In vitro activity of a novel oxazolidinone,AZD2563, against randomly selected and multiresistant Gram-positive cocci

The in vitro activity of AZD2563, a novel oxazolidinone, was assessed against 595 Gram-positive cocci, comprising recent surveillance isolates and a collection of resistant (including multiresistant), epidemiologically diverse isolates. The MICs of AZD2563 for staphylococci, pneumococci and enterococci had narrow ranges, 0.25-2 mg/L, with modal MICs of 1 mg/L for staphylococci and pneumococci, and 1-2 mg/L for enterococci. AZD2563 was equally active against the surveillance isolates and those that had been selected for their multiresistance to other agents. The MICs of AZD2563 were either the same as those of linezolid or two-fold lower.     

Survey of blood stream infections attributable to gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Program. SENTRY Participants Group

The SENTRY Antimicrobial Surveillance Program was established in January, 1997 to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a network of sentinel hospitals in the United States (30 sites), Canada (eight sites), Latin America (10 sites), and Europe (24 sites). During the first 12-month study period (January to December, 1997), a total of 9519 blood stream infections (BSI) were reported by SENTRY participants in the U.S. (6150), Canada (1727), and Latin America (1642). The Gram-positive cocci, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), enterococci, and streptococci accounted for 53.9% (5131 infections) of all BSI (56.5% U.S., 55.7% Canada, and 42.9% Latin America). The staphylococci, Enterococcus spp., S. pneumoniae, beta-hemolytic streptococci, and viridans group streptococci accounted for 6 of the top 11 BSI pathogens in the U.S. and Canada, whereas only S. aureus (1st), CoNS (3rd), and Enterococcus spp. (9th) were among the top 11 pathogens in Latin American hospitals. The results of this survey affirm the importance of Gram-positive cocci as causes of BSI in both North America and Latin America and demonstrate that important antimicrobial resistance exists among isolates of staphylococci, streptococci, and enterococci from all three geographic regions. This includes oxacillin-resistance among S. aureus (26.9% U.S., 29.2% Latin America, and 4.0% Canada) and CoNS (71.5% U.S., 68.4% Latin America, and 65.6% Canada), penicillin resistance among viridans group streptococci (48.5% U.S., 45.1% Canada, and 33.3% Latin America) and pneumococci (36.1% U.S., 27.5% Canada, and 65.6% Latin America), high-level resistance (HLR) to aminoglycosides among enterococci (27.2 to 70.1% U.S., 33.3 to 75.7% Canada and 16.7 to 51.5% Latin America), and macrolide resistance among beta-hemolytic streptococci (12.4 to 14.2% U.S., 10.5 to 12.3% Canada, and 0.0 to 4.0% Latin America), viridans group streptococci (32.4 to 39.7% U.S., 22.5-35.2% Canada, and 20.0% Latin America), and pneumococci (10.0 to 10.6% U.S., 9.8-10.8% Canada, and 9.4-18.7% Latin America). BSI isolates of Gram-positive cocci from the U.S. and Latin America were considerably more resistant than those from Canada. New agents with Gram-positive activity will be essential for optimal treatment of BSI attributable to Gram-positive cocci in both North and Latin America.     

2010年中国12所教学医院革兰阳性球菌耐药性研究

目的调查2010年我国12所教学医院临床分离的革兰阳性球菌的耐药性。方法收集2010年6-12月9个城市12所教学医院临床分离的1 181株非重复革兰阳性球菌。采用琼脂稀释法测定抗菌药物的最低抑菌浓度(MIC)值,计算不同病原菌对常用临床抗菌药物的耐药率。结果金葡菌和凝固酶阴性葡萄球菌中耐苯唑西林菌株分别占40.6%(191/470)和79.6%(187/236);不同标本苯唑西林耐药金葡菌(MRSA)检出率为22.2%～72.7%。在ICU患者中,MRSA的检出率为71.4%,高于MRSA在住院患者中的比率。未发现对替考拉宁、万古霉素和利奈唑胺耐药的金葡菌;替加环素对金葡菌的MIC值范围为0.032～0.5 mg/L。在肠球菌属中发现10株屎肠球菌和2株粪肠球菌对万古霉素耐药。粪肠球菌和屎肠球菌对替加环素的敏感率均为100%,对利奈唑胺的敏感率分别为98.3%和100%。按青霉素非脑膜炎株折点判读,肺炎链球菌中青霉素耐药株(PRSP)的比率为6.0%(14/232),其中5岁以下儿童中PRSP的比率为13.8%(9/65),65岁以上的老人中PRSP的发生率为5.1%(3/59);未发现对替考拉宁、万古霉素、利奈唑胺、替加环素耐药的肺炎链球菌。结论葡萄球菌中MRSA检出率在ICU患者中较门诊和住院患者高,MRSA主要分离自呼吸道标本和各种分泌物和脓液标本。万古霉素耐药的肠球菌在我国发生率低。PRSP在5岁以下儿童中的比率明显高于其他年龄组。替考拉宁、万古霉素、利奈唑胺、替加环素对葡萄球菌、粪肠球菌、屎肠球菌和肺炎链球菌具有很好的抗菌活性。     

In vitro susceptibility of Gram-positive pathogens to linezolid and teicoplanin and effect on outcome in critically ill patients

OBJECTIVES: To determine the prevalence of teicoplanin and linezolid resistance amongst Gram-positive pathogens isolated in the intensive care unit (ICU) and the impact of any resistance on clinical outcome. METHODS: Gram-positive isolates were collected from two critical care units over 1 year. All patients were screened weekly for methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to teicoplanin and linezolid was tested by Etest. The length of hospital and critical care unit stay and the use of antibiotics in each patient were recorded. RESULTS: Reduced susceptibility to teicoplanin (MIC>or=16 mg/L) was found in 21 [3.3% (95% CI 2.0-5.0%) 6 patients] of 643 strains of MRSA versus none of 374 methicillin-susceptible S. aureus (MSSA) [<0.3% (95% CI 0-0.9%)]. Of 49 enterococci 3 were teicoplanin-resistant. All Gram-positive isolates were susceptible to linezolid. The length of treatment with teicoplanin and outcome of patients infected with these strains were similar to that of susceptible strains. MRSA was a more common cause of infection than MSSA but a less frequent colonizer. CONCLUSIONS: Resistance to teicoplanin remains at a comparatively low level and there was no clear relationship between susceptibility and outcome in this critically ill population. There was no resistance in Gram-positives to linezolid but this should be kept as a reserve antibiotic to maintain its activity.     

Prevalence of resistance to macrolide, lincosamide and streptogramin antibiotics in Gram-positive cocci isolated in a Korean hospital

To investigate the prevalence of resistance to macrolide, lincosamide and streptogramin (MLS) antibiotics in Gram-positive cocci isolated in a Korean hospital, we tested the antibiotic susceptibility of 1097 clinical isolates of Staphylococcus aureus, coagulase-negative staphylococci (CNS) and enterococci to the macrolides erythromycin, clarithromycin, azithromycin and josamycin, the lincosamide clindamycin and the streptogramin pristinamycin. These three groups of organisms were mostly resistant to macrolides and lincosamide, but were commonly susceptible to pristinamycin. The resistance phenotypes of erythromycin-resistant isolates were determined by the double-disc test with erythromycin and clindamycin, which showed that most exhibited constitutive MLS resistance. In order to determine the prevalence of the resistance genotypes and the resistance mechanisms, the presence of the erm(A), erm(B), erm(C) and mef genes in the erythromycin-resistant isolates was identified by PCR analysis. The resistance was due mainly to the presence of erm(A) in S. aureus (82.5%), erm(B) in enterococci (55%) and erm(C) in CNS (47.2%).     

In vitro activity of linezolid against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new oxazolidinone antimicrobial agent linezolid against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 20 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by < or = 4 ug/ml of linezolid. All isolates of methicillin-resistant S. aureus were inhibited by < or = 8 ug/ml of linezolid. All isolates of penicillin-resistant S. pneumoniae were inhibited by < or = 2 ug/ml of linezolid. Linezolid inhibits strains of multidrug resistant Gram-positive cocci in vitro at concentrations < or = 8 ug/ml.     

Zyvox Annual Appraisal of Potency and Spectrum Program Results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from 16 countries

The Zyvox Annual Appraisal of Potency and Spectrum Program has completed its fifth year of monitoring for emerging resistance to linezolid and other Gram-positive active agents on the continents of Europe, Asia, Australia, and Latin America. In 2006, 4216 Gram-positive isolates from 16 nations were submitted for analysis from 6 organism groups including Staphylococcus aureus (54.0%), coagulase-negative staphylococci (CoNS) (14.6%), enterococci (10.0%), Streptococcus pneumoniae (9.4%), viridans group streptococci (5.0%), and beta-hemolytic streptococci (7.0%). Linezolid retained potent activity against S. aureus (MIC(50) and MIC(90), 2 microg/mL; 39.8% methicillin resistant) and CoNS (MIC(50) and MIC(90), 1 microg/mL; 74.3% methicillin resistant). Despite endemicity of vancomycin-resistant enterococci (up to 30.0%) in several nations, linezolid inhibited >99% of strains at 相似文献   

In vitro activity of linezolid and 11 other antimicrobials against 566 clinical isolates and comparison between NCCLS microdilution and Etest methods

The in vitro activity of linezolid and 11 other antimicrobials was determined for 566 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, some of them resistant to several antibiotics, using a broth microdilution method and the Etest method. All Gram-positive organisms tested were inhibited by a concentration of 相似文献   

Antimicrobial resistance trends among 5608 clinical Gram-positive isolates in China: results from the Gram-Positive Cocci Resistance Surveillance program (2005-2010)

A total of 5608 clinical isolates of Gram-positive bacteria were collected from 12 teaching hospitals across China from 2005 to 2010. The minimum inhibitory concentrations (MICs) of 19 antimicrobial agents were determined by the agar dilution method at the central laboratory. Overall, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRSCoN) were 46.8% and 81.5%, respectively. Isolates from inpatients exhibited a higher rate of MRSA than that from outpatients (52.3% versus 26.2%, P < 0.001). The prevalence of MRSA in respiratory infections (67.5%) was higher than in other sources of infections (P < 0.001). A shift in vancomycin MICs from <0.5 to 1.0 μg/mL was observed during the 6-year period. In 2005, 70.5% of S. aureus isolates were inhibited at the vancomycin MIC of 0.5 μg/mL, while in 2010, 89% of the isolates were inhibited at the vancomycin MIC of 1 μg/mL. With the use of penicillin oral breakpoints, penicillin-resistant Streptococcus pneumoniae (PRSP) increased from 28.6% in 2005 to 59.5% in 2010 and varied among different age groups, with an average rate of 70.6% for children under 5 years old. Importantly, an obvious penicillin MIC right shift was observed from 0.032 to 4 μg/mL during the study period. Serotyping for the isolates from 2005 and 2010 indicated that the high rate of PRSP could be due to the increased prevalence of serogroup 19. The prevalence of vancomycin-resistant enterococci (VRE) increased from 0 in 2005 to 4.9% in 2010. Of the 27 VRE isolates, vanA gene was the most prevalent gene. During the study period, 97.9-100% of different species tested were susceptible to teicoplanin. Linezolid and tigecycline showed potent activities, and no resistant isolate was identified. In conclusion, although the prevalence of MRSA and MRSCoN remained stable over the 6 years, a sharp increase in the prevalence of PRSP was identified. In addition, MIC shifts, including the MICs of penicillin against S. pneumoniae and vancomycin against S. aureus, were observed. Continuous surveillance is warranted to evaluate the resistance trend of clinically important Gram-positive organisms in the future.     

Activity of linezolid against multi-resistant gram-positive bacteria from diverse hospitals in the United Kingdom

The in vitro activity of linezolid, an oxazolidinone, was assessed against 374 gram-positive cocci, with an emphasis on testing multi-resistant, epidemiologically unrelated isolates. MICs of linezolid for staphylococci, pneumococci and streptococci had a narrow range, from 0.5 to 2 mg/L, whereas MICs for enterococci were uniformly 4 mg/L. For all the species tested, the MICs of linezolid were unrelated to those of other antimicrobials. Linezolid appears to be a potentially useful drug for infections caused by gram-positive cocci.     

2010年中国CHINET血流感染的病原菌分布及耐药性

目的了解2010年CHINET血培养分离菌的菌种分布和耐药性。方法对CHINET细菌耐药监测网2010年1月至2010年12月所有血标本按常规方法进行细菌分离、培养、鉴定。按统一方案用K-B纸片扩散法进行抗菌药敏感试验。结果 2010年自血液标本中共获分离细菌5 646株,其中革兰阳性球菌占64.3%,革兰阴性杆菌占35.6%。最常见的分离菌分别为凝固酶阴性葡萄球菌(47.0%)、大肠埃希菌(1 5.0%)、肠球菌属细菌(7.4%)、克雷伯菌属细菌(6.0%)、金葡菌(5.6%)、不动杆菌属细菌(3.9%)、假单胞菌属细菌(2.9%)、草绿色链球菌(2.9%)、肠杆菌属细菌(1.9%)、沙门菌属细菌(1.2%)和嗜麦芽窄食单胞菌(1.1%),占分离菌株的94.8%。MRSA及MRCNS分别占金葡菌和凝固酶阴性葡萄球菌的51.1%和56.8%。粪肠球菌对高浓度庆大霉素和氨苄西林的耐药率分别为34.3%和14.7%,屎肠球菌对多数测试药物的耐药率显著高于粪肠球菌。草绿色链球菌对青霉素的耐药率为11.2%。葡萄球菌、肺炎链球菌和其他链球菌属细菌中均未发现万古霉素、替考拉宁和利奈唑胺耐药菌株,粪肠球菌和屎肠球菌对万古霉素的耐药率分别为2.1%和7.0%。大肠埃希菌、克雷伯菌属、肠杆菌属、沙雷菌属、变形菌属和枸橼酸菌属细菌等肠杆菌科细菌对亚胺培南、美罗培南的耐药率在0～10%,但克雷伯菌属、肠杆菌属、沙雷菌属和变形菌属细菌对厄他培南的耐药率达10%～20%。不发酵糖革兰阴性杆菌对碳青霉烯类抗生素耐药率较高,铜绿假单胞菌对碳青霉烯类抗生素的耐药率为18.3%～22%,但不动杆菌属细菌耐药率达57%。结论 2010年CHINET监测资料显示革兰阳性菌,尤其是CNS在血流感染中占重要地位,血培养分离株对常用抗菌药严重耐药,因此应合理应用抗菌药物,并加强医院感染控制措施以抑制耐药菌传播。     

2006年中国七家教学医院革兰阳性球菌耐药性研究

目的 调查2006年我国革兰阳性球菌的耐药性.方法 收集2006年6-12月全国7家教学医院分离的非重复革兰阳件菌674株,以琼脂稀释法测定抗菌药物的MIC.结果 100株肺炎链球菌中,青霉素耐药的肺炎链球菌(PRSP)和青霉素中介的肺炎链球菌(PISP)分别占1%和19%.所有肺炎链球菌均对万古霉素和替考拉宁高度敏感;对左氧氟沙星和莫西沙星的敏感率分别为97%和98%;对阿莫西林/克拉维酸、头孢曲松和氯霉素的敏感率依次为96%、87%和73%;青霉素敏感的肺炎链球菌(PSSP)全部对头孢丙烯和头孢克罗的敏感率分别为62.0%和55.7%,而PISP和PRSP对这2种抗菌药物均耐药;所有肺炎链球菌埘大环内酯类、甲氧苄啶/磺胺甲恶(噁)唑(TMPCo)和四环素的敏感率均小于35%.金黄色葡萄球菌和凝固酶阴性葡萄球菌(SCON)中耐甲氧西林菌株分别占48%(33%～84%)和81%(69%～94%).耐甲氧西林金黄色葡萄球菌(MRSA)对TMPCo、氯霉素和利福平敏感率分别为72%、66%和45%;对大环内脂类、氨基糖苷类、四环素和氟喹诺酮类的敏感率低于18%.粪肠球菌和屎肠球菌对高浓度庆大霉素耐药率分别为56%(30%～86%)和80%(50%～100%).未发现对万古霉素和替考拉宁耐药的葡萄球菌和粪肠球菌;但在杭州发现对该2种抗菌药物同时耐药的屎肠球菌.除氯霉素和四环素外,粪肠球菌对其他所测抗菌药物的敏感率均高于屎肠球菌.结论 各地区革兰阳件耐药性有所差异,且对大部分抗菌药物的耐药率较2005年本项目的 监测结果有所升高.替考拉宁和万古霉素对革兰阳性球菌仍保持很高的抗菌活性.     

