米诺环素对224株肠球菌的体外抗菌活性研究

目的:考察米诺环素对224株肠球菌的体外抗菌活性.方法:用二倍琼脂稀释法对224株肠球菌进行体外抗菌实验,并与多西环素、替考拉宁、万古霉素等进行抗菌效果对比.结果:米诺环素对169株粪肠球菌和51株屎肠球菌的MIC90分别为4和2μg·ml-1,而多西环素对169株粪肠球菌和51株屎肠球菌的MIC90则分别为4和4μg·ml-1.结论:米诺环素对肠球菌的抗菌效果与多西环素相似.     

安息香提取物（XCQ）联合庆大霉素对铜绿假单胞菌的抗菌增效作用研究

目的：考察安息香提取物XCQ联合庆大霉素体内、外抗铜绿假单胞菌的抗菌增效作用。方法：采用体外药物敏感性实验筛选铜绿假单胞菌临床株的多重耐药性菌株,并测定庆大霉素、左氧氟沙星和XCQ对铜绿假单胞菌临床株的最小抑菌浓度（minimum inhibitory concentration,MIC）;采用牛津管法评价不同剂量XCQ联合庆大霉素的体外抗菌活性差异;通过小鼠尾静脉注射铜绿假单胞菌菌液构建小鼠细菌感染性疾病动物模型,造模前3h灌胃XCQ溶液和造模后立即灌胃给予庆大霉素溶液,统计5 d内感染小鼠的生存率。结果：筛选出一株铜绿假单胞菌多重耐药菌株,该菌株对庆大霉素的MIC值为1μg﹒mL-1;XCQ在体外能提高庆大霉素的抗菌活性,并存在量效关系;XCQ在体内能提高庆大霉素对感染小鼠的保护性,提高模型动物存活率。结论：安息香提取物XCQ在体内、外均能提高庆大霉素对抗铜绿假单胞菌的抗菌作用。     

Sansanmycin A对铜绿假单胞菌体内外抗菌活性的初步研究

目的评价sansanmycin A对临床分离铜绿假单胞菌的体内、外抗菌活性。方法体外试验以微量肉汤稀释法测定sansanmycin A同时对照10种药物对150株铜绿假单胞菌的最低抑菌浓度(MIC),以平皿计数法测定最低杀菌浓度(MBC);半体内试验以微量稀释法测定sansanmycin A的血清抑菌活性(SBS)和血清杀菌活性(SBA)。结果 Sansanmycin A对铜绿假单胞菌体外抗菌活性与哌拉西林相似,其MIC50和MBC50分别为8和16μg/mL,MIC范围为2~>512μg/mL,MBC范围为2~>512μg/mL,头孢曲松和替卡西林对铜绿假单胞菌的MIC50和MBC50较sansanmycin A高2~4倍。Sansanmycin A对铜绿假单胞菌显示浓度依赖性杀菌作用。Sansanmycin A对铜绿假单胞菌峰时SBS和SBA中位数分别为1:256和1:128。结论 Sansanmycin A对铜绿假单胞菌显示较强的体外和体内杀菌活性,有进一步研究和开发的价值。     

甘氨环素类药物替加环素的研究进展

由于导致严重感染的多药耐药菌发生率上升，临床迫切需要寻求新型抗菌药物，尤其需要能够有效克服现有耐药机制的全新药物。替加环素为新型抗菌甘氨环素类药物，即米诺环素的衍生物，能够克服与四环素类绝大部分相关的耐药机制。体外试验显示替加环素尽管对铜绿假单胞菌无效，对变形杆菌属的作用较差，但对耐万古霉素肠球菌、耐甲氧西林金黄色葡萄球菌、耐青霉素肺炎链球菌和其他多药耐药革兰阴性菌均具有良好活性。Ⅲ期临床试验已就替加环素治疗由多药耐药菌引起危及生命的感染的作用进行了研究，其抗菌谱新颖广阔，具有良好的临床应用前景。     

