Comparison of BL-S786 with cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice.

The activity of BL-S786 was compared to that of cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. In broth dilution tests, the activity of BL-S786 was less than cephalothin or cefamandole against Staphylococcus aureus and less than cefamandole or cefoxitin against Haemophilus influenzae. BL-S786 and cefamandole were the two most active drugs against cephalothin-sensitive Enterobacteriaceae. In tests with cephalothin-resistant Enterobacteriaceae, BL-S786 was generally less active than cefamandole but more active than cefoxitin against all strains except Proteus and Providencia. Regardless of the comparative in vitro activity of the four drugs, BL-S786 was the most effective drug in treatment of mice lethally infected with Enterobacteriaceae. Protection from lethality was associated with clearance of bacteremia by each of the four drugs. In several tests where in vitro activity was not predictive of in vivo efficacy, selection of resistance in vivo was found to have occurred.     

Comparative inhibitory activity of BL-S640 and two other cephalosporins.

In vitro antibacterial activity of BL-S640 was compared to that of cephalothin and cephalexin against Gram-negative and Gram-positive bacteria isolated from clinical specimens. BL-S640 demonstrated the best activity on nearly all microbial species studied, except for Haemophilus influenzae and Diplococcus pneumoniae against which cephalothin was slightly more active.     

肠杆菌科细菌3年耐药性监测

目的了解我院2008年—2010年间临床常见肠杆菌科细菌的耐药情况及研究耐碳青霉烯类大肠埃希菌碳青霉烯酶基因型,为临床合理使用抗菌药物提供依据。方法收集我院2008-2010年间临床分离的常见肠杆菌科细菌,药敏试验使用纸片扩散法,数据分析采用WHONET5.4软件;筛选出对碳青霉烯类耐药的大肠埃希菌进行碳青霉烯酶基因的PCR检测及基因序列分析。结果 3年分离病原株共4916株,肠杆菌科共1980株,其中列前三位的是大肠埃希菌(873/1980),克雷伯菌属(605/1980)及肠杆菌属(268/1980),其次为变形菌属和沙雷菌属。主要来源于痰液、尿液及分泌物、血液、脓液等。重要肠杆菌科细菌对碳青霉烯类耐药率均小于10%,对头孢哌酮/舒巴坦、阿米卡星、哌拉西林/三唑巴坦者<30%,对广谱青霉素类及头孢菌素类者为40.9%～98.7%。变形菌属除对氨苄西林的耐药率>75%外,对其余抗生素的耐药率均低于40%,。3年来产超广谱β-内酰胺酶大肠埃希菌为33.97%及肺炎克雷伯菌57.50%,对大多数抗生素的耐药率显著高于非ELSBs菌株,且呈多重耐药。3年耐碳青霉烯类的大肠埃希菌共23株,其中产碳青霉烯酶者2株,PCR检测基因型阴性。结论本院肠杆菌科细菌大肠埃希菌和肺炎克雷伯菌检出率较高,碳青霉烯类对肠杆菌科细菌的抗菌活性最高,产ESBLs肠杆菌的耐药严重,实验室应加强对产ESBLs细菌的监测与报告。未检测出我院大肠埃希菌碳青霉烯酶基因型。治疗肠杆菌科细菌感染可选择碳青霉烯类,哌拉西林/三唑巴坦,头孢哌酮/舒巴坦,阿米卡星。     

