their production. Faba bean-wheat intercropping is often used to alleviate this disease. This study investigates the effect of benzoxazinoids (BXs) secreted by wheat root on the pathogenicity of Fusarium oxysporum f. sp. Fabae (FOF) and underlying molecular mechanisms. The effects of DIMBOA(2,4-dihydroxy-7-methoxy-1,4-benzoxazine-4-one) and MBOA(6-methoxybenzoxazolin-2-one) on the activity of cell-wall-degrading enzymes in FOF(cellulase, pectinase, amylase, and protease), FOF Toxin (fusaric acid, FA) content were investigated through indoor culture experiments. The effect of BXs on the metabolic level of FOF was analyzed by metabonomics to explore the ecological function of benzoxazines intercropping control of Fusarium wilt in faba bean. The results show that the Exogenous addition of DIMBOA and MBOA decreased the activity of plant-cell-wall-degrading enzymes and fusaric acid content and significantly weakened the pathogenicity of FOF. DIMBOA and MBOA significantly inhibited the pathogenicity of FOF, and metabolome analysis showed that DIMBOA and MBOA reduced the pathogenicity of FOF by down-regulating related pathways such as nucleotide metabolism and linoleic acid metabolism, thus effectively controlling the occurrence of Fusarium wilt in faba bean.

Managing faba bean wilt disease through intercropping with wheat and reasonable nitrogen application: enhancing nutrient absorption and biochemical resistance in faba beans.

Faba bean wilt disease is a key factor limiting its production. Intercropping of faba bean with wheat has been adopted as a prevalent strategy to mitigate this disease. Nitrogen fertilizer improves faba bean yield, yet wilt disease imposes limitations. However, faba bean-wheat intercropping is effective in controlling wilt disease. To investigate the effect of intercropping under varying nitrogen levels on the incidence of faba bean wilt disease, nutrient uptake, and biochemical resistance in faba bean. Field and pot experiments were conducted in two cropping systems: faba bean monocropping (M) and faba bean-wheat intercropping (I). At four nitrogen levels, we assessed the incidence rate of wilt disease, quantified nutrient uptake, and evaluated biochemical resistance indices of plants. The application of N decreased the incidence rate of wilt disease, with the lowest reduction observed in intercropping at the N2 level. N application at levels N1, N2, and N3 enhanced the content of N, P, K, Fe, and Mn as well as superoxide dismutase (SOD), phenylalanine ammonia lyase (PAL), and polyphenol oxidase (PPO) activities and defense gene expression in monocultured plants. Additionally, these levels increased the contents of total phenols, flavonoids, soluble sugars, and soluble proteins, and all reached their maximum in intercropping at the N2 level. The application of intercropping and N effectively controlled the occurrence of faba bean wilt disease by promoting nutrient absorption, alleviating peroxidation stress, and enhancing resistance in plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01466-1.

Proteomic analysis of the faba bean-wheat intercropping system in controlling the occurrence of faba bean fusarium wilt due to stress caused by Fusarium oxysporum f. sp. fabae and benzoic acid.

