首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
Among 10 coagulase-negative staphylococci, telavancin, quinupristin/dalfopristin, and tigecycline were the most potent antimicrobials. Telavancin exhibited bactericidal effect to 9 strains out of 10 tested at 4× MIC after 24 h of exposure similar to those of vancomycin and daptomycin. By contrast, linezolid was mainly bacteriostatic and teicoplanin was bactericidal to 7 strains tested at 4× MIC after 24 h.  相似文献   

2.
Our objective was to evaluate and compare the in vitro activity of daptomycin, linezolid, and quinupristin/dalfopristin against clinical bloodstream isolates of Gram-positive pathogens from a large cancer center in the Northeastern United States. Minimum inhibitory concentrations (MICs) were determined for daptomycin, quinupristin/dalfopristin, and linezolid against 258 isolates; bactericidal activity was evaluated using time-kill experiments against 14 representative pathogens. Vancomycin-resistant enterococci represented the largest proportion of bacteria tested (32% of the isolates), followed by methicillin-resistant coagulase-negative staphylococci (23%), and vancomycin sensitive enterococci (14%). Against staphylococci, the MIC90 was 1 microg/mL for both daptomycin and quinupristin/dalfopristin and 4 microg/mL for linezolid. Against enterococci, the MIC90 for both daptomycin and linezolid was 4 microg/mL and was 16 microg/mL for quinupristin/dalfopristin. The quinupristin/dalfopristin MIC90 for Enterococcus faecium was 2 microg/mL. Two enterococci were linezolid resistant and remained susceptible to daptomycin. In vitro time-kill studies found daptomycin to be rapidly bactericidal against the majority of organisms tested, killing 99.9% of bacteria within 6 h. Quinupristin/dalfopristin was bactericidal against staphylococci and bacteriostatic against most enterococci. Linezolid was bacteriostatic against all organisms evaluated. Daptomycin, quinupristin/dalfopristin, and linezolid each demonstrated in vitro activity against this collection of organisms. Future clinical studies to evaluate a potential role for these agents in the management of infections in cancer patients, including the treatment of febrile neutropenia, appear warranted.  相似文献   

3.
OBJECTIVES: This study compared the activity of telavancin, a novel multivalent lipoglycopeptide with rapid bactericidal activity, with those of five standard antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) against isolates of community-associated MRSA (CA-MRSA). METHODS: Microdilution tests performed according to CLSI guidelines using cation-adjusted Mueller-Hinton broth were used to determine the MIC values of telavancin, quinupristin/dalfopristin, vancomycin, trimethoprim/sulfamethoxazole, linezolid and daptomycin versus 60 CA-MRSA isolates. MBC values of telavancin were determined according to CLSI guidelines and American Society for Microbiology standards. PFGE was performed using the restriction enzyme SmaI. Samples from three predominant pulsed-field types were typed by multilocus sequence typing. Staphylococcal cassette chromosome mec typing was determined by multiplex PCR. The Panton-Valentine leucocidin (PVL) genes (lukS-PV and lukF-PV) were identified by PCR. RESULTS: The telavancin MIC90 and MBC90 values for this collection of 60 CA-MRSA isolates were 0.5 and 1 mg/L, respectively, with MIC and MBC values both ranging from 0.25 to 1 mg/L. Telavancin was found to be bactericidal in this study, as its MBC was no more than 2-fold higher than its MIC for all CA-MRSA isolates tested except one. (A single isolate yielded an MBC/MIC ratio of 4.) PVL- and non-PVL-producing strains demonstrated similar susceptibility to telavancin and comparator agents. CONCLUSIONS: Based on in vitro activity, telavancin should be an effective agent against CA-MRSA.  相似文献   

4.
OBJECTIVES: To compare extracellular and intracellular activities of telavancin (versus vancomycin) against Staphylococcus aureus (MSSA, MRSA, VISA and VRSA). METHODS: Determination of cfu changes (3-24 h) in culture medium and in macrophages at concentrations ranging from 0.01 to 1000x MIC. RESULTS: Extracellularly, telavancin displayed a fast, concentration-dependent bactericidal activity against all strains. The concentration-effect relationship was bimodal for MSSA and MRSA [two successive sharp drops in bacterial counts (0.3-1x MIC and 100-1000x MIC) separated by a zone of low concentration dependency]. When compared at human total drug Cmax (vancomycin, 50 mg/L; telavancin, 90 mg/L) towards MSSA, MRSA and VISA, telavancin caused both a faster and more marked decrease of cfu, with the limit of detection (>5 log decrease) reached already at 6 versus 24 h for vancomycin. Intracellularly, the bactericidal activity of telavancin was less intense [-3 log (MSSA) to -1.5 log (VRSA) at Cmax and at 24 h]. A bimodal relationship with respect to concentration (at 24 h) was observed for both MSSA and MRSA. In contrast, vancomycin exhibited only marginal intracellular activity towards intraphagocytic MSSA, MRSA and VISA (max. -0.5 log decrease at 24 h and at Cmax). CONCLUSIONS: Telavancin showed time- and concentration-dependent bactericidal activity against both extracellular and intracellular S. aureus with various resistance phenotypes. The data support the use of telavancin in infections where intracellular and extracellular S. aureus are present. Bimodality of dose responses (MSSA and MRSA) could indicate multiple mechanisms of action for telavancin.  相似文献   