2008年中国十二家教学医院革兰阳性球菌耐药性研究

目的 调查2008年我国革兰阳性球菌临床分离株的耐药性.方法 收集2008年6至12月12家教学医院临床分离的1171株非重复革兰阳性球菌.采用琼脂稀释法测定抗菌药物的MIC值.结果 金黄色葡萄球菌和凝同酶阴性葡萄球菌中耐苯唑西林菌株分别占49.9%(232/465)和74.0%(179/242);不J司地区MRSA发生率在33.3%～65.0%之间;不同标本MRSA分离率分别为:呼吸道标本71.1%(108/152),血液标本48.3%(28/58),脓、伤口和无菌体液标本36.0%(68/189).MRSA对复方磺胺和氯霉素的敏感率为81.5%(183/232)和89.7%(208/232);对喹诺酮类、庆大霉素、红霉素、克林霉素、四环素和利福平的敏感率为3.9%～35.0%;未发现对替考拉宁、万古霉素和利奈唑胺耐药的葡萄球菌.共发现3株VRE;粪肠球菌和屎肠球菌对利奈唑胺的敏感率分别为96.2%(101/105)和97.0%(130/134),对高浓度庆大霉素耐药率分别为48.6%(51/105)和75.4%(101/134);粪肠球菌对氯霉素和四环素的敏感率低于屎肠球菌,但对其他所测试抗菌药物均有较高的敏感性;屎肠球菌对除糖肽类抗菌药及利奈唑胺以外的其他所测抗菌药物的敏感率均较低.225株PISP分离率为24.9%(56/225),未发现PRSP.≤3岁儿童组肺炎链球菌中PNSSP分离率为36.6%(15/41),其他年龄组患者中PNSSP分离率为15.4%～26.6%.青霉素敏感的肺炎球菌(PSSP)对头孢丙烯、头孢呋辛和头孢克罗敏感率分别为67.5%(114/169)、66.3%(112/169)和61.5%(104/169),而PISP对这3种药物均耐药;所测225株肺炎链球菌对万古霉素、替考拉宁和利奈唑胺高度敏感,对加替沙星、左氧氟沙星和莫西沙星的敏感率分别为96.9%,97.8%和98.2%,对头孢曲松、氯霉素和阿莫西林/克拉维酸的敏感率分别为81.3%、77.3%和68.0%,对大环内酯类、复方磺胺和四环素的敏感率为11.6%～23.6%.结论 我国VRE发生率低,而葡萄球菌中苯唑西林耐药菌株分离率高.≤3岁儿童组PNSSP分离率高于其他年龄组.替考拉宁、万古霉素和利奈唑胺对葡萄球菌、粪肠球菌、屎肠球菌和肺炎链球菌具有很好的抗菌活性.     

In vitro activities of 28 antimicrobial agents against Staphylococcus aureus isolates from tertiary-care hospitals in Korea: a nationwide survey

Staphylococcus aureus, one of the most frequently isolated pathogens in both hospitals and the community, has been particularly efficient at developing resistance to antimicrobial agents. As methicillin-resistant S. aureus (MRSA) has prevailed and, furthermore, as S. aureus with reduced susceptibility to vancomycin has emerged, the therapeutic options for the treatment of S. aureus infections have become limited. To update the current status of antibiotic resistance, clinical S. aureus isolates were collected from eight university-affiliated hospitals from June 1999 to January 2001. Susceptibility tests with 28 antibiotics were performed by the disk diffusion method. Among a total of 682 isolates, the methicillin resistance rate was 64% (439 of 682), and most of the MRSA isolates were resistant to multiple classes of antibiotics. Although a constitutive macrolide-lincosamide-streptogramin B resistance phenotype was common, no isolates were resistant to quinupristin-dalfopristin or linezolid. Rifampin, fusidic acid, trimethoprim-sulfamethoxazole, and arbekacin showed superior in vitro activity compared with the other antibiotics against the MRSA isolates. No isolates showed reduced susceptibility to vancomycin.     