哌拉西林／舒巴坦对临床分离功的体外抗菌活性研究

目的比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林/舒巴坦(21),对临床分离309株需氧菌和30株厌氧菌的体外抗菌活性及其影响因素(研究哌拉西林/舒巴坦(21)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线).方法采用琼脂平板稀释法及肉汤稀释法测定MIC值,Nitrocefin纸片法测定细菌产生的β-内酰胺酶,时间杀菌曲线采用肉汤10倍稀释法.结果对临床分离的339株需氧菌及厌氧菌体外抗菌活性研究结果显示,哌拉西林及其与舒巴坦联合时,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC5o为1～4μg/ml,MIC90多数低于128μg/ml,优于革兰氏阴性杆菌,其MIC50为1～128μg/ml,MIC90多数高于128μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差,多数菌的MICso及MIC90分别为64及256μg/ml.对革兰氏阴性杆菌及厌氧菌,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林;对于革兰氏阳性球菌,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌.哌拉西林对产酶株的MIC高于非产酶株,联合舒巴坦后,产酶株MIC降低而非产酶株MIC变化不明显.不同比例联合的体外抗菌活性比较发现,以哌拉西林/舒巴坦21联合时效果较好.哌拉西林与舒巴坦21联合时,对多数临床分离菌的体外抗菌活性与阿莫西林/舒巴坦(21)的体外抗菌活性相当.本研究中,I临床分离细菌对哌拉西林的耐药率以假单胞菌属最高,达61.5%,其次是肠杆菌属细菌及大肠埃希氏菌,分别为50.8%、50.0%.哌拉西林联合舒巴坦后,所有细菌的耐药率明显下降.体外杀菌效果研究表明,当哌拉西林联合舒巴坦21时,4×MIC浓度作用于金葡球菌、大肠埃希氏菌及铜绿假单胞菌后,细菌数均随时间延长而呈指数级减少,在作用于8h细菌均被杀灭.1×MIC及2×MIC作用于以上细菌后,杀菌效果不及4×MIC.各种细菌的体外抗菌活性主要受培养基pH值及接种菌量的影响,几乎不受小牛血清白蛋白浓度的影响.结论哌拉西林/舒巴坦对β-内酰胺酶产生菌株的体外抗菌活性优于哌拉西林,以21联合效果最好,杀菌效果以4×MIC浓度最好,体外抗菌活性受培养基pH值及接种量的影响.     

哌拉西林/舒巴坦对临床分离菌的体外抗菌活性研究

目的　比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林 /舒巴坦 (2∶1) ,对临床分离 3 0 9株需氧菌和 3 0株厌氧菌的体外抗菌活性及其影响因素 (研究哌拉西林 /舒巴坦 (2∶1)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线 )。方法　采用琼脂平板稀释法及肉汤稀释法测定MIC值 ,Nitrocefin纸片法测定细菌产生的 β 内酰胺酶 ,时间杀菌曲线采用肉汤 10倍稀释法。结果　对临床分离的3 3 9株需氧菌及厌氧菌体外抗菌活性研究结果显示 ,哌拉西林及其与舒巴坦联合时 ,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC50 为 1～ 4μg/ml,MIC90 多数低于 12 8μg/ml,优于革兰氏阴性杆菌 ,其MIC50 为 1～12 8μg/ml ,MIC90 多数高于 12 8μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差 ,多数菌的MIC50 及MIC90 分别为 64及 2 5 6μg/ml。对革兰氏阴性杆菌及厌氧菌 ,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林 ;对于革兰氏阳性球菌 ,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌。哌拉西林对产酶株的MIC高于非产酶株 ,联合舒巴坦后 ,产酶株MIC降低而非产酶株MIC变化不明显。不同比例联合的体外抗菌活性比较发现 ,以哌拉西林 /舒巴坦 2∶1联合时效果较好。     

