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Objectives To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli , Klebsiella pneumoniae , Enterobacter cloacae , Acinetobacter baumannii and Staphylococcus aureus , from a multi-centre study in China. Methods We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline. Results The MICs of eravacycline against all the strains were in the range of 0.004–16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli , 2 mg/L for K. pneumonia and E. cloacae , and 0.25 mg/L for A. baumannii and S. aureus , consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder. Conclusions The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens. [ABSTRACT FROM AUTHOR]

The polymyxins are important antimicrobial agents against antibiotic-resistant gram-negative bacilli. In 2020, the Clinical and Laboratory Standards Institute modified the clinical breakpoints for polymyxin susceptibility test by eliminating the "susceptible" interpretive category, only reporting intermediate (≤2 mg/L) and resistant (≥4 mg/L). However, the European Committee on Antimicrobial Susceptibility Testing recommended the use of clinical breakpoints of ≤2 mg/L as susceptible and >2 mg/L as resistant. The first-line laboratorians and clinicians in China have been perplexed by the inconsistence of international polymyxin clinical breakpoints and discouraged by the difficulty of conducting polymyxin susceptibility testing. Therefore, it is urgently needed to make it clear for the laboratorians in China to know how to accurately carry out polymyxin susceptibility testing and standardize the interpretation of susceptibility testing results. To this end, the experts from relevant fields were convened to formulate this consensus statement on the testing and clinical interpretation of polymyxin susceptibility. Relevant recommendations are proposed accordingly for laboratorians and clinicians to streamline their daily work.

Objective To explore the clinical and laboratory characteristics and the prognosis of disseminated non-tuberculous mycobacteria(NTM)diseases in human immunodeficiency virus(HIV)negative patients. Methods Cases of disseminated NTM disease were retrospectively collected in Peking Union Medical College Hospital from January 2012 to October 2018.Clinical manifestations,laboratory findings,treatment,and prognosis of these cases were retrieved from the electronic medical record system. Results Among the 23 HIV negative patients with disseminated NTM disease,21 had underlying diseases,with rheumatoid immune disease(n=7)as the most common one.The main clinical manifestation was fever(n=23).Laboratory tests showed anemia [hemoglobin(85.78±25.47)g/L],hypoalbuminemia [albumin 29(27-32)g/L],elevated erythrocyte sedimentation rate [(85.73±43.78)mm/h] and hypersensitive C-reactive protein [(112.00±70.90)mg/L],and reduction of lymphocyte count [0.69(0.29-2.10)×10 9 /L].Lymphocyte subset analysis indicated reduction in CD4 + T cells [213(113-775)/μl],CD8 + T cells [267(99-457)/μl],B cells [39(4-165)/μl],and NK cells [88(32-279)/μl] and elevation of human leukocyte antigen-D related(HLA-DR),and CD38 expression in CD8 + T cells [HLA-DR + CD8 + /CD8 + ,60(40-68)%;CD38 + CD8 + /CD8 + ,81(65-90)%].The most common species of NTM was Mycobacterium intracellular(n=6).Lymphocyte,CD8 + T cell,B cell,and NK cell counts were significantly lower in dead patients than surviving patients(P =0.045,P=0.045,P=0.032,and P=0.010,respectively). Conclusions Disseminated NTM disease in HIV negative patients is mainly manifested as fever,anemia,hypoalbuminemia,and elevated inflammatory indicators.It is more likely to occur in immunocompromised patients.Patients with decreased lymphocytes,CD8 + T cells,B cells and NK cells tend to have a poor prognosis.