5.
A spectrum of pneumococci with varying susceptibilities to beta-lactams, macrolides and quinolones was tested for susceptibility to nine antibiotics, including the novel lipopeptide daptomycin. Daptomycin was active against all strains (MIC range 90% killing at 1 h.  相似文献   

6.
OBJECTIVE: We compared the in vitro activity of telavancin with that of vancomycin, teicoplanin, linezolid, quinupristin/dalfopristin, moxifloxacin and ampicillin, penicillin or oxacillin as appropriate, by the NCCLS/EUCAST and BSAC methods. METHODS: The organisms (n = 401) included in the study were patient isolates from St Thomas' Hospital and were selected to include representatives of the clinically important Gram-positive aerobic species. Susceptibility testing was performed by agar dilution methods on Mueller-Hinton agar according to the NCCLS/EUCAST guidelines, in comparison with Iso-Sensitest agar according to the BSAC guidelines. RESULTS: Telavancin was active against all the Gram-positive species tested and nearly 90% of isolates included in the study had telavancin MICs 64 mg/L had telavancin MIC ranges of 0.5-8 and 2-16 mg/L, respectively. There was no evidence of cross-resistance with other comparator drugs. The results for telavancin for the two susceptibility testing methods were mostly either the same or within one doubling dilution. CONCLUSION: The susceptibility breakpoints for telavancin have yet to be established, but it would appear that telavancin has superior potency to the other tested glycopeptides, and on a weight-for-weight basis displays activity that is comparable to, or better than, that of the other agents tested.  相似文献   

7.
Using the chequerboard technique we studied the in vitro activity of the broad spectrum antibiotic fosfomycin in combination with vancomycin, rifampicin, linezolid, quinupristin/ dalfopristin, cefazolin, meropenem and moxifloxacin against two Staphylococcus epidermidis strains (ATCC 12228, DSM 3269) and five Staphylococcus aureus isolates (ATCC 29213, DSM 683, DSM 46320, GISA 323/93, MRSA 3558/00). The phenomena of 'trailing' and 'skipped wells' did not present a problem. Synergy was the most common effect of all drugs tested in combination with fosfomycin; only combination with vancomycin showed antagonism for two of seven isolates. Using a killing-curve technique fosfomycin showed cidal activity, where increasing the drug concentration above the MIC did not enhance killing velocity. Inhibitory concentrations of vancomycin plus fosfomycin against DSM 46320 caused effects identical to those observed with vancomycin alone. The combination of fosfomycin plus linezolid exerted the bacteriostatic effect found with linezolid alone. Fosfomycin plus quinupristin/dalfopristin exhibited the bactericidal effect found with fosfomycin alone (in contrast to the rapidly bactericidal effect of quinupristin/dalfopristin). Electron microscopy showed that fosfomycin given in combination with linezolid, quinupristin/dalfopristin or moxifloxacin (substances that do not cause morphological alterations when given alone) resulted in 'cauliflower-shaped' distortion as caused by fosfomycin alone. Our in vitro data indicate considerable potential for fosfomycin used in combination with other antistaphylococcal antimicrobials, especially linezolid or quinupristin/dalfopristin.  相似文献   

8.
OBJECTIVES: To evaluate the antibiotic susceptibilities of Propionibacterium acnes isolates from central nervous system (CNS) infections to agents used in current treatment regimens. METHODS: MICs of 16 reference antibiotics were determined by an agar dilution method for 24 consecutive strains of P. acnes isolated from individual patients with intracranial empyema or brain abscess. Bactericidal activities of antibiotics against P. acnes PAN14 were studied at 0.25-2 x MIC using a time-kill method. RESULTS: All of the isolates were resistant to fosfomycin, intermediate or resistant to metronidazole and susceptible to all the other antibiotics tested, except for nine strains, which were intermediate to ofloxacin. Among antibiotics tested alone in time-kill experiments, vancomycin was the most effective drug and exhibited bactericidal activity after 24 h at 1x and 2 x MIC, whereas cefotaxime and ciprofloxacin were bactericidal after 48 h at 2 x MIC. No significant bactericidal activity could be demonstrated with the other antibiotics tested alone. The addition of cefotaxime to vancomycin resulted in bactericidal activity at lower concentrations (0.5 x MIC), whereas synergy was observed between quinupristin/dalfopristin and cefotaxime at 2 x MIC. In contrast, antagonism was observed between cefotaxime and linezolid, and ciprofloxacin and clindamycin. CONCLUSION: Our data suggest that P. acnes isolates causing CNS infections remain highly susceptible to most antibiotics used for the treatment of such infections. Moreover, we showed that cefotaxime, vancomycin and ciprofloxacin possess good bactericidal activities against P. acnes, and that these activities may be enhanced when vancomycin is combined with cefotaxime or when cefotaxime is combined with quinupristin/dalfopristin.  相似文献   

9.
Among 10 hospital- and community-acquired Staphylococcus aureus strains with differing methicillin and vancomycin resistotypes, all strains were susceptible to ceftobiprole at MICs 相似文献   

10.
This study updates the activity of telavancin against Gram-positive pathogens collected from USA hospitals (2007-2009). Telavancin (MIC50/90, 0.12/0.25 μg/mL) was active against coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (100% susceptible), for which only daptomycin (MIC50/90, 0.25/0.5 μg/mL; 99% susceptible) and quinupristin/dalfopristin (MIC50/90, ≤0.25-0.5/0.5 μg/mL; 99% susceptible) exhibited similar activity. Telavancin (MIC50/90, 0.25/0.5 μg/mL) inhibited 96.5% of Enterococcus faecalis at the Food and Drug Administration breakpoint (MIC, ≤1 μg/mL), where ampicillin (99.9% susceptible), daptomycin (99.9% susceptible), and linezolid (100% susceptible) also demonstrated high-level coverage. Telavancin inhibited, respectively, 100.0% and 91.7% of VanB-phenotype E. faecalis and E. faecium at ≤1 μg/mL, whereas it was less active against VanA strains. Telavancin was uniformly active against Streptococcus pneumoniae and resistant subsets, and demonstrated good potency (MIC90, 0.06-0.12 μg/mL) against other streptococci, regardless of resistance to other drugs. This assessment reveals potent activity of telavancin against Gram-positive isolates collected from USA hospitals with no evidence of emergence of resistance.  相似文献   

11.
The in vitro activity of AZD2563, a new oxazolidinone, was compared with that of linezolid, vancomycin, quinupristin/dalfopristin, amoxicillin, levofloxacin, penicillin, erythromycin, azithromycin and clindamycin against a range of pneumococci by microdilution and time-kill studies. Against 300 pneumococci (99 penicillin susceptible, 86 penicillin intermediate, 115 penicillin resistant, 185 erythromycin resistant, 35 quinolone resistant), both oxazolidinones remained active against isolates less susceptible to other agents, with MICs ranging between 0.125 and 2 mg/L; AZD2563 MICs were generally one dilution lower than those of linezolid. Both quinupristin/dalfopristin and vancomycin were active against all groups (MIC ranges 0.125-2 and 0.125-0.25 mg/L, respectively). Apart from 35 isolates with levofloxacin MICs > or= 8 mg/L, levofloxacin MICs were < or =0.25-4 mg/L. MICs of amoxicillin and erythromycin rose with penicillin G MICs; most macrolide-resistant isolates were either penicillin-intermediate or -resistant. Against 16 organisms with differing beta-lactam, macrolide and quinolone MICs, time-kill studies showed that AZD2563 was bactericidal (99.9% killing) at 4 x MIC against nine strains at 24 h, with 90% killing of all 16 strains at 2 x MIC after 12 h. Similar results were obtained with linezolid. Both oxazolidinones were bacteriostatic at the MIC against all 16 strains. Amoxicillin, levofloxacin and vancomycin, at 2 x MIC, were bactericidal against 15 of the 16 strains after 24 h. Quinupristin/dalfopristin yielded the most rapid killing, with bactericidal activity against 13 of 16 strains at the MIC after 3 h and against 15 strains at 2 x MIC after 24 h. Erythromycin was bactericidal against all 10 strains with MICs < or= 8 mg/L at 4 x MIC after 24 h.  相似文献   

12.
LTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistant Staphylococcus aureus (MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity against S. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.  相似文献   

13.
This study evaluated telavancin activity against 3868 Staphylococcus aureus and 1003 coagulase-negative staphylococci (CoNS) collected from 33 European hospitals (2009-2010). Studies of telavancin potency included analysis of strains with decreased susceptibility to glycopeptides. Telavancin (MIC50/90, 0.12/0.25 μg/mL) showed high activity against S. aureus and CoNS, regardless of the stratification analysis performed (year sampled, infection source, or methicillin susceptibility). In addition, telavancin (MIC50/90, 0.25/0.5 μg/mL) retained activity against S. aureus isolates with higher vancomycin (MIC, 2 μg/mL) or teicoplanin (MIC, 2-8 μg/mL) MIC results. Overall, telavancin exhibited higher potency (at least 2-fold greater) than tested comparators (vancomycin, daptomycin, and linezolid) against European staphylococci. Alongside published clinical data, the telavancin in vitro activity observed against these pathogens supports this drug as an option for treating S. aureus infections in Europe, including those infections caused by strains with decreased susceptibility to vancomycin and/or teicoplanin.  相似文献   

14.
The in-vitro activity of linezolid (U-100766) and tentative breakpoints   总被引:10,自引:0,他引:10  
The in-vitro activity of linezolid, a novel oxazolidinone, was investigated in comparison with those of amoxycillin, cefuroxime, quinupristin/dalfopristin, trovafloxacin and vancomycin against 420 recent Gram-positive and anaerobic clinical isolates. Linezolid was equally active (MIC90 1 mg/L) against methicillin-susceptible and -resistant Staphylococcus aureus. It demonstrated uniform activity against streptococci and enterococci and no cross-resistance with other agents. The time-kill kinetic data demonstrated that the in-vitro activity of linezolid was predominantly bacteriostatic; slow bactericidal activity was only observed at the higher concentration with streptococci. An increase in inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs (MIC90 within one dilution step) of linezolid and an increase in inoculum from 10(5) to 10(7) cfu/mL had no notable effect on the in-vitro bactericidal activity. A tentative linezolid breakpoint of 2 mg/L was chosen after analysis of distribution of susceptibilities.  相似文献   

15.
OBJECTIVES: To determine in vitro susceptibilities of a large series of speciated coagulase-negative staphylococci (CNS) against three new antibiotics, linezolid, quinupristin/dalfopristin and telithromycin. METHODS: Susceptibilities to three new antibiotics and oxacillin, vancomycin, clindamycin and erythromycin were determined by the agar dilution method, as described by the NCCLS. RESULTS: Resistance to linezolid was not observed in any isolates, although MIC90 values varied between species. Fifteen of 658 (2.3%) isolates were resistant to quinupristin/dalfopristin, but < 1% of the clinically most important isolates of Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus hominis demonstrated resistance to this agent. Susceptibility to clindamycin correlated with susceptibility to quinupristin/dalfopristin; however, resistance to clindamycin did not predict quinupristin/dalfopristin resistance. Telithromycin was the least active of the new agents tested, showing activity similar to that of clindamycin. Susceptibility and resistance to clindamycin were predictive of susceptibility and resistance to telithromycin. CONCLUSION: Clindamycin susceptibility can be used as a surrogate marker for susceptibility to quinupristin/dalfopristin and telithromycin. Quinupristin/dalfopristin and linezolid show good activity against both mecA-positive and -negative CNS.  相似文献   

16.
Staphylococcus aureus strain HMC3 isolated at the Hershey Medical Center, was resistant to vancomycin (VRSA) through the presence of the vanA resistance gene; it also contained mecA, erm(A), erm(B), tet(K) and aac(6')-aph(2"), conferring resistance to licensed beta-lactams, macrolides, tetracycline and aminoglycosides. HMC3 also had alterations in GyrA and GrlB and was resistant to available quinolones. Experimental drugs with low MICs (<2 mg/L) for VRSA HMC3 included cephalosporins BAL9141 and RWJ-54428; glycopeptides oritavancin and dalbavancin; the lipopeptide daptomycin; the glycolipodepsipeptide ramoplanin; new fluoroquinolones WCK 771 A, WCK 1153, DK-507k and sitafloxacin; and the DNA nanobinder GS02-02. These agents were all bactericidal as were trimethoprim/sulfamethoxazole and teicoplanin (MIC 4 mg/L). Oxazolidinones linezolid and ranbezolid; the injectable streptogramin quinupristin/dalfopristin; DNA nanobinders GS2-10547 and GS02-104; peptide deformylase inhibitors NVP-PDF713 and GS02-12; tetracycline derivative tigecycline; the antifolate iclaprim; mupirocin and fusidic acid were all active in vitro but bacteriostatic.  相似文献   

17.
We examined the activity of CB-181963, a novel cephalosporin, against methicillin-resistant Staphylococcus aureus (MRSA) (n = 200), methicillin-susceptible S. aureus (MSSA) (n = 50), glycopeptide-intermediate Staphylococcus species (GISS) (n = 47), and VRSA (n = 2) isolates. CB-181963 exhibited MIC profiles similar to those of linezolid against MRSA and GISS; however, activity against MSSA was similar to that of vancomycin. Time-kill study results of investigations of activity against MRSA, MSSA, and GISS at 24 h were as follows: CB-181963 activity = vancomycin activity > linezolid activity (P < 0.001); CB-181963 = quinupristin-dalfopristin = vancomycin > linezolid (P < 0.05); CB-181963 > linezolid (P = 0.003); and CB-181963 = quinupristin-dalfopristin = vancomycin. CB-181963 may provide an alternative treatment for multidrug-resistant staphylococci.  相似文献   

18.
Daptomycin-nonsusceptible (DNS) Staphylococcus aureus strains have been reported over the last several years. Telavancin is a lipoglycopeptide with a dual mechanism of action, as it inhibits peptidoglycan polymerization/cross-linking and disrupts the membrane potential. Three clinical DNS S. aureus strains, CB1814, R6212, and SA-684, were evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated endocardial vegetations (starting inoculum, 10(8.5) CFU/g) for 120 h. Simulated regimens included telavancin at 10 mg/kg every 24 h (q24h; peak, 87.5 mg/liter; t(1/2), 7.5 h), daptomycin at 6 mg/kg q24h (peak, 95.7 mg/liter; t(1/2), 8 h), and vancomycin at 1 g q12h (peak, 30 mg/liter; t(1/2), 6 h). Differences in CFU/g between regimens at 24 through 120 h were evaluated by analysis of variance with a Tukey's post hoc test. Bactericidal activity was defined as a ≥3-log(10) CFU/g decrease in colony count from the initial inoculum. MIC values were 1, 0.25, and 0.5 mg/liter (telavancin), 4, 2, and 2 mg/liter (daptomycin), and 2, 2, and 2 mg/liter (vancomycin) for CB1814, R6212, and SA-684, respectively. Telavancin displayed bactericidal activities against R6212 (32 to 120 h; -4.31 log(10) CFU/g), SA-684 (56 to 120 h; -3.06 log(10) CFU/g), and CB1814 (48 to 120 h; -4.9 log(10) CFU/g). Daptomycin displayed initial bactericidal activity followed by regrowth with all three strains. Vancomycin did not exhibit sustained bactericidal activity against any strain. At 120 h, telavancin was significantly better at reducing colony counts than vancomycin against all three tested strains and better than daptomycin against CB1814 (P < 0.05). Telavancin displayed bactericidal activity in vitro against DNS S. aureus isolates.  相似文献   

19.
In search of treatment alternatives against vancomycin-resistant S. aureus (VRSA), an in vitro pharmacodynamic model with simulated endocardial vegetations incorporating protein and a high inoculum was used to simulate daptomycin, linezolid, quinupristin-dalfopristin, and vancomycin against the Michigan VRSA strain. Daptomycin and quinupristin-dalfopristin exhibited the greatest bacterial reductions, and all tested agents except vancomycin exhibited bactericidal activity against the VRSA.  相似文献   

20.
OBJECTIVES: To assess the in vitro activity of the novel lipoglycopeptide telavancin against staphylococcal biofilms using an in vitro pharmacokinetic model. METHODS: Using the Sorbarod model, biofilms were established. The strains tested included methicillin-susceptible and -resistant strains of Staphylococcus aureus and coagulase-negative staphylococci, as well as glycopeptide-intermediate S. aureus (GISA). The biofilms were exposed to exponentially decreasing concentrations of telavancin and four comparator antibiotics, vancomycin, teicoplanin, linezolid and moxifloxacin and the bactericidal activity of the antibiotics was assessed. The concentrations of the antibiotics used in these experiments corresponded to peak serum levels achievable in humans and the rates at which drug concentrations were decreased corresponded to their elimination half-lives. RESULTS: All of the drugs tested produced a reduction in the number of bacteria eluted from the biofilms. Telavancin was more effective than the commercially available glycopeptides, vancomycin and teicoplanin, and of the three, was the most active agent against both the non-GISA and GISA strains. Of all the antibiotics tested, moxifloxacin produced the greatest reduction in biofilm cells, but only against the non-GISA strains. CONCLUSIONS: Telavancin exhibited substantial antimicrobial activity against staphylococcal biofilms, including GISA strains. This study supports the case for the evaluation of telavancin in the treatment of staphylococcal biofilm-associated infections.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号