Purpose:Latamoxef has been used to treat various bacterial infections. To provide data supporting the rational clinical use of latamoxef, bacterial resistance over 10 years was analyzed at multiple centers throughout China. The results were used to develop tentative epidemiological cut-off values (TECOFFs) for latamoxef. Methods:A total of 46,716 strains of common Enterobacteriaceae were collected from patients with bloodstream infections at 72 hospitals in 21 provinces of China between 2014 and 2023. The in vitro antimicrobial activities of latamoxef were compared with those of other commonly used cephalosporin and carbapenem. The distribution of minimum inhibitory concentrations was subjected to cumulative log-normal fitting to obtain the TECOFFs of latamoxef for common Enterobacteriaceae. Results:The sensitivities of Escherichia coli (E. coli), Salmonella species, Serratia marcescens (S. marcescens) and Proteus mirabilis (P. mirabilis) to latamoxef ranged from 94.37% to 98.08%. Klebsiella oxytoca (K. oxytoca) and Enterobacter aerogenes (E. aerogenes) had sensitivities of 89.91% and 87.21%, respectively, whereas Klebsiella pneumoniae (K. pneumoniae) and Enterobacter cloacae (E. cloacae) had lower sensitivities. The in vitro activity of latamoxef against these bacteria, especially extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, was similar to the activities of ertapenem and meropenem and significantly higher than the activities of ceftriaxone, ceftazidime, and cefepime. The sensitivities of ESBL (+) E. coli and ESBL (+) P. mirabilis to latamoxef were similar to their sensitivities to ertapenem and meropenem. ESBL (+) K. pneumoniae and ESBL (+) K. oxytoca exhibited comparable but lower rates of sensitization to latamoxef, ertapenem, and meropenem. Latamoxef had TECOFFs of 2 µg/mL for E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, E. aerogenes, Salmonella, and S. marcescens, and 4 µg/mL for E. cloacae. Conclusion:Latamoxef has good and stable in vitro antimicrobial activity against Enterobacteriaceae, including ESBL-producing Enterobacteriaceae. The calculated TECOFFs of latamoxef provide an important reference for subsequent use of this antibiotic against Enterobacteriaceae.

To examine the characteristics and spatiotemporal changes in the phenotypes and genotypes of extended-spectrum β-lactamases (ESBLs) in Escherichia coli strains isolated from bloodstream infections (BSIs) across China between 2014 and 2021. 983 ESBL-positive E. coli strains were collected from BSIs in 66 hospitals across different geographic regions in China from 2014 to 2021. The phenotypic confirmation of ESBL was performed through the double-disc diffusion method. The genetic type was determined using polymerase chain reaction (PCR) followed by DNA sequencing. Between 2014 and 2021, the prevalence of ESBL-positive E. coli steadily decreased from 61.2 to 49.6

Treating multidrug-resistant (MDR) infections has become progressively dependent on limited therapeutic options, particularly polymyxins, such as colistin. This reliance has precipitated a concerning epidemiological trend: the emergence and global propagation of plasmid-mediated (mcr) as well as chromosome-mediated polymyxin resistance. Consequently, escalating resistance rates will certainly lead to diminished clinical efficacy of colistin, correlating with elevated mortality in septic patients who already face therapeutic limitations. Utilizing antimicrobial potentiators to restore the sensitivity of resistant pathogens to polymyxins represents a promising pharmacological strategy for reinvigorating the clinical utility of these agents. Here, we demonstrate that dronedarone hydrochloride (DH) exhibits significant synergistic bactericidal activity with colistin against colistin-resistant strains. DH enhances the antibacterial potency of colistin by approximately 32-fold (MIC from 8 μg/mL to 0.25 μg/mL in ExPEC ECQ001), effectively reversing resistance phenotypes. In vivo therapeutic efficacy studies demonstrated that combination therapy achieved a statistically significant reduction in bacterial burden compared to colistin therapy alone. Mechanistic studies revealed that DH has the capacity for specific molecular interactions with two critical phospholipid components: cardiolipin and phosphatidylglycerol (PG) in bacterial membranes. This binding induces membrane disruption, impairs energy production, and stimulates oxidative stress, which collectively augment the bactericidal activity of colistin. These findings position DH as a viable antibiotic adjuvant with translational potential for combination therapies against MDR pathogens. The dual targeting of membrane integrity and redox homeostasis presents a strategic advantage in circumventing conventional resistance mechanisms, thereby extending the application potential of colistin in contemporary antimicrobial regimens.IMPORTANCEColistin remains a last resort antibiotic for treating infections caused by extensively drug-resistant pathogens. However, the emergence of colistin resistance has significantly compromised its clinical utility. Our research identifies and characterizes that dronedarone hydrochloride (DH) restores bacterial sensitivity to colistin by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Mechanistic studies revealed that DH bound specifically to CL and PG, thereby enhancing membrane disruption, impairing energy production, and stimulating oxidative stress levels, which collectively augment the bactericidal activity of colistin. These findings present DH as a lead compound for combating colistin resistance, while offering novel mechanistic insights into its role as a colistin potentiator.