BACKGROUND: In faba bean, continuous cropping severely affects plant growth and increases the incidence of fusarium wilt due to the accumulation of pathogens and autotoxic substances. The intercropping of faba bean and wheat is commonly used to alleviate the occurrence of fusarium wilt in the faba bean. OBJECTIVE: To investigate the role of Fusarium oxysporum f. sp. Fabae(FOF) and benzoic acid in the occurrence of faba bean fusarium wilt and unravel the potential mechanism of intercropping in alleviating its occurrence. METHODS: Hydroponic experiment was carried out using monocropping faba bean (M) and intercropping faba bean and wheat (I) patterns under FOF alone stress (M + F, I + F), FOF and benzoic acid double stress (M + F + B, I + F + B). The growth of faba bean seedlings under FOF and benzoic acid dual stresses were analyzed as well as the protein expression profile of monocropping and intercropping faba bean roots. RESULT: Under FOF stress, the growth of faba bean seedlings was inhibited, and the inhibitory effect was enhanced under the dual stress of FOF and benzoic acid. However, faba bean-wheat intercropping alleviated the inhibitory effect of FOF and benzoic acid on faba bean growth. In faba bean, the up-regulated protein was involved in different functions, such as redox, hydrogen peroxide decomposition, and metabolic processes under FOF stress (M + F, I + F) compared to the control. Compared with FOF stress (M + F, I + F), under the dual stress of FOF and benzoic acid (M + F + B, I + F + B), the up-regulated protein in faba bean were involved in intracellular redox balance, defense, and maintenance of cell integrity. Compared with monocropping (M, M + F, M + F + B), the up-regulated protein function of intercropping(I, I + F, I + F + B) was mainly involved in the biosynthesis of secondary metabolites, redox balance, biological carbon fixation of photosynthesis, and so on. KEGG enrichment analysis results showed that intercropping increased ethylene and jasmonic acid synthesis and other related pathways to improve resistance against fusarium wilt in the faba bean. CONCLUSION: The growth of faba bean was inhibited under FOF stress and the inhibitory effect was enhanced under the dual stress of FOF and benzoic acid, which promoted the occurrence of faba bean fusarium wilt. This might be due to the down-regulation of energy and cytoplasmic matrix proteins under FOF and benzoic acid stress. The faba bean wheat intercropping alleviated the inhibition of FOF and benzoic acid stress by up-regulating the biosynthesis of secondary metabolites, redox homeostasis, photosynthetic carbon fixation, and other related proteins. Besides, it also promoted the biosynthesis of ethylene, and jasmonic acid, improved the resistance of faba bean plants, and alleviated the occurrence of faba bean fusarium wilt. This provides a theoretical basis for the determination of jasmonic acid and ethylene content.

Evaluation of the EUCAST Rapid Antimicrobial Susceptibility Test for Enterobacterales-Containing Blood Cultures in China.

Bloodstream infection (BSI) is defined by the presence of microbes in the bloodstream and has high mortality. Early antimicrobial therapy is key to treating BSI patients. Because of potential antimicrobial resistance, rapid evaluation for the most suitable antimicrobial therapy is important for appropriate treatment. In China, the current workflow of microbiological diagnosis in BSI involves blood culture, species identification, and antimicrobial susceptibility testing, which takes around 3 days. However, this delay could lead to worse symptoms. To rapidly and accurately assess antimicrobial susceptibility, in this study, we applied EUCAST rapid antimicrobial susceptibility testing (RAST) to determine the antimicrobial susceptibilities of the most frequently detected Enterobacterales sampled in China, including Escherichia coli and Klebsiella pneumoniae. Based on EUCAST guidelines, we evaluated its efficiencies with six commercially available antimicrobials, including imipenem (10 µg), meropenem (10 µg), ciprofloxacin (5 µg), levofloxacin (5 µg), amikacin (30 µg), and trimethoprim-sulfamethoxazole (1.25/23.75 µg), with bacterium-spiked blood cultures. In addition, we developed potential breakpoints for a recently introduced antimicrobial, 30/20 µg ceftazidime-avibactam, which has high potential for treating multidrug-resistant Enterobacterales. Our results showed that EUCAST RAST is a reliable method for rapidly determining the antimicrobial susceptibilities of BSI-causing bacteria in China, with an overall categorical agreement rate at 8 h of ≥90%. The breakpoints developed in this study can categorize the isolates sampled in this study with an accuracy of 93%. Results from our experiments can be applied to clinically determine the microbial susceptibility of BSI-causing bacteria within 8 h and benefit clinical diagnostics for BSI patients.

Evaluation of respiratory samples in etiology diagnosis and microbiome characterization by metagenomic sequencing.