2008年我院感染病原菌的分布及药物敏感性分析

目的分析院内感染病原菌的分布趋势及药物敏感性,为临床合理用药提供依据。方法药物敏感试验采用K—B纸片扩散法,以自行研制的院内感染监控系统软件进行数据统计分析。结果医院临床分离率居前10位的细菌分别为大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌、白假丝酵母、屎肠球菌、粪肠球菌、阴沟肠杆菌、表皮葡萄球菌。其中耐甲氧西林金黄色葡萄球菌（MRSA）的分离率已达到65．23％,产超广谱β-内酰胺酶（ESBLs）的大肠杆菌和肺炎克雷伯菌分别为58．20％和67．90％,革兰阳性（G^＋）球菌对万古霉素、替考拉宁的敏感率均保持在98％以上;肠杆菌科中大肠埃希菌、肺炎克雷伯菌、产酸克雷伯菌、阴沟肠杆菌对亚胺培南的敏感率均在90％以上;非发酵菌中铜绿假单胞菌和鲍曼不动杆菌敏感率最高的是头孢哌酮舒巴坦。结论万古霉素、替考拉宁对G^＋球菌始终保持着高活性,未发现万古霉素耐药的葡萄球菌;碳青酶烯类仍然是对肠杆菌科细菌活性最好的药物;非发酵菌中铜绿假单胞菌和鲍曼不动杆菌的耐药性不断增加,并出现了多重耐药菌株。     

头孢拉宗等9种抗菌药物对产ESBLs大肠埃希菌和肺炎克雷伯菌的体外抗菌活性研究

目的:对比研究头孢拉宗等9种抗菌药物对产超广谱β-内酰胺酶(ESBLs)大肠埃希菌以及肺炎克雷伯菌的体外抗菌活性。方法:采用琼脂平板二倍稀释法测定头孢拉宗等9种抗菌药物对临床分离的产ESBLs大肠埃希菌115株、肺炎克雷伯菌30株的最低抑菌浓度(MIC)。结果:产ESBLs大肠埃希菌和肺炎克雷伯菌对亚胺培南/西司他丁(100%和96.7%)、美罗培南的敏感率最高(100%和96.7%),对头孢拉宗(98.3%和93.3%)、头孢美唑(93.0%和96.7%)和阿米卡星(95.7%和96.7%)的敏感率较高,对哌拉西林/他唑巴坦(92.1%和60.0%)、头孢他啶(62.6%和73.3%)比较敏感,但对头孢噻肟(3.5%和0)、头孢哌酮/舒巴坦(43.5%和36.7%)的耐药率很高。结论:头孢拉宗对产ESBLs的大肠埃希菌和肺炎克雷伯菌均有很强的体外抗菌活性。     

头孢哌酮/舒巴坦对346株革兰阴性杆菌抗菌活性的分析

目的：调查头孢哌酮/舒巴坦对医院常见革兰阴性杆菌的体外抗菌活性。方法：收集我院2007年1月～2009年12月从临床标本中分离到的革兰阴性杆菌346株,采用VITEK-32全自动微生物分析仪进行鉴定,用K-B纸片法对头孢哌酮/舒巴坦进行药敏实验。结果：医院肠杆菌科细菌以肺炎克雷伯菌、大肠埃希菌、阴沟肠杆菌为主;其对头孢哌酮/舒巴坦的耐药率分别为9.6%、3.2%、8.7%。非发酵菌以铜绿假单胞菌、鲍曼不动杆菌、嗜麦芽寡养单胞菌为主,其对头孢哌酮/舒巴坦的耐药率分别为33.7%、17.1%、50%。结论：除嗜麦芽寡养单胞菌外,其余革兰阴性杆菌耐药率均〈40%,头孢哌酮/舒巴坦具有很强的体外抗菌活性,是治疗革兰阴性杆菌感染的理想药物。     

头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性

目的　评价第四代头孢菌素头孢吡肟对 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性。方法　收集 2 0 0 1年 3～ 10月福州地区 4家医院分离的肺炎克雷伯氏菌和大肠埃希氏菌 4 2 6株 ,用 Kirby-Bauer琼脂扩散法作药敏试验 :用表型确认试验检测 ESBL s。结果　 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌中 ,头孢吡肟的敏感性为 94 .37% ,仅次于亚胺培南 (10 0 % )、头孢哌酮 /舒巴坦 (10 0 % )和哌拉西林 /三唑巴坦(99.5 3% ) ,明显高于青霉素类抗生素哌拉西林 (48.83% )和第二代头孢菌素头孢呋辛 (6 0 .0 9% ) ,也高于第三代头孢菌素头孢曲松 (6 2 .91% )、头孢噻肟 (6 4 .79% )、头孢哌酮 (6 5 .73% )和头孢他啶 (88.2 6 % )。经表型确认试验证实 14 2株 (33.33% )为产超广谱 β-内酰胺酶 (ESBL s)菌 ;头孢吡肟对产 ESBL s菌和非产 ESBL s菌体外敏感性分别为 84 .5 1%、99.30 %。结论　头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外抗菌活性高于第三代头孢菌素 ,低于亚胺培南、头孢哌酮 /舒巴坦和哌拉西林 /三唑巴坦 ,头孢吡肟可考虑作为医院内感染的经验性一线用药。     

