In vitro antibacterial activity of LY333328, a new semisynthetic glycopeptide.

LY333328 is a semisynthetic N-alkyl derivative of LY264826, a naturally occurring structural analog of vancomycin. LY333328 was evaluated for its in vitro inhibitory and bactericidal activities in comparison with those of the two currently available glycopeptides (vancomycin and teicoplanin). Glycopeptide-susceptible test strains included a total of 311 isolates (most of clinical origin) from the genera Staphylococcus, Enterococcus, Streptococcus, Aerococcus, Gemella, Lactococcus, Listeria, Corynebacterium, and Clostridium. Test strains resistant or intermediate to vancomycin and/or teicoplanin included 56 clinical isolates of Enterococcus (of the VanA, VanB, and VanC phenotypes) and 32 clinical isolates of Staphylococcus (S. haemolyticus, S. epidermidis, and S. aureus), 31 strains of gram-positive genera outside the spectrum of activity of vancomycin (Leuconostoc, Pediococcus, Lactobacillus, and Erysipelothrix), and laboratory-derived organisms obtained after exposure of susceptible Staphylococcus isolates to teicoplanin (6 strains) or laboratory-derived organisms with resistance determinants received from VanA enterococci (2 Enterococcus and 25 Listeria transconjugants). LY333328 was highly active against staphylococci, enterococci, and listeriae (whether they were clinical or laboratory-derived strains) resistant to the currently available glycopeptides. In particular, the MICs of LY333328 did not vary substantially between teicoplanin-susceptible and teicoplanin-resistant staphylococci and between vancomycin-susceptible and vancomycin-resistant enterococci. LY333328 demonstrated fairly good inhibitory activity even against most strains of Leuconostoc, Pediococcus, and Erysipelothrix (MIC range, 1 to 8 microg/ml), whereas it proved less active (although much more active than vancomycin or teicoplanin) against Lactobacillus strains. In minimal bactericidal concentration (MBC) and time-kill studies, LY333328 demonstrated excellent bactericidal activity; enterococci, in particular, which were largely tolerant of vancomycin and teicoplanin, were uniformly killed by LY333328, with MBC-to-MIC ratios of 4 to 8 for most vancomycin-susceptible and vancomycin-resistant strains. In attempts to select for resistant clones, no survivors stably growing in the presence of 10 microg of LY333328 per ml were obtained from the Staphylococcus and Enterococcus test strains exposed to the drug.     

Activity of tigecycline (GAR-936), a novel glycylcycline,against Enterococci in the mouse peritonitis model

A novel glycylcycline agent, tigecycline (GAR-936), was evaluated in vivo in the mouse model of peritonitis against three Enterococcus faecalis and four Enterococcus faecium isolates with different susceptibilities to vancomycin and tetracyclines, all of which were inhibited by 相似文献   

Time-kill and synergism studies of ceftobiprole against Enterococcus faecalis, including beta-lactamase-producing and vancomycin-resistant isolates

Ceftobiprole (BAL9141) is an investigational cephalosporin with broad in vitro activity against gram-positive cocci, including enterococci. Ceftobiprole MICs were determined for 93 isolates of Enterococcus faecalis (including 16 beta-lactamase [Bla] producers and 17 vancomycin-resistant isolates) by an agar dilution method following the Clinical and Laboratory Standards Institute recommendations. Ceftobiprole MICs were also determined with a high inoculum concentration (10(7) CFU/ml) for a subset of five Bla producers belonging to different previously characterized clones by a broth dilution method. Time-kill and synergism studies (with either streptomycin or gentamicin) were performed with two beta-lactamase-producing isolates (TX0630 and TX5070) and two vancomycin-resistant isolates (TX2484 [VanB] and TX2784 [VanA]). The MICs of ceftobiprole for 50 and 90% of the isolates tested were 0.25 and 1 microg/ml, respectively. All Bla producers and vancomycin-resistant isolates were inhibited by concentrations of 相似文献   

European survey of vancomycin-resistant enterococci in at-risk hospital wards and in vitro susceptibility testing of ramoplanin against these isolates