BACKGROUND: The application of clinical mNGS for diagnosing respiratory infections improves etiology diagnosis, however at the same time, it brings new challenges as an unbiased sequencing method informing all identified microbiomes in the specimen. METHODS: Strategy evaluation and metagenomic analysis were performed for the mNGS data generated between March 2017 and October 2019. Diagnostic strengths of four specimen types were assessed to pinpoint the more appropriate type for mNGS diagnosis of respiratory infections. Microbiome complexity was revealed between patient cohorts and infection types. A bioinformatic pipeline resembling diagnosis results was built based upon multiple bioinformatic parameters. RESULTS: The positive predictive values (PPVs) for mNGS diagnosing of non-mycobacterium, Nontuberculous Mycobacteria (NTM), and Aspergillus were obviously higher in bronchoalveolar lavage fluid (BALF) demonstrating the potency of BALF in mNGS diagnosis. Lung tissues and sputum were acceptable for diagnosis of the Mycobacterium tuberculosis (MTB) infections. Interestingly, significant taxonomy differences were identified in sufficient BALF specimens, and unique bacteriome and virome compositions were found in the BALF specimens of tumor patients. Our pipeline showed comparative diagnostic strength with the clinical microbiological diagnosis. CONCLUSIONS: To achieve reliable mNGS diagnosis result, BALF specimens for suspicious common infections, and lung tissues and sputum for doubtful MTB infections are recommended to avoid the false results given by the complexed respiratory microbiomes. Our developed bioinformatic pipeline successful helps mNGS data interpretation and reduces manual corrections for etiology diagnosis.

Infection Control in the Era of Antimicrobial Resistance in China: Progress, Challenges, and Opportunities.

More than 3 decades have passed since infection control was implemented nationwide in China in 1986. A comprehensive set of regulations and guidelines has been developed, and almost all hospitals have established infection control teams. However, compliance is variable and is usually suboptimal. The incidence of certain multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP), is increasing, and associated infections are mainly hospital-acquired in China. Carbapenem-resistant Pseudomonas aeruginosa has remained relatively stable, whereas methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterobacter faecium have been decreasing. The spread of CRAB and CRKP in China is largely mediated by dominant high-risk lineages, namely, clonal complex 92 for CRAB and sequence type 11 for CRKP. However, challenges owing to MDROs bring opportunities for rethinking, taking coordinated action, building capacity, changing behavior, and performing studies that reflect everyday situations in the Chinese healthcare system.

Diagnosis and Management of Intraabdominal Infection: Guidelines by the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons.

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.

Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice.

Background: Metagenomic next-generation sequencing (mNGS) was suggested to potentially replace traditional microbiological methodology because of its comprehensiveness. However, clinical experience with application of the test is relatively limited. Methods: From April 2017 to December 2017, 511 specimens were collected, and their retrospective diagnoses were classified into infectious disease (347 [67.9%]), noninfectious disease (119 [23.3%]), and unknown cases (45 [8.8%]). The diagnostic performance of pathogens was compared between mNGS and culture. The effect of antibiotic exposure on detection rate was also assessed. Results: The sensitivity and specificity of mNGS for diagnosing infectious disease were 50.7% and 85.7%, respectively, and these values outperformed those of culture, especially for Mycobacterium tuberculosis (odds ratio [OR], 4 [95% confidence interval {CI}, 1.7-10.8]; P < .01), viruses (mNGS only; P < .01), anaerobes (OR, ∞ [95% CI, 1.71-∞]; P < .01) and fungi (OR, 4.0 [95% CI, 1.6-10.3]; P < .01). Importantly, for mNGS-positive cases where the conventional method was inconclusive, 43 (61%) cases led to diagnosis modification, and 41 (58%) cases were not covered by empirical antibiotics. For cases where viruses were identified, broad-spectrum antibiotics were commonly administered (14/27), and 10 of 27 of these cases were suspected to be inappropriate. Interestingly, the sensitivity of mNGS was superior to that of culture (52.5% vs 34.2%; P < .01) in cases with, but not without, antibiotic exposure. Conclusions: mNGS could yield a higher sensitivity for pathogen identification and is less affected by prior antibiotic exposure, thereby emerging as a promising technology for detecting infectious diseases.

Antimicrobial susceptibilities of aerobic and facultative gram-negative bacilli isolated from Chinese patients with urinary tract infections between 2010 and 2014.

BACKGROUND: The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission. METHODS: From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method. RESULTS: Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China). CONCLUSION: E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China.

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolates from 17 Chinese cities from 2011 to 2016.

