3年2436株临床分离革兰阴性杆菌对头孢吡肟耐药趋势观察

目的：调查我院1999－2001年间2436株革兰阴性杆菌分离株对第4代头孢菌素头孢吡肟的耐药状况，为临床合理用药提供依据。方法：用K－B法检测头孢吡肟对8种2436株临床分离菌的抑菌环，按1999年NCCLS判断标准得出耐药结果，并与其他3种第3代头孢菌素比较。结果：头孢吡 肟对ESBL阴性大肠杆菌和克雷伯菌属，肠杆菌属，枸橼酸杆菌属，变形杆菌，不动杆菌属，铜绿假单胞菌和嗜麦芽窄食单胞菌等临床主要分离革兰阴性杆菌耐药性变化不大，1999－2001年耐药率分别为20．6％，20．4％和28％，与第3代头孢菌素比较，头孢吡肟，头孢他啶，头孢噻肟，头孢曲松总的细菌耐药率分别为24．6％，26．3％，38．5％和37．0％。结论：头孢吡肟对临床分离的大部分革兰阴性杆菌具有良好的体外抗菌活性，尤其对易产Bush-I型头孢菌素的肠杆菌属的菌株及枸橼酸杆菌属的抗菌活性远优于其他第3代头孢菌素。     

头孢吡肟等5种抗生素对革兰阴性杆菌抗菌活性比较

目的研究头孢吡肟等5种抗生素对革兰阴性杆菌抗菌活性。方法用纸片扩散法对临床分离的革兰阴性杆菌进行药敏检测，比较头孢吡肟与其他4种临床常用抗生素的抗菌活性。结果分离出245株革兰阴性杆菌。其中：以不动杆菌（48．2％）和铜绿假单胞菌（11．0％）为主的非发酵菌占65．3％。多数革兰阴性杆菌对头孢类菌素的敏感率为44％～68％；除嗜麦芽窄食单胞菌外，其他革兰阴性杆菌对亚胺培南敏感率最高为93．9％。头孢吡肟对阴沟肠杆菌的抗菌活性优于头孢他啶和头孢哌酮／舒巴坦；而对嗜麦芽窄食单胞菌的抗菌活性明显较低，其他与头孢他啶相近；2004年较2003年，头孢吡肟除对肺炎克雷伯菌抗菌活性略升高外，对其他革兰阴性杆菌均有不同程度降低；而头孢他啶和头孢哌酮／舒巴坦抗菌活性保持稳定。结论第4代头孢菌素头孢吡肟可用于ICU危重病人抗感染治疗。     

头孢吡肟对重症监护病房院内感染细菌的体外抗菌活性研究

目的 :观察头孢吡肟对重症监护病房(ICU)院内感染细菌的体外抗菌活性。方法 :以纸片扩散法检测头孢吡肟与其他 15种常用抗菌药对ICU院内细菌感染病人感染部位培养分离出的 174株革兰阴性 (G- )杆菌 ,74株革兰阳性 (G+)球菌体外抗菌活性。结果 :头孢吡肟对G- 杆菌的抗菌活性高于常用第 2代和第 3代头孢菌素 ,与环丙沙星和庆大霉素类似 ,低于亚胺培南 西司他丁、阿米卡星、头孢哌酮 舒巴坦等。头孢吡肟对G+球菌的抗菌活性高于第 2代和第 3代头孢菌素 ,与亚胺培南 西司他丁及阿米卡星和奈替米星类似 ,但对耐甲氧西林的金黄色葡萄球菌和表皮葡萄球菌的抗菌活性很低。结论 :在ICU院内感染流行病学监测指导下 ,头孢吡肟可作为经验性治疗院内细菌感染的首选抗生素之一。     