A survey in eight European countries, including 13 hospitals, of vancomycin-resistant enterococci (VRE) in at-risk hospital wards (such as the ICU and the haematology ward) was performed in 2001, and the in vitro susceptibility of the isolates ramoplanin and other drugs was tested. A total of 1314 non-duplicate clinical enterococcal isolates were collected, and 38 (2.9%) were vancomycin resistant: 27 Enterococcus faecium and 11 Enterococcus faecalis; 35 VanA and three VanB phenotypes. Rates of VRE among clinical enterococcal isolates varied between 0 and 1.7% for the participating countries, except the UK (10.4%) and Italy (19.6%). One hundred and twenty-three (3.5%) VRE were found among 3499 stool samples tested for the presence of these organisms: 111 (3.2%) E. faecium and 12 (0.3%) E. faecalis; 114 (3.3%) VanA and nine (0.3%) VanB phenotypes. Rates of intestinal colonization with VRE varied between 0 and 1.2% for the participating countries, except Italy (7.5%) and the UK (32.6%). In vitro susceptibility testing showed that the Italian and UK VRE are multi-resistant (including resistance to ampicillin and high-level resistance to gentamicin and streptomycin), and that ramoplanin was active against all strains of VRE, with an MIC90 of 0.5 mg/L for clinical isolates. Pulsed-field gel electrophoresis showed that the high prevalence of VRE in the Italian and UK centres was related to the monoclonal emergence and spread of three centre-specific clones. This survey suggests that in some centres in Europe, a similar situation may be encountered to that in the USA (monoclonal spread of multi-resistant VRE in at-risk wards).     

Use of primers selective for vancomycin resistance genes to determine van genotype in enterococci and to study gene organization in VanA isolates.

Vancomycin resistance in enterococci is an emerging therapeutic problem. Resistance is not always detected by standard microbiological methods. Oligonucleotide primers for PCR were designed to target amplification of defined regions of genes of the vanA cluster, as well as vanB and vanC1. These primers correctly identified 30 vancomycin-resistant isolates tested (17 VanA, 7 VanB, and 6 Enterococcus gallinarum). No amplification was observed with Enterococcus casseliflavus or vancomycin-susceptible strains. Using PCR and Southern blotting, we found that all 17 VanA isolates had orf-1, orf-2, vanR, vanS, vanH, vanA, and vanY genes in the same sequence and that the intergenic distances in the vanR-vanA segments were the same. The described methods should be applicable to the rapid detection of the different vancomycin resistance genotypes in enterococci.     

Absence of synergistic activity between ampicillin and vancomycin against highly vancomycin-resistant enterococci.

The emergence of clinical enterococcal isolates resistant to both ampicillin and vancomycin is a cause of great concern, as there are few therapeutic alternatives for treatment of infections caused by such organisms. We evaluated the effects of the combination of ampicillin with vancomycin against vancomycin-resistant clinical enterococcal isolates. Using both the checkerboard technique and time-kill curves, we examined 28 strains of enterococci (17 Enterococcus faecalis and 11 Enterococcus faecium strains) with different levels of resistance to vancomycin. Of these, 15 strains were also highly gentamicin resistant, and 9 demonstrated resistance to ampicillin. Only seven strains of E. faecalis were inhibited synergistically by the combination of vancomycin with ampicillin, and even then, the concentrations of vancomycin at which synergism was demonstrated were above levels achievable in serum. None of the ampicillin-resistant isolates (all E. faecium) were inhibited synergistically at any concentration of the drugs. In no instance was bactericidal synergism observed, and in most cases the combination resulted in less killing than with ampicillin alone. Antagonism was not observed at clinically relevant concentrations. The results of this study suggest that the combination of vancomycin with ampicillin has little to offer against these emerging pathogens.     

CPT-EIA assays for the detection of vancomycin resistant vanA and vanB genes in enterococci

Cycling Probe Technology (CPT) was combined with a colorimetric enzyme-immuno assay (EIA) to develop two assays for the detection of vanA and vanB genes in vancomycin resistant enterococci (VRE). The CPT-EIA assay employs a gene-specific fluorescein labeled DNA-RNA-DNA probe that gets cleaved within the probe : target duplex. The cleaved DNA probe fragments dissociate from the target, making it available for further cycling. Following the separation of cleaved probe fragments, anti-fluorescein-horseradish peroxidase antibodies are used for the detection of uncleaved probes. The two CPT-EIA assays were used to screen a collection of 440 clinical isolates (Modrusan et al., 1999). All of the 154 VanA and 131 VanB isolates were correctly identified in the vanA and vanB CPT-EIA, respectively. The VanA and VanB isolates were differentiated from vancomycin sensitive enterococci (VSE) and also from the VanC isolates. In addition, an accurate VRE detection in the CPT-EIA assay was shown with cultures grown on eight different media.     