In vitro activities of LTX-109, a synthetic antimicrobial peptide, against methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, daptomycin-nonsusceptible, and linezolid-nonsusceptible Staphylococcus aureus

LTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistant Staphylococcus aureus (MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity against S. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.     

In Vitro Activity of Cephalosporin RWJ-54428 (MC-02479) against Multidrug-Resistant Gram-Positive Cocci

RWJ-54428 (MC-02479) is a novel cephalosporin that binds to penicillin-binding protein (PBP) PBP 2' (PBP 2a) of methicillin-resistant staphylococci. Its in vitro activity was assessed against 472 gram-positive cocci, largely selected as epidemiologically unrelated isolates with multidrug resistance. The MIC at which 50% of isolates are inhibited (MIC(50)) and MIC(90) of RWJ-54428 for methicillin-resistant Staphylococcus aureus (MRSA) were 1 and 2 microg/ml, respectively, whereas they were 0.5 and 0.5 microg/ml, respectively, for methicillin-susceptible S. aureus. The MIC(50) and MIC(90) were 1 and 4 microg/ml, respectively, for methicillin-resistant coagulase-negative staphylococci (MRCoNS), whereas they were 0.25 and 1 microg/ml, respectively, for methicillin-susceptible isolates. The highest MICs for MRSA and MRCoNS isolates were 2 and 4 microg/ml, respectively. The MIC(50) and MIC(90) of RWJ-54428 for Enterococcus faecalis were 0.5 and 1 microg/ml, respectively, but they were 4 and 8 microg/ml, respectively, for Enterococcus faecium. For penicillin-susceptible, -intermediate, and -resistant pneumococci, the MIC(90)s of RWJ-54428 were 0.03, 0.25, and 0.5 microg/ml, respectively, with the highest MIC for a pneumococcus being 1 microg/ml, recorded for a strain for which penicillin and cefotaxime MICs were 8 and 4 microg/ml. MICs for Lancefield group A, B, C, and G streptococci were < or =0.008 microg/ml; those for viridans group streptococci, including isolates not susceptible to penicillin, were from 0.015 to 0.5 microg/ml. RWJ-54428 did not select resistant mutants of MRSA or enterococci in challenge experiments and has the potential to be useful for the treatment of infections caused by gram-positive cocci.     

Linezolid in vitro: mechanism and antibacterial spectrum

Oxazolidinones are prominent among the new Gram-positive antimicrobial agents now becoming available. They were discovered by DuPont Pharmaceuticals in the late 1980s but linezolid, the first analogue suitable for development, was found only when the family was re-examined by Pharmacia in the 1990s. Oxazolidinones bind to the 50S subunit of the prokaryotic ribosome, preventing formation of the initiation complex for protein synthesis. This is a novel mode of action; other protein synthesis inhibitors either block polypeptide extension or cause misreading of mRNA. Linezolid MICs vary slightly with the test method, laboratory, and significance attributed to thin hazes of bacterial survival, but all workers find that the susceptibility distributions are narrow and unimodal, with MIC values between 0.5 and 4 mg/L for streptococci, enterococci and staphylococci. Full activity is retained against Gram-positive cocci resistant to other antibiotics, including methicillin-resistant staphylococci and vancomycin-resistant enterococci. MICs are 4-8 mg/L for Moraxella, Pasteurella and Bacteroides spp. but other Gram-negative bacteria are resistant as a result of endogenous efflux activity. Resistance is difficult to select in vitro but has been reported during therapy in a few enterococcal infections and in two MRSA cases to date; the mechanism entails mutation of the 23S rRNA that forms the binding site for linezolid. Risk factors for selection of resistance include indwelling devices, undrained foci, protracted therapy and underdosage.     

Linezolid

Multiple antibiotic resistance is increasing worldwide in Gram-positive bacteria, especially in hospitals. Problem organisms include multiply resistant strains of pneumococci, Staphylococcus aureus and enterococci; for many of these the glycopeptide vancomycin has become the treatment of last resort. This situation has been made worse by the emergence of vancomycin-resistant enterococci and vancomycin-intermediate S. aureus. Fortunately, several compounds active against resistant Gram-positive bacteria are in active development. One of these is linezolid, the first of the oxazolidinones, a new class of antibacterial. Linezolid is a synthetic agent which is active against all the clinically important Gram-positive bacteria, including multiply resistant strains. It has good pharmacokinetics, with equal bioavailability by both oral and intravenous routes and no need for dose adjustment in patients with renal impairment. The drug has a good safety profile and clinical trials have given excellent results in a variety of skin and soft tissue, respiratory and bloodstream infections. Linezolid is a promising drug, which, together with prudent antibiotic use and the prevention and control of hospital infection, will help in the battle against multiply antibiotic resistant Gram-positive bacteria.     

Comparative activities of daptomycin and several agents against staphylococcal blood isolates. Glycopeptide tolerance

The activity of daptomycin was evaluated against 702 staphylococcal blood isolates (316 methicillin-susceptible Staphylococcus aureus, 187 methicillin-resistant S. aureus [MRSA], and 199 coagulase-negative staphylococci [CoNS]) collected in 41 Spanish hospitals. Glycopeptide tolerance and the incidence of heterogeneous glycopeptide-intermediate (hGISA) isolates were also examined. Vancomycin MICs determined by the Etest were compared with those obtained by the reference broth microdilution method. Daptomycin exhibited good activity, and only 2 isolates were nonsusceptible to this antibiotic. Resistance to linezolid was observed in 2 MRSA isolates and in 16 CoNS. The cfr gene was detected in 7 of these 18 isolates. Vancomycin and teicoplanin tolerance was 9.6% and 21.9%, respectively, in MRSA isolates. We detected the hGISA phenotype in 5.8% of MRSA isolates. Vancomycin MICs by the Etest were slightly higher than those obtained by broth microdilution. Daptomycin retained activity against isolates that were not susceptible to linezolid, teicoplanin, or quinupristin-dalfopristin.     

Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001-2002: the BSAC Bacteraemia Resistance Surveillance Programme

OBJECTIVES: To describe the current patterns of antimicrobial resistance in the major pathogens of bacteraemia in the UK and Ireland, to highlight any unexpected resistance patterns and to act as a reference baseline for future studies. METHODS: In 2001 and 2002, 5092 blood culture isolates were collected by 29 laboratories distributed across the UK and Ireland. A single central laboratory re-identified the isolates and measured MICs by the BSAC agar dilution method. RESULTS: Oxacillin resistance was found in 42% of Staphylococcus aureus and 76% of coagulase-negative staphylococci. Streptococci were generally susceptible to beta-lactams, but tetracycline resistance was common (except in Streptococcus pneumoniae) and particularly common among group B isolates (82% resistant). Nine percent of S. pneumoniae had reduced susceptibility to penicillin (MICs 0.12-1 mg/L), but none required >/=2 mg/L for inhibition. High-level gentamicin resistance was seen in 43% of Enterococcus faecalis, often in combination with raised ciprofloxacin MICs (>/=32 mg/L), but these isolates remained susceptible to ampicillin and imipenem. Only linezolid and tigecycline showed in vitro potency against a large proportion of Enterococcus faecium. Vancomycin resistance was restricted to enterococci (20% of E. faecium, 3% of E. faecalis) and a single isolate of coagulase-negative staphylococci (0.2%, MIC of 8 mg/L). Escherichia coli isolates were commonly resistant to amoxicillin (56%) and tetracycline (88%) but remained susceptible to ceftazidime, piperacillin/tazobactam and imipenem. Extended-spectrum beta-lactamases were detected in 2% of E. coli (none in 2001, 3.2% in 2002), 5% of Klebsiella spp. and 8% of Enterobacter spp. Resistance rates of Pseudomonas aeruginosa to ciprofloxacin, ceftazidime, gentamicin, imipenem and piperacillin/tazobactam were between 4% and 7%. Among the newly licensed and developmental agents, there was no resistance to linezolid in Gram-positive organisms. Ertapenem had a wide spectrum, covering Enterobacteriaceae, streptococci and oxacillin-susceptible staphylococci. MICs of tigecycline were low for Gram-positive species and Enterobacteriaceae except Proteeae and Enterobacter spp. CONCLUSION: Antimicrobial resistance among major bloodstream pathogens to those antimicrobials often selected for empirical therapy was relatively uncommon in 2001-2002, usually <10%. An important exception was oxacillin resistance in S. aureus.