阴沟肠杆菌Amp C酶的特性研究

本文对阴沟肠杆菌ＡｍｐＣ酶进行了以下５个方面研究。其内容和结果分别为：（１）联合药敏实验：用平皿二倍稀释法研究第四代头孢菌素头孢吡肟,第三代头孢菌素头孢他啶、头孢噻肟、头孢呋辛与－β－内酰胺酶抑制剂舒巴坦联合对３４株头孢他啶耐药菌,６株头孢他啶中敏菌及１５株头孢他啶敏感菌的体外抗菌活性。结果表明舒巴坦使头孢他啶对３２．７％（１８／５５）的阴沟肠杆菌的抗菌作用有明显抗菌增效作用。９６．４％（５３／５５）的阴沟肠杆菌对第四代头孢菌素头孢吡肟敏感。（２）酶稳定性实验：紫外测定法测定４株标准菌和６株临床分离菌产生的ＡｍｐＣ酶对β－内酰胺类抗生素的水解率。结果表明阴沟肠杆菌产生的β－内酰胺酶对第一代头孢菌素头孢唑林、头孢氨苄,第二代头孢菌素头孢克洛,第三代头孢菌素头孢哌酮及青霉素、氨苄西林、哌拉西林的水解率高,对第二代头     

头孢吡肟与其它广谱β-内酰胺类抗生素体外抗菌活性比较

测定头孢吡肟对１００株临床分离菌的最低抑菌浓度（ＭＩＣ）,并与头孢他啶,头孢曲松,亚胺培南,头孢哌酮／舒巴坦等广谱β－内酰胺类抗生素体外抗菌活性进行比较。结果：头孢吡肟对革兰氏阴性杆菌有良好抗菌活性;对铜绿假单胞菌亦有较强的抗菌活性,其ＭＩＣ５０为３ｍｇ／Ｌ,和头孢他啶相当,苯唑青霉素敏感的葡萄球菌对头孢吡肟也较敏感,ＭＩＣ９０≤４ｍｇ／Ｌ。表明头孢吡肟较第三代头孢菌素抗菌谱更广,抗菌活性更强。     

第四代头孢菌素头孢吡肟与5种β-内酰胺类体外抗菌活性比较

目的 比较第四代头孢菌素头孢吡肟与５种已上市β－内酰胺类抗生素对主要致病菌的体外抗菌活性和抗菌谱,方法 用浓度梯度法（Ｅ－ｔｅｓｔ）检测６种抗菌药物对１０种１００株临床分离菌株的最低抑菌浓度（ＭＩＣ）。结果 头孢吡肟对肠杆菌细菌,铜绿假单胞菌,不动杆菌,苯唑西林敏感葡萄球菌具有很强的抗菌活性,结论 头孢吡肟对Ｇ＾＋球菌和Ｇ＾－杆菌均有很好的抗菌活性。     

新的第四代头孢菌素头孢吡肟

第三代头孢菌素如头孢他啶对绿脓杆菌及其它革兰阴性菌有优良的活性,但对革兰阳性致病菌却较第一代头孢菌素差,最新出现的头孢菌素试图保持对革兰阳性和阴性菌的作用而避免许多耐药问题,如公认的第四代头孢菌素具有这些优势。头孢吡肟(cefepime)即属第四代头孢菌素,对革兰阴性菌,特别是肠杆菌、绿脓杆菌具有良好的活性,同时保持了对革兰阳性菌的作用。Okamoto等综述了头孢吡肟的化学、药理特性、抗菌谱、药代动力学、临床疗效、不良反应及剂量。     

头孢吡肟治疗老年人细菌性下呼吸道感染疗效分析

<正>头孢吡肟(马斯平)是一种新型第四代头孢菌素,它对需氧革兰阴性菌和革兰阳性菌均具有良好的抗菌活性,头孢吡肟对细菌染色体编码的β-内酰胺酶亲和力低,高度耐受多数     

第4代头孢菌素——头孢匹罗

头孢匹罗作为第４代头孢菌素,比第３代头孢菌素具有更广的抗菌谱,对肠杆菌科比第３代头孢菌素有更好的抗菌活性,头孢匹罗是已知第３和４代头孢菌素中对革兰阳性细菌抗菌活性最强的抗生素。     

第4代头孢菌素——头孢切罗

头孢匹罗作为第４代头孢菌素，比第３代头孢菌素具有广的抗菌谱，对肠杆菌比第３代头孢菌素有更好的抗菌活性，头孢匹罗是已知第３和４代头孢菌素中对革兰阳性细菌抗菌活性是最强的抗生素。     

Comparison of the in vitro and in vivo antibacterial activities of cefepime (BMY-28142) with ceftazidime, cefuzonam, cefotaxime and cefmenoxime