BACKGROUND: Streptococcus pneumoniae, the leading pathogen of bacterial infections in infants and the elderly, is responsible for pneumococcal diseases with severe morbidity and mortality. Emergence of drug-resistant strains presented new challenges for treatment and prevention. Vaccination has proven to be an effective means of preventing pneumococcal infection worldwide. Detailed epidemiological information of antibiotic susceptibilities and serotype distribution will be of great help to the management of pneumococcal infections. METHODS: A total of 881 S. pneumoniae isolates were collected from patients at 23 teaching hospitals in 17 different cities from 2011 to 2016. The main specimen types included sputum, blood, broncho-alveolar lavage fluid, pharyngeal swabs, and cerebrospinal fluid. Minimum inhibitory concentrations (MICs) were determined using the agar dilution method. Capsular serotypes were identified using latex agglutination and quellung reaction test. Molecular epidemiology was investigated using multilocus sequence typing. RESULTS: S. pneumoniae isolates were highly resistant to macrolides, tetracycline, and trimethoprim/sulfamethoxazole. The rate of resistance to penicillin was 51.6% (oral breakpoint). However, levofloxacin and moxifloxacin maintained excellent antimicrobial activity and all of the isolated strains were susceptible to vancomycin. Twenty-two serotypes were identified among the 881 isolates. Prevalent serotypes were 19F (25.7%), 19A (14.0%), 15 (6.8%), 6B (3.6%), 6A (3.0%), and 17 (2.8%). The overall vaccine coverage rates for 7- and 13-valent pneumococcal conjugate vaccines were 37.5% and 58.3%, respectively. Vaccine coverage rates in young children and economically underdeveloped regions were higher than those in older adults and developed regions. Vaccine-covered serotypes demonstrated higher resistance compared with uncovered serotypes. Molecular epidemiological typing demonstrated that S. pneumoniae showed significant clonal dissemination and that ST271 (120, 28.3%), ST320 (73, 17.2%) and ST81 (27, 6.6%) were the major STs. CONCLUSIONS: High resistance to clinical routine antibiotics was observed for all 881 S. pneumoniae strains. Drug resistance varied among different serotypes and age groups. Prevalent serotypes among the isolates were 19F, 19A, 15, 6B, 6A, and 17. Community-acquired strains should also be included in future studies to gain a better understanding of the prevalence and resistance of S. pneumoniae in China.

Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.

BACKGROUND: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. METHODS: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. RESULTS: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively. CONCLUSIONS: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.

Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013.

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum ß-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

Sources of sporadic Pseudomonas aeruginosa colonizations/infections in surgical ICUs: Association with contaminated sink trap.

BACKGROUND: Many studies have reported the hospital outbreaks of Pseudomonas aeruginosa due to cross-contamination between patients and water fittings, but the importance of water fittings as sources of sporadic P. aeruginosa colonizations/infections remains ambiguous. AIM: To investigate the sources of sporadic P. aeruginosa colonizations/infections in a clinical intensive surveillance, and further analysis the potential of sink trap for P. aeruginosa transmission in intensive care units (ICUs). METHODS: Patients monitoring and targeted environmental screening for P. aeruginosa was performed prospectively over a 27-week period, in absence of recognized outbreak, in two surgical intensive care units (SICUs). All isolates were genotyped by Pulsed field gel electrophoresis analysis. FINDINGS: 18.9% (46/244) of water fitting samples harbored P. aeruginosa, and active screening samples from 9.2% (55/595) of hospitalized patients carried with P. aeruginosa. According to genotype results, approximately 50% of P. areuginosa colonizations/infections of patients were of exogenous origin. 64.7% (11/17) of exogenous sourced cases were associated with contaminated sink traps. There was a significant correlation between the incidence of exogenous colonization/infection and the prevalence of P. areuginosa in water fitting in SICU-2 (rs = 0.972; p = 0.014). Furthermore, P. areuginosa from sink trap possessed a higher level of resistance to multi-antibiotics as opposed to cross-transmission from other patients. CONCLUSION: Water fitting especially sink trap act as an important role in sporadic P. aeruginosa transmission in SICU patients. This report highlights the necessity of identification of potential environmental reservoirs, such as sinks, for control of infections of environmentally hardy multi-resistant P. areuginosa.

First multicenter study on multidrug resistant bacteria carriage in Chinese ICUs.

