Objective To evaluate the efficacy and safety of eravacycline in the treatment of complicated intra-abdominal infection(cIAI)in Chinese adult patients.Methods In this multicenter,randomized,double-blind phase Ⅲ study,cIAI patients were randomly assigned to receive either eravacycline(1.0 mg/kg,q12h)or ertapenem(1 g,q24h)by intravenous infusion for 5 to 14 days.The primary and secondary efficacy endpoints included the clinical efficacy and microbiological efficacy in different populations,including modified intention-to-treat(MITT)population,clinically evaluable(CE)population,and microbiologically evaluable(ME)population,at different time points after treatment.Clinical cure rates at specific visits were summarized and compared between treatment groups in different populations.The microbial eradication rate was calculated for the patients with baseline pathogens.The incidence of adverse events(AE)and drug-related treatment emergent adverse event(TEAE)was analyzed by treatment group.Results A total of 144 patients with cIAI who received at least one dose of the study drug were included in the MITT population.The clinical cure rate was 77.8％(56/72)in eravacycline-treated patients and 90.3％(65/72)in ertapenem-treated patients at 25-31 days after the first dose(TOC visit).When the patients who received insufficient treatment(＜72 hours)were excluded,the clinical cure rate was 83.6％(56/67)in eravacycline group and 90.3％(65/72)in ertapenem.For CE and ME patients,the clinical cure rate at TOC visit was 91.1％(51/56)and 83.3％(25/30)in eravacycline group,95.3％(61/64)and 90.9％(30/33)in ertapenem group.Eravacycline treatment achieved microbiological eradication rate of 91.3％(21/23)against Escherichia coli at TOC visit in micro-MITT population while ertapenem treatment resulted in a microbiological eradication rate of 96.2％(25/26).The microbiological efficacy of eravacycline and ertapenem against Klebsiella pneumoniae was 4/5 and 3/3,respectively.The incidence of TEAE was similar in eravacycline and ertapenem groups(75.0％vs.70.8％),most of which were mild or moderate.The AEs associated with eravacycline were mainly infusion site phlebitis(9.7％,7/72)and infusion site pain(8.3％,6/72).Conclusions Similar to ertapenem,eravacycline has good clinical and microbiological efficacy in treating cIAI.It is also safe and well-tolerated in the patients.

Objective To analyze the concentration and exposure of vancomycin in children with gram-positive coccal infection,and the corresponding clinical efficacy and safety to support rational use of vancomycin in children.Methods We prospectively collected the clinical and laboratory data of 87 children with gram-positive coccal infection in the Children's Hospital of Fudan University from January 2012 to March 2021.Therapeutic drug monitoring(TDM)was conducted for vancomycin simultaneously,to acquire the data of serum through concentration(Cmin),peak concentration(Cmax),the area under the drug concentration-time curve in a 24-h interval(AUC0-24h)and the ratio ofAUC0-24h to the minimum inhibitory concentration(AUC0-24h/MIC).Results The median(P25,P75)age of the children enrolled in this study was 3.60(1.20,20.00)months.The median dose of vancomycin was 39.23(30.00,46.51)mg/kg.The median serum Cmin was 3.30(1.50,7.10)mg/L.Cmin achieved the target(5-15 mg/L)in 23 cases(26.4％).The median AUC0-24h was 213(174,293)mg·h/L and the median AUC0-24h/MIC was 221(128,349).Adaily dose of above 60 mg/kg in children could achieve the median value of AUC0-24h and AUC0-24h/MIC greater than 400,and the corresponding median age was 28.50(6.85,36.00)months.Multivariate logistic analysis showed a good correlation between Cmin and AUC0-24h(P=0.002).At the end of treatment,the clinical efficacy rate was 85.1％(74/87)and the bacterial eradication rate was 95.4％(83/87).No renal injury occurred during the treatment.Conclusions In this study,the median daily dosage,Cmin and A UC0-24h/MIC of vancomycin were below the recommended range at home and abroad.However,good clinical and microbiological efficacy were achieved in children at low vancomycin exposure.The probability of target attainment(PTA)for A UC0-24h and AUC0-24h/MIC ≥400 increased when the daily dose of vancomycin was＞60 mg/kg(corresponding to the median age of 28.50 months)or Cmin ≥ 5 mg/L.