Cefepime (BMY-28142), a new semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefuzonam, cefotaxime and cefmenoxime. Cefepime showed a well-balanced, broad spectrum of activity against a number of clinical isolates collected in Japan. The activity of cefepime against Gram-positive bacteria was several times greater than that of ceftazidime, nearly comparable to cefotaxime and cefmenoxime, and slightly weaker than cefuzonam. Against Enterobacteriaceae, cefepime showed superior activity to the reference cephalosporins against Proteus inconstans, Providencia rettgeri, Morganella morganii, Citrobacter freundii and Enterobacter cloacae. The activity of cefepime against Pseudomonas aeruginosa was nearly comparable to that of ceftazidime. Cefotaxime, cefuzonam and cefmenoxime were substantially less active against P. aeruginosa. Cefepime was more stable than cefuzonam, cefotaxime and cefmenoxime to various types of beta-lactamases from Gram-negative bacteria. The high in vitro activity of cefepime was reflected in its in vivo efficacy against experimental infections in normal and immuno-suppressed mice. Cefepime was the most effective among the cephalosporins tested against four Gram-negative bacterial infections.     

Sustained activity and spectrum of selected extended-spectrum beta-lactams (carbapenems and cefepime) against Enterobacter spp. and ESBL-producing Klebsiella spp.: report from the SENTRY antimicrobial surveillance program (USA, 1997-2000)

Enterobacter spp. and Klebsiella spp. are important clinical pathogens that frequently exhibit resistance to third-generation cephalosporins. In Enterobacter spp. strains, resistance is usually due to derepression of the Amp C locus, whereas plasmid-encoded extended-spectrum beta-lactamases (ESBLs) are primarily responsible for resistance in Klebsiella spp. Here we report the results from the SENTRY Antimicrobial Surveillance Program concerning the rates and trends of resistance to extended-spectrum beta-lactams and other antimicrobial agents in Enterobacter spp. and Klebsiella spp. isolated between 1997 and 2000 in participating hospitals in the United States. Among Enterobacter spp., resistance (MIC>or=32 mg/l) to aztreonam, ceftazidime and ceftriaxone ranged from 12.3 to 21.2% over the 4 years, whereas resistance in Klebsiella (MIC>or=2 mg/l) ranged from 5.9 to 6.8%. There was no trend toward increased resistance to these beta-lactam agents over the monitored period. Carbapenems (imipenem, meropenem) and cefepime had excellent activity against both ceftazidime-susceptible and -resistant Enterobacter spp. and Klebsiella spp. (>99% susceptible), although the minimum inhibitory concentration values of cefepime were higher in ceftazidime-resistant isolates compared with ceftazidime-susceptible isolates. Co-resistance to other antimicrobial agents was common in both tested genus groups.     

In vitro activity of cefepime and cefpirome compared to other third-generation cephem antibiotics against gram-negative nosocomial pathogens

The in vitro activities of new expanded spectrum of fourth-generation cephalosporins, cefepime and cefpirome, were compared with those of three third-generation cephalosporins, cefoperazone, ceftazidime, and ceftriaxone, that are commonly used in the treatment of serious infections caused by aerobic gram-negative bacteria. The agar dilution method described by the US National Committee for Clinical Laboratory Standards was used to determine the minimum inhibitory concentrations of antibiotics tested. 302 clinical isolates, representing a cross-section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa were tested. Cefepime was considerably more active than other antibiotics tested, against Klebsiella species and Enterobacter species, and demonstrated activity similar to ceftazidime against Pseudomonas aeruginosa. Ceftazidime was active against Pseudomonas aeruginosa but was less potent against Enterobacter species. Cefoperazone and ceftriaxone were less active than ceftazidime against Pseudomonas aeruginosa. Cefepime had slightly greater activity than cefpirome against the gram-negative bacteria tested. However, cefepime and cefpirome were found to be highly active against many resistant organisms that traditionally have been difficult to treat.     

Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in China: the 2002-2009 Study for Monitoring Antimicrobial Resistance Trends (SMART)

The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli (GNB) isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2009, minimum inhibitory concentrations of 14 antibiotics for 3420 aerobic and facultative GNB from up to eight hospitals in six cities were determined by the broth microdilution method. Enterobacteriaceae comprised 82.9% (2834/3420) of the total isolates, with Escherichia coli (49.2%) being the most commonly isolated species followed by Klebsiella pneumoniae (17.0%), Enterobacter cloacae (5.8%) and Citrobacter freundii (2.3%). Amongst the antimicrobial agents tested, the three carbapenems (ertapenem, imipenem and meropenem) were the most active agents against Enterobacteriaceae, with susceptibility rates of 96.1-99.6% (2002-2009), 98.2-100% (2002-2009) and 99.6-100% (2002-2004), respectively, followed by amikacin (86.8-95.1%) and piperacillin/tazobactam (84.5-94.3%). Susceptibility rates of all tested third- and fourth-generation cephalosporins against Enterobacteriaceae declined by nearly 30%, with susceptibility rates of 40.2%, 39.1%, 56.3% and 51.8% in 2009 for ceftriaxone, cefotaxime, ceftazidime and cefepime, respectively. The occurrence of extended-spectrum β-lactamases increased rapidly, especially for E. coli (from 20.8% in 2002 to 64.9% in 2009). Susceptibility of E. coli to ciprofloxacin decreased from 57.6% in 2002 to 24.2% in 2009. The least active agent against Enterobacteriaceae was ampicillin/sulbactam (SAM) (25.3-44.3%). In conclusion, Enterobacteriaceae were the major pathogens causing IAIs, and carbapenems retained the highest susceptibility rates over the 8-year study period. Third- and fourth-generation cephalosporins, fluoroquinolones and SAM may not be ideal choices for empirical therapy of IAIs in China.     

Pathogen occurrence and antimicrobial resistance trends among urinary tract infection isolates in the Asia-Western Pacific Region: report from the SENTRY Antimicrobial Surveillance Program, 1998-1999

Worldwide surveillance of antimicrobial resistance among urinary tract pathogens is useful to determine important trends and geographical variation for common Gram-positive and -negative species. The most common causative uropathogens often have intrinsic or acquired resistance mechanisms which include ESBL production among enteric bacilli, multi-drug resistant staphylococci and non-fermentative Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter spp. and vancomycin-resistant Enterococcus spp. This study evaluates pathogen frequency and the resistance rates among urinary tract infection (UTI) pathogens in 14 medical centres in the Asia-Pacific region between 1998 and 1999. The isolates were referred to a central monitor for reference NCCLS broth microdilution testing, identification confirmation and patient demographic analysis. Over 50% of the 958 pathogens were Escherichia coli and Klebsiella spp. followed by P. aeruginosa, Enterococcus spp. and Enterobacter spp. Susceptibility for the three enteric bacilli was high for carbapenems (100%), 'fourth-generation' cephalosporins (cefepime 94.9-98.6%) and amikacin (> or = 93.0%). Beta-lactamase inhibitor compounds were more active against E. coli (piperacillin/tazobactam; > 90% susceptible) than the other two enteric species and all other tested agents had a narrower spectra of activity. The rank order of anti-pseudomonal agents was amikacin (91.5% susceptible)> imipenem > piperacillin/tazobactam > tobramycin > ceftazidime and cefepime (77.4 and 76.4% susceptible, respectively). Susceptibility to quinolones for the P. aeruginosa isolates was only 63.2-67.0%. Only one vancomycin-intermediate Enterococcus spp. (van C phenotype) was detected among the 103 strains tested. Newer fluoroquinolones (gatifloxacin; MIC(50), mg/l) were more potent against enterococci than ciprofloxacin (MIC(50), 2 mg/l) and high-level resistance to aminoglycosides was common (41.7%). The data presented are compared to studies of similar design from other areas which are part of the SENTRY surveillance network.     

Evaluation of antimicrobial activity of beta-lactam antibiotics using Etest against clinical isolates from 60 medical centres in Japan

An antimicrobial resistance surveillance study was carried out in 60 medical centres across Japan. Resistance to piperacillin was 10.8% in clinical isolates of Escherichia coli, while 1.3% or fewer isolates were resistant to other beta-lactams. Klebsiella spp. were more susceptible to imipenem, cefepime and cefpirome. Isolates of Enterobacter spp., Citrobacter spp., indole-positive Proteus and Serratia spp. were susceptible to imipenem, cefepime and cefpirome, while Acinetobacter spp. were most susceptible to cefoperazone/sulbactam, imipenem, ceftazidime (5.8% resistance) and cefepime (7.6%). Isolates of Pseudomonas aeruginosa were more susceptible to ceftazidime (12.3% resistance), cefoperazone/sulbactam (12.5%) and cefepime (12.6%) than to piperacillin (15.0%), cefpirome (22.6%) and imipenem (30.8%). The percentage of Japanese imipenem resistant P. aeruginosa clinical isolates was around 30%.     

Trends in antimicrobial susceptibility in UK centres: the MYSTIC Programme (1997-2002)

Trends in antimicrobial susceptibilities in three UK centres participating in the MYSTIC Programme were examined from 1997 to 2002. Isolates were tested using standard methodology to determine the susceptibility breakpoints of meropenem and several other antimicrobial agents including imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Data are grouped in 2-year blocks. The carbapenems were the most active agents tested against the Enterobacteriaceae (99-100% and 98-100% susceptibility to meropenem and imipenem, respectively) and non-fermenters, including Pseudomonas spp. and Acinetobacter spp. With the exception of susceptibility to ciprofloxacin, which decreased among Enterobacteriaceae at the end of the 6-year period, all antibiotics tested retained their levels of activity. The proportion of extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae increased during the study (4.8% and 11.3% in 1997-1998; 7.4% and 16.7% in 2001-2002, respectively). Both meropenem and imipenem retained their potency against these ESBL- and AmpC-producing isolates (100% for all time periods). All the other antimicrobial agents tested had much lower susceptibility against these resistant isolates and this decreased further over the 6-year period, with the exception of tazobactam, which maintained its low levels. Although all antibiotics tested retained acceptable activity, the carbapenems remained the most active antimicrobial agents against Gram-negative bacteria, including ESBL- and AmpC-producing isolates.     

The kinetics of CAZ-5, a novel SHV-related plasmid-mediated beta-lactamase with enhanced hydrolytic activity against ceftazidime

The kinetic constants for "CAZ-5", a novel plasmid-mediated beta-lactamase with noticeable activity against third-generation cephalosporins and particularly ceftazidime have been determined. Two closely-related plasmid-mediated beta-lactamases have also been studied: SHV-2 and PIT-2 (also known as SHV-1). These enzymes were synthesized constitutively; they were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam and they lacked activity against the cephamycins and imipenem. PIT-2/SHV-1 had poor hydrolytic activity against the third-generation cephalosporins, SHV-2 was markedly active against cefotaxime and related compounds, whereas the new enzyme, which was also active against these cephalosporins, had a noticeably greater activity against ceftazidime. Aztreonam was slowly hydrolysed by CAZ-5 beta-lactamase, but demonstrated an unusually high affinity for this enzyme.     

Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001)

Originating from 25 selected intensive care units (ICUs) in North America, a total of 1,321 bacterial strains from blood, respiratory tract, urine and wound sites were processed at a central laboratory as part of the SENTRY Antimicrobial Surveillance Program (2001) to assess their occurrence rates and antimicrobial susceptibility profiles. The rank order of pathogens recovered was Staphylococcus aureus (24.1%), Pseudomonas aeruginosa (12.2%), Escherichia coli (10.1%), Klebsiella spp. (8.9%), Enterococcus spp. (7.2%), coagulase-negative staphylococci (7.0%) and Enterobacter spp. (7.0%). Although oxacillin resistance among S. aureus was 51.4%, no resistance was detected to vancomycin, linezolid and quinupristin/dalfopristin. The most active agents tested against P. aeruginosa were amikacin, cefepime, tobramycin, meropenem and piperacillin/tazobactam (3.1-13.0% resistance). Among agents tested against the Enterobacteriaceae, amikacin, cefepime, imipenem and meropenem showed greatest in vitro activity (0.0-3.4% resistance). Extended-spectrum beta-lactamase-producing phenotype rates were 11.2 and 16.2% in E. coli and Klebsiella spp., respectively. Linezolid was most active against enterococci (1.1% resistance; G2576U ribosomal mutation) whereas 28.4% of isolates were resistant to vancomycin. Cefepime and the carbapenems (imipenem or meropenem) for Gram-negative isolates and linezolid for Gram-positive isolates, provided the broadest spectrum of in vitro activity against contemporary ICU pathogens in North America.