Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006 to 2010

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n = 423), vancomycin-resistant enterococci (VRE) (n = 219), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n = 1,141), ESBL-producing Klebsiella pneumoniae (n = 1,330), Acinetobacter baumannii (n = 1,645), and Stenotrophomonas maltophilia (n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC(90), 0.03 μg/ml), and only one MRSA isolate (MIC(90), 0.5 μg/ml) and three VRE isolates (MIC(90), 0.125 μg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC(90), 0.5 μg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC(90), 2 μg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC(90), 4 μg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.     

Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008 to 2010

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.     

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.     

替加环素对414株需氧革兰阴性和革兰阳性临床分离菌株的体外抗菌活性

目的测定替加环素等15种抗菌药物对我院2004年和2005年临床分离的414株革兰阴性菌和革兰阳性需氧菌的体外抗菌活性。方法采用微量肉汤稀释法测定替加环素等15种抗菌药物对所测菌株的MIC,数据分析采用WHONET5.3软件。结果MRSA对替加环素、利奈唑胺及万古霉素的敏感率均为100%,替加环素对MRSA的MIC90是所测抗菌药物中最低者;万古霉素耐药肠球菌(VRE)对替加环素及利奈唑胺敏感率均为100%,替加环素对所有肠球菌的MIC90分别是利奈唑胺和万古霉素的MIC90的1/8和1/16;替加环素对青霉素中介肺炎链球菌(PISP)的MIC90为0.5mg/L,对青霉素耐药肺炎链球菌(PRSP)的MIC范围是0.25~1mg/L,其他抗菌药物对PISP和PRSP的MIC90是替加环素的1~32倍;替加环素对亚胺培南耐药的鲍曼不动杆菌的MIC范围是其他抗菌药物的1/2~1/64;对铜绿假单胞菌的MIC90是32mg/L;产ESBLs大肠埃希菌和肺炎克雷伯菌对替加环素、美罗培南和亚胺培南敏感率均为100%。结论替加环素对铜绿假单胞菌的抗菌活性较差,对其他需氧革兰阴性杆菌有较好的体外抗菌活性;对需氧革兰阳性球菌的抗菌活性最强。     

In vitro activity of cefditoren and other antimicrobial agents against 288 Streptococcus pneumoniae and 220 Haemophilus influenzae clinical strains isolated in Zaragoza, Spain

In vitro cefditoren antimicrobial activity was tested against 288 Streptococcus pneumoniae and 220 Haemophilus influenzae clinical strains isolated in our hospital from January 2005 to May 2006 by agar dilution and broth microdilution method, respectively. MICs were also determined for 13 and 10 comparison drugs, respectively. The pneumococci tested comprised 113 (39.2%) penicillin susceptible, 91 (31.6%) penicillin intermediate, and 84 (29.2%) penicillin resistant. Cefditoren was the most active drug on the basis of the MICs (MIC(90)=0.5 microg/mL), followed by ceftriaxone and levofloxacin (MIC(90)=1 microg/mL). Cefditoren MICs ranged from 0.25 to 1 microg/mL for ceftriaxone-resistant isolates, with a modal MIC of 0.5 microg/mL and an MIC(90) of 1.0 microg/mL. No S. pneumoniae isolates evaluated in this study showed MICs to cefditoren higher than 1 microg/mL (MIC range, 4 microg/mL). Against H. influenzae (Hi beta+), the rank order of intrinsic activity (MIC(90), microg/mL) was cefditoren (0.03) < cefixime (0.06)8.0).     

Antimicrobial susceptibility among pathogens collected from hospitalized patients in the United States and in vitro activity of tigecycline, a new glycylcycline antimicrobial

The activities of tigecycline and comparators against isolates collected from 76 U.S. centers between January 2004 and September 2005 were assessed. Tigecycline MIC(90)s were < or =2 microg/ml for Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, and Streptococcus agalactiae.     

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.     

Antimicrobial susceptibility of 3931 organisms isolated from intensive care units in Canada: Canadian National Intensive Care Unit Study, 2005/2006

We tested the in vitro activity of 15 antimicrobials against Gram-positive cocci and 12 antimicrobials against Gram-negative bacilli versus 3931 isolates (20 most common organisms) obtained between September 1, 2005, and June 30, 2006, from 19 intensive care units (ICUs) across Canada. The most active (based upon MIC only) agents against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis were dalbavancin, daptomycin, linezolid, tigecycline, and vancomycin with MIC(90) (microg/mL) of 0.06 and < or =0.03, 0.25 and 0.12, 2 and 1, 0.5 and 0.5, and 1 and 2, respectively. The most active agents against vancomycin-resistant enterococci were daptomycin, linezolid, and tigecycline with MIC(90) (microg/mL) of 1, 4, and 0.12, respectively. The most active agents against Escherichia coli were amikacin, cefepime, meropenem, piperacillin/tazobactam, and tigecycline with MIC(90) (microg/mL) of 4, < or =1, < or =0.12, 8, and 0.5, respectively. The most active agents against extended-spectrum beta-lactamase-producing E. coli were meropenem and tigecycline with MIC(90) (microg/mL) of < or =0.12 and 1, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, meropenem, and piperacillin/tazobactam with MIC(90) (microg/mL) of 16, 32, 16, and 64, respectively. The most active agents against Stenotrophomonas maltophilia were tigecycline and trimethoprim/sulfamethoxazole with MIC(90) (microg/mL) of 4 and 4, respectively. The most active agents against Acinetobacter baumannii were fluoroquinolones (e.g., levofloxacin), meropenem, and tigecycline with MIC(90) (microg/mL) of 0.5, 1, and 2, respectively. In conclusion, the most active agents versus Gram-positive cocci and Gram-negative bacilli obtained from Canadian ICUs were daptomycin, linezolid, tigecycline, dalbavancin and amikacin, cefepime, meropenem, piperacillin/tazobactam, and tigecycline (not P. aeruginosa), respectively.     

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.     

Contemporary re-evaluation of the activity and spectrum of grepafloxacin tested against isolates in the United States

Grepafloxacin potency and spectrum of activity were re-evaluated against contemporary pathogens collected from clinical infections in 2001-2002. A total of 995 isolates were tested for grepafloxacin by the reference agar dilution method and these results were compared to those of 25 other antimicrobial agents. Grepafloxacin activity remained comparable to that of ciprofloxacin, levofloxacin and gatifloxacin against Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae (MIC(90), 0.03-2 microg/ml; 0.0-7.7% resistance rates). For Pseudomonas aeruginosa, grepafloxacin was active against ciprofloxacin-susceptible (MIC(90), 2 microg/ml), but not against ciprofloxacin-resistant (MIC(90), >8 microg/ml) isolates. Against methicillin-susceptible Staphylococcus aureus, grepafloxacin susceptibility rate was 91.4%, equal to that of levofloxacin. None of the fluoroquinolones showed reasonable activity against methicillin-resistant staphylococci. Gatifloxacin and grepafloxacin had the same MIC(90) against beta-hemolytic streptococci (0.25 microg/ml) and penicillin-susceptible Streptococcus pneumoniae (0.25 microg/ml). Grepafloxacin and other fluoroquinolone activities were not influenced by penicillin resistance in S. pneumoniae. Grepafloxacin was very active against Haemophilus influenzae (MIC(90), 0.03 microg/ml), Moraxella catarrhalis (MIC(90), 0.03 microg/ml) and Legionella spp. (MIC(90), 0.5 microg/ml). These results on recently isolated organisms indicate that grepafloxacin has a sustained potency and spectrum against most clinically important and indicated pathogens.     

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.     

Antibiotic coresistance in extended-spectrum-beta-lactamase-producing Enterobacteriaceae and in vitro activity of tigecycline

The spread of extended-spectrum-beta-lactamase (ESBL)-producing organisms, particularly those harboring the CTX-M-type enzymes, both in the hospital and in the community, is difficult to discontinue due to the successful mobilization and evolution of the genetic elements harboring ESBL genes and coresistance rates in these isolates. The activities of tigecycline against 285 non-clonally related isolates (172 from Escherichia coli, 84 from Klebsiella spp., 20 from Enterobacter spp., 5 from Salmonella spp., and 4 from Citrobacter spp.) expressing well-characterized ESBLs and recovered in our hospital and its community area of influence were comparatively assessed (CLSI microdilution). Susceptibility rates for meropenem, imipenem, tigecycline, amikacin, and piperacillin-tazobactam were 100%, 100%, 97.5%, 93.3%, and 93%, respectively. Tigecycline (mode MIC, 0.5 microg/ml; MIC(90), 1 microg/ml) was 4- to 256-fold more active than doxycycline and minocycline (mode MIC range, 2 to 128 microg/ml). CTX-Ms were the most frequent ESBLs (61.4%), 65.8% in community and 58.6% in nosocomial isolates. CTX-M-9 (22%), CTX-M-14 (15.8%), and CTX-M-10 (14%) were the most represented derivatives. SHV and TEM variants constituted 22.8% and 15.8% of the ESBLs, respectively. Overall coresistance rates were as follows: gentamicin, 27.4%; tobramycin, 27.4%; amikacin, 6.7%; and chloramphenicol, 29.1%. Sulfonamide (61.7%), trimethoprim (52.3%), streptomycin (50.5%), and ciprofloxacin (37.2%) resistance levels were significantly (P < 0.001) associated with CTX-M-9 producers. No tigecycline resistance was observed, although seven Klebsiella pneumoniae isolates exhibited intermediate MICs (4 mug/ml). Tigecycline, lacking cross-resistance with other compounds, could represent an opportunity to reduce the intensity of selection for ESBL-producing organisms derived from the use of other antimicrobial agents. However, this in vitro promise requires support from clinical studies.     

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.     

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.     

Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.     

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.     

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.     

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.     

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.     

临床常见革兰阴性杆菌对替加环素的药敏情况分析

目的 了解临床常见革兰阴性杆菌对替加环素的耐药情况。方法 收集2012年9月～10月浙江省9个城市15家医院的393株鲍曼不动杆菌复合群以及2012年1月～12月浙江大学医学院附属第二医院的115株大肠埃希菌,110株肺炎克雷伯菌和99株鲍曼不动杆菌复合群。用Vitek-2 Compact全自动微生物鉴定仪对细菌做鉴定及药物敏感性试验。393株分离自全省的鲍曼不动杆菌复合群用基质辅助激光解析/电离飞行时间质谱仪(matrix-assisted laser desorption/ionization time of flight mass spectrometr,MALDI-TOF MS)进行鉴定。另外挑取393株鲍曼不动杆菌复合群中GN-AST16药敏卡MIC值≥8 μg/ml或4 μg/ml的所有菌株以及少部分MIC值在≤0.5 μg/ml～2 μg/ml之间的不动杆菌159株,这些菌株同时采用Etest法和GN-AST16药敏卡对替加环素的药敏情况进行比较。结果 393株鲍曼不动杆菌复合群经MALDI-TOF MS鉴定为317株鲍曼不动杆菌,32株皮氏不动杆菌和44株医院不动杆菌。采用FDA标准,115株大肠埃希菌对替加环素的耐药率为0.0%; 110株肺炎克雷伯菌对替加环素的耐药率为7.3%; 99株鲍曼不动杆菌复合群对替加环素的耐药率为6.1%。替加环素耐药革兰阴性杆菌中,85.7%(12/14)对碳青霉烯类耐药; 而碳青霉烯类耐药革兰阴性杆菌中,仅10.0%(12/120)对替加环素耐药。结论 替加环素对临床常见的多重耐药甚至泛耐药革兰阴性杆菌有较好的抗菌活性。不管采用FDA还是EUCAST判读标准,Etest方法的耐药率比GN-AST16药敏卡方法稍低。