利奈唑胺对万古霉素敏感及耐药屎肠球菌的抗菌活性

目的 评价利奈唑胺对临床分离万古霉素敏感及耐药屎肠球菌的体外抗菌活性.方法 多重PCR法鉴定屎肠球菌万古霉素耐药基因类型,平皿二倍稀释法测定利奈唑胺等11种抗菌药物MIC值.结果 75株临床分离万古霉素耐药屎肠球菌均携带vanA基因.万古霉素敏感及耐药屎肠球菌对利奈唑胺均敏感,MIC范围1～2mg/L.与红霉素、氨苄西林、左氧氟沙星和利福平相比,万古霉素敏感及耐药屎肠球菌的耐药率均在80%以上.万古霉素敏感屎肠球菌对高浓度庆大霉素、高浓度链霉素、四环素和氯霉素的耐药率分别为80.2%、13.9%、38.6%和37.6%;万古霉素耐药屎肠球菌对上述4种药物的耐药率分别为64.5%、8.0%、18.5%和5.3%.结论 利奈唑胺对我国临床分离万古霉素敏感和耐药屎肠球菌均具有很好的体外抗菌活性.     

In vitro activity of linezolid against multidrug-resistant Mycobacterium tuberculosis isolates

Information in the literature regarding the activity of linezolid against multidrug-resistant (MDR) Mycobacterium tuberculosis strains is scarce. We therefore tested the in vitro activity of this drug against 39 MDR M. tuberculosis strains isolated from clinical specimens using the Bactec 460 TB system. All strains were inhibited by < or = 8 mg/L (minimum inhibitory concentration (MIC); MIC50 = 4 mg/L, MIC90 = 8 mg/L). Although the MIC values are higher than in other studies, based on proposed breakpoints all strains were found to be susceptible to linezolid. Further investigations to prove its usefulness in the treatment of MDR tuberculosis should be carried out.     

In vitro activity of phenothiazine derivatives in Enterococcus faecalis and Enterococcus faecium

The antimicrobial activity of the phenothiazine derivatives thioridazine and prochlorperazine have been evaluated with 11 Enterococcus faecalis strains and 9 Enterococcus faecium strains, originating from human infections and animal faecal flora. We found that all E. faecalis and E. faecium strains, regardless of their susceptibility to commonly used antibiotics, were inhibited by thioridazine at a concentration of 16-32 microg/ml and by prochlorperazine at a concentration of 32-64 microg/ml. Combinations of the antibiotics vancomycin or ampicillin and thioridazine and prochlorperazine at subinhibitory concentrations, could render vancomycin- or ampicillin-resistant bacteria sensitive to each of the antibiotics. Verapamil and reserpine, inhibitors of P-glycoprotein-mediated multidrug resistance, did not reduce resistance. Our results outline modification of resistance in enterococci induced by phenothiazine derivatives unrelated to P-glycoprotein-mediated multidrug resistance.     

Peritoneal dialysis fluid concentrations of linezolid in the treatment of vancomycin-resistant Enterococcus faecium peritonitis

OBJECTIVE: To determine linezolid concentrations in peritoneal dialysis fluid after multiple oral doses of the drug in a 46-year-old man with vancomycin-resistant Enterococcus faecium peritonitis who was undergoing peritoneal dialysis. METHODS: After administration of oral linezolid 600 mg twice/day was started, peritoneal dialysis fluid was collected at the end of several 4- and 8-hour dwell times and submitted for analysis of linezolid concentration. Before linezolid therapy was begun, and immediately after several peritoneal dialysis exchanges, 30 ml of expended peritoneal dialysis fluid was collected in a sterile container and immediately frozen at -70 degrees C until analysis by high-performance liquid chromatography. RESULTS: Peritoneal dialysis concentrations of linezolid greater than 4 microg/ml were achieved after the first dose of linezolid and maintained after repeated doses. During the course of therapy, mean linezolid concentrations in peritoneal dialysis fluid tended to increase (mean 7.60 pg/ml, range 3.54-16.2 microg/ml). All assayed peritoneal dialysis samples demonstrated linezolid concentrations greater than 4 microg/ml at the end of 4- or 8-hour dwell times, except for one level after a missed dose on linezolid treatment day 3. Duration of dwell times did not appear to correlate with linezolid concentrations. CONCLUSION: In this patient, linezolid 600 mg twice/day penetrated into peritoneal dialysis fluid at or above the concentrations necessary to treat common gram-positive bacteria. Linezolid therapy is likely to have a role in peritoneal dialysis-associated peritonitis based on its antimicrobial activity, pharmacokinetic properties, ease of administration, and tolerability.     

Differential antimicrobial susceptibility between human and chicken isolates of vancomycin-resistant and sensitive Enterococcus faecium

To compare the differential antimicrobial susceptibilities of Enterococcus faecium from humans and whole chicken carcasses, MICs of 12 antimicrobial agents were determined for 54 clinical-isolates (31 vancomycin-resistant [VREF]) and 60 chicken-isolates (29 VREF). Chicken VREF were slightly but consistently more resistant to vancomycin, teicoplanin and avoparcin, compared with human VREF (P<0.01). MICs of LY333328 were 相似文献   

In vitro activity of minocycline combined with fosfomycin against clinical isolates of methicillin-resistant Staphylococcus aureus

This study aimed to evaluate the in vitro activity of minocycline combined with fosfomycin against isolates of methicillin-resistant Staphylococcus aureus (MRSA). A total of 87 clinical isolates of MRSA collected from three Chinese hospitals were included in the study. The checkerboard method with determination of the fractional IC index (FICI) was used to determine whether antibiotic combinations act synergistically against these isolates. The susceptibility results for minocycline and fosfomycin were interpreted according to the most relevant criteria. The results demonstrated the following interactions: 76 isolates (87.4%) showed synergistic interactions (FICI0.5) and 11 isolates (12.6%) showed indifferent interactions (0.5相似文献   

Molecular epidemiology of urinary tract isolates of vancomycin-resistant Enterococcus faecium from North America

Vancomycin-resistant Enterococcus faecium (VRE) are a common cause of nosocomial infections and are important agents of gastrointestinal colonisation. As the prevalence of VRE in hospitalised patients continues to increase, implementation of appropriate infection control measures requires routine surveillance of VRE transmission patterns. The purpose of the present study was to investigate the molecular epidemiology of VRE isolates within the USA and Canada. Two hundred and eighty-three urinary tract isolates of VRE were collected in the year 2000 from ten Canadian hospitals and 28 US tertiary care medical centres representing seven of the nine geographic regions of the United States Bureau of the Census. The in vitro activity of vancomycin, teicoplanin and nine comparators was determined by broth microdilution. The genetic relatedness among isolates was evaluated by pulsed-field gel electrophoresis (PFGE). Resistance rates (intermediate and resistant) were 100% for vancomycin and 78.7% for teicoplanin. Resistance was lowest with linezolid, chloramphenicol and nitrofurantoin at 0.3%, 0.3% and 0.5%, respectively. PFGE revealed that genetic heterogