In vitro activity of tigecycline against 3989 Gram-negative and Gram-positive clinical isolates from the United States Tigecycline Evaluation and Surveillance Trial (TEST Program; 2004)

The Tigecycline Evaluation and Surveillance Trial (TEST Program) determined the in vitro activity of tigecycline over a large population of organisms from geographically diverse sites. Tigecycline was compared to amikacin, ampicillin, amoxicillin/clavulanic acid, imipenem, cefepime, ceftazidime, ceftriaxone, levofloxacin, minocycline, piperacillin/tazobactam, linezolid, penicillin, and vancomycin against 3989 commonly encountered clinical Gram-negative and Gram-positive pathogens collected from sites in the United States during 2004. The tigecycline activity was equivalent to imipenem against Enterobacteriaceae. Tigecycline inhibited extended-spectrum beta-lactamase and AmpC phenotypes at MIC90 values (minimum inhibitory concentration) of < or =2 microg/mL. In vitro results for tigecycline were similar to other broad-spectrum antimicrobial agents against nonfermenters with MIC90 results of 2 microg/mL against Acinetobacter spp. and >16 microg/mL against Pseudomonas aeruginosa. Tigecycline demonstrated potent activity against Staphylococcus aureus (MIC90, 0.25 microg/mL) and enterococci (MIC90, 0.12 microg/mL) regardless of methicillin or vancomycin susceptibility. Tigecycline MIC values were unaffected by penicillin nonsusceptibility and beta-lactamase production among fastidious respiratory pathogens (Streptococcus pneumoniae [MIC90, 0.5 microg/mL] and Haemophilus influenzae [MIC90, 0.25 microg/mL]). Tigecycline offers excellent activity against most of the commonly encountered nosocomial and community-acquired bacterial pathogens.     

Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.     

In vitro activity of tigecycline against 6792 Gram-negative and Gram-positive clinical isolates from the global Tigecycline Evaluation and Surveillance Trial (TEST Program, 2004)

Tigecycline, a new glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrug-resistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (microg/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 microg/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 microg/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 microg/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new glycylcycline agent for the treatment of many types of pathogens with varying resistance phenotypes.     

Antimicrobial activity of tigecycline against clinical isolates from Spanish medical centers. Second multicenter study

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 1102 bacterial isolates from 20 centers in Spain. The MIC of tigecycline at which 90% (MIC(90)) of the pneumococci tested were inhibited was the lowest (0.06 microg/mL) of all the antibiotics tested. The MICs of tigecycline against enterococci ranged from 0.03 to 0.125 microg/mL. All staphylococci were inhibited by < or =0.25 microg/mL of tigecycline, and 99.6% of Enterobacteriaceae isolates were inhibited by < or =2 microg/mL of tigecycline. Tigecycline demonstrated good activity against Bacteroides fragilis group organisms with an MIC(90) of 4 microg/mL. The results of this study confirm the excellent activity of tigecycline against multiresistant Gram-positive and Gram-negative pathogens.     

Tigecycline activity tested against multidrug-resistant Enterobacteriaceae and Acinetobacter spp. isolated in US medical centers (2005-2009)

We evaluated the activity of tigecycline against Enterobacteriaceae (9563 isolates) and Acinetobacter spp. (835) with various resistance phenotypes collected from 31 US medical centers in 2005-2009. The isolates were tested for susceptibility by the reference broth microdilution method against tigecycline and various comparators. Among Escherichia coli and Klebsiella spp., 6.8% and 15.4% exhibited an extended-spectrum β-lactamase (ESBL) phenotype, respectively; and 22.2% of Enterobacter spp. strains were ceftazidime-resistant. Tigecycline was active against E. coli [minimum inhibitory concentration (MIC(50/90)), 0.12/0.25 μg/mL; 100.0% susceptible] independent of ESBL phenotype or resistance to other antimicrobials. Among Klebsiella spp., 97.9% of ESBL-producing Klebsiella spp. and 98.2% of imipenem-non-susceptible strains were susceptible to tigecycline (MIC(50/90), 0.5/1 μg/mL for both subsets). Tigecycline was active against Enterobacter spp. (MIC(50/90), 0.25/1 μg/mL; 98.4% susceptible), including ceftazidime-resistant strains (MIC(50/90), 0.5/2 μg/mL; 97.1% susceptible). Tigecycline inhibited 94.4% of Acinetobacter spp. overall (MIC(50/90), 0.5/2 μg/mL) and 86.2% of imipenem-non-susceptible (MIC(50/90), 1/4 μg/mL) strains at ≤2 μg/mL. No trend toward decreased tigecycline activity overtime was observed for any of the organisms or resistant subsets during the study period. These results indicate that tigecycline has sustained potent in vitro activity and a broad spectrum against these clinically important Gram-negative pathogens causing infections in US medical centers, including multidrug-resistant organism subsets.     

Antimicrobial activity of tigecycline tested against organisms causing community-acquired respiratory tract infection and nosocomial pneumonia

Emerging antimicrobial resistance among respiratory tract pathogens has created a critical need for development of new antimicrobial agents that are not affected by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel broad-spectrum parenteral glycylcycline, has been shown to be active against many of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including strains highly resistant to commonly prescribed antimicrobials and was recently approved by the US Food and Drug Administration for treating infections of skin and skin structures, and for intra-abdominal infections. In this study, tigecycline spectrum and potency were evaluated against a global collection of pathogens (2000-2004) recovered from community-acquired respiratory infections (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among community-acquired infections, the ranking pathogens were Haemophilus influenzae (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7% penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline displayed potent activity by inhibiting 100% of the 3 species at clinically achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%), and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL, tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S. aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5 microg/mL, respectively) with all strains inhibited at < or =1 microg/mL. Streptococci recovered from hospitalized patients (beta-hemolytic and S. pneumoniae) were also very susceptible to tigecycline with the highest MIC being 0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta-lactamase [ESBL] phenotype) were inhibited by < or =1 microg/mL, and all Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4 microg/mL, respectively). Further clinical studies should consider the role that tigecycline may play in the therapy for severe respiratory tract infections, both of nosocomial and community origin.     

Potency and spectrum of tigecycline tested against an international collection of bacterial pathogens associated with skin and soft tissue infections (2000-2004)

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 5289 bacterial isolates recovered from hospitalized patients with skin and soft tissue infections during 2000-2004. Strains were submitted from >70 medical centers in North America, Latin America, and Europe, and were tested centrally using reference broth microdilution methods. The top 10 ranking pathogens (95% of total) recovered included Staphylococcus aureus (55.2%), Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%), beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%), Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase-negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline. The broad spectrum of activity exhibited by this glycylcycline included tetracycline-resistant organism subsets, as well as oxacillin-resistant S. aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase-producing enteric bacilli strains. Tigecycline represents a new choice among broad-spectrum parenteral agents for the common Gram-positive and -negative pathogens producing serious infections of skin and soft tissues.     

Baseline in vitro activity of tigecycline among key bacterial pathogens exhibiting multidrug resistance

Tigecycline is the first clinically available semisynthetic glycylcycline approved for clinical use. This study was done to establish a baseline for ongoing surveillance of tigecycline's activity as this agent's clinical use increases. Against 1,796 Staphylococcus aureus (559 multidrug resistant), tigecycline had the lowest minimal inhibitory concentration (MIC(90); 0.12 microg/ml) among all agents tested and 99.8% of the isolates were susceptible. For Acinetobacter spp., tigecycline again demonstrated the lowest MIC(90) (2 microg/ml) and the highest percent susceptibility (96.9%). Among Enterobacteriaceae, the 2 most active agents were tigecycline (MIC(90) = 1 microg/ml; 99% susceptible) and imipenem (MIC(90) = 1 microg/ml; 99.5% susceptible). Tigecycline also demonstrated high activity against Streptococcus pneumoniae, Streptococcus pyogenes,Haemophilus influenzae and Enterococcus spp. In summary, tigecycline currently exhibits potent activity against a broad array of bacteria species. Given the dynamics of resistance development, careful monitoring of tigecycline activity against these organisms should remain a significant aspect of ongoing surveillance.     

In vitro activity of tigecycline (GAR-936) tested against 11,859 recent clinical isolates associated with community-acquired respiratory tract and gram-positive cutaneous infections

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains; MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5 microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25 microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25 microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12 microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections.     

2009年中国13家教学医院院内感染病原菌的抗生素耐药性监测

目的 监测2009年我国不同地区13家教学医院院内获得病原菌的分布和体外药物敏感性.方法 收集来自13家医院院内BSI、HAP和IAI患者标本的病原菌.菌株经中心实验室复核后,采用琼脂稀释法测定替加环素等抗菌药物的MIC值,数据输入WHONET5.6软件进行耐药性分析.结果 共收集到2 502株病原菌.引起BSI的前3位病原菌分别为大肠埃希菌[27.1%(285/1 052)]、凝固酶阴性葡萄球菌[12.6%(133/1 052)]和肺炎克雷伯菌[10.8%(114/1 052)];引起HAP的前3位病原菌分别为鲍曼不动杆菌[28.8%(226/785)]、铜绿假单胞菌[16.1%(126/785)]和肺炎克雷伯菌[14.6%(115/785)];而IAI的主要病原菌为大肠埃希菌[31.0%(206/665)]、肺炎克雷伯菌[11.3%(75/665)]和屎肠球菌[10.8%(72/665)].对于大肠埃希菌和克雷伯菌,敏感率大于80%的药物包括亚胺培南和美罗培南(98.1%～100%)、替加环素(95.3%～100%)、哌拉西林-三唑巴坦(88.6%～97.1%)和阿米卡星(88.3%～92.5%).对于肠杆菌属、柠檬酸杆菌属和沙雷菌属,替加环素的敏感率为93.5%～100%,亚胺培南和美罗培南的敏感率为92.9%～100%,敏感率较高的抗萧药物还包括阿米卡星(85.2%～96.7%)、哌拉西林-三唑巴坦(82.4%～96.4%)、头孢吡肟(79.6%～96.7%)和头孢哌酮-舒巴坦(78.7%～90.0%).铜绿假单胞菌对多黏菌素B的敏感率最高(100%),其次为阿米卡星和哌拉西林-三唑巴坦(81.9%和80.1%).鲍曼不动杆菌对多黏菌素B的敏感率最高(98.8%),其次为替加环素(90.1%)和米诺环素(72.O%).CRAB的发生率为60.1%.金黄色葡萄球菌中MRSA的发生率为60.2%,凝固酶阴性葡萄球菌中MRSCoN的发生率为84.2%.所有葡萄球菌对替加环素、万占霉素和利奈唑胺敏感,仅有1株溶血葡萄球菌对替考拉宁中介.本次监测发现2株利奈唑胺中介的粪肠球菌和1株万古霉素和替考拉宁耐药的屎肠球菌,替加环素对这3株肠球菌的MIC值范围为0.032～0.064μg/ml.结论 替加环素、碳青霉烯类、哌拉西林-三唑巴坦、阿米卡星和头孢吡肟对医院分离的肠杆菌科菌保持了较高的抗菌活性;多黏菌素B对铜绿假单胞菌和鲍曼不动杆菌体现出高抗菌活性,替加环素对鲍曼不动杆菌抗菌活性较高;替加环素、万古霉素和替考拉宁、利奈唑胺对院内获得革兰阳性球菌保持了较高的抗菌活性.

Abstract：

Objective To investigate distribution and antimicrobial resistance among nosocomial pathogens from 13 teaching hospitals in China in 2009. Methods Non-repetitive pathogens from nosocomial BSI, HAP and IAI were collected and sent to the central lab for MIC determination by agar dilution method.WHONET5.6 software was used to analyze the data. Results A total of 2 502 clinical isolates were collected. The top three pathogens of BSI were Escherichia coli [27. 1% (285/1 052 )] , coagulase-negutive staphylococcus [12. 6% ( 133/1 052)] and Klebsiella pneumoniae [10. 8% ( 114/1 052)]. The top three pathogens of HAP were Acinetobacter baumannii [28. 8% (226/785)], Pseudomonas aeruginosa [16. 1% (126/785)] and Klebsiella pneumoniae [14.6% (115/785 )] . The top three pathogens of IAI were Escherichia coli[31.0% ( 206/665 )], Klebsiella pneumonia [11.3% ( 75/665 )] and Enterococcus faecium [10. 8% (72/665)]. Against Escherichia coil and Klebsiella spp. , the antimicrobial agents with higher than 80% susceptibility rate included imipenem and meropenem (98. 1%-100% ), tigecycline (95.3%-100% ), piperacillin-tazobactam ( 88.6% -97. 1% ) and amikacin ( 88. 3% -92. 5% ). Against Enterobacter spp. , Citrobacter spp. and Serratia spp. , the susceptibility rates of tigecycline were 93.5% -100% whereas the value of imipenem and meropenem were 92.9% -100%. Other antimicrobial agents with high activity included amikacin ( 85.2% -96. 7% ), pipcracillin-tazobactam ( 82.4% -96.4% ), cefepime ( 79. 6% -96. 7% ) and cefoperazonc-sulbactam (78. 7%-90. 0% ). Polymyxin B showed the highest susceptibility rateagainst Pseudomonas aeruginosa ( 100% ), followed by amikacin ( 81.9% ) and piperacillin-tazobactam (80.1% ). Polymyxin B also showed the highest susceptibility rate against Acinetobacter baumannii (98. 8% ), followed by tigecycline (90. 1% ) and minocycline (72. 0% ). The incidence of carbapenemresistant Acinetobacter baumannii was 60. 1%. The MRSA rate was 60. 2% and the MRSCoN rate was 84. 2%. All Staphylococcus strains were susceptible to tigecycline, vancomycin, teicoplanin and linezolid except for one isolate of Staphylococcus haemolysis with intermediate to teicoplanin. Two Enterococcus faecalis isolates which were intermediate to linezolid and one Enterococcus faecium isolate which was resistant to vancomycin and teicoplanin was found in this surveillance, while the MICs of tigecycline against these three isolates were 0. 032-0. 064 μg/ml. Conclusions Tigecycline, carbapenems, piperacillin-tazobactam,amikacin and cefepime remain relatively high activity against nosocomial Enterobacteriaceae. Pseudomonas aeruginosa exhibite high susceptibility to polymyxin B, while Acinetobacter baumanni shows high susceptibility to polymyxin B and tigecycline. Tigecycline, vancomycin, teicoplanin and linezolid remain high activity against nosocomial gram-positive cocci.     

Aureobasidium pullulans infection: fungemia in an infant and a review of human cases

Steadily increasing resistance among the Enterobacteriaceae to beta-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and trimethoprim/sulfamethoxazole has compromised the utility of these commonly used antimicrobial classes for many community- or hospital-acquired infections. The development of tigecycline, the sentinel representative of a novel class of broad-spectrum agents (the glycylcyclines), represents an important milestone in addressing this critical need. Resistance to tigecycline might be expected to occur via the same mechanisms that produce tetracycline resistance; however, tigecycline remains stable and largely unaffected by the commonly occurring efflux and ribosomal protection resistance mechanisms. In this study, an international collection of Enterobacteriaceae (11327 isolates; 32.8% tetracycline-resistant) from global surveillance studies (2000-2004) were evaluated against tigecycline and other comparator antimicrobials. Although the most active agents were the carbapenems and aminoglycosides (97.5-99.7% susceptible), tigecycline displayed high potency (MIC50 and MIC90, 0.25 and 1 microg/mL) with 95.7% of all strains being inhibited at < or =2 microg/mL. Despite higher MIC values observed with Serratia spp. and Proteae, between 90.5% and 97.5% of isolates were inhibited by < or =4 microg/mL of tigecycline. Tetracycline-resistant populations demonstrated only modest decreases in potency to tigecycline, which appeared to be species-dependent (up to 2-fold only for Escherichia coli, Salmonella spp., Shigella spp., and Panteoa agglomerans; and up to 4-fold for Klebsiella spp., Enterobacter spp., and Citrobacter spp.). Among E. coli (263 isolates) and Klebsiella spp. (356) that meet recognized screening definitions for extended-spectrum beta-lactamase production, 100.0% and 94.4% were inhibited by tigecycline at 2 microg/mL, respectively. These findings confirm that tigecycline exhibits potency, breadth of spectrum, and stability to the commonly occurring resistance mechanisms found in contemporary Enterobacteriaceae isolates, attributes that make this parenteral agent an attractive candidate for use against serious infections produced by these species.     

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   

Potency and spectrum trends for cefepime tested against 65746 clinical bacterial isolates collected in North American medical centers: results from the SENTRY Antimicrobial Surveillance Program (1998-2003)

We evaluated the antimicrobial spectrum and potency of cefepime and selected comparators agents against clinical bacterial strains collected in North America over a 6-year period (1998-2003). Isolates were consecutively collected from bloodstream (44%), respiratory tract (41%), urinary tract (6%), and skin/soft tissue (5%) infections in 48 medical centers. Isolates were susceptibility tested by reference broth microdilution methods in a central laboratory. Oxacillin-resistant staphylococci and enterococci were excluded from the analysis. Imipenem (MIC90 = 1 microg/mL, 99.9% susceptible) was the most active compound tested against Enterobacteriaceae (22860 isolates tested) followed by cefepime (MIC90 = 0.25 microg/mL, 99.5% susceptible) > amikacin (99.4% susceptible) > ceftriaxone (95.6% susceptible) > aztreonam (95.1% susceptible). Among comparators, the lowest susceptibility rate for Enterobacteriaceae was observed with ciprofloxacin (92.8% susceptible). Imipenem was also the most active compound against ESBL-producing Klebsiella spp. and Escherichia coli (99.3% and 100% susceptible, respectively), followed by amikacin (81.4% and 97.2% susceptible, respectively) and cefepime (92.5% and 93.8% susceptible, respectively). Cefepime activity against Pseudomonas aeruginosa (85.2% susceptible) was similar to that of imipenem (86.9% susceptible). Against oxacillin-susceptible Staphylococcus aureus, cefepime (MIC90 = 4 microg/mL, 100.0% susceptible) was 4-fold more active than ceftazidime (MIC90 = 16 microg/mL, 86.4% susceptible) and showed a higher susceptibility rate than ciprofloxacin (93.2% susceptible). Cefepime was the most active compound tested against Streptococcus pneumoniae (MIC90 = 1 microg/mL, 97.4% susceptible), ranked after gatifloxacin and levofloxacin (99.2% susceptible). The activity of cefepime remained stable during the study period evaluated with the susceptibility rates varying from 99.3% to 99.8% among the Enterobacteriaceae and 84.4% to 88.4% among P. aeruginosa isolates. In summary, cefepime has retained broad activity and spectrum against Enterobacteriaceae, P. aeruginosa, and Gram-positive cocci (except oxacillin-resistant staphylococci and enterococci) isolated from North American medical centers in the 1998-2003 period. Continued resistance surveillance is critical to monitor the effectiveness of widely used parenteral antimicrobial agents such as cefepime.     

Tigecycline activity tested against 11808 bacterial pathogens recently collected from US medical centers

Tigecycline activity was evaluated against 11 808 pathogens isolated from 30 US medical centers. Susceptibility testing was performed by reference broth microdilution methods. Tigecycline (MIC_50/90, 0.12/0.25 μg/mL) was highly active against Staphylococcus aureus and coagulase-negative staphylococci, regardless of oxacillin resistance. This glycylcycline (MIC₅₀, 0.12 μg/mL) was 8- and 16-fold more potent than penicillin and linezolid against enterococci and was the most potent agent tested versus Streptococcus pneumoniae. Against Enterobacteriaceae, tigecycline (MIC₉₀, 1 μg/mL; 98.9% susceptible) was as active as imipenem. This study demonstrated the sustained potency of tigecycline against contemporary clinically relevant Gram-positive and Gram-negative pathogens; tigecycline resistance was rare (0.3%).     

Activities of the glycylcycline tigecycline (GAR-936) against 1,924 recent European clinical bacterial isolates

The in vitro activities of tigecycline against 1,924 clinical isolates were examined. The new glycylcycline exhibited excellent activity against all gram-positive cocci (MICs at which 90% of the isolates tested were inhibited [MIC(90)s], 相似文献   

Comparative activity of meropenem in US medical centers (2007): initiating the 2nd decade of MYSTIC program surveillance

Since 1997, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program has monitored the antimicrobial activity of broad-spectrum agents against pathogens from hospitalized patients. In the United States, 2894 isolates were submitted in 2007 from 15 sites, including 1392 Enterobacteriaceae, 643 nonfermentative Gram-negative bacilli, and 829 Gram-positive cocci. All isolates were tested by broth microdilution methods. Meropenem (MIC(90) range, 0.12-2 microg/mL) exhibited the lowest resistance rates (1.9-2.4%) against Enterobacteriaceae, and fluoroquinolones had the highest rates of resistance (17.3-18.3%). KPC carbapenemases, usually found in Klebsiella pneumoniae, were also detected in Citrobacter freundii, Enterobacter spp., and Escherichia coli. Confirmed extended-spectrum beta-lactamase-producing isolate rates for E. coli, Klebsiella spp., and Proteus mirabilis isolates were 6.0%, 12.0%, and 0.0%, respectively. Meropenem remained active against Gram-positive pathogens such as staphylococci (methicillin-susceptible; MIC(90), 0.12-0.25 microg/mL), Streptococcus pneumoniae (MIC(90), 0.5 microg/mL), and beta-hemolytic and viridans group streptococci (MIC(90) range, 0.06-0.25 microg/mL). These US MYSTIC Program results demonstrate the continued emergence of novel beta-lactamases and multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem activities against Enterobacteriaceae species as well as nonfermentative bacilli.     

Tigecycline activity tested against 11 808 bacterial pathogens recently collected from US medical centers

Tigecycline activity was evaluated against 11 808 pathogens isolated from 30 US medical centers. Susceptibility testing was performed by reference broth microdilution methods. Tigecycline (MIC_50/90, 0.12/0.25 μg/mL) was highly active against Staphylococcus aureus and coagulase-negative staphylococci, regardless of oxacillin resistance. This glycylcycline (MIC₅₀, 0.12 μg/mL) was 8- and 16-fold more potent than penicillin and linezolid against enterococci and was the most potent agent tested versus Streptococcus pneumoniae. Against Enterobacteriaceae, tigecycline (MIC₉₀, 1 μg/mL; 98.9% susceptible) was as active as imipenem. This study demonstrated the sustained potency of tigecycline against contemporary clinically relevant Gram-positive and Gram-negative pathogens; tigecycline resistance was rare (0.3%).     

In vitro activity of tigecycline against extended-spectrum β-lactamase-producing Enterobacteriaceae and MRSA clinical isolates from Mexico: a multicentric study

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin resistant Staphylococcus aureus (MRSA) are important nosocomial pathogens. This study reports the in vitro activity of tigecycline against 573 and 482 ESBL-producing Enterobacteriaceae and MRSA isolates, respectively. More than 94% of all tested isolates were susceptible to tigecycline; MIC(90) found was 0.25 to 2 mg/L for ESBL-producing Enterobacteriaceae and was 0.125 mg/L for MRSA. Tigecycline demonstrated excellent in vitro activity against a wide spectrum of nosocomial pathogens.     

Comprehensive assessment of tigecycline activity tested against a worldwide collection of Acinetobacter spp. (2005-2009)

A total of 5127 Acinetobacter spp. were collected from 140 hospitals in 32 countries in North America (17.1%), Europe (22.9%), Latin America (25.2%), and the Asia-Pacific (APAC) region (34.8%). Tigecycline MIC distributions were bimodal against isolates from North America and APAC region, while a unimodal pattern was noted for strains from Latin America. A variable MIC distribution was noted in Europe. Only tigecycline (MIC(50/90), 0.5/2 μg/mL) and polymyxin B (MIC(50/90), 0.5/1 μg/mL; 98.6% susceptible) exhibited high activity against Acinetobacter spp. Overall, tigecycline inhibited at least 90.0% of Acinetobacter spp. isolates from all countries evaluated at ≤2 μg/mL, as well as 95.0% of those displaying multidrug resistance. Other tested agents showed limited activity and a significant (P < 0.001) trend toward decreased susceptibility during the study period.     

Dalbavancin activity against selected populations of antimicrobial-resistant Gram-positive pathogens

Dalbavancin, a dimethylaminepropyl amide derivative of the lipoglycopeptide A40926, was tested against 375 antimicrobial-resistant Gram-positive pathogens collected worldwide during 2001-2003. The isolates were tested by reference and Clinical Laboratory Standards Institute broth microdilution susceptibility methods, and dalbavancin was compared with over 20 other antimicrobials. Vancomycin resistance determinants among enterococci were identified using PCR primer sets for vanA and vanB. Dalbavancin was generally more potent than vancomycin or teicoplanin. Dalbavancin was highly active against penicillin- and ceftriaxone-resistant Streptococcus pneumoniae strains (MIC(90), < or = 0.016 microg/mL). Dalbavancin was also very active against teicoplanin-nonsusceptible coagulase-negative staphylococci (CoNS; MIC range, 0.03-0.25 microg/mL), but dalbavancin MIC results were slightly elevated compared with wild type strains. Dalbavancin inhibited vanB enterococci (MIC range, 0.03-0.12 microg/mL) and was active against other resistant, non-vanA enterococcal species. However, vanA enterococcal strains were not as susceptible to dalbavancin (MIC50, 16 microg/mL). In summary, dalbavancin was very active against a wide spectrum of resistant Gram-positive isolates and demonstrated greater potency than vancomycin or teicoplanin.