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Background: Klebsiella pneumoniae (Kp) is a common community-acquired and nosocomial pathogen. Carbapenem-resistant and hypervirulent (CR-hvKp) variants can emerge rapidly within healthcare facilities and impacted by other infectious agents such as COVID-19 virus., Methods: To understand the impact of COVID-19 virus on the prevalence of CR-hvKp, we accessed Kp genomes with corresponding metadata from GenBank. Sequence types (STs), antimicrobial resistance genes, and virulence genes, and those scores and CR-hvKp were identified. We analyzed population diversity and phylogenetic characteristics of five most common STs, measured the prevalence of CR-hvKp, identified CR-hvKp subtypes, and determined associations between carbapenem resistance gene subtypes with STs and plasmid types. These variables were compared pre- and during the COVID-19 pandemic., Findings: The proportion of CR-hvKp isolates increased within multiple STs in different continents during the COVID-19 pandemic and persistent CR-hvKp subtypes were found in common STs. bla KPC was dominant in CG258, bla KPC-2 was detected in 97 % of the ST11 CR-hvKp, bla NDM subtypes were prominent in ST147 (87.4 %) and ST307 (70.8 %); bla OXA-48 and its subtypes were prevalent in ST15 (80.5 %). The possession of carbapenemase genes was different among subclades from different origins in different periods of time within each ST. IncFIB/IncHI1B hybrid plasmids contained virulence genes and carbapenemase genes and were predominant in ST147 (67.37 %) and ST307 (56.25 %)., Interpretation: The prevalence of CR-hvKp increased during the COVID-19 pandemic, which was evident by an increase in local endemic clones. This process was facilitated by the convergence of plasmids containing carbapenemase genes and virulence genes. These findings have implications for the appropriate use of antimicrobials and infection prevention and control during outbreaks of respiratory viruses and pandemic management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses global challenges, with limited options available for targeted therapy. Polymyxin was been regarded as one of the most important last-resort antimicrobial agents. Many factors could accelerate the resistance evolution of polymyxin. Insertion sequence (IS) inserted into mgrB is the main polymyxin resistance mechanism in K. pneumoniae. In this study, two CRKPs (KP31157 and KP31311) were isolated from the urine of a patient, shifting from susceptible to resistant as the mgrB inserted by ISkpn14. We intended to explore the origin of the IS and underlying mechanisms resulting in polymyxin resistance., Methods: The within-host evolution relationship and molecular features of both CRKPs were determined by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). pKP31311&#95;KPC-2 plasmid genome structures contained in the above two CRKPs were aligned with the homologic plasmids, retrieved from the NCBI genome database via comparative genomic analysis. The plasmids encoding ISkpn14 elements flanked by direct repeat (DR) or not were analyzed. The mRNA expression, plasmid curing and in vitro antibiotics inducing experiment were employed to understand the potential mechanism of polymyxin resistance., Results: Both strains, sharing homology, exhibited polymyxin resistance due to the insertion of ISkpn14 into the mgrB gene, influenced by minocycline exposure. Minocycline and tigecycline could accelerate polymyxin resistance (P < 0.05), validated by an in vitro induction experiment. The ISkpn14 without DR flanked expressed about 4 times higher than that with DR. The frequency of the mgrB insertion induced by polymyxin was significantly reduced (0 strain detected) after the bla KPC-2 -carrying plasmid was eliminated., Conclusions: This study provides direct experimental evidence that the ISkpn14 element causing mgrB inactivation and polymyxin resistance in K. pneumoniae originates from bla KPC-2 -carrying plasmids. Minocycline exposure will accelerate the evolution of polymyxin resistance. Understanding the dynamics of IS transposition and its association with antibiotic exposure is crucial for developing effective strategies to reduce the emergence of polymyxin resistance in CRKP., (© 2024. The Author(s).)

Objectives: This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent Klebsiella pneumoniae (hvKp)., Methods: Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted., Results: Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes bla CTX-M-15 and bla CTX-M-71 , respectively, but KP30086 lost both. Cloning of gene bla CTX-M-71 and conjugation experiment of bla CTX-M-71 -carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105., Conclusions: In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying bla CTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.

Background: Resistance to ceftazidime-avibactam was reported, and it is important to investigate the mechanisms of ceftazidime/avibactam resistance in K. pneumoniae with mutations in bla KPC ., Results: We report the mutated bla KPC is not the only mechanism related to CZA resistance, and investigate the role of outer porin defects, efflux pump, and relative gene expression and copy number of bla KPC and ompk35/36. Four ceftazidime/avibactam-sensitive isolates detected wild type bla KPC-2 , while 4 ceftazidime/avibactam-resistant isolates detected mutated bla KPC (bla KPC-51 , bla KPC-52 , and bla KPC-33 ). Compared with other ceftazidime/avibactam-resistant isolates with the minimal inhibitory concentration of ceftazidime/avibactam ranging 128-256 mg/L, the relative gene expression and copy number of bla KPC was increased in the isolate which carried bla KPC-51 and also showed the highest minimal inhibitory concentration of ceftazidime/avibactam at 2048 mg/L. The truncated Ompk35 contributes rare to ceftazidime/avibactam resistance in our isolates. No significant difference in minimal inhibitory concentration of ceftazidime/avibactam was observed after the addition of PABN., Conclusions: Increased gene expression and copy number of mutated bla KPC can cause high-level ceftazidime/avibactam resistance., (© 2021. The Author(s).)

Background: Inappropriate antibiotic use greatly accelerates antimicrobial resistance. The appropriateness of antibiotic prescriptions is well evaluated, using big observational data, in some high-income countries, whereas the evidence of this appropriateness is scarce in China. We aimed to assess the appropriateness of antibiotic prescriptions in ambulatory care settings in China to inform future antimicrobial stewardship., Methods: We used data from the Beijing Data Center for Rational Use of Drugs, which was a national database designed for monitoring rationality of drug use. 139 hospitals that uploaded diagnosis and prescription information were included from 28 provincial-level regions of mainland China. Outpatient prescriptions were classified as appropriate, potentially appropriate, inappropriate, or not linked to any diagnosis for antibiotic use by following a published classification scheme. Antibiotic prescription rates for various diagnosis categories and proportions of inappropriate antibiotic prescriptions for different subgroups were estimated. Antibiotic prescribing patterns and proportions of individual antibiotics prescribed for different diagnosis categories were analysed and reported., Findings: Between Oct 1, 2014, and April 30, 2018, 18 848 864 (10·9%) of 172 704 117 outpatient visits ended with antibiotic prescriptions. For conditions for which antibiotic use was appropriate, potentially appropriate, and inappropriate, 42·2%, 30·6%, and 7·6% of visits were associated with antibiotic prescriptions, respectively. Of all 18 848 864 antibiotic prescriptions, 9 689 937 (51·4%) were inappropriate, 5 354 224 (28·4%) were potentially appropriate, 2 893 102 (15·3%) were appropriate, and 911 601 (4·8%) could not be linked to any diagnosis. A total of 23 266 494 individual antibiotics were prescribed, of which 18 620 086 (80·0%) were broad-spectrum and the top four most prescribed antibiotics were third-generation cephalosporins (5 056 058 [21·7%]), second-generation cephalosporins (3 823 410 [16·4%]), macrolides (3 554 348 [15·3%]), and fluoroquinolones (3 285 765 [14·1%])., Interpretation: Inappropriate antibiotic prescribing was highly prevalent nationwide in China. Over half of the antibiotic prescriptions were inappropriate in secondary-level and tertiary-level hospitals, suggesting an urgent need for outpatient antibiotic stewardship aimed at optimising antibiotic prescribing to achieve the goals set in China's 2016 national action plan to contain antimicrobial resistance., Funding: The National Natural Science Foundation of China., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP)., Methods: 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis., Results: The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH < 7.3, PaO 2 /FiO 2  < 200 mmHg, sodium < 130 mmol/L, healthcare-associated pneumonia, white blood cells > 10,000/mm 3 , pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors., Conclusions: Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP., Trial Registration: A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb.

Objective: We aimed to evaluate the validity of an algorithm to classify diagnoses according to the appropriateness of outpatient antibiotic use in the context of Chinese free text., Setting and Participants: A random sample of 10 000 outpatient visits was selected between January and April 2018 from a national database for monitoring rational use of drugs, which included data from 194 secondary and tertiary hospitals in China., Research Design: Diagnoses for outpatient visits were classified as tier 1 if associated with at least one condition that 'always' justified antibiotic use; as tier 2 if associated with at least one condition that only 'sometimes' justified antibiotic use but no conditions that 'always' justified antibiotic use; or as tier 3 if associated with only conditions that never justified antibiotic use, using a tier-fashion method and regular expression (RE)-based algorithm., Measures: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the classification algorithm, using classification made by chart review as the standard reference, were calculated., Results: The sensitivities of the algorithm for classifying tier 1, tier 2 and tier 3 diagnoses were 98.2% (95% CI 96.4% to 99.3%), 98.4% (95% CI 97.6% to 99.1%) and 100.0% (95% CI 100.0% to 100.0%), respectively. The specificities were 100.0% (95% CI 100.0% to 100.0%), 100.0% (95% CI 99.9% to 100.0%) and 98.6% (95% CI 97.9% to 99.1%), respectively. The PPVs for classifying tier 1, tier 2 and tier 3 diagnoses were 100.0% (95% CI 99.1% to 100.0%), 99.7% (95% CI 99.2% to 99.9%) and 99.7% (95% CI 99.6% to 99.8%), respectively. The NPVs were 99.9% (95% CI 99.8% to 100.0%), 99.8% (95% CI 99.7% to 99.9%) and 100.0% (95% CI 99.8% to 100.0%), respectively., Conclusions: The RE-based classification algorithm in the context of Chinese free text had sufficiently high validity for further evaluating the appropriateness of outpatient antibiotic prescribing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Treatment of ventilated pneumonia is often unsuccessful, even when patients are treated according to established guidelines. Therefore, we aimed to investigate the efficacy of the combination drug device Amikacin Inhale as an adjunctive therapy to intravenous standard-of-care antibiotics for pneumonia caused by Gram-negative pathogens in intubated and mechanically ventilated patients., Methods: INHALE was a prospective, double-blind, randomised, placebo-controlled, phase 3 study comprising two trials (INHALE 1 and INHALE 2) done in 153 hospital intensive-care units in 25 countries. Eligible patients were aged 18 years or older; had pneumonia that had been diagnosed by chest radiography and that was documented as being caused by or showing two risk factors for a Gram-negative, multidrug-resistant pathogen; were intubated and mechanically ventilated; had impaired oxygenation within 48 h before screening; and had a modified Clinical Pulmonary Infection Score of at least 6. Patients were stratified by region and disease severity (according to their Acute Physiology and Chronic Health Evaluation [APACHE] II score) and randomly assigned (1:1) via an interactive voice-recognition system to receive 400 mg amikacin (Amikacin Inhale) or saline placebo, both of which were aerosolised, administered every 12 h for 10 days via the same synchronised inhalation system, and given alongside standard-of-care intravenous antibiotics. All patients and all staff involved in administering devices and monitoring outcomes were masked to treatment assignment. The primary endpoint, survival at days 28-32, was analysed in all patients who received at least one dose of study drug, were infected with a Gram-negative pathogen, and had an APACHE II score of at least 10 at diagnosis. Safety analyses were done in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, numbers NCT01799993 and NCT00805168., Findings: Between April 13, 2013, and April 7, 2017, 807 patients were assessed for eligibility and 725 were randomly assigned to Amikacin Inhale (362 patients) or aerosolised placebo (363 patients). 712 patients received at least one dose of study drug (354 in the Amikacin Inhale group and 358 in the placebo group), although one patient assigned to Amikacin Inhale received placebo in error and was included in the placebo group for safety analyses. 508 patients (255 in the Amikacin Inhale group and 253 in the placebo group) were assessed for the primary endpoint. We found no between-group difference in survival: 191 (75%) patients in the Amikacin Inhale group versus 196 (77%) patients in the placebo group survived until days 28-32 (odds ratio 0·841, 95% CI 0·554-1·277; p=0·43). Similar proportions of patients in the two treatment groups had a treatment-emergent adverse event (295 [84%] of 353 patients in the Amikacin Inhale group vs 303 [84%] of 359 patients in the placebo group) or a serious treatment-emergent adverse event (101 [29%] patients vs 97 [27%] patients)., Interpretation: Our findings do not support use of inhaled amikacin adjunctive to standard-of-care intravenous therapy in mechanically ventilated patients with Gram-negative pneumonia., Funding: Bayer AG., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose of Review: This review summarizes the latest discoveries regarding the use of clinical indicators and biomarkers to guide antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and it analyzes the advantages and disadvantages of various indicators and markers., Recent Findings: For AECOPD patients admitted to emergency departments and medical wards, procalcitonin (PCT)-guided antibiotic therapy reduced antibiotic use without adverse outcomes. In contrast, for severe AECOPD patients admitted to ICUs, PCT-guided antibiotic therapy increased the overall mortality in a 3-month follow-up period, and antibiotic use was not decreased., Summary: PCT is the most promising biomarker to guide antibiotic use in patients with AECOPD. However, patients with severe AECOPD admitted in ICU may not benefit from PCT-guided antibiotic therapy.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) strains are a major threat to global health. The development of effective control measures requires more detailed phenotypic and genotypic characterization of CRE., Methods: CRE isolates were collected from 65 hospitals in 25 provinces across China between January 1, 2012, and December 31, 2016. The isolates were characterized by antimicrobial susceptibility testing and multilocus sequence typing. Genes encoding carbapenemases, mobilized colistin resistance (mcr-1), and β-lactamases were detected by polymerase chain reaction and DNA sequencing., Results: A total of 1801 independent CRE isolates (1201 Klebsiella pneumoniae, 282 Escherichia coli, and 179 Enterobacter cloacae) were collected during the study period. Overall, 96.9%, 89.7%, 54.5%, 49.9%, and 40% of CRE strains were susceptible to colistin, tigecycline, amikacin, minocycline, and fosfomycin, respectively. Notably, 1091/1201 (91%) K. pneumoniae, 225/282 (80%) E. coli, and 129/179 (72%) E. cloacae harbored carbapenemase gene. K. pneumoniae carbapenemase (KPC) was predominant in K. pneumoniae (77%), whereas New Delhi metallo-β-lactamase (NDM) was predominant in E. coli (75%) and E. cloacae (53%). The mcr-1 gene was detected in 13 NDM-carrying E. coli isolates (4.6%). Sequence type (ST)11 and ST167 were predominant among the 100 K. pneumoniae and 47 E. coli STs, respectively. KPC-ST11, which accounted for 64% of K. pneumoniae isolates, had higher levels of resistance than non-ST11 strains to aztreonam, fosfomycin, and amikacin (P < .001). The proportions of KPC and NDM enzymes in CRE increased from 2012 to 2016 (54%-59% and 12%-28%, respectively)., Conclusions: The number of CRE strains harboring carbapenemase is increasing. KPC-ST11 K. pneumoniae, the predominant strain, shows a reduced susceptibility to most available antibiotics.

Introduction: Although evidence indicates that use of procalcitonin to guide antibiotic decisions for the treatment of acute respiratory infections (ARI) decreases antibiotic consumption and improves clinical outcomes, algorithms used within studies had differences in PCT cut-off points and frequency of testing. We therefore analyzed studies evaluating procalcitonin-guided antibiotic therapy and propose consensus algorithms for different respiratory infection types. Areas covered: We systematically searched randomized-controlled trials (search strategy updated on February 2018) on procalcitonin-guided antibiotic therapy of ARI in adults using a pre-specified Cochrane protocol and analyzed algorithms from 32 trials that included 10,285 patients treated in primary care settings, emergency departments (ED), and intensive care units (ICU). We derived consensus algorithms for use of procalcitonin by the type of ARI including community-acquired pneumonia, bronchitis, chronic obstructive pulmonary disease or asthma exacerbation, sepsis, and post-operative sepsis due to respiratory infection. Consensus algorithm recommendations differ with regard to timing of treatment (i.e. timing of initiation in low-risk patients or discontinuation in high-risk patients) and procalcitonin cut-off points for the recommendation/strong recommendation to discontinue antibiotics (≤ 0.25/≤ 0.1 µg/L in ED and inpatients, ≤ 0.5/≤ 0.25 µg/L in ICU patients, and reduction by ≥ 80% from peak levels in sepsis patients). Expert commentary: Our proposed algorithms may facilitate safe and efficient implementation of procalcitonin-guided antibiotic protocols in diverse healthcare settings. Still, the decision about initiation and cessation of antibiotic treatment remains a clinical decision based on the patient assessment and the severity of illness and use of procalcitonin should not delay empirical treatment in high risk situations.

Community-acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline., (© 2017 John Wiley & Sons Ltd.)

Objectives: To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China., Design: This was a multicentre, retrospective, observational study., Setting: 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 PARTICIPANTS: Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms., Primary and Secondary Outcome Measures: Resource use for CAP management., Results: Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0-1 and Pneumonia Severity Index risk class I-II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%., Conclusions: These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China., Trial Registration Number: NCT02489578; Results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings., Methods: Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects., Findings: We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001)., Interpretation: Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance., Funding: National Institute for Health Research., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

Background: Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship., Objectives: The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017., Selection Criteria: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment., Data Collection and Analysis: Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis., Main Results: From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results., Authors' Conclusions: This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.

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.

To evaluate the in vitro antimicrobial activities of tedizolid, linezolid and other comparators against clinically significant Gram-positive cocci isolates from hospital-acquired pneumonia (HAP), skin and soft tissue infection (SSTI) and bloodstream infection (BSI), 2140 nonduplicate isolates (23.7 % isolated from HAP, 46.8 % from SSTI and 29.5 % from BSI) were consecutively collected in 26 hospitals in 17 cities across China during 2014. These pathogens included 632 methicillin-resistant Staphylococcus aureus, 867 methicillin-sensitive Staphylococcusaureus, 299 coagulase-negative Staphylococcus (CoNS), 104 Enterococcus faecalis, 99 Enterococcusfaecium, 13 Streptococcus pneumoniae, 23 α-haemolytic Streptococcus and 103 β-haemolytic Streptococcus. MICs of routine clinical antibiotics were determined by broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines 2015. Tedizolid, linezolid, vancomycin, daptomycin, teicoplanin and tigecycline showed high in vitro activity against Gram-positive pathogens (≥98.0 % susceptible), and tedizolid exhibited four- to eight fold greater activity than linezolid against the pathogens tested, with MIC90s of methicillin-resistant Staphylococcus aureus, α-haemolytic Streptococcus and β-haemolytic Streptococcus (0.25 vs 2 µg ml-1); methicillin-sensitive Staphylococcu saureus, E. faecalis and E. faecium (0.5 vs 2 µg ml-1); methicillin-resistant CoNS and methicillin-sensitive CoNS (0.25 vs 1 µg ml-1); and Streptococcuspneumoniae (0.125 vs 0.5 µg ml-1). Tedizolid MIC90s associated with different infections did not show significant differences, and the drug exhibited excellent activity against surveyed Gram-positive pathogens associated with HAP, SSTI and BSI, including linezolid-nonsusceptible strains. These data suggest that tedizolid could be an alternative to linezolid for the treatment of infections caused by Gram-positive organisms.

Objective: The majority of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have low serum procalcitonin (PCT) values. The aim of this study was to determine whether these patients may benefit from antibiotic treatment., Methods: A total of 457 patients with AECOPD were screened; 194 patients with AECOPD and PCT <0.1 ng/ml were assigned randomly to an antibiotic group or a control group. In the per-protocol (PP) population, the antibiotic group subjects were required to have used antibiotics for at least 3 days, and the control group subjects were required not to have used antibiotics within the 10 days after admission. The intention-to-treat (ITT) population was defined as the patients who were randomized. The primary outcome was the treatment success rate on day 10 after admission. Secondary outcomes were symptoms assessed on a visual analog scale (VAS), length of hospitalization, mortality, exacerbation rate, and re-hospitalization within 30 days of follow-up (study registered at chictr.org.cn: ChiCTR-TRC-14004726)., Results: 95 patients in the antibiotic group and 96 patients in the control group completed the study. In the ITT population, the overall treatment success rate in the control group (95.8%) was similar to that in the antibiotic group (93.7%), with no significant difference (p=0.732). Five patients in the antibiotic group died, either in hospital or within 30 days of discharge. In the control group, two died within 30 days of discharge. Antibiotic use in the control group was 17.7% (17/96), and age ≥75 years was a predictive risk factor for requiring antibiotic therapy in the control group (odds ratio 4.055, 95% confidence interval 1.297-12.678; p=0.012). According to the PP analysis, the treatment success rate on day 10 after admission was 98.7% (78/79) in the control group and 93.7% (89/95) in the antibiotic group, also with no significant difference (p=0.193). No secondary outcome was significantly different between the two groups., Conclusion: Antibiotic treatment is no better than placebo in AECOPD with a PCT level <0.1 ng/ml., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study investigated the antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates causing adult community-acquired respiratory tract infections (CARTIs) in China. A multicentre resistance surveillance study (CARTIPS) investigating 1046 clinical isolates from 19 hospitals in China was conducted from 2013 to 2014. Based on the minimum inhibitory concentration (MIC) breakpoints of oral penicillin, the percentages of penicillin-resistant, penicillin-intermediate and penicillin-susceptible S. pneumoniae were 44.1%, 13.7%, and 42.2%, respectively. The rates of penicillin-non-susceptible S. pneumoniae ranged from 27.9% to 72.2% in different cities, with the highest rate in Nanchang. Macrolides, including azithromycin, clarithromycin and erythromycin, showed the lowest activities against S. pneumoniae isolates, with resistance rates of 90.5%, 92.2% and 93.0%, respectively. However, 98% of these strains were susceptible to levofloxacin and moxifloxacin. For H. influenzae isolates, most of the antimicrobials agents exhibited good activities. However, ampicillin and trimethoprim/sulfamethoxazole showed relatively lower activity against H. influenzae, with resistance rates of 35.0% and 54.4%, respectively. β-lactamase production rates amongst H. influenzae and M. catarrhalis were 31.0% and 87.1%, respectively. In addition, a total of 15 β-lactamase-negative ampicillin-resistant (BLNAR) strains identified in this study were resistant to ampicillin, amoxicillin/clavulanic acid, cefaclor and cefuroxime. Most of the antimicrobial agents showed excellent activity against M. catarrhalis, with susceptibility rates of >90%. The results from the current study confirmed the regional variations in antimicrobial susceptibility of major CARTI pathogens and provided some choices for the treatment of these organisms. Continuous national surveillance of the epidemiology of CARTIs is strongly warranted in China., (Copyright © 2016 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Objectives: Hypervirulent Klebsiella pneumoniae (hvKP) infections occur worldwide, but carbapenem-resistant hvKP strain has rarely been observed., Methods: A retrospective study was conducted in 28 cases of carbapenem-resistant K. pneumoniae (CRKP) infections from 9 cities in China. Clinical data were collected from medical records. All the isolates were characterized by antimicrobial susceptibility testing, string test, multilocus sequence typing, and capsular genotyping. All the hypermucoviscous CRKP strains were analyzed by virulence gene profiles, serum killing assay, and mouse lethality assay., Results: Of 28 CRKP isolates, five were positive for string test. Importantly, one of the hypermucoviscous strains isolated from blood sample was identified as hvKP. The hypervirulent CRKP strain showed highly resistant to carbapenems (MIC > 32 μg/mL), decreased expression of ompK35/36, and ESBLs production. Significantly increased resistance to serum killing and mice mortality were found in the hypervirulent CRKP strain compared to the other CRKPs. Capsular polysaccharide synthesis genotyping revealed that the hypervirulent strain belongs to K2 serotype, while others belong to K-nontypable serotype. The K2 hypervirulent CRKP strain carried rmpA, aerobactin, entB, and mrkD genes., Conclusions: The newly emerged hypervirulent carbapenem-resistant K. pneumoniae might cause a serious threat to public health, suggesting an urgent need to enhance clinical awareness and epidemiologic surveillance., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

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 β-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., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The objective of this study was to better understand the in vitro activity of flomoxef against clinical extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. A total of 401 ESBL-producing isolates, including 196 Escherichia coli, 124 Klebsiella pneumoniae and 81 Proteus mirabilis, were collected consecutively from 21 hospitals in China in 2013. Minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. Phenotypic identification of ESBL production was detected as recommended by the Clinical and Laboratory Standards Institute (CLSI). ESBL genes were detected by PCR and sequencing. Flomoxef, doripenem, meropenem, ertapenem, cefmetazole and piperacillin/tazobactam exhibited good activity against ESBL-producing isolates, with susceptibility rates >90%. Tigecycline showed good activity against E. coli and K. pneumoniae (100% and 97.6%, respectively). Cefotaxime and cefepime showed very low activities against ESBL-producing isolates, with susceptibility rates of 0-0.8% and 1.0-13.6%, respectively. blaCTX-M were the major ESBL genes, with occurrence in 99.5% of E. coli, 91.1% of K. pneumoniae and 97.5% of P. mirabilis. blaCTX-M-14 was the predominant ESBL gene, detected in 46.9% (188/401) of the isolates, followed by blaCTX-M-15 (21.4%), blaCTX-M-55 (17.2%), blaCTX-M-65 (12.7%) and blaCTX-M-3 (6.7%). Flomoxef exhibited excellent activity against the different CTX-M-type ESBL-producing isolates, with MIC50 and MIC90 values of 0.064-0.125μg/mL and 0.25-0.5μg/mL, respectively. Against the isolates solely producing CTX-M-14, -15, -55, -3 or -65, flomoxef showed susceptibility rates of 98.6%, 98.0%, 98.1%, 100.0% and 97.4%, respectively. In conclusion, flomoxef showed good activity against ESBL-producing Enterobacteriaceae and may be a choice to treat infections caused by these isolates in China., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Nosocomial pneumonia (NP; encompassing hospital-acquired, health care-associated and ventilator-associated pneumonia) is one of the most common nosocomial infections and is associated with a mortality rate of 18.7%-40.8% in Asian countries. The burden of methicillin-resistant Staphylococcus aureus (MRSA) infections in Asia is high, and approximately 13% of NP cases in Asia are caused by this pathogen. Evidence regarding optimal management of MRSA NP continues to evolve and is complicated by the fact that a significant proportion of cases are likely to be caused by isolates with reduced susceptibility to the main therapeutic agent, vancomycin. The Asian Consensus Taskforce on MRSA Nosocomial Pneumonia has developed this statement to provide consensus points on diagnosis, antimicrobial treatment and prevention strategies for MRSA NP in the Asian context, based on our review of Asian data, previous international guidelines and recent scientific evidence., (© 2014 John Wiley & Sons Ltd.)

While antibiotic resistance in bacteria is rapidly increasing, the development of new antibiotics has decreased in recent years. Antivirulence drugs disarming rather than killing pathogens have been proposed to alleviate the problem of resistance inherent to existing biocidal antibiotics. Here, we report a nontoxic biogenic nanomaterial as a novel antivirulence agent to combat bacterial infections caused by Pseudomonas aeruginosa. We synthesized, in an environmentally benign fashion, tellurium nanorods (TeNRs) using the metal-reducing bacterium Shewanella oneidensis, and found that the biogenic TeNRs could effectively inhibit the production of pyoverdine, one of the most important virulence factors in P. aeruginosa. Our results suggest that amyloids and extracellular polysaccharides Pel and Psl are not involved in the interactions between P. aeruginosa and the biogenic TeNRs, while flagellar movement plays an important role in the cell-TeNRs interaction. We further showed that the TeNRs (up to 100 µg/mL) did not exhibit cytotoxicity to human bronchial epithelial cells and murine macrophages. Thus, biogenic TeNRs hold promise as a novel antivirulence agent against P. aeruginosa., (© 2013 Wiley Periodicals, Inc.)

Objective: To explore the tendency of macrolide resistance in Mycoplasma pneumoniae infection in community-acquired pneumonia (CAP) patients in Beijing., Methods: Adult CAP patients of ≥ 18 yrs were enrolled in 3 medical centers in Beijing , China. Throat swab samples were taken from all the patients to perform the culture of M. pneumoniae . All the isolated M. pneumoniae strains were subjected to susceptibility evaluation for 6 agents, including macrolides such as erythromycin and azithromycin. In strains showing macrolide resistance, the 23S rRNA gene was analyzed., Results: A total 53 strains of M. pneumoniae were isolated from 321 enrolled patients. Thirty-eight of the isolated strains (71.7%) were resistant to erythromycin and 32 of them (60.4%) were resistant to azithromycin. Six strains with moderate or low level of erythromycin-resistance were still susceptible to azithromycin. No fluoroquinolone-resistant or tetracycline-resistant strains were observed in our study. Point transition of A2063G in the 23S ribosomal RNA gene was the main reason for the high prevalence of macrolide resistance., Conclusions: The prevalence of macrolide resistance in M. pneumoniae is very high in adult CAP patients in Beijing. Studies are needed to clarify the clinical meaning of prevalence of macrolide-resistant M. pneumoniae in adults CAP patients.

Genetic characterisation of linezolid-resistant Gram-positive cocci in a multicentre study in China has not been reported previously. To study the mechanism underlying the resistance of linezolid-resistant isolates, nine Enterococcus faecalis, one Enterococcus faecium and three Staphylococcus cohnii isolates with various levels of resistance were collected from five hospitals across China in 2009-2012. The nine E. faecalis isolates were classified into seven sequence types, indicating that these linezolid-resistant E. faecalis isolates were polyclonal. Enterococci isolates had reduced susceptibility to linezolid (MICs of 4-8 mg/L) and had mutation of ribosomal protein L3, with three also having mutation of L4, but without the multidrug resistance gene cfr or the 23S rRNA mutation G2576T. The three S. cohnii isolates were highly resistant to linezolid (MICs of 64 mg/L to >256 mg/L), harboured the cfr gene and had the 23S rRNA mutation G2576T. Southern blotting indicated that the cfr gene of these three isolates resided on different plasmids (pHK01, pRM01 and pRA01). In plasmid pHK01, IS21-558 and the cfr gene were integrated into transposon Tn558. In plasmids pRM01 and pRA01, the cfr gene was flanked by two copies of an IS256-like insertion sequence, indicating that the transferable form of linezolid resistance is conferred by the cfr gene. In conclusion, the emergence of linezolid-resistant Gram-positive cocci in different regions of China is of concern. The cfr gene and the 23S rRNA mutation contribute to high-level linezolid resistance in S. cohnii, and the L3 and L4 mutations are associated with low-level linezolid resistance in enterococci., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Using layer-by-layer (LbL) assembly method, we fabricated novel silver nanocomposite LbL-Ag nanofiltration (NF) and forward osmosis (FO) membranes. The incorporation of silver nanoparticles (AgNPs) in the membranes did not adversely affect the membrane separation performance in NF and FO processes at low AgNPs incorporation levels (0.22-1.19 wt.% as silver). The FO performance of the xLbL-Ag membranes was better than or comparable to most NF-like FO membranes reported in the literature. In addition, the silver nanocomposite membranes exhibited excellent antibacterial properties against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli. Our results showed that the performances of the silver nanocomposite membranes are highly dependent on silver incorporation in the membranes, which could be controlled by using different membrane synthesis routines and doping of AgNPs. To the best knowledge of the authors, this is the first study on fabrication and characterization of novel antibacterial silver nanocomposite NF and FO membranes through LbL assembly approach., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A total of 146 group B streptococcus isolates from 8 cities across China belonged to four serotypes. Serotype Ia was more common in children. A high prevalence of resistance was observed for levofloxacin (37.7%), erythromycin (71.2%), clindamycin, (53.4%), and tetracycline (81.5%). The levofloxacin and clindamycin resistances among the 4 serotypes differed significantly. Eighty percent of fluoroquinolone-resistant isolates belonged to the sequence type 19 (ST19)/serotype III clone, with GyrA-ParC-ParE triple substitutions. This clone carried the erm(B), mef(E), and tet(M) genes.