In recent decades, Acinetobacter baumannii has become a major global nosocomial pathogen, with bloodstream infections (BSIs) exhibiting mortality rates exceeding 60% and imposing substantial economic burdens. However, limited large-scale genomic epidemiology has hindered understanding of its population dynamics. Here, we analyzed 1506 non-repetitive BSI-causing A. baumannii isolates from 76 Chinese hospitals over a decade (2011-2021). We identified 149 sequence types (STs) and 101 K-locus types (KLs), revealing increased population diversity. International clone (IC) 2 accounted for 81.74% of isolates, with a notable shift in prevalent STs: ST208 increased while ST191 and ST195 declined, aligning with global trends. ST208 exhibited higher virulence, greater antibiotic resistance, enhanced desiccation tolerance, and more complex transmission patterns compared to ST191 and ST195. Its genomic plasticity drives its adaptation and spread. Using the high-resolution Oxford MLST scheme, this study uncovered greater diversity and genetic factors behind ST208's rise. A. baumannii is evolving from a low-virulence, multidrug-resistant pathogen to a more virulent one, highlighting the urgent need to address its growing threat. These findings have critical implications for infection control and public health policies.

The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative beta-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People's Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People's Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What's more, as a vast nation, People's Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.

The optimal regimens of piperacillin/sulbactam (PIS 2:1), piperacillin/tazobactam (PTZ 8:1), and cefoperazone/sulbactam (CSL 2:1) are not well defined in patients based on renal function. This study was conducted to identify optimal regimens of BLBLIs in these patients. The antimicrobial sensitivity test was performed by a two-fold agar dilution method. Monte Carlo simulation (MCS) was used to simulate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for various dosing regimens in patients with different renal functions. For strains with an MIC ≤ 8/4 mg/L, PIS 4.5 g q6h achieved 99.03%PTA in the subset of patients with creatinine clearance (CrCL) > 90 mL/min. For patients with CrCL 60–90 mL/min, PIS 4.5 g q6h achieved 81.2% CFR; for those with CrCL 40–59 mL/min, PIS 4.5 g q8h achieved 80.25% CFR. However, for patients infected by ESBL-producing Enterobacteriaceae, PIS 4.5 g q6h achieved a CFR lower than 80%. For patients infected by A. baumannii with a CrCL of 31–60 mL/min, PIS 6.0 g q8h and 4.5 g q6h achieved 81.24% and 82.42% CFR, respectively. For those infected by P. aeruginosa, PIS 4.5 g q6h reached 90% CFR. PIS and PTZ achieved a similar CFR when piperacillin was at the same dose. The CFRs of CSL were much lower than those of the other two agents in Enterobacteriaceae and P. aeruginosa infections. The antibacterial spectrum of PIS is superior to that of PTZ and CSL. Higher dosages and dosing adjustment according to renal function should be considered to treat Gram-negative bacterial BSIs.