Objective To compare the differences in the levels of lactate dehydrogenase(LDH),creatine kinase(CK),and neuron-specific enolase(NSE)in the cerebrospinal fluid(CSF)between the patients with purulent meningitis(PM)and those with tuberculous meningitis(TBM)and evaluate the utility of the three biomarkers in the differentiation of PM and TBM.Methods Thirty-five PM patients and 45 TBM patients who attended the Department of Neurology from December 2019 to December 2021 were enrolled in this study.The CSF samples were collected from the patients before treatment.The levels of LDH,CK,NSE,and glucose,protein,and chloride in CSF were measured and compared between PM and TBM patients.The correlation between the biomarkers in CSF was analyzed by Pearson correlation coefficient.Linear regression analysis was performed to analyze the risk factors for the occurrence of TBM.Receiver operating characteristic(ROC)curves were plotted to evaluate the discriminative value of CSF LDH,CK,NSE alone or in combination in differential diagnosis of PM and TBM.Results Patient age,gender,clinical features such as fever,pathological signs,vomiting,limb twitching,and CSF levels of glucose and protein did not show significant difference between TBM patients and PM patients(P＞0.05).TBM was associated with significantly higher LDH and NSE levels in CSF and significantly lower CK level and chloride in CSF compared to PM(P＜0.05).Pearson correlation analysis showed that LDH level in CSF was negatively correlated with CK and chloride(r＜0,P＜0.05),and positively correlated with NSE(r＞0,P＜0.05).CK was negatively correlated with NSE(r＜0,P＜0.05),and positively correlated with chloride(r＞0,P＜0.05).NSE was negatively correlated with chloride(r＜0,P＜0.05).Linear regression analysis showed that LDH,CK,NSE,and chloride levels in CSF were all associated with the occurrence of TBM(P＜0.05).ROC curves demonstrated that the AUCs of CSF levels of LDH,CK,NSE alone and in combination for differentiation between PM and TBM were 0.849(95％CI:0.768-0.930),0.858(95％CI:0.779-0.937),0.851(95％CI:0.771-0.931),and 0.954(95％CI:0.911-0.996),respectively.Conclusions The clinical features are similar for PM and TBM patients.However,the levels of LDH,CK,and NSE in CSF are different between PM and TBM.LDH,CK,NSE in combination may improve the differential diagnosis between PM and TBM.

Objective To investigate the epidemiological characteristics,clinical manifestations,diagnosis and treatment of non-O1/non-O139 Vibrio cholerae infection in order to improve the understanding of the disease.Methods A retrospective analysis was conducted on the clinical manifestations,laboratory examinations,treatment,and outcomes of a patient with non-O1/non-O139 Vibrio cholerae bloodstream infection.Relevant cases were identified by searching Wanfang,VIP,CNKI,and PubMed databases using the keywords"non-O1/non-O139 Vibrio cholerae"and"bloodstream infection".The clinical characteristics and diagnosis and treatment methods of non-O1/non-O139 Vibrio cholerae bloodstream infection were reviewed.Results Six months after the operation for hilar cholangiocarcinoma,the 69-year-old male patient experienced abdominal distention,fever,but no diarrhea.Blood culture found Vibrio cholerae,which was identified as Vibrio cholerae by mass spectrometry,VITEK 2XL,and 16S rRNA gene.The serology test confirmed it as non-O1/non-O139 group.After 10-day treatment with piperacillin,the patient recovered and was discharged from hospital.Literature review showed that most of the 26 patients with non-O1/non-O139 Vibrio cholerae bloodstream infection had underlying diseases of chronic hepatitis,cirrhosis or other digestive tract diseases.The main symptoms were acute diarrhea,abdominal distention and pain,fever,nausea and vomiting.The strain was susceptible to a variety of antibiotics.After antimicrobial and symptomatic treatment,80.77％of the patients were discharged.Overall,15.38％of the patients died,mainly due to multiple organ failure caused by septic shock.Conclusions Bloodstream infection caused by non-O1/non-139 Vibrio cholerae tends to occur in patients with immune deficiency,especially in patients with chronic hepatitis,cirrhosis,malignant tumor,or diabetes mellitus.Timely blood culture and accurate identification of pathogen are very important for diagnosis.Early use of active antimicrobial agents will lead to a relatively good outcome.