Objective To explore the influence of the iodine disinfection on nasal bacterial colonization through the transsphenoidal approach. Methods Totally 133 pituitary adenoma patients who underwent transsphenoidal surgery in our department from January to August 2017 were enrolled in this study. Before disinfection,pharyngeal swabs of inferior turbinate root secretions were taken for bacterial culture. After iodine disinfection,pharyngeal swabs were taken again at the same site. Changes in the nasal bacterial spectrum before and after disinfection were compared. Patients were followed up for three months after the surgery,during which any intracranial infection/bacteraemia was recorded,and its correlation with nasal bacteria colonization was analyzed. Results Nasal bacterial colonization was detected in 45 (33.8%) of 133 patients before iodine disinfection and in only 6 cases (4.5%) after iodine disinfection (χ 2 =34.5,P=0.000). Thus,iodine disinfection eliminated 86.7%(39/45) of the colonized bacteria. The most common nasal bacterium was Staphylococcus aureus (24.4%,11/45),followed by Klebsiella pneumoniae (24.4%,11/45),and Staphylococcus epidermidis (13.3%,6/45). One patient had high fever and chills 2 days after surgery,but blood culture and cerebrospinal fluid culture showed negative Results . After the administration of third-generation cephalosporins,the symptoms disappeared after two days. Conclusion sThere are colonized bacteria in nasal cavity. Iodine disinfection of nasal cavity can effectively clear most of the nasal bacteria. The possibility of intracranial infection/bacteremia after transsphenoidal approach is low.

Objective: To evaluate the microbial spectrum and clinical characteristics of microbiological diagnosed bloodstream infections (BSI) with identified infective sources., Methods: The hospitalized patients microbiologically diagnosed as BSI with identified infective sources were included in this study from January 2008 to December 2009. Data were collected retrospectively and analyzed by software SPSS 17.0., Results: In this 2-year study, 301 strains of microbes were isolated from 249 patients. There were 205 (82.33%) patients with monomicrobial BSI, while the other 44 (17.67%) patients with polymicrobial BSI. The most common identified source of bloodstream infections was lower respiratory tract infection (125, 41.5%), followed by intraabdominal infection (55, 18.3%) and intravascular devices related infection (54, 17.9%). The four most common isolated pathogens were Acinetobacter species (60, 19.9%), Escherichia coli (50, 16.6%), Pseudomonas species (35, 11.6%) and Staphylococcus Aureus (34, 11.3%). Eighty-eight (35.3%) patients died during hospitalization due to all causes, out of which 62 (24.9%) patients died owing to BSI. The patients with BSI originated from lower respiratory tract had a higher crude in-hospital case-fatality ratio than those with BSI originated from other resources (OR = 2.186; 95%CI 1.260 - 3.792; χ(2) = 7.879, P = 0.005). In the multivariate regression, age ≥ 65, invasive mechanical ventilation, reservation of central line and polymicrobial BSI during hospitalization were independent risk factors of death due to all causes., Conclusions: Lower respiratory tract is the most common originated source of BSI with microbiological identified sources. Gram-negative bacillus taking advantage, the microbial spectrum of BSI with identified sources in our study is different from those reported before both in primary and secondary BSI. The patients with BSI originated from respiratory tract have a higher crude in-hospital case-fatality ratio.

Objective: Evaluate the microbiological and epidemiological characteristics of primary bloodstream infections as well as the associated patients' clinical features at Peking Union Medical College Hospital., Method: Microbiological and clinical data of the adult patients with primary bloodstream infections during January 1, 2008 and December 31, 2009 were retrospectively collected and evaluated. Pearson χ(2) test was used to compare the difference between proportions and Logistic regression was used in multivariate analysis., Result: Five hundred and eighty-six strains of microbes were isolated from 494 adult patients with primary bloodstream infections. There were 80 patients with polymicrobial primary bloodstream infection of the 586 isolates, coagulase-negative staphylococci (175, 29.9%) was the most common, followed by Escherichia coli (93, 15.9%), Enterococcus species (60, 10.2%), Streptococcus species (41, 7.0%), and Staphylococcus Aureus (39, 6.7%). Central-line was the leading suspected infective source among the suspected infective source involving 108 (18.4%) isolates. Excluded the 108 isolates with suspected sources, 77 (45.3%) out of 167 patients with the primary bloodstream infections caused by coagulase-negative staphylococci or Staphylococcus Aureus had a central-line, with a higher proportion of the patients with a central-line than the patients with bloodstream infection caused by other pathogens (χ(2) = 10.419, P = 0.001). One hundred and fourteen patients died during hospitalization, with the crude mortality rate 23.0%. Fifty-nine patients (11.9%) died due to primary bloodstream infection. The patients with polymicrobial bloodstream infection were with a higher attributable mortality (OR = 2.159;95%CI 1.165 - 4.002; χ(2) = 6.194, P = 0.013). In the multivariate analysis, the independent risk factors of crude mortality rate to primary bloodstream infections were elderly patients, central neurological disorder, mechanical ventilation, and reservation a central-line., Conclusion: The most common microbe causing primary bloodstream infections was G+ cocci. Polymicrobial primary bloodstream infection added risk to attributable in-hospital fatality ratio. Elderly patients, neurological disorder, reservation of central-line, and mechanical ventilation were the independent risk factors of crude in-hospital fatality ratio.