目的 利用蒙特卡洛模拟评价万古霉素治疗金黄色葡萄球菌和表皮葡萄球菌引起血流感染的合理性.方法 由全国血流感染细菌耐药监测联盟(BRICS)收集全血标本中分离的1438株金黄色葡萄球菌和409株表皮葡萄球菌,采用微量肉汤稀释法对分离的菌株进行最低抑菌浓度(minimum inhibitory concentration,MIC)的测定.万古霉素4种给药方案分别为500mg q6 h、1000mgq12h、1500 mg q12 h和2000mgql2h.通过蒙特卡洛模拟10000例次后,获得4种给药方案的fAUC/MIC达标概率(probability of target attainment,PTA)和累计反应分数(cumulative fraction of response,CFR).CFR≥90％时的给药方案是经验性用药的最佳选择.结果 当对葡萄球菌MIC≤0.5 mg/L时,万古霉素4种给药方案fAUC/MIC均可达到满意的抗菌活性(PTA=100％),当MIC=1 mg/L时,1500 mg q12 h和2000 mg q12 h两种给药方案可达到目标PTA.万古霉素给药剂量500 mg q6 h、1000 mg q12 h、1500mgq12h、2000 mg q12 h对金黄色葡萄球菌的fAUC/MIC CFR分别为83％、83％、87％和98％;对应表皮葡萄球菌的CFR分别为53％、53％、59％和92％.结论 万古霉素用于因金黄色葡萄球菌和表皮葡萄球菌引起的血流感染时,应根据MIC值的不同而选择不同的给药剂量进行治疗,经验性选择万古霉素进行抗感染治疗时,给药剂量需达到2000 mg q12 h方能达到较好的抗菌效果.

OXA-232 carbapenemase, being a vital resistance mechanism against carbapenems, has recently been increasingly reported. In China, the identified OXA-232-producing K. pneumoniae isolates almost belonged to ST15 and were not hypervirulent, despite harboring a virulence plasmid. Klebsiella pneumoniae, a notorious pathogen for opportunistic health care-associated infections, represents increasing multidrug resistance, particularly to carbapenems. OXA-232 carbapenemase, as a variant of OXA-48, has been increasingly reported worldwide. ST231, an epidemic, multidrug resistant (MDR) K. pneumoniae clone in south and southeast Asia, has been found in other regions, including Europe. In the study, five OXA-232 carbapenemase-producing Klebsiella pneumoniae isolates, four of which belong to sequence type 231 (ST231) and one of which belongs to ST15, were isolated from two hospitals in China. All isolates displayed a MDR phenotype, being susceptible to only polymyxin B and colistin, and the bla(OXA-232) gene was located on a ColKP3-type nonconjugative plasmid of 6.1 kb. A phylogenetic analysis of the global ST231 K. pneumoniae isolates (n = 231) suggested that the four ST231 isolates from this study gathered with strains from south Asia (especially India), indicating that the emerging Chinese ST231 clone was more closely related to south Asia isolates and might have spread from south Asia, where ST231 was a successful epidemic clone. Virulence assays suggested that the four ST231 strains were not highly virulent, as they displayed significantly lower virulence potential, compared with a ST23 K1 hypervirulent isolate in a G. mellonella infection and in mouse intraperitoneal infection models, although three ST231 strains harbored a plasmid-borne aerobactin-encoding iuc gene cluster. This is the first report of ST231 K. pneumoniae clinical strains bearing bla(OXA-232) in China, and it highlights the emergence of the ST231 clone causing bloodstream infections in a health care setting as well as calls attention to the transmission of this emerging clone in China.IMPORTANCE OXA-232 carbapenemase, being a vital resistance mechanism against carbapenems, has recently been increasingly reported. In China, the identified OXA-232-producing K. pneumoniae isolates almost belonged to ST15 and were not hypervirulent, despite harboring a virulence plasmid. Here, we report the first occurrence in China of a MDR OXA-232-producing K. pneumoniae ST231 clone that is an epidemic ST type in south and southeast Asia. A phylogenetic analysis indicated that this emerging Chinese ST231 clone was more closely related to Indian isolates. The occurrence of this clone may have been driven through the transnational importation of Indian ST231 K. pneumoniae clones. Moreover, this study is the first to assess the virulence potential of ST231 clones that have never been estimated in previous studies. While the high burden of MDR K. pneumoniae is concerning, genomic surveillance can shed light on the transmission chains of novel MDR clones, and active surveillance should be enforced to restrict the spread of MDR isolates.