Macrolide resistance rates of Mycoplasma pneumoniae in the Beijing population were as high as 68.9%, 90.0%, 98.4%, 95.4%, and 97.0% in the years 2008 to 2012, respectively. Common macrolide-resistant mobile genetic elements were not detected with any isolate. These macrolide-resistant isolates came from multiple clones rather than the same clone. No massive aggregation of a particular clone was found in a specific period.

The aim of this study was to evaluate the in vitro activity of cefditoren and comparators against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis causing community-acquired respiratory tract infections (CARTIs). A total of 391 Streptococcus pneumoniae, 266 H. influenzae, and 76 M. catarrhalis were isolated from 10 centers located at 6 cities in China from January 2009 to May 2010. The microdilution method was used to determine minimum inhibitory concentrations (MICs). The pneumococci comprised 189 (48.3%) penicillin susceptible, 129 (33.0%) penicillin intermediate, and 73 (18.7%) penicillin resistant. Moxifloxacin and levofloxacin showed the highest activity (99.2% and 97.7%, respectively) against Streptococcus pneumoniae, followed by parenteral penicillin G (95.7%), cefditoren (83.1%) and amoxicillin-clavulanic acid (79.3%). Among the 266 H. influenzae isolates, 26 (9.8%) were ampicillin-resistant β-lactamase-producing strains and 24 (9.0%) were ampicillin-resistant β-lactamase-nonproducing strains (BLNAR). Most of antimicrobial agents demonstrated good activity (>97% susceptibility) against H. influenzae except ampicillin, cefuroxime, and cefaclor, which showed relatively lower activity (81.2%, 88.7%, and 88%, respectively). Cefditoren showed excellent activity with the lowest MIC(50) and MIC(90) (≤0.016/0.064 μg/mL) among all tested drugs, which is independent of β-lactamase production or ampicillin resistance. Cefditoren at a concentration of 0.5 μg/mL inhibited all BLNAR strains. Seventy of 76 isolates of M. catarrhalis produced β-lactamase. Cefditoren also showed excellent activity with MIC(90) of 0.064 μg/mL against β-lactamase-nonproducing strains and 0.5 μg/mL against β-lactamase-producing strains. In conclusion, the excellent intrinsic activity of cefditoren suggests that it may be a good choice for the treatment of CARTIs caused by Streptococcus pneumoniae, H. influenzae, and M. catarrhalis in China, while the activity should be closely monitored., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A total of 5608 clinical isolates of Gram-positive bacteria were collected from 12 teaching hospitals across China from 2005 to 2010. The minimum inhibitory concentrations (MICs) of 19 antimicrobial agents were determined by the agar dilution method at the central laboratory. Overall, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRSCoN) were 46.8% and 81.5%, respectively. Isolates from inpatients exhibited a higher rate of MRSA than that from outpatients (52.3% versus 26.2%, P < 0.001). The prevalence of MRSA in respiratory infections (67.5%) was higher than in other sources of infections (P < 0.001). A shift in vancomycin MICs from <0.5 to 1.0 μg/mL was observed during the 6-year period. In 2005, 70.5% of S. aureus isolates were inhibited at the vancomycin MIC of 0.5 μg/mL, while in 2010, 89% of the isolates were inhibited at the vancomycin MIC of 1 μg/mL. With the use of penicillin oral breakpoints, penicillin-resistant Streptococcus pneumoniae (PRSP) increased from 28.6% in 2005 to 59.5% in 2010 and varied among different age groups, with an average rate of 70.6% for children under 5 years old. Importantly, an obvious penicillin MIC right shift was observed from 0.032 to 4 μg/mL during the study period. Serotyping for the isolates from 2005 and 2010 indicated that the high rate of PRSP could be due to the increased prevalence of serogroup 19. The prevalence of vancomycin-resistant enterococci (VRE) increased from 0 in 2005 to 4.9% in 2010. Of the 27 VRE isolates, vanA gene was the most prevalent gene. During the study period, 97.9-100% of different species tested were susceptible to teicoplanin. Linezolid and tigecycline showed potent activities, and no resistant isolate was identified. In conclusion, although the prevalence of MRSA and MRSCoN remained stable over the 6 years, a sharp increase in the prevalence of PRSP was identified. In addition, MIC shifts, including the MICs of penicillin against S. pneumoniae and vancomycin against S. aureus, were observed. Continuous surveillance is warranted to evaluate the resistance trend of clinically important Gram-positive organisms in the future., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A multicentre resistance surveillance study [Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS)] investigating the susceptibilities of 2963 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, meticillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus spp. from Asia against 12 antimicrobial agents was undertaken from 2009 to 2010. Based on the breakpoints for oral penicillin V recommended by the Clinical and Laboratory Standards Institute, the prevalence of penicillin-non-susceptible S. pneumoniae (PNSSP) ranged from 46% to 100%. Azithromycin and clarithromycin exhibited variable resistance rates of 0-88% against S. pneumoniae, 0-57% against MSSA and 0-76.5% against Streptococcus spp. isolates. The prevalence of extended-spectrum β-lactamase-producing K. pneumoniae varied from 5.1% to 58.5%. β-Lactamase production rates amongst H. influenzae isolates ranged from 15% to 46.6% and amongst M. catarrhalis isolates from 90% to 100%. Amongst M. catarrhalis isolates, macrolide resistance and cefaclor resistance rates of 5.8% and 1.2%, respectively, were found, mainly in Mainland China. Levofloxacin resistance rates of 0-3.9% with a MIC(90) (minimum inhibitory concentration causing inhibition of 90% of isolates) of 1-2mg/L and moxifloxacin resistance rates of 0-1.7% with a MIC(90) of 0.125-0.5mg/L were found amongst PNSSP isolates. Moxifloxacin was very active against Streptococcus spp., H. influenzae and M. catarrhalis isolates, with MIC(90) values of 0.125-0.25, 0.032-0.5 and 0.064-0.125mg/L, respectively. These results from the CARTIPS study have confirmed some significant regional differences in the antimicrobial susceptibilities of S. pneumoniae, MSSA, K. pneumoniae, H. influenzae and Streptococcus spp. and emphasise the importance of antimicrobial surveillance programmes for guiding empirical therapy and for focusing interventional control of antimicrobial resistance in distinct geographic areas., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