Objective: To investigate the drug-resistance rates of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010., Methods: A total of 1793 strains (S. aureus 421, S. pneumoniae 420, K. pneumoniae 404, H. influenzae 313, other Streptococcus. spp 149, and M. catarrhalis 86) of non-duplicated community-acquired respiratory tract pathogens were isolated from 11 hospitals in 6 cities. The MIC values were determined by the broth microdilution method, and the production of β-lactamase was tested using a nitrocefin-based test., Results: All of the S.aureus isolates were methicillin-sensitive (MSSA). Of the MSSA isolates, less than 1% (4/421) was resistant to β-lactamase inhibitor combinations, about 13.1% (55/421) and 9% (38/421) resistant to levofloxacin and moxifloxacin, and 57% (240/421), 53.2% (224/421), and 88.7% (373/421) resistant to azithromycin, clarithromycin, and penicillin, respectively. No S. aureus isolates resistant to vancomycin were detected in this study. Based on different criteria, the percentages of penicillin-sensitive S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 24.4% (102/420), 27.3% (115/420), 48.3% (203/420) (Oral) and 1.9% (8/420), 9% (38/420), 89.1% (374/420) (parenteral), respectively. The resistance rates of S. pneumonia to azithromycin, clarithromycin, cefaclor, cefuroxime, ceftriaxone and amoxicillin with clavulanic acid were 88.2% (370/420), 87.4% (367/420), 45.3% (190/420), 41.9% (176/420), 10.2% (43/420), and 5.2% (22/420), respectively. About 2.6% (11/420) and 0.2% (1/420) of S. pneumonia isolates were resistant to levofloxacin and moxifloxacin. More than 70% (104/149) of β-hemolytic streptococci isolates were resistant to azithromycin and clarithromycin, and about 10.1% (15/149) of isolates were resistant to levofloxacin. The resistance rates of K.pneumonia to most antibiotics were > 20% (81/404), and that of ceftazidime was lower than cefuroxime, cefaclor, and ceftriaxone. The mean prevalence value of ESBL producing K. pneumonia was 38.8% (157/404), with significantly regional variations. More than 90% of H. influenza and M. catarrhalis were susceptible to most antibiotics, with resistance rate of < 5% (16/313, H. influenza; 4/86, M. catarrhalis). The mean productions of β-lactamase in H. influenza and M. catarrhalis were 13.1% (41/313) and 91.7% (79/86), respectively., Conclusions: The percentage of PRSP increased significantly, and the resistance rates of community-acquired respiratory tract pathogens to common antibiotics such as macrolide and cephalosporins increased gradually. New fluoroquinolones such as moxifloxacin showed a high antimicrobial activity against most of the respiratory pathogens.

In an in silico search for gonand specific expressed genes, we have identified zRAP55 which is enriched in the ovary of zebrafish . zRAP55 encodes a protein of 382 amino acids with a highly conserved Lsm domain. zRAP55 protein shares more than 56% identities with that of other vertebrate species. RT-PCR results show that it is predominantly expressed in the ovary. In situ hybridization and immunohistochemistry studies reveal that zRAP55 is ubiquitously dispersed throughout the cytoplasm of stages I and II oocytes, whereas no expression is observed in stages III and IV oocytes. As an RNA associated protein, zRAP55 might function in the control of protein translation at the early stages of oogenesis in zebrafish.