头孢哌酮钠/舒巴坦钠对铜绿假单胞菌的最低抑菌浓度和防突变浓度研究

目的:研究头孢哌酮钠/舒巴坦钠对铜绿假单胞菌的最低抑菌浓度(MIC)和防突变浓度(MPC),为控制细菌耐药提供参考。方法:采用肉汤法富集铜绿假单胞菌标准菌株及14株临床分离菌株,采用琼脂平板稀释法考察头孢哌酮钠/舒巴坦钠对铜绿假单胞菌的MIC、MPC值,计算MIC90、MPC90、选择指数(SI)。结果:头孢哌酮钠/舒巴坦钠对15株铜绿假单胞菌的MIC、MPC均为4³2μg/ml,MIC90、MPC90均为32μg/ml,SI为1。结论:头孢哌酮钠/舒巴坦钠在临床治疗浓度下不容易引起铜绿假单胞菌耐药突变菌株的富集。     

替加环素对临床常见多重耐药菌的体外抗菌活性分析

目的:分析替加环素对临床常见多重耐药菌的体外抗菌活性.方法:我院2013年8月～2015年12月检验室采用微量肉汤稀释法检测经替加环素分离的400株多重耐药菌.多重耐药菌中包括金黄色葡萄球菌、鲍曼不动杆菌、肠球杆菌等细菌的最小抑菌浓度,并与其他菌种的药物进行分析比较.结果:金黄色葡萄球菌、肠球菌属细菌、鲍曼不动杆菌与肠杆菌属细菌对替加环素耐药性、敏感性与使用最低浓度均显著优于氨苄西林、头孢曲松、米诺环素(P＜0.05).结论:替加环素抗生素类药物对革兰氏阴性菌及革兰氏阳性菌2种多重耐药菌均具有较佳的体外抑菌活性.     

莫西沙星联用头孢哌酮舒巴坦对8种耐药菌的抗菌效应研究

目的探讨莫西沙星与头孢哌酮舒巴坦联用对临床常见耐药菌的抗菌效果。方法采用Vitek-32型全自动细菌鉴定仪,测定莫西沙星与头孢哌酮舒巴坦单用和联用分别对60株金黄色葡萄球菌、大肠埃希菌（ATCC25922）、铜绿假单胞菌、肺炎克雷伯菌和30株粪肠球菌、大肠埃希菌（ATCC35218）、阴沟肠杆菌及幽门螺杆菌的最低抑菌浓度（MIC）,并计算联合药敏指数（FIC值）。结果两药联用对临床分离的360株常见耐药致病菌的MIC均明显降低且抗菌作用增强,对金黄色葡萄球菌、粪肠球菌和幽门螺杆菌的体外抗菌作用为协同作用,对大肠埃希菌（ATCC25922）、铜绿假单胞菌、肺炎克雷伯菌、大肠埃希菌（ATCC35218）和阴沟肠杆菌均为相加作用。结论研究结果对指导医院常见耐药菌感染的治疗具有重要意义。     

2016年临床分离菌的分布及耐药性分析

目的 了解2016年本单位临床分离菌种分布及对常用抗菌药物的耐药性。方法 收集本院所有初次分离的菌株,药敏试验采用纸片扩散法或全自动仪器法检测,E-test法检测肺炎链球菌对青霉素不敏感的最低抑菌浓度(minimal inhibitory concentration, MIC)。采用WHONET 5.6软件进行数据统计分析。结果 共分离临床菌株4201株,革兰阳性菌34.8%(1461/4201),革兰阴性菌65.2%(2740/4201)。革兰阳性菌主要为金黄色葡萄球菌11.1%(463/4201),凝固酶阴性葡萄球菌12.1%(507/4201),其中耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus, MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(methicillin resistant coagulase-negative staphylococci, MRCNS)的检出率为(25.3%和70.2%),未发现万古霉素、替加环素和利奈唑胺耐药株。肠球菌属以粪肠球菌和屎肠球菌为主,屎肠球菌对所检测抗菌药物的耐药率明显高于粪肠球菌,二者未检测出万古霉素和利奈唑胺耐药株。革兰阴性菌位列前5位依次是大肠埃希菌17.7%、克雷伯菌属14.1%、铜绿假单胞菌8.7%、鲍曼不动杆菌7.1%和阴沟肠杆菌2.8%。大肠埃希菌和克雷伯菌属中产超广谱β-内酰胺酶(ESBLs)株的检出率分别占55.7%和25.4%。肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌对亚胺培南的耐药率分别为22.5%、20.6%和61.5%。肠杆菌科细菌中耐替加环素菌株检出率为4.4%。结论 临床常见细菌耐药性仍较严重,尤其是肠杆菌科细菌对替加环素以及克雷伯菌对亚胺培南耐药率上升明显,感染控制部门应采取有效防范措施,避免耐药菌株的进一步传播。     

In vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci

Tigecycline is a glycylcycline with promising broad-spectrum activity, including resistant Gram-positive organisms. This study characterizes in vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae (QRSP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). An in vitro pharmacodynamic model generated specific bacterial kill profiles for tigecycline against clinical isolates of QRSP, MRSA and VRE. Tigecycline produced a 6.6 log total reduction and cleared QRSP from the pharmacodynamic model by 18 h. Tigecycline and vancomycin were unable to achieve 3-log reductions in the MRSA and VRE isolates; log reductions in MRSA and VRE were 1.5 and 1.2 logs for tigecycline and 2.8 and zero for vancomycin, respectively. Area under the concentration time curve to minimum inhibitory concentration (AUC/MIC) values for tigecycline ranged from 79 to 158 microg h/mL and tigecycline concentrations remained above the MIC (T>MIC) throughout the simulated dosing interval. Tigecycline showed in vitro activity against the QRSP, MRSA and VRE isolates studied. Low MIC values, prolonged elimination half-life and the associated post-antibiotic effect (PAE) observed with tigecycline are desirable attributes that make it a potentially attractive option for treating resistant Gram-positive organisms.     

In vitro activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli

STUDY OBJECTIVE: To evaluate the activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli. DESIGN: In vitro susceptibility and time-kill analysis. SETTING: University-affiliated research laboratory. ISOLATES: Ten K. pneumoniae and 10 E. coli clinical strains known to produce ESBL. MEASUREMENTS AND MAIN RESULTS: Minimum inhibitory concentration (MIC) testing was performed at 5.5 and 7.0 log(10) colony-forming units (cfu)/ml. Time-kill studies were performed over 24 hours with a high inoculum of 7.0 log(10) cfu/ml for cefepime, imipenem, tigecycline, and gentamicin at 1 times MIC. Combination studies were tested for cefepime plus tigecycline, cefepime plus imipenem, imipenem plus tigecycline, and for adjunctive gentamicin with cefepime, imipenem, or tigecycline. At the high inoculum, the MIC ranges for cefepime, imipenem, tigecycline, and gentamicin were 0.25-256 (MIC for 90% of tested strains [MIC(90)] = 32), 0.125-2 (MIC(90) = 1), 0.25-16 (MIC(90) = 4), and 0.25-4 mg/L (MIC(90) = 1), respectively, for all isolates. At the higher inoculum, MICs shifted for cefepime, imipenem, and tigecycline. Change in log(10) cfu/ml from baseline to 24 hours for cefepime, imipenem, and tigecycline alone ranged from 4.85-0.71, 5-4.22, and 3.5-1.01, respectively, for all isolates. Bactericidal activity was observed for cefepime alone (10 [50%] of 20 isolates), imipenem alone (20 [100%] of 20), and tigecycline alone (3 [15%] of 20). Combination studies with cefepime plus tigecycline resulted in synergy against 4 (20%) of 20 isolates. Combination studies with gentamicin resulted in synergy against 6 isolates (30%) with cefepime and 4 isolates (20%) with tigecycline. No synergy was observed with imipenem combinations. No antagonism was observed. With the exception of cefepime, correlations were observed between MIC and terminal densities for studied agents. CONCLUSIONS: Cefepime exhibited bactericidal activity but was unrelated to susceptibility. Tigecycline exhibited predictable bacteriostatic activity and synergy in combination against a subset of study isolates. Imipenem exhibited predictable bactericidal activity against all isolates. The utility of combination regimens with novel agents requires further exploration.     