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To investigate the distribution and antibiotic resistance profiles of the bacterial strains isolated from urine samples in a tertiary Traditional Chinese Medicine hospital in Shanghai in the 12-year period from 2010 through 2021 for better empirical antibiotic use in clinical practice.Methods The clinical data of patients with urinary tract infection,including the species and antibiotic resistance of the bacterial strains isolated from urine samples from January 2010 to December 2021 were retrospectively analyzed.Results A total of 5 231 nondupliate bacterial strains were isolated,among which E.coli was the most common(52.8％),followed by Enterococcus spp(19.1％)and Klebsiella spp(11.1％).Most of the urinary isolates(76.0％)were isolated from the elderly aged 60-89,and only 3.1％of the strains were isolated from the young people aged under 44.Most of the bacterial strains were isolated from female patients(75.8％),however,more P.aeruginosa and A.baumannii were isolated from male patients compared to female patients(55.3％vs 44.7％and 67.7％vs 32.3％).About 13.7％of the strains were collected from the Department of Nephrology,more than the strains from any other clincial department.In intensive care unit(ICU),the proportion of E.coli was the lowest,while the proportion of Enterococcus spp was the highest.Enterobacterales showed lower resistance raets to carbapenems,cephamycin,amikacin,cefepime,and β-lactam/β-lactamase inhibitor combinations.P.aeruginosa showed higher susceptibility rates to carbapenems,aminoglycosides and β-lactam/β-lactamase inhibitor combinations compared to A.baumannii(≥54.6％vs≤39.8％).Gram-positive cocci were highly sensitive to glycopeptide antibiotics.No SS.aureus or E.faecalis isolates were found resistant to vancomycin.About 2.7％of the E.faecium isolates were resistant to vancomycin.The prevalence of drug-resistant bacteria was the highest in elderly patients,and in the strains isolated from ICU and emergency department.Conclusions Compared with general hospitals,a high proportion of elderly patients were treated in this hospital.It should be more cautious in the treatment of patients with urinary tract infection.The major bacterial species isolated from urine were E.coli,Enterococcus,and K.pneumoniae.Empirical treatment should be prescribed considering patient age and gender as well as the species and distribution of pathogenic bacteria.Urine culture and antibiotic susceptibility testing should be performed proactively.Appropriate antimicrobial agents should be selected according to the results of antimicrobial susceptibility testing.Antimicrobial ressitance surveillance should also be strengthened.

Objective To examine the quinolone resistance and mechanisms of resistance,including prevalence of transferable mechanisms of quinolone resistance(TMQR)genes in carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods Antimicrobial susceptibility was tested for CRKP isolated from 7 hospitals in China during 2019 by broth microdilution method.Genome sequencing analysis was performed on Illumina HiseqX sequencing platform.The virulence genes,multilocus sequence typing(MLST),chromosome quinolone resistance-determining region(QRDR)variation,and prevalence of TMQR genes in CRKP were analyzed.Results Overall,98.4％and 99.2％of the 481 CRKP strains were non-susceptible to levofloxacin and ciprofloxacin,respectively.ST11(77.8％)and ST15(15.8％)were the dominant clones.Among the 303 CRKP strains carrying virulence gene(CV-CRKP),ST11 type and ST15 type strains accounted for 92.1％and 5.0％,respectively,while ST11 and ST15 type strains accounted for 53.4％and 34.3％in the 178 CRKP strains without the virulence gene(non-CV-CRKP).All of the ST11 and ST 15 type strains were resistant to quinolones associated with gyrA and parC mutation.All of the quinolone-sensitive strains were not ST11 type or not ST15 type.TMQR analysis showed that qnrS1(61.1％,294 strains),qnrB4(10.0％,48 strains)and aac(6)-Ib-cr(18.7％,90 strains)were most prevalent in CRKPs,while qnrB1(4 strains),qnrB2(2 strains),qnrD1(2 strains)and qnrB6(1 strain)were infrequently identified in CRKPs.Specifically,qnrB4 was mainly identified in high-level levofloxacin-resistant strains(MIC≥8 mg/L),while aac(6)-Ib-cr was found mainly in ciprofloxacin-resistant strains(MIC＞8 mg/L).Conclusions Clinical CRKPs were highly resistant to quinolone.The rate of QRDR variation were high in quinolone resistant CRKP strains,with high TMQR gene carriage.