Objective: To investigate the antimicrobial resistance of community respiratory pathogens isolated in China., Methods: The strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes were isolated from patients with community-acquired respiratory tract infections at 14 Chinese hospitals from 2005 to 2007. Etest and disk diffusion methods were used to survey the susceptibility of 14 antibiotics against these strains. These antibiotics included penicillin G, ampicillin, amoxicillin/clavulanic acid, cefaclor, cefprozil, ceftriaxone, cefepime, levofloxacin, gatifloxacin, ciprofloxacin, tetracycline, clindamycin, erythromycin and trimethoprim/sulfamethoxazole (SXT)., Results: A total of 1870 strains were collected including S. pneumoniae (n = 997), S. pyogenes (n = 176), H. influenzae (n = 499) and M. catarrhalis (n = 198). The 2005 - 2007 prevalence of penicillin-susceptible S. pneumoniae (PSSP) were 92.6%, 73.9%, 74.1% and penicillin-intermediate S. pneumoniae (PISP) 4.5%, 9.5%, 14.3% and penicillin-resistant S. pneumoniae (PRSP) 2.9%, 16.6%, 11.6% respectively. 36.9% of S. pneumoniae strains isolated from or= 92.9%., Conclusions: Antimicrobial resistance in S. pneumoniae is rising. The prevalence of PNSSP isolated from children < or = 6 years old is higher than other age groups. Amoxicillin-clavulanic acid, ceftriaxone, cefepime, gatifloxacin and levofloxacin remain highly active against common community respiratory pathogens.

Objective: To evaluate the in vitro activity of daptomycin, vancomycin, teicoplanin, tigecycline, ceftobiprole and linezolid against 499 strains of blood-isolated gram-positive cocci., Methods: Determination of the minimal inhibitory concentration (MICs) of daptomycin with microbrothdilution method and the MICs of other 9 antimicrobial agents with agar dilution method against 499 strains of blood-isolated gram positive cocci was carried out. The data was analyzed with WHONET 5.4 software., Results: The susceptibility rates of staphylococci to daptomycin, tigecycline, linezolid, ceftobiprole, vancomycin and teicoplanin were 100%. All staphylococcus strains were inhibited by daptomycin at a MIC of 1 mg/L. The MIC(50) and MIC(90) of daptomycin were both 0.5 mg/L against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus coagulase-negative (MRSCoN). Among Enterococcus spp, the highest MIC of daptomycin was 4 mg/L. The MIC(50) and MIC(90) of daptomycin were both 2 mg/L against E.faecalis, whereas they were 2 mg/L and 4 mg/L against E.faecium. One strains of linezolid-resistant E.faecalis (MIC: 8 mg/L) was susceptible to daptomycin (MIC: 1 mg/L). Three strains of E.faecium carrying vanA gene with vancomycin MICs above 32 mg/L and teicoplanin MICs also 32 mg/L were susceptible to daptomycin, tigecycline and linezolid. The MIC range of daptomycin against Streptococcus pneumoniae and Streptococcus viridans was 0.032 - 0.25 mg/L and 0.125 - 1.000 mg/L separately., Conclusions: Daptomycin has excellent in vitro activity against common gram-positive pathogens isolated from blood. It may be a good choice for clinicians to treat drug-resistant gram-positive cocci.