目的 基于蒙特卡洛模拟优化万古霉素与替考拉宁治疗耐甲氧西林葡萄球菌血流感染的给药方案.方法 由全国血流感染耐药监测联盟筛选来源于全国56家医院的1235株血流感染相关的耐甲氧西林葡萄球菌,所有菌株采用质谱鉴定.采用头孢西丁纸片检测耐甲氧西林葡萄球菌,采用微量肉汤稀释法检测万古霉素与替考拉宁最低抑菌浓度,具体操作和判定标准遵照临床实验室标准化协会文件.结合不同肾功能情况下万古霉素与替考拉宁在成人体内的药动学参数,应用水晶球软件进行蒙特卡洛模拟得到相应目标获得概率(PTA)与累计反应分数(CFR).结果 4种万古霉素给药方案研究显示,3种肾功能情况下,MIC≥0.5μg·mL-1时,PTA达标概率较低;MIC=0.25μg·mL-1时,PTA均达到100％.4种替考拉宁给药方案研究显示,3种肾功能情况下,MIC≤0.5μg·mL-1时,PTA值均达到100％;MIC≥4μg·mL-1时,PTA值均<90％;MIC值1～2μg·mL-1时,PTA值随MIC值波动.正常肾功能状态下,4种万古霉素给药方案对菌群CFR均<90％;中度或重度肾功能不全时,给药方案1000 mg、q12h和1000 mg、q8h的CFR可能达到90％.在3种肾功能下,4种替考拉宁给药方案对金黄色葡萄球菌与溶血葡萄球菌的CRF值均<90％;部分给药方案可能对人葡萄球菌、表皮葡萄球菌和头状葡萄球菌的CRF值>90％.结论 当经验性治疗耐甲氧西林葡萄球菌所致菌血症时,万古霉素1000 mg、q8h和替考拉宁600 mg、q12h是最可能达到疗效的给药方案,但需要考虑患者肾功能状态.MIC值有利于提前评估万古霉素与替考拉宁疗效,并决策联合其他抗菌药物治疗的必要性.

目的 借助全国血流感染耐药监测联盟(BRICS)平台收集的链球菌属细菌,评价头孢曲松、左氧氟沙星及莫西沙星给药方案,以期为临床医生合理用药提供依据.方法 采用琼脂稀释法测定头孢曲松、左氧氟沙星及莫西沙星药物敏感情况,应用蒙特卡洛模拟方法研究三种药物不同给药方案的达标概率和累计反应分数(CFR).结果 最低抑菌浓度(MIC)检测结果显示,头孢曲松、左氧氟沙星和莫西沙星对肺炎链球菌的敏感率分别为82.22％、97.78％、97.78％,对其他链球菌的敏感率分别为97.66％、80.14％、81.07％.蒙特卡洛模拟结果显示,头孢曲松以1、2 g/24 h剂量治疗链球菌属细菌感染,获得的CFR均≥90％.左氧氟沙星以750 mg/24 h剂量治疗其他链球菌感染,获得的CFR为93％;左氧氟沙星500 mg/24 h剂量治疗链球菌属细菌感染,获得的CFR值<90％.莫西沙星以400、800 mg/24 h剂量给药治疗其他链球菌感染,获得的CFR均>90％,治疗肺炎链球菌感染获得的CFR均<90％.结论 采用头孢曲松、左氧氟沙星和莫西沙星治疗链球菌引起的血流感染时,头孢曲松对其MIC值不同时必须选择不同给药剂量才能进行有效治疗,左氧氟沙星以750 mg/24 h给药疗效明显高于以500 mg/24 h给药,若莫西沙星对链球菌属细菌MIC值不在敏感范围内,则不建议用于其感染的治疗.

目的 应用蒙特卡洛模拟研究头孢哌酮/舒巴坦、替加环素和多黏菌素B治疗鲍曼不动杆菌血流感染的疗效,预测和评价不同抗菌药物的抗菌效果,进而优化临床给药方案.方法 借助全国血流感染细菌耐药监测联盟(BRICS)平台收集2018-2019年血流感染来源的鲍曼不动杆菌514株,使用文献公开发表的头孢哌酮/舒巴坦、替加环素和多黏菌素B的药动学参数,基于药动学/药效学(PK/PD)理论利用蒙特卡洛模拟法,计算不同给药方案在各特定的MIC值获得的目标概率,即达标概率(PTA)和累积反应分数(CFR),以PTA或CFR≥90％作为临床疗效评价的指标.结果 治疗鲍曼不动杆菌引起的血流感染,头孢哌酮/舒巴坦给药方案4.5 gq6h在最低抑菌浓度(MIC)≤1 mg/L时,可获得大于或接近90％的目标PTA值,临床分离菌的CFR值为21.53％.替加环素推荐剂量(50 mg q12 h),在MIC≤0.25 mg/L时,可获得大于90％的目标PTA值,100 mg q12 h的给药方案对临床菌株的CFR值为81.04％.多黏菌素B 1.25 mg/kg 1h输注q12 h给药方案,可使MIC≤1 mg/L的细菌的PTA达到90％以上,高剂量的多黏菌素给药方案[负荷2 mg/kg 2 h输注后2.5 mg/(kg·d)持续输注]在MIC为2 mg/L时,可提供较高的PTA(96.83％),临床CFR可达到96.26％.结论 头孢哌酮/舒巴坦治疗鲍曼不动杆菌感染时,应考虑到大剂量的给药方案.同时由于鲍曼不动杆菌对头孢哌酮/舒巴坦群体耐药率较高导致CFR值较低,临床治疗中可能需要使用其他抗生素或将头孢哌酮/舒巴坦与其他抗菌药物联合使用取得更好的治疗效果.替加环素建议使用100 mg q12h的给药方案,多黏菌素B建议使用负荷2.5 mg/kg 2 h输注后1.5 mg/kg 1 h输注q12 h或负荷2 mg/kg 2 h输注后2.5 mg/(kg·d)持续输注的给药方案.

目的 比较哌拉西林(PIP)、哌拉西林/他唑巴坦(TZP)、哌拉西林/舒巴坦(PIS,2 ∶ 1,4 ∶ 1)和头孢哌酮/舒巴坦(CSL,2 ∶ 1)对革兰阴性菌的体外抗菌活性,为临床用药提供参考.方法 采用琼脂二倍稀释法测定上述抗菌药物对6319株临床分离菌的最低抑菌浓度.结果 大多数非碳青霉烯耐药肠杆菌科细菌对PIP的敏感率均高于50％[除产超广谱β-内酰胺酶(ESBL)大肠埃希菌、产ESBLs肺炎克雷伯菌和沙门菌属外].TZP、PIS(2 ∶ 1)和CSL对产ESBLs大肠埃希菌具有较强的体外抗菌活性,MIC90分别为128/4,64/32和64/32 mg·L-1,敏感率分别为75.9％,66.2％和72.1％.而产ESBLs肺炎克雷伯菌对4种β-内酰胺酶抑制剂复方制剂的敏感率均低于50％.对非碳青霉烯耐药鲍曼不动杆菌,CSL、PIS 2 ∶ 1和4 ∶ 1具有很强的体外抗菌活性,MIC90分别为16/8、16/8和32/8 mg·L-1,敏感率分别为76.7％,83.6％和82.8％.对非碳青霉烯耐药铜绿假单胞菌,5种抗菌药物均展现很强的体外抗菌活性,敏感率均高于80％.结论 4种复方制剂对产ESBLs大肠埃希菌具有突出抗菌活性,CSL和PIS(2 ∶ 1)对非碳青霉烯耐药鲍曼不动杆菌和铜绿假单胞菌具有较强抗菌活性;对肠杆菌科细菌,PIS(2 ∶ 1)的体外抗菌活性优于PIS(4 ∶ 1),对鲍曼不动杆菌及铜绿假单胞菌,两者活性相似.

目的 利用蒙特卡洛模拟评估替加环素不同给药方案对血流感染中革兰阴性杆菌感染的治疗效果.方法 对全国血流感染细菌耐药监测联盟(BRICS)2018—2019年收集的9674株革兰阴性杆菌进行替加环素最低抑菌浓度(MIC)测定,利用替加环素的群体药动学模型与参数进行患者群体的蒙特卡洛模拟,计算替加环素4种给药方案治疗不同MIC细菌感染的fAUC0-24/MIC达标概率(PTA),并预测经验治疗的累计应答率(CFR).结果 血流感染革兰阴性杆菌中肠杆菌科细菌和鲍曼不动杆菌MIC≤2 mg·L-1的菌株比例分别为99.7％和85.8％.当感染菌株MIC≤0.5 mg·L-1时,4种给药方案的PTA均>90％.菌株MIC在1～4 mg·L-1时,增加给药剂量才能显著提高PTA.首剂100 mg、维持50 mg、q12h的给药方案治疗肠杆菌科细菌感染的CFR>90％.首剂200 mg、维持100 mg、q12h的给药方案治疗鲍曼不动杆菌感染的CFR<50％.结论 替加环素可用于经验治疗肠杆菌科细菌导致的血流感染,但不适用于鲍曼不动杆菌相关血流感染.

Objective:To predict and evaluate the antibacterial efficacy of linezolid, teicoplanin and daptomycin against Staphylococci bloodstream infections with Monte Carlo simulation, and to optimize the clinical administration program. Methods:A total of 1 847 Staphylococci strains isolated from blood samples between January 2018 to December 2019 were collected with the help of the Blood Bacterial Resistant Investigation Collaborative System (BRICS). Minimum inhibitory concentrations (MIC) of linezolid and daptomycin were detected by broth dilution method, while MIC of teicoplanin were detected by agar dilution method. The dosage regimens of linezolid were 800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours. The dosage regimens of teicoplanin were 400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours, and 1 000 mg once every 12 hours. The dosage regimens of daptomycin were 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1and 12 mg·kg -1·d -1. The probability of target attainment (PTA) and cumulative fraction of response (CFR) of three different dosage regimens were calculated by Monte Carlo simulation. A dosage regimen with CFR≥90.0% was a reasonable choice for empirical antimicrobial therapy. Results:PTA of linezolid against Staphylococci when MIC≤0.500 mg/L at four dosage regimens (800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours) were all over 90.0%. When MIC was 1.000 mg/L, the PTA of linezolid against Staphylococci under the dosages of 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours were 92.2%, 96.6% and 97.6%, respectively. The CFR of the four dosage regimens of linezolid were 73.9%, 83.7%, 90.8% and 95.3%, respectively. When MIC≤1.000 mg/L, PTA of teicoplanin against Staphylococci were all 100.0% at four dosage regimens (400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours and 1 000 mg once every 12 hours). When MIC was 2.000 mg/L, the PTA of teicoplanin (800 mg once every 12 hours and 1 000 mg once every 12 hours) against Staphylococci were both 100.0%. The CFR of the four dosage regimens of teicoplanin were 90.8%, 92.8%, 93.5% and 94.6%, respectively. When MIC≤0.500 mg/L, PTA of daptomycin against Staphylococci under the five dosages of 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1 were all over 90.0%. When MIC was 1.000 mg/L, the PTA of daptomycin against Staphylococci under the three dosages of 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1were 96.9%, 100.0% and 100.0%, respectively. The CFR of the five dosage regimens of daptomycin against Staphylococci were 97.4%, 99.2%, 99.9%, 100.0% and 100.0%, respectively. Conclusions:Linezolid (600 mg once every 12 hours), teicoplanin (400 mg once every 12 hours) and daptomycin (4 mg·kg -1·d -1) can achieve satisfactory antibacterial activity for Staphylococci bloodstream infections.

Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP). Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations. Results: The MIC 90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried bla KPC-2 and bla NDM-1 . A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%. Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

目的:基于药代动力学/药效学理论，利用蒙特卡洛模拟研究评价和优化碳青霉烯类药物治疗产超广谱β-内酰胺酶(ESBLs)肠杆菌科细菌血流感染的给药方案。方法:收集全国血流感染细菌耐药监测联盟2018至2019年分离自患者血液的产ESBLs肠杆菌科细菌3 225株，其中大肠埃希菌2 731株，肺炎克雷伯菌494株。采用蒙特卡洛模拟计算并比较亚胺培南、美罗培南、厄他培南3种药物不同给药方案对肠杆菌科细菌感染的达标概率(PTA)和累积反应分数(CFR)。结果:对于亚胺培南，当肠杆菌科细菌最低抑菌浓度(MIC)≤0.25 μg/mL时，所有给药方案的PTA值均>93.00%；当MIC＝0.5或1 μg/mL时，除500 mg次/12 h所得PTA不达标外，其余给药方案PTA值均>97.00%；当MIC＝2 μg/mL时，仅500 mg次/6 h，750 mg次/8 h，750 mg次/6 h和1 g次/6 h四种方案的PTA值>90.00%。对于美罗培南，当肠杆菌科细菌MIC＝0.007 μg/mL时，8种给药方案所得PTA值均>90.00%；当MIC≤0.125 μg/mL时，除500 mg次/12 h和1 g次/12 h两种方案外，其余PTA值均>92.00%；当MIC＝0.25 μg/mL时，仅500 mg次/6 h，750 mg次/6 h，1 g次/8 h和2 g次/8 h四种方案的PTA值>90.00%；当MIC＝0.5 μg/mL时，仅500 mg次/6 h，750 mg次/6 h和2 g次/8 h三种方案PTA值>90.00%；当MIC＝1 μg/mL时，8种给药方案PTA值均不达标。对于厄他培南，当肠杆菌科细菌MIC≤0.125 μg/mL时，3种方案PTA值均>92.00%；当MIC＝0.25 μg/mL时，500 mg次/24 h和750 mg次/24 h两种方案的PTA值分别为57.22%和82.75%，1 g次/24 h方案PTA值为92.87%；当MIC≥0.5 μg/mL时，3种给药方案PTA值均<60.00%。亚胺培南7种给药方案CFR值均>92.00%。美罗培南除500 mg次/12 h和1 g次/12 h两种方案的CFR值分别为69.92%和82.33%外，其余6种给药方案CFR值均>98.00%。厄他培南3种给药方案CFR值均>92.00%。结论:通过蒙特卡洛模拟分析，亚胺培南、美罗培南、厄他培南的推荐经验给药方案分别为500 mg次/8 h、500 mg次/8 h或500 mg次/6 h、1 g次/24 h。目的给药需根据肠杆菌科细菌实际MIC值适当调整方案。

Purpose: To evaluate the administration regimen of ceftazidime/avibactam (CZA) for bloodstream infections caused by Enterobacteriaceae and Pseudomonas aeruginosa. Methods: The minimal inhibitory concentrations (MICs) of CZA against Enterobacteriaceae and P. aeruginosa isolated from blood cultures at member hospitals in BRICS (Blood Bacterial Resistant Investigation Collaborative System) in 2019 were determined by broth micro-dilution methodology. A 10,000-patient Monte Carlo simulation (MCS) was used to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) for different CZA dosage regimens to evaluate their efficacies and optimize the best initial dosage regimen. Results: Altogether, 6487 Enterobacteriaceae and P. aeruginosa strains were isolated from the blood cultures. The overall CZA resistance rate was 2.31%, of which the Enterobacteriaceae and P. aeruginosa rates were 1.57% and 14.29%, respectively. The MCS showed that the greater the MIC value, the worse the therapeutic effect. When the CZA MIC was <= 8 mg/L, the standard dose (2.5g iv q8h) achieved 90% PTA in the subset of patients with creatinine clearance (CrCl) values from 51 to 120 mL/min. Although the high-dose regimen (3.75g iv q8h) achieved 90% PTA in patients with CrCl values from 121 to 190 mL/min, implementing the low-dose regimen (1.25g iv q8h) was also effective for patients in the 51-89 mL/min CrCl range. Generally, the high-dose regimen (3.75g iv q8h) reached 90% CFR against all of the strains. Conversely, in patients with CrCl values of 121-190 mL/min, the standard dose (2.5g iv q8h) failed to reach 90% CFR against some Enterobacteriaceae members and P. aeruginosa. When the dose was reduced to the low-dose regimen (1.25g iv q8h), no patients reached 90% CFR against some Enterobacteriaceae members and P. aeruginosa. Conclusion: CZA has good antibacterial activity against Enterobacteriaceae and P. aeruginosa in bloodstream infections. Clinicians could make individualized treatment regimens in accordance with the sensitivity of the strains and the level of renal function in their patients to best predict the drug-related clinical responses.

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Objectives The aim of this work was to investigate the activity of ceftazidime–avibactam (CZA) and aztreonam–avibactam (AZA) against bloodstream infections caused by carbapenem-resistant organisms (CROs). Methods Non-duplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected using the Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentrations (MICs) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. The MICs of CZA and AZA were further determined with avibactam at 8 and 16 mg/L, respectively. Results The resistance rate of polymyxin B against CROs was less than 5%. Only one CR-Kpn was resistant to tigecycline. The resistance rates of CZA against CR-Eco, CR-Kpn, and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. The MIC 90 values of AZA against CR-Eco, CR-Kpn, and CR-Pae were 2/4, 1/4, and 64/4 mg/L, respectively. Among the CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn, and 1 (8.3%) CR-Pae isolates harbored metallo-β-lactamase genes. The increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn. Conclusions The in vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.