Ciprofloxacin: a comparative evaluation of its bactericidal activity in human serum against four enterobacterial species

Serum bactericidal titres following a 200 mg i.v. dose of ciprofloxacin were measured in healthy volunteers and compared with those achieved with standard doses of ceftazidime, piperacillin and gentamicin, given alone or in combination. Five strains of each of four enterobacterial species were included in the study. Bactericidal titres 1 h after infusion of ciprofloxacin exceeded 1:16 for Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Enterobacter cloacae. While ceftazidime produced higher peak bactericidal titres against the Enterobacteriaceae, piperacillin was less effective than ciprofloxacin against three of the four enterobacterial species tested. Among the combinations, only piperacillin/gentamicin showed synergistic activity against some strains. Studies of bacterial killing kinetics again confirmed the high bactericidal activity of ciprofloxacin for the Enterobacteriaceae. The combination of ciprofloxacin with gentamicin resulted in more rapid killing of some strains of Klebsiella pneumoniae and Proteus vulgaris.     

In vitro and in vivo antibacterial activities of meropenem, a new carbapenem antibiotic.

The in vitro and in vivo antibacterial activities of meropenem were compared with those of imipenem, ceftazidime, flomoxef, cefuzonam and cefotiam. Meropenem showed a broad antibacterial spectrum against clinical isolates of Gram-positive and Gram-negative bacteria. Against Gram-negative bacteria, with the exception of Acinetobacter calcoaceticus, meropenem exhibited the most potent activity among the drugs tested. It inhibited all 330 strains of Enterobacteriaceae at 0.78 mg/l. Meropenem was sensitive against several cephem-resistant strains of Enterobacteriaceae. Against Pseudomonas aeruginosa, meropenem was four-fold more active than imipenem and eight-fold more active than ceftazidime, with an MIC90 of 0.78 mg/l. The therapeutic effect of meropenem on systemic infection in mice was ten to twenty-fold less than that of imipenem against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. However, meropenem was as effective as imipenem on infections of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Meropenem was eliminated from mice plasma two-fold faster than imipenem, with a plasma half-life of 7.6 min. From the above results the authors concluded that meropenem is a promising drug for clinical use.     

Comparative activity of ceftizoxime against aminoglycoside-resistant aerobic gram-negative bacilli

The in vitro activity of ceftizoxime was compared with that of other beta-lactam antibiotics against 331 aminoglycoside (AG)-resistant clinical isolates. Two hundred and six AG-resistant, beta-lactamase producing, R-plasmid harbouring Enterobacteriaceae strains had MICs ranging from 0.0125 to 0.063 mg/l. AG-resistant Escherichia coli (36 strains) and Klebsiella pneumoniae (19) had MIC 90 values of 8 mg/l. Proteus rettgeri and P. vulgaris as well as Morganella morganii, resistant to several AGs, had MICs ranging from 0.5 to 4 mg/ml. Against all six isolates of AG-resistant Salmonella enteritidis the MIC90 was 0.5 mg/l. Twenty-seven strains of Serratia marcescens, most of which were resistant to beta-lactam and AG antibiotics, had MICs ranging from 0.5 to 8 mg/l. The AG-resistant strains of Enterobacteriaceae producing several AG-modifying enzymes (AAC(3); AAC(2'); AAC(6'); APH(3')) showed MICs ranging from 0.6 to 4 mg/l. Against 10 AG-resistant strains of Pseudomonas aeruginosa producing AAC(3), AAC(6') and APH(3') enzymes, the MICs ranged from 16 to 64 mg/l. In conclusion, ceftizoxime was equally or more active than cefotaxime, cefoperazone, ceftazidime and moxalactam against AG-resistant E. coli, Klebsiella, Morganella, Proteus, Serratia, Salmonella and R-plasmid harbouring Enterobacteriaceae. Ceftizoxime was less active than cefotaxime, moxalactam and ceftazidime against P. aeruginosa.     