Objective: To investigate the antimicrobial resistance among the nosocomial gram-negative pathogens from 15 teaching hospitals located in different areas in China in 2005., Methods: A total of 1927 non-repetitive nosocomial gram-negative pathogens were collected from 15 teaching hospitals in different areas in China and sent to the central lab for reidentification and susceptibility testing. The levels of minimal inhibitory concentration (MIC) of 18 antimicrobial agents were determined by agar dilution method. WHONET 5.4 software was used to analyze the data., Results: The strains of Escherichia coli, Klebsiella pneumoniae, and Proteous mirabilis isolates that did not produce extended spectrum beta lactamases (ESBLs) showed high sensitivity to beta-lactams. The antibiotics with a susceptibility rates over 80% against the strains of Entorobacter cloacae, Enterobacter aerogene, Citrobacter spp, Serratia spp, and Proteous vulgaris producing AmpC enzyme included meropenem, imipenem, and piperacillin-tazobactam, and these 3 drugs showed a susceptibility rate of more than 80% against the ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Other antimicrobial agents showing a relatively high activity against Enterobacter spp, Citrobacter spp, Serratia spp and Proteous vulgaris included cefepime (67.3% - 100%), amikacin (67.3% - 95.2%), ceftazidime (52.9% - 100%) and cefoperazone-sulbactam (51.9% - 100%). The susceptibility rate of fluoroquinolones was 34.8% - 36.1% against non-ESBL-producing Escherichia coli and was 13.4% - 17.1% against ESBL-producing isolates. The most active agent against Pseudomonas aeruginosa was polymyxin B (95.6%). The agents with the activity rates of 70% - 80% included meropenem, imipenem, amikacin, and piperacillin-tazobactam. The antibiotic with a high susceptible rate against Acinetobacter baumannii was polymyxin B (98.3%), followed by imipenem (80.8%), meropenem (76.2%), and minocycline (67.4%). The susceptible rates of other agents were all below 60%. The agents with relatively high activity against Stenotrophomonas maltophilia included minocycline (85%), levofloxacin (82.5%), and trimethoprim-sulfamethoxazole (77.5%). The agents with a relatively high activity against Burkholderia cepacia included minocycline (77.2%) and meropenem (61.4%)., Conclusion: Carbapenem, piperacillin-tazobactam, amikacin and cefepime remained relatively high activity against nosocomial Enterobacteriaceae, Non-fermenting pathogens have lower susceptibility to the antimicrobial agents than before.

Objective: To investigate the molecular mechanism of multiple-drug and pan-drug resistance among Acinetobacter species., Methods: Non-repetitive 90 carbapenem-resistant strains of Acinetobacter species were collected in Beijing, Guangzhou, and Fuzhou 1999-2004. The homology of the isolates was determined by both pulsed field gel electrophoresis and randomly amplified polymorphic DNA typing. Seven representative clones were selected from the 90 strains of Acinetobacter isolated from different hospitals to be used for further study. Analytical isoelectric focusing was used to measure the isoelectric point of the beta-lactamase. Plasmid DNA was extracted and purified Genes of different beta-lactamase, including bla(TEM--), bla(SHV-), bla(PER-), blaI(MP-), bla(VIM-), and bla(OXA-) genes, in these clone strains were amplified and sequenced. PCR was used to analyze the integrons., Results: The P clone strain isolated during an outbreak of pan-drug-resistant Acinetobacter species in Peking Union Medical College Hospital 2004 was not susceptible to most common antimicrobial agents tested. The 7 representative clones produced multiple beta-lactamases: TEM-1, high-level AmpC, SHV-type, OXA-23 carbapenemase and IMP-8 and metalloenzyme respectively. One clone produced PER-1 enzyme. These 7 clone strains were resistant to most beta-lactams (including carbapenems), erythromycin, chloramphenicol, and rifampin. Two clone strains were susceptible to cefoperazone/sulbactam and amikacin while 4 clone strains susceptible to levofloxacin. All of the 7 clones were susceptible to minocycline and colistin. Five different integrons were found, harboring the genes mediating the resistance to aminoglycosides, rifampin, chloramphenicol, and carbapenems (bla(IMP-8))., Conclusion: The molecular bases of multiple-drug or pan-drug resistance in Acinetobacter species include production of OXA-23 carbapenemase or IMP type metalloenzyme and integrons with different resistance gene cassettes. Pan-drug-resistant Acinetobacter species are susceptible to old antimicrobials agents, such as colistin and minocycline.