BACKGROUND: The importance of multidrug-resistant organisms (MDRO) in Chinese hospitals is not clearly delineated. Thus we sought to assess the prevalence of MDRO in Chinese intensive care units (ICUs). METHODS: Prospective study of inpatients admitted consecutively to eight ICUs in four Chinese cities in 2009-10. Admission and weekly screenings were performed by using selective media for methicillin resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa. For the two latters, resistance to ceftazidime defined MDRO. Backward logistic regression models were designed to assess factors independently associated with MDRO carriage on admission and MDRO acquisition within ICUs. RESULTS: 686 patients were included, and the MDRO prevalence rate on admission was 30.5 % (32.7 % for ESBL-positive Enterobacteriaceae, 3.2 % for MRSA). Antibiotic treatment prior to ICU admission was independently associated with carriage on admission (OR: 1.4) in multivariate analysis. A total of 104 patients acquired ≥1 MDRO in ICU (overall attack rate: 23.7 %; 14.9 % for ESBL-positive Enterobacteriaceae, and 5.1 % for MRSA). The MDRO attack rate increased from 13.2 % in the first week to 82.1 % for ICU stay > 3 weeks. Duration of antibiotic exposure (OR: 1.16; 1.1-1.2) and prior antibiotic treatment before ICU (OR: 2.1; 1.1-3.3) were associated with MDRO acquisition in multivariate analysis. The MDRO prevalence rate on ICU discharge was 51.2 % and the global prevalence density rate 71 per 1000 hospital-days. CONCLUSION: More than one out of two patients was MDRO carrier on ICU discharge in Chinese hospitals. This is the result of the combination of a high MDRO prevalence rate on ICU admission and a high MDRO acquisition rate within ICU.

[Analysis of pathogen spectrum and resistance of clinical common organisms causing bloodstream infections, hospital-acquired pneumonia and intra-abdominal infections from thirteen teaching hospitals in 2013].

OBJECTIVE: To investigate the spectrum and antimicrobial resistance of major pathogensthat causing nosocomial infections in China, 2013. METHODS: Nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 13 teaching hospital around China were collected. The minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The CLSI M100-S23 criteria were used for interpretation. RESULTS: Of all cases, 1 022 cases were from BSI, 683 from HAP and 674 from IAI.Escherichia coli and Klebsiella pneumoniae were the most prevalent pathogens causing BSI and IAI while Acinetobacter baumanii (34.6%) and Pseudomonas aeruginosa were dominated in HAP. Tigecycline, imipenem and meropenem exhibited high potency against Enterobacteriaceae and the susceptibilities rates were 95.6%, 94.2%and 95.2% respectively. Enterobacteriaceae demonstrated high resistance against cephalosporins (52.3%) and fluoroquinolones (38.9%) but were susceptible to ß-lactam+inhibitor. Of all the Enterobacteriaceae, 30.5% were ESBLs positive and 4.3% were carbapenem resistant. Acinetobacter baumanii showed low susceptibilities to the microbial agents except for tigecycline (90.5%) and colistin (100%). The rate of carbapenem resistant Acinetobacter baumanii was 76.6%. Amikacin, ciprofloxacin, cefepime and piperacillin/tazobactam showed high antibacterial activity against Pseudomonas aeruginosa with susceptible rate 88.5%, 77.6%, 72.7% and 64.5% respectively. The resistant rate to imipenem and meropenem were 42.1% and 32.2%. All Staphylococcus aureus (166 strains) were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. MRSA accounted for 46.9% of all the Staphylococcus aureus. The prevalence of MRSA in IAI (55.2%) and HAP (54.4%) were higher that that in BSI (35.0%). No Enterococcus strains were found resistant to tigecycline, linezolid and daptomycin. VRE was found in Enterococcus faecium, accounting for 1.9% of all Enterococcus faecium strains. CONCLUSIONS: Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are the most common pathogens causing nosocomial infections. Nosocomial pathogens showed high susceptibilities against tigecycline. For ESBLs-producing Enterobacteriaceae strains, ß-lactam+Inhibitor show high antibacterial activities. Vancomycin, teicoplanin and linezolid exhibit high potency to Staphylococcus aureus and Enterococcus.

[Resistance surveillance of major pathogens for adult community-acquired respiratory tract infections in China: a multicenter study 2012].