The resistance rate of 67 Mycoplasma pneumoniae isolates from 356 ambulatory adult patients with respiratory tract infection was 69% (46 of 67). All 46 macrolide-resistant strains harbored point mutations in the 23S ribosomal RNA gene. Patients infected with macrolide-resistant M. pneumoniae required significantly longer durations of antibiotic therapy and had longer time to resolution of fever.

Objective: To investigate the impact of intervention program upon improvement of utilization quality of carbapenems and glycopeptides., Methods: Multifaceted intervention program of carbapenems and glycopeptides was conducted at our hospital. It involved written justification forms, expert consultation committee meetings, audit, feedback and re-feedback. From November 1, 2007 until October 31, 2008, retrospective audit and feedback were performed on all patients dosed with carbapenems or glycopeptides. Case reports were reviewed and data of ratio of appropriate antibiotic use, length of hospital stay, total cost, mortality and rate of vancomycin-resistant Enterococci (VRE) were collected and compared between the first and second half year of antibiotic intervention program., Results: A total of 397 cases were reviewed, 75 cases discussed at expert committee meetings and 58 feedback letters delivered to responsible doctors. The consumption of both carbapenems and glycopeptides decreased. The appropriate use of carbapenems and glycopeptides increased from 37.8% (45/119) to 53.5% (48/127, P < 0.05) and from 45.6% (36/79) to 63.9% (46/72, P < 0.05) respectively. The total cost and mortality of patients dosed with glycopeptides decreased from a median of RMB 65,700 (30,300 - 146,900) yuan to 55,700 (36,700 - 90,900) yuan, and from 39.2% to 26.4% respectively. The rate of VRE decreased from 5.63% in 2007 to 3.80% during the second half year of 2008., Conclusion: Antibiotic intervention program of carbapenems and glycopeptides is effective in decreasing the inappropriate antibiotic use.

Background: Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003-2004 among CAP of adult Chinese urban populations., Methods: Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed., Results: Non-viral pathogens were found in 324/610 (53.1%) patients among whom M. pneumoniae was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of S. pneumoniae to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with beta-lactam antibiotics alone and with combination of a beta-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed M. pneumoniae and/or C. pneumoniae infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a beta-lactam plus a macrolide, or a fluoroquinolone) than with beta-lactam alone (75.8% vs. 42.9%, p = 0.045)., Conclusion: In Chinese adult CAP patients, M. pneumoniae was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With S. pneumoniae, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.

Objective: To study the etiology of influenza-like illness (ILI) in Beijing, and to investigate the impact of antibiotic treatment on outcomes., Methods: This was a prospective cohort study. Patients with diagnosis of influenza-like illness were prospectively enrolled for study of bacterial and viral pathogens. Demographic characteristics, underlying diseases, respiratory and extrapulmonary symptoms, laboratory tests were also collected for analysis of relationship between drug therapy and outcomes., Results: A total of 476 cases were enrolled between Dec. 2006 and Apr. 2007, of whom 454 cases were used for analysis. Influenza virus was the most common pathogen( n = 197, 43.4%), with other pathogens rarely seen. The mean age of the patients was (33 +/- 13) years, and the ratio of male to female was 1.1:1. Twenty four patients (5.3% ) received influenza vaccine. The rate of antibiotic prescription after onset of illness was 63.4%, but none received antiviral drugs such as Oseltamivir and amantadine. Compared with influenza-negative patients, patients with influenza were older, had more underlying diseases and had greater severity of symptoms such as cough, sore throat, headache and myalgia (but with no statistical differences). The influenza syndrome (T > or = 39 degrees C plus cough, sore throat and headache or myalgia) was more common in the influenza group compared to the influenza-negative patients (P < 0.05). The ratio of antibiotic prescription was 67% in the influenza group, and the total white blood cell and platelet count, percentage of neutrophils were higher in antibiotic treatment patients compared with non-antibiotic treatment patients (P < 0.01). The cost in patients who received antibiotics was twice as much as non-antibiotic treatment patients (P < 0.05), but the defervescence time and respiratory symptom alleviation time did not differ. Cox regression analysis showed that the total white blood count and the differentials (OR value 1.049 and 1.014, respectively), but not antibiotic use were the independent risk factors for longer defervescence time., Conclusion: Influenza virus was the most common pathogen for adult patients with ILI in Beijing city during the winter and the spring seasons. Antibiotic treatment of adult patients with ILI did not improve illness resolution, while the cost was increased significantly.

The total synthesis of ustiloxin D, a highly potent inhibitor of microtubule assembly, has been achieved. Notable features are the use of nucleophilic aromatic substitution (SNAr) for the construction of a chiral tertiary alkyl-aryl ether linkage, Sharpless asymmetric aminohydroxylation for the formation of the beta-hydroxytyrosine moiety, macrolactamization, and regioselective methylation.