Therapeutic efficacy of GAR-936, a novel glycylcycline, in a rat model of experimental endocarditis

GAR-936, a novel glycylcycline, was investigated with a rat model of experimental endocarditis. It was compared with vancomycin against both vancomycin-susceptible and -resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus. GAR-936 exhibited the lowest MICs (2 log(10) CFU, compared to those in untreated controls, for both vancomycin-susceptible and -resistant (VanA and VanB) E. faecalis strains and >4 log(10) CFU for a methicillin-resistant S. aureus isolate. The glycylcycline was more efficacious at a lower administered dose in the rat model of endocarditis than was vancomycin. The efficacy of GAR-936 in this model was apparently not enhanced by a factor in rat serum, as was observed for vancomycin with a time-kill curve. The results of this study demonstrate the therapeutic potential of GAR-936 for the treatment of enterococcal and staphylococcal infections and warrant further investigation.     

258株肠球菌耐药性分析及耐万古霉素基因检测

目的研究肠球菌的耐药率及耐万古霉素肠球菌(VRE)的耐药表型和基因型。方法按照美国临床和实验室标准化研究所(CLSI)2009年推荐的微量稀释法进行临床分离肠球菌对各类药物的最小抑菌浓度(MIC)检测,VRE进一步用E-test药敏试验确认;PCR法检测VRE的耐药基因。结果 2010年7月至2011年11月沈阳军区总医院共检出粪肠球菌95株,屎肠球菌163株。粪肠球菌对万古霉素、替考拉宁保持较高敏感度,对氨苄西林、青霉素、呋喃妥因三种抗菌药物敏感度也在65%以上,对其他抗菌药物敏感度低,统计期内未检出耐万古霉素粪肠球菌菌株。屎肠球菌对多数抗菌药物表现为耐药,对氯霉素敏感率为70%,对万古霉素、替考拉宁敏感度下降,为90.7%。期间检出15株VRE,其耐药表型为多重耐药,PCR扩增结果显示,15株万古霉素耐药屎肠球菌VanA基因扩增均为阳性,产物长度在700～1000bp之间,约783bp,符合预期;VanB、VanC引物扩增均阴性。15株万古霉素耐药屎肠球菌对多数抗菌药物耐药,仅对氯霉素、四环素相对敏感,对万古霉素MIC>256mg/L,对替考拉宁也表现为耐药。结论屎肠球菌耐药性高于粪肠球菌,VRE多为多重耐药,给临床治疗带来困难,医院应加强对其预防监测。     

In-vitro activity of fosfomycin against vancomycin-resistant enterococci

The effect of fosfomycin against 69 vancomycin-resistant isolates of Enterococcus faecium (VanA), five of E. faecium (VanB), 11 of Enterococcus faecalis (VanA), three of E. faecalis (VanB), 10 of Enterococcus gallinarum (VanC1) and two of Enterococcus casseliflavus (VanC2) and glycopeptide-sensitive E. faecium (n = 8) and E. faecalis (n = 10) was tested in vitro. Fosfomycin inhibited 97%, 94% and 96% of the vancomycin-resistant strains, according to results of agar dilution, broth microdilution, and a disc diffusion method (DIN 58940). The disc diffusion test by the NCCLS method does not include fosfomycin; using breakpoints suggested by Andrews et al. (< or = 11 mm, resistant; > or = 18 mm, susceptible), 5% of the vancomycin-resistant strains tested would have been considered fosfomycin resistant. Minimal inhibitory concentrations of most vancomycin-resistant isolates were in the intermediate sensitivity range, yielding an MIC50 of 32 mg/L and an MIC90 of 64 mg/L. Moreover the majority of inhibitory zone sizes by the disc diffusion method (DIN 58940) corresponded to intermediate susceptibility. These results suggest that fosfomycin at a high dosage and possibly used in combination with other drugs could be a potentially useful drug for the treatment of infections caused by vancomycin-resistant enterococci.     

Surveillance of vancomycin-resistant <Emphasis Type="Italic">Enterococcus</Emphasis> in hospitals in Ibaraki prefecture

We surveyed the prevalence of vancomycin-resistant Enterococcus (VRE) in six hospitals in Ibaraki prefecture. Three hundred and fifty-five fecal specimens were examined and 18 Enterococcus intermediately resistant to vancomycin were isolated. All of them were vanC genotypes (16 vanC-1 and 2 vanC-2 genotypes) and susceptible or intermediately resistant to ampicillin, teicoplanin, linezolid, and quinupristin-dalfopristin. Neither the vanA nor vanB gene was detected. Two of the vanC genotypes were not motile. We concluded that VRE of either VanA or VanB phenotype or those highly resistant to the antibiotics commonly used against enterococcal infection were not epidemic in this prefecture to date. In addition, we consider that detection of vancomycin-resistant genes should be encouraged for the characterization of VRE, because the vanC genotypes are occasionally motility-negative and can be misinterpreted as other Enterococcus species.     

Measurement of ampicillin, vancomycin, linezolid and gentamicin activity against enterococcal biofilms

BACKGROUND: Enterococci frequently cause biofilm infections but susceptibility of clinical isolates growing in biofilms has not been investigated. The minimum biofilm eradicating concentration (MBEC) has been suggested as a guide to treatment of biofilm infections. We measured an alternative endpoint, the minimum biofilm inhibitory concentration (MBIC) and compared the results with MIC and MBC. OBJECTIVES: To compare the MIC, MBC and MBIC of ampicillin, vancomycin and linezolid against enterococcal biofilms, to assess the impact of additional gentamicin and correlate findings with clinical outcome. METHODS: MIC and MBC were measured using standard techniques. MBICs were measured using a modification of the Calgary biofilm device method. Fifty-eight enterococcal isolates from episodes of intravascular catheter-related bloodstream infection were tested. RESULTS: Tolerance to ampicillin, vancomycin and linezolid was seen in 93%, 100% and 93% of isolates, respectively. MIC(90)s of ampicillin, vancomycin and linezolid were all 4 mg/L for Enterococcus faecalis isolates. MBC(90)s of ampicillin, vancomycin and linezolid for E. faecalis isolates were 1024, >128 and 2048 mg/L, respectively. MBIC(90)s of ampicillin, vancomycin and linezolid for E. faecalis isolates were 8192, 4096 and 4096 mg/L, respectively. Results for Enterococcus faecium were similar for vancomycin and linezolid but this species was generally more resistant to ampicillin. Adding 10 mg/L gentamicin had a variable effect on MIC, MBC or MBIC, which was not predictable by gentamicin susceptibility on disc testing. CONCLUSIONS: Very high concentrations of ampicillin, vancomycin and linezolid are required to inhibit enterococcal biofilms in vitro. Combining these agents with gentamicin significantly reduced MIC, MBC and MBIC against only a proportion of enterococcal isolates. No correlation between MBIC and outcome was found.     

Impact of elements containing glycopeptide resistance genes on expression of virulence in Enterococcus faecalis peritonitis: a pilot study with rats

The relationship between virulence and chromosomal elements containing glycopeptide resistance genes was experimentally assessed for two transconjugant strains of Enterococcus faecalis (VanA and VanB phenotypes) and compared to that for a susceptible wild-type strain. Microbiologic and inflammatory effects were assessed in a polymicrobial rat model of peritonitis. Mean peritoneal enterococcus concentrations +/- standard deviations at day 1 were 2.1 +/- 1.9, 1.3 +/- 1.1, and 1.7 +/- 2.0 log(10) CFU/ml for susceptible, VanA, and VanB strains, respectively (P < 0.05). At day 3 also there were lower concentrations of glycopeptide-resistant enterococcal strains in peritoneal fluid (3.2 +/- 3.4, 1.8 +/- 1.8, and 2.1 +/- 2.4 log(10) CFU/ml for susceptible, VanA, and VanB strains, respectively [P < 0.05]). Transconjugant glycopeptide-resistant strains were associated with increased peritoneal cell counts at the different evaluation times of the experiment (P < 0.001). Plasma alpha1-acid glycoprotein concentrations were lower in the presence of the susceptible strain (667 +/- 189 mg/liter) than in the presence of the VanA or VanB strain (1,193 +/- 419 or 1,210 +/- 404 mg/liter, respectively [P < 0.05]), while concentrations of tumor necrosis factor alpha and interleukin-6 in peritoneal fluid remained similar for the strains. These results suggest a trend toward variation of virulence of transconjugant strains compared to the wild-type strain in this peritonitis model.     

Characterization of Vancomycin-Resistant Enterococcus faecium Isolates from the United States and Their Susceptibility In Vitro to Dalfopristin-Quinupristin

In the course of clinical studies with the investigational streptogramin antimicrobial dalfopristin-quinupristin, isolates of vancomycin-resistant Enterococcus faecium were referred to our laboratory from across the United States. Seventy-two percent of the strains were of the VanA type, phenotypically and genotypically, while 28% were of the VanB type. High-level resistance to streptomycin or gentamicin was observed in 86 and 81%, respectively, of the VanA strains but in only 69 and 66%, respectively, of the VanB strains. These enterococci were resistant to ampicillin (MIC for 50% of the isolates tested [MIC₅₀] and MIC₉₀, 128 and 256 μg/ml, respectively) and to the other approved agents tested, with the exception of chloramphenicol (MIC₉₀, 8 μg/ml) and novobiocin (MIC₉₀, 1 μg/ml). Considering all of the isolates submitted, dalfopristin-quinupristin inhibited 86.4% of them at concentrations of ≤1 μg/ml and 95.1% of them at ≤2 μg/ml. However, for the data set comprised of only the first isolate submitted for each patient, 94.3% of the strains were inhibited at concentrations of ≤1 μg/ml and 98.9% were inhibited at concentrations of ≤2 μg/ml. Multiple drug resistance was very common among these isolates of vancomycin-resistant E. faecium, while dalfopristin-quinupristin inhibited the majority at concentrations that are likely to be clinically relevant.     

Novel antibiotic regimens against Enterococcus faecium resistant to ampicillin, vancomycin, and gentamicin.

Enterococci have emerged as significant nosocomial pathogens. Enterococci with resistance to commonly used antibiotics are appearing more frequently. We encountered at our institution several infections caused by Enterococcus faecium with high-level resistance to ampicillin, vancomycin, and gentamicin. The optimal antibiotic therapy for serious infections with unusually resistant enterococci has not been established. Using time-kill studies, we tested the effectiveness of various antibiotic combinations against 15 isolates of multidrug-resistant enterococci. No antibiotic was consistently effective when used alone. The combination of ampicillin plus ciprofloxacin was bactericidal for the 12 isolates for which the ciprofloxacin MIC was < or = 8 micrograms/ml. The combination of ciprofloxacin plus novobiocin also demonstrated activity against these isolates. No combination was found to be bactericidal for the remaining three isolates, which were highly ciprofloxacin resistant. These antibiotic combinations may be important for the future treatment of serious infections caused by these resistant pathogens.     

Constitutively vancomycin-resistant Enterococcus faecium resistant to synergistic beta-lactam combinations.

Vancomycin resistance among enterococci has recently been recognized. Synergy between vancomycin and penicillin has been shown in vitro for isolates of Enterococcus faecium resistant to both of these antibiotics. We describe three isolates of vancomycin-resistant E. faecium which demonstrate unique phenotypic characteristics. The isolates exhibited high-level resistance to both vancomycin and teicoplanin, consistent with the VanA phenotype. However, resistance in these isolates could not be induced or cured, and mating experiments failed to detect a transfer of resistance. The combination of vancomycin and penicillin did not significantly change the MIC of penicillin for any of the three isolates. Immunoblotting with polyclonal anti-VanB antibody showed no reaction with the cellular proteins of these strains. Probing with a vanA oligonucleotide revealed hybridization with chromosomal but not plasmid DNA. The mechanism of constitutive resistance of those strains remains unclear. A second mutational change, perhaps involving PBP 5, may explain the presence of resistance to synergistic combination penicillin-vancomycin therapy. In vitro evaluation of penicillin-vancomycin should be carried out in all clinical cases where this therapeutic regimen is being considered.     

Beta-Lactam-beta-lactamase-inhibitor combinations are active in experimental endocarditis caused by beta-lactamase-producing oxacillin-resistant staphylococci.