OBJECTIVE: To investigate antimicrobial resistance among pathogens responsible for adult community-acquired respiratory tract infections from 11 hospitals of China. METHODS: From January to December 2012, a total of 599 strains causing adult community-acquired respiratory tract infection were collected from 11 hospitals, including 381 Streptococcus pneumonia, 137 Haemophilus influenza, and 81 Moraxella catarrhalis. The minimal inhibitory concentration (MIC) of antibacterial agents was determined by agar dilution method. RESULTS: Of all the strains, 50% (300/599 strains) were from adults more than 60 years old and only 16.2% (97/599 strains) were from patients aged less than 40 years. According to oral penicillin breakpoints, 56.7% (216/381 strains) of Streptococcus pneumoniae were penicillin non-susceptible strains (PNSSP). More than 90% (345/381 strains) and 39.9% (152/381 strains)-50.7% (193/381 strains) of Streptococcus pneumoniae were resistant to macrolides and oral cephalosporins respectively, but over 97.8% (372/381 strains) and 99% (377/381 strains) were susceptible to levofloxacin and moxifloxacin. PNSSP strains exhibited significant higher resistance to ceftriaxone, amoxicillin/clavulanate, cefaclor and cefuroxime compared with penicillin susceptible Streptococcus pneumoniae (PSSP). The susceptibility rates of Haemophilus influenza to the antimicrobial agents were over 90% except for ampicillin (71.5%, 272/381 strains) and cefaclor (75.2%, 286/381 strains). The prevalence of ß-lactamase positive Haemophilus influenza were 21.9% (30/137 strains), and ß-lactamase positive Haemophilus influenza strains were more resistant to ampicillin, cefaclor, chloramphenicol and tetracycline compared with ß-lactamase-negative strains. Moraxella catarrhalis strains were extremely susceptible to all the antimicrobial agents tested except for clindamycin, azithromycin and clarithromycin. CONCLUSIONS: The activities of macrolides and oral cephalosporins against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were limited. Levofloxacin and moxifloxacin exhibited good activities against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

[An analysis of clinical characteristics, etiologies and prognosis of 218 patients with infective endocarditis].

OBJECTIVE: To describe the profile of patients with infective endocarditis (IE) and assess prognostic factors of IE. METHODS: Clinical and etiology data of 218 patients with IE were collected retrospectively from January 2011 to January 2013. The distribution and antimicrobial susceptibilities of pathogens causing IE were evaluated. Prognostic factors associated with IE were determined by univariate and multivariate regression analysis. RESULTS: There were 148 men and 70 women with age of (46.0 ± 14.6) years. Ninety-five (43.6%) of them had heart diseases, including 72 cases (33.0%) of congenital heart disease and 23 cases (10.6%) of chronic rheumatic heart disease. Vegetations were detected by echocardiography in 171 (78.4%) patients. Microorganisms causing IE were identified in 84 cases (38.5%) cases. Streptococcus viridans was the dominant pathogen, accounted for 63.1% of all the pathogens, followed by Staphylococcus (13.1%) and Enterococcus (4.8%). Totally 7/11 Streptococcus viridans was susceptible to penicillin, while 100% susceptible to the third and fourth generation cephalosporins, vancomycin and linezolid. One hundred and eighty cases underwent operations. The in-hospital mortality rate of IE was 3.2%. In univariate regression, health care-associated infection, prosthetic valve, anemia and chest symptoms (distress or pain) were related to the increased risk of mortality in patients with IE, while surgery appeared to be a protective factor. In the logistic regression model, the variables significantly associated with IE prognosis were health care-associated infection (OR = 17.03, 95%CI 1.76-164.75, P = 0.014) and anemia (Hb < 90 g/L) (OR = 13.47, 95%CI 2.46-73.60, P = 0.003) and surgery treatment (OR = 0.17, 95%CI 0.03-0.97, P = 0.047). CONCLUSIONS: Although Streptococcus viridans is the most common pathogen causing IE, the pathogens of IE become versatile. The antibacterial activity of penicillin against Streptococcus viridans is low. Health care-associated infection and anemia are risk factors of IE prognosis, while surgery treatment is a protective factor of severe IE.