Activity of tigecycline against clinical isolates of Staphylococcus aureus and extended-spectrum beta-lactamase-producing Escherichia coli in Granada, Spain

We evaluated the in vitro activity of tigecycline using the Etest and disk diffusion method according to Clinical and Laboratory Standards Institute guidelines against clinical isolates of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) as well as for CTX-M-9 extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and SHV ESBL-producing E. coli. All isolates were susceptible to tigecycline according to US Food and Drug Administration cut-off points. There were no differences in the activity of tigecycline between MSSA and MRSA isolates or between the presence of either type of ESBL. For each type of microorganism studied, we established the equation relating the minimum inhibitory concentration to the diameter of the zone of inhibition.     

In vitro activity of tigecycline (GAR-936) and other antimicrobials against tetracycline- and ciprofloxacin-resistant Campylobacter clinical isolates

During 2003 in our hospital, 236 clinical faecal Campylobacter spp. were isolated, of which 166 (70%) were resistant to tetracycline and 199 (84%) were resistant to ciprofloxacin by the disk diffusion method. Resistance to both antimicrobial agents was found in 146 isolates (62%). The in vitro activity of tigecycline was compared with that of erythromycin, clindamycin and amoxicillin/clavulanic acid using the agar dilution method against 116 selected Campylobacter spp. that were resistant to both tetracycline and ciprofloxacin. The minimum inhibitory concentration at which 90% of the isolates were inhibited (MIC90) was 0.06 mg/L for tigecycline and 4, 2 and 1 microg/mL for amoxicillin/clavulanic acid, erythromycin and clindamycin, respectively. The high in vitro activity of tigecycline against tetracycline- and ciprofloxacin-resistant strains suggests a potential therapeutic role in the treatment of infections that involve Campylobacter spp.     

鲍曼不动杆菌8种RND外排泵介导替加环素耐药表型的研究

目的 探讨鲍曼不动杆菌中8种RND外排泵基因的分布与替加环素耐药表型间的关系。方法 微量肉汤稀释法检测120株鲍曼不动杆菌对替加环素的耐药性,PCR扩增8种外排泵及调控基因。琼脂二倍稀释法测定替加环素耐药菌株对18种抗菌药物的最低抑菌浓度(minimal inhibitory concentration, MIC),利用5种外排泵抑制判定外排泵表型。采用实时荧光定量PCR检测外排泵基因的表达水平。结果 筛选出替加环素耐药菌8株,对18种抗菌药物耐药情况严重,其中6株为广泛耐药菌;3种外排泵抑制剂CCCP、PAβN及维拉帕米的表型阳性率分别为50%、37.5%和12.5%。耐替加环素菌株除ACICU_02904和ACICU_03412基因外均为阳性;替加环素敏感菌中外排泵(adeABC-adeRS、adeFGH-adeL和adeIJK-adeN)基因检测率为38.4%,新近发现外排泵(ACICU_00143、ACICU_03066和ACICU_03646)基因检测率为50.9%,然而,ACICU_02904和ACICU_03412基因检出率为0.9%。在转录水平上,替加环素耐药组的adeB相对表达量是敏感组的23.5倍。结论 鲍曼不动杆菌中adeB相对表达量伴随菌株对替加环素MIC值增加而升高,主动外排泵表达活性增加是替加环素耐药的一个重要机制。     

Evaluation of alternative antibiotics for susceptibility of gonococcal isolates from China