Multi-resistance to antimicrobial agents for the ten most frequently isolated bacterial pathogens

Cross-resistance and multi-resistance to selected antibiotics was determined for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Amikacin-resistant Enterobacteriaceae often showed cross-resistance to ss-lactam antibiotics. Only 1% of the Escherichia coli isolates showed resistance to more than four antibiotics from a set of seven. This rate was higher for other Enterobacteriaceae and there were high levels of cross-resistance for P. aeruginosa. The cross-resistance of oxacillin with other antibiotics is well known in staphylococci. Penicillin-resistant pneumococcal isolates were cross-resistant to macrolides. Cross-resistance was only a minor problem in H. influenzae and M. catarrhalis. Cross- and multi-resistance are important problems for Gram-negative and Gram-positive bacteria but not for fastidious bacteria with the exception of penicillin-resistant S. pneumoniae.     

肠杆菌科细菌分布及耐药分析

目的 动态观察并分析该院临床标本分离的肠杆菌科细菌的分布及耐药情况.方法 采用2000年美国临床实验室标准化委员会(NCCLS)颁布的纸片扩散法中的筛选试验和确认试验,药敏试验采用K-B法.结果 最常见的肠杆菌科细菌为大肠埃希菌、肺炎克雷伯菌、福氏志贺菌、变形杆菌属和沙雷菌属.耐药分析显示,亚胺培南一直对所有常见肠杆菌科细菌保持良好的抗菌活性,其次为阿米卡星、头孢哌酮/舒巴坦和头孢吡肟/舒巴坦.氟喹诺酮类药物对除大肠埃希菌以外的其他肠杆菌细菌抗菌活性好.大肠埃希菌和肺炎克雷伯菌产超广谱β-内酰胺酶的比例逐年增高.结论 院内细菌耐药性监测不仅能指导临床合理使用抗菌药,还能延缓耐药性的产生和蔓延.     

Susceptibility of clinically isolated bacterial strains to imipenem/cilastatin sodium

In vitro antibacterial activities of imipenem/cilastatin sodium (imipenem) and other beta-lactams against clinically isolated 353 bacterial strains were investigated. The results obtained in this study are summarized as follows: 1. Imipenem (IPM) showed potent antibacterial activities against Gram-positive cocci such as Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus agalactiae. 2. IPM had inferior or equivalent antibacterial activities to beta-lactams against clinically isolated Enterobacteriaceae, that is, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Enterobacter aerogenes and Proteus spp. 3. IPM showed potent antibacterial activities against clinically isolated Pseudomonas aeruginosa, Acinetobacter anitratus but not against Xanthomonas maltophilia.     

In vitro activity of tigecycline and comparators against Gram-negative pathogens isolated from blood in Europe (2004-2009)