Optimal therapeutic strategies for serious infections caused by borderline and heterotypic oxacillin-resistant Staphylococcus aureus (BORSA and ORSA) strains have not been fully characterized. Recent evidence suggests that the dominant penicillin-binding protein of ORSA strains (PBP 2a) shows good affinity for ampicillin and that these strains commonly produce beta-lactamase. Therefore, we compared the in vivo efficacy of the combination of ampicillin plus sulbactam with that of vancomycin against ORSA strains. Also, the moderate resistance of BORSA strains appears to be attributable mainly to the hyperproduction of beta-lactamase. Therefore, we also studied the in vivo efficacy of ampicillin plus sulbactam against such organisms. Experimental aortic endocarditis was induced in rabbits by the following three strains: beta-lactamase-producing BORSA strain VP-986, beta-lactamase-producing ORSA strain 67-0, and its beta-lactamase-negative clone. In animals with BORSA endocarditis, ampicillin plus sulbactam and oxacillin were highly effective in reducing mean intravegetation bacterial densities, with each being significantly better than either ampicillin alone or no therapy. In animals with endocarditis caused by the beta-lactamase-producing ORSA strain, ampicillin plus sulbactam was significantly better at reducing mean vegetation bacterial densities than the other regimens. For endocarditis caused by the beta-lactamase-negative ORSA clone, ampicillin was better than vancomycin in reducing mean intravegetation bacterial densities. These data show that infections caused by beta-lactamase-producing BORSA strains respond therapeutically in a manner similar to that of infections caused by oxacillin-susceptible strains, with both oxacillin and ampicillin plus sulbactam being highly efficacious. Moreover, high-dose ampicillin treatment strategies were effective in the therapy of ORSA endocarditis; this efficacy is presumably related to the relatively high affinity profile of this compound (compare with that of oxacillin) for the functionally dominant ORSA PBP 2a.     

Influence of high-level gentamicin resistance and beta-hemolysis on susceptibility of enterococci to the bactericidal activities of ampicillin and vancomycin.

The bactericidal activities of ampicillin and vancomycin against 40 recent isolates of Enterococcus faecalis were examined by kill-kinetic studies at concentrations of 4 x the MIC and 20 micrograms/ml. Greater killing was seen with ampicillin (3.57 +/- 0.87 and 2.50 +/- 1.09 log10 CFU/ml, respectively; mean +/- standard deviation) than with vancomycin (1.23 +/- 0.65 and 1.05 +/- 0.57 log10 CFU/ml, respectively). Highly gentamicin-resistant strains showed a tendency toward reduced susceptibility to killing; beta-hemolytic strains were more susceptible than nonhemolytic strains when exposed to ampicillin at 20 micrograms/ml. Within each group, individual isolates demonstrated great variability in susceptibility to killing by the drugs.     

Treatment evaluation of experimental staphylococcal infections: comparison of beta-lactam, lipopeptide, and glycopeptide antimicrobial therapy

LY 146032, teicoplanin, vancomycin, oxacillin, cephalothin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam were studied against six isolates of staphylococci (including both Staphylococcus aureus and coagulase negative staphylococci) using in vivo and in vitro methods. In vitro susceptibility measurements demonstrated that all six isolates were sensitive to LY 146032 and vancomycin and that five of six isolates were sensitive to tiecoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam. Comparison of antimicrobial therapy in an in vivo rabbit model demonstrated that cefoperazone plus sulbactam was active against the greatest number of isolates (five of six) based on a reduction of greater than or equal to 5.0 log10 colony forming units per milliliter (CFU/ml) from growth control at the end of the animal treatment study. Vancomycin and oxacillin were equal in achieving reductions of greater than or equal to 5.0 log10 CFU/ml in four of the six isolates. Comparing each isolate's in vivo outcome to in vitro data shows that in vitro susceptibility tests overpredict the sensitivity of these six isolates to LY 146032 and vancomycin, are variable for teicoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam, and underpredict for oxacillin.     

Comparative surveillance study of telavancin activity against recently collected gram-positive clinical isolates from across the United States

Telavancin is an investigational, rapidly bactericidal lipoglycopeptide antibiotic that is being developed to treat serious infections caused by gram-positive bacteria. A baseline prospective surveillance study was conducted to assess telavancin activity, in comparison with other agents, against contemporary clinical isolates collected from 2004 to 2005 from across the United States. Nearly 4,000 isolates were collected, including staphylococci, enterococci, and streptococci (pneumococci, beta-hemolytic, and viridans). Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range, 0.03 to 1.0 microg/ml), independent of resistance to methicillin or to multiple agents. Telavancin activity was particularly potent against all streptococcal groups (MIC(90)s, 0.03 to 0.12 microg/ml). Telavancin had excellent activity against vancomycin-susceptible enterococci (MIC(90), 1 microg/ml) and was active against VanB strains of vancomycin-resistant enterococci (MIC(90), 2 microg/ml) but less active against VanA strains (MIC(90), 8 to 16 microg/ml). Telavancin also demonstrated activity against vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains (MICs, 0.5 microg/ml to 1.0 microg/ml and 1.0 microg/ml to 4.0 microg/ml, respectively). These data may support the efficacy of telavancin for treatment of serious infections with a wide range of gram-positive organisms.