The efficacy of the currently recommended first-line treatments for gonococcal infections – ceftriaxone monotherapy or ceftriaxone/azithromycin dual therapy – is waning rapidly, and efficient alternative antimicrobials are needed urgently to ensure that future treatment of gonorrhoea remains available. As such, the aim of this study was to screen alternative clinically approved antimicrobials for in-vitro activity against Neisseria gonorrhoeae. The susceptibility levels of 504 clinical isolates from Zhejiang Province, China to ertapenem, tigecycline, gentamicin, fosfomycin, gemifloxacin, doxycycline and rifampicin were investigated using the agar dilution method. The presence of resistance determinants was identified by polymerase chain reaction and sequencing. The minimum inhibitory concentration inhibiting 90% of growth (MIC₉₀) was 0.06 mg/L for ertapenem, 0.25 mg/L for tigecycline, 16 mg/L for doxycycline, 4 mg/L for gemifloxacin, 16 mg/L for gentamicin, 32 mg/L for fosfomycin and 128 mg/L for rifampicin. All strains appeared to be susceptible to tigecycline (MIC ≤0.5 mg/L), while a poor correlation between tigecycline and tetracycline susceptibility was observed, indicating that tetracycline resistance determinants have little impact on tigecycline susceptibility. For ertapenem, 30 isolates showed an MIC >0.125 mg/L, but the correlation between ertapenem and ceftriaxone susceptibility was low and only two strains showed an MIC >0.125 mg/L for both antibiotics. Therefore, it appeared that most ceftriaxone-resistant isolates were still susceptible to ertapenem. In conclusion, tigecycline and ertapenem showed good activity against N. gonorrhoeae and limited cross-resistance with previously used antibiotics. Therefore, they might be interesting candidates for further evaluation of their suitability as alternative antigonococcal therapies.     

In vitro activity of tigecycline and comparators against Gram-positive and Gram-negative isolates collected from the Middle East and Africa between 2004 and 2011

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was established in 2004 to monitor longitudinal changes in bacterial susceptibility to numerous antimicrobial agents, specifically tigecycline. In this study, susceptibility among Gram-positive and Gram-negative isolates between 2004 and 2011 from the Middle East and Africa was examined. Antimicrobial susceptibilities were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, and minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. US Food and Drug Administration (FDA)-approved breakpoints were used for tigecycline. In total, 2967 Gram-positive and 6322 Gram-negative isolates were examined from 33 participating centres. All Staphylococcus aureus isolates, including meticillin-resistant S. aureus, were susceptible to tigecycline, linezolid and vancomycin. Vancomycin, linezolid, tigecycline and levofloxacin were highly active (>97.6% susceptibility) against Streptococcus pneumoniae, including penicillin-non-susceptible strains. All Enterococcus faecium isolates were susceptible to tigecycline and linezolid, including 32 vancomycin-resistant isolates. Extended-spectrum β-lactamases were produced by 16.6% of Escherichia coli and 32.9% of Klebsiella pneumoniae. More than 95% of E. coli and Enterobacter spp. were susceptible to amikacin, tigecycline, imipenem and meropenem. The most active agents against Pseudomonas aeruginosa and Acinetobacter baumannii were amikacin (88.0% susceptible) and minocycline (64.2% susceptible), respectively; the MIC₉₀ (MIC required to inhibit 90% of the isolates) of tigecycline against A. baumannii was low at 2 mg/L. Tigecycline and carbapenem agents were highly active against most Gram-negative pathogens. Tigecycline, linezolid and vancomycin showed good activity against most Gram-positive pathogens from the Middle East and Africa.     