Here we report on the antimicrobial resistance amongst Gram-negative isolates (excluding Acinetobacter spp.) collected from blood culture sources at European study sites as part of the global Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) from the study start in 2004 until August 2009. All isolates were collected and tested for minimum inhibitory concentrations using Clinical and Laboratory Standards Institute methodology. Over the collection period, extended-spectrum β-lactamase (ESBL) production was recorded in 21.1% of Klebsiella pneumoniae, 2.6% of Klebsiella oxytoca and 11.3% of Escherichia coli, primarily in Croatia, Greece, Hungary, Italy, Poland, Romania and the Slovak Republic. ESBL rates stabilised amongst K. pneumoniae over 2006-2009, but doubled amongst E. coli in 2008-2009. The patterns of antimicrobial resistance changed accordingly for both organisms. Generally, Greece had the highest antimicrobial resistance for K. pneumoniae, Italy for E. coli, Serratia marcescens and Enterobacter spp., and Croatia for Pseudomonas aeruginosa. High resistance rates amongst K. pneumoniae were also seen in Croatia and Italy. Imipenem resistance amongst K. pneumoniae was reported exclusively in Greece (13.8%); amongst other Enterobacteriaceae, imipenem resistance was absent or low. Similarly, meropenem resistance was low amongst the Enterobacteriaceae except K. pneumoniae from Greece (42.6%). Across Europe, the most active antimicrobial agents against the Enterobacteriaceae were tigecycline, amikacin and the carbapenems, each with <10% resistance each year. Against the other antimicrobials, significant increases in non-susceptibility were reported for K. pneumoniae and E. coli, both important causative pathogens of bacteraemia.     

Regional variations in multidrug resistance among Enterobacteriaceae in the USA and comparative activity of tigecycline, a new glycylcycline antimicrobial

We report here on the activity of tigecycline and comparators against multidrug-resistant (resistant to >or=3 antimicrobial classes; MDR) Enterobacteriaceae from the USA collected between January 2004 and January 2006 as part of the Tigecycline Evaluation and Surveillance Trial (TEST). Nationally, 131 (5.9%) Escherichia coli, 174 (10.1%) Klebsiella pneumoniae, 4 (1.2%) Klebsiella oxytoca, 24 (4.9%) Enterobacter aerogenes, 126 (9.5%) Enterobacter cloacae and 20 (2.6%) Serratia marcescens isolates were MDR. Four isolates (two K. pneumoniae and two E. cloacae) were resistant to nine antimicrobials. Tigecycline performed well against MDR E. coli (MIC(90) 0.5 microg/mL, 0% resistant) and K. pneumoniae (MIC(90) 4 microg/mL, 9.2% resistant). A MIC(90) of 8 microg/mL was reported for tigecycline against the other MDR organisms studied here, notably lower than those of most comparators.     

澳格门汀和四种抗生素协同作用研究

介绍澳格门汀(A UG)与硫酸丁胺卡那霉素(A MK)、硫酸庆大霉素(GM)、头孢唑啉钠(CEZ)和邻氯青霉素钠(CLOX)联合对162株临床分离产酶菌的协同作用。结果表明;在8mg/L棒酸+16mg/L羟氨苄青霉素的AUG浓度与所有实验的联合对金葡菌、肺炎克雷伯氏菌、痢疾杆菌的联合药敏结果均为100%协同作用。AUG与AMK及GM联合时的协同作用分别为:对大肠杆菌均为93.33%对变形杆菌为80 %及85%;对阴沟肠杆菌为17.86%及42.86%。AUG与CEZ联合对大肠杆菌、变形杆菌的协同作用分别为100%及85%对阴沟肠杆菌无协同作用,为100%拮抗。     

Antibiotic susceptibility of bacteria most commonly isolated from bone related infections: the role of cephalosporins in antimicrobial therapy

Bone infections, which can be acute or chronic, often require aggressive antibiotic therapy, whether treated at home or in the community. Surveillance programmes are essential tools in the monitoring of antimicrobial resistance and can act as a resource to maintain effective prescribing. The Surveillance Network (TSN), which collects organism and patient-specific data from a network of laboratories across the United States, was used to analyse susceptibility of common bacterial species isolated from bone infections during 2000-2002. Narrow-spectrum antimicrobials such as vancomycin, quinupristin-dalfopristin and linezolid demonstrated good activity against Staphylococcus aureus and streptococci, and were active against 100% of isolates. However, Gram-negative species were also commonly isolated from these sites of infection. Later-generation cephalosporins, represented by ceftriaxone, cefotaxime and cefepime, exhibited a broad spectrum of activity including Enterobacteriaceae, streptococci and methicillin-susceptible S. aureus, but they were not active against methicillin-resistant S. aureus (MRSA) and showed variable activity against Pseudomonas aeruginosa. Using ceftazidime as a marker for extended spectrum beta-lactamase (ESBL) expression, less than 3% of Escherichia coli or Klebsiella pneumoniae expressed this phenotype. Based on current in vitro activity, the third-generation cephalosporins provide broad-spectrum coverage useful for the empirical therapy of suspected bone infections, especially for patients treated in the community or hospitalised with community-acquired infections.     

In vitro activity of ceftiofur tested against clinical isolates of Escherichia coli and Klebsiella pneumoniae including extended spectrum beta-lactamase producing strains

In vitro activity of ceftiofur, a cephalosporin used in veterinary practice was compared using ceftriaxone-resistant (producing extended spectrum beta-lactamase (ESBL)) and -susceptible clinical isolates of Esherichia coli and Klebsiella pneumoniae. The ceftriaxone-susceptible isolates exhibited a lower range of ceftiofur MICs (MIC50, 0.5 mg/l, MIC90 1.0 mg/l). Those isolates known to produce an ESBL were also resistant to ceftiofur (MIC50, > or = 32 mg/l). The latter isolates were also less susceptible to other comparator drugs (cefquinome, gentamicin and trimethoprim/sulphamethoxazole) in contrast to the ceftriaxone-susceptible strains. The clinical isolates showed high correlation between ceftriaxone and ceftiofur MICs (y = 2.6 + 0.89x, r = 0.95). Using the current ceftiofur susceptible breakpoint (< or = 2 mg/l) used for veterinary practice (respiratory tract pathogens), the ESBL-producing strains of E. coli and K. pneumoniae could be accurately separated from susceptible strains. This ceftiofur breakpoint MIC corresponds to the National Committee for Clinical Laboratory Standards ESBL screening concentration for ceftriaxone set at < or = 1 mg/l = negative for ESBL production. Ceftiofur was also observed to be very active in vitro against ampicillin-resistant, non-ESBL producing enteric isolates. This new cephem appears to be very potent against the tested Enterobacteriaceae and of potential wide clinical veterinary utility.     

Moxifloxacin activity against clinical isolates compared with the activity of ciprofloxacin

The activity of moxifloxacin, a new 8-methoxyquinolone, was compared in vitro with the activity of ciprofloxacin against clinical strains isolated from various sites of infection. The mode MIC values of moxifloxacin were superior to those of ciprofloxacin against Streptococcus pneumoniae, methicillin-susceptible and -resistant Staphylococcus aureus, Enterococcus spp., Escherichia coli and Acinetobacter spp., while ciprofloxacin was more active against Klebsiella pneumoniae and Pseudomonas spp. Both antibiotics had similar activity against Haemophilus influenzae, Moraxella catarrhalis and Enterobacter spp.     

Comparative in vitro evaluation of BMY-28142, a new broad-spectrum cephalosporin, versus other beta-lactams against multiresistant gram-negative isolates

The in vitro activity of the new parenteral cephalosporin BMY-28142 was compared with that of cephalothin, cefoxitin, cefotaxime, ceftriaxone, moxalactam, aztreonam and ceftazidime, against a total of 374 recent multiresistant Gram-negative microorganisms of nosocomial origin. Against all species of Enterobacteriaceae resistant to the first- and second-generation cephalosporins, BMY-28142 had superior inhibitory activity than the newer beta-lactams tested, with intrinsic activity against E. coli and Pr. mirabilis slightly less than that of cefotaxime and ceftriaxone. BMY-28142 differed from the other beta-lactams mainly in being at least 16-fold more active against E. cloacae, while BMY-28142 and ceftazidime showed comparable activity against Ps. aeruginosa strains. Against strains of Ps. aeruginosa resistant to both BMY-28142 and amikacin, the combination of the two antibiotics proved to be synergistic in vitro.