Antimicrobial activity of tigecycline (GAR-936) against Enterococcus faecium and Staphylococcus aureus used alone and in combination

STUDY OBJECTIVE: To evaluate the antimicrobial properties of tigecycline, both alone and in combination with other antibiotics, against multidrug-resistant strains of Enterococcus faecium and Staphylococcus aureus. DESIGN: In vitro study. SETTING: University laboratory. MEASUREMENTS AND MAIN RESULTS: Tigecycline, both alone and in combination with other antimicrobial agents, was evaluated against two strains of vancomycin-resistant E. faecium (VREF), three glycopeptide-intermediately resistant S. aureus strains, and one methicillin-resistant S. aureus strain. Tigecycline's activity was compared with that of vancomycin, gentamicin, rifampin, and doxycycline, using time-kill studies and analysis of minimum inhibitory concentrations and minimum bactericidal concentrations. Tigecycline also was evaluated in combination with vancomycin, gentamicin, rifampin, and doxycycline in time-kill studies. The number of log10 colony-forming units/ml at 24 hours was compared among treatment groups and growth control by analysis of variance. All isolates were susceptible to tigecycline, regardless of their susceptibilities to vancomycin or doxycycline. In time-kill studies, tigecycline significantly inhibited the bacterial inoculum of all isolates (p < 0.05). Although none of the tigecycline combinations studied had enhanced killing activity against VREF, when gentamicin was combined with tigecycline, improved effects were found against both strains. Against three of the S. aureus strains tested, the combination of gentamicin and tigecycline demonstrated enhanced or improved activity independently of each strain's susceptibility to gentamicin. CONCLUSION: The multidrug-resistant, gram-positive bacteria tested, including doxycycline-resistant isolates, were susceptible to tigecycline. The combination of tigecycline and gentamicin may have improved or enhanced activity against strains of vancomycin-resistant enterococci and S. aureus.     

Combination carbapenem-sulbactam therapy for critically ill patients with multidrug-resistant Acinetobacter baumannii bacteremia: four case reports and an in vitro combination synergy study

Infections caused by multidrug-resistant Acinetobacter baumannii have become a therapeutic challenge for clinicians worldwide. Although colistin and tigecycline have been successful in treating patients with these infections, these agents are not available on a worldwide basis. We describe four critically ill patients in Taiwan who were diagnosed with multidrug-resistant Acinetobacter baumannii bacteremia. All bacterial isolates from these patients were resistant to commonly available antibiotics, including carbapenems and sulbactam; however, combination therapy with a carbapenem and sulbactam led to favorable clinical outcomes in all four patients. We also conducted an in vitro study using isolates from these patients that showed that this drug combination had a synergistic effect with enhanced antibacterial activity against the isolates. Thus, a carbapenem-sulbactam combination may be a therapeutic alternative for multidrug-resistant Acinetobacter baumannii bacteremia in countries where colistin and tigecycline are not available for clinical use.     

替加环素与临床常用抗菌药物对碳青霉烯类耐药肠杆菌科细菌的协同作用研究

目的评价替加环素与临床常用抗菌药物对碳青霉烯类耐药肠杆菌科细菌(CRE)的协同作用。方法收集2014—2016年临床分离的非重复CRE共235株。琼脂稀释法进行药物敏感性试验并分析替加环素和9种常用抗菌药物的耐药率。选取替加环素非敏感的35株作为研究对象,并采用棋盘稀释法检测替加环素联合其他9种抗菌药物(亚胺培南、美罗培南、头孢他啶、头孢噻肟、氨曲南、左氧氟沙星、阿米卡星、哌拉西林/三唑巴坦和头孢哌酮/舒巴坦)对CRE的协同作用。结果肺炎克雷伯菌、沙雷菌属、产气肠杆菌、阴沟肠杆菌对替加环素的耐药率较高,分别是5.1%(7/137)、5.6%(1/18)、7.7%(1/13)和8.3%(1/12)。替加环素与头孢他啶、哌拉西林/三唑巴坦联合效果最明显,协同百分比都是28.6%(10/35)。替加环素与头孢噻肟(9/35,25.7%)、左氧氟沙星(8/35,22.9%)和头孢哌酮/舒巴坦(7/35,20.0%)也显示出较好的协同作用。研究中未出现药物拮抗的作用。结论替加环素与头孢他啶、哌拉西林/三唑巴坦联合对CRE的协同作用比较明显。替加环素的联合治疗可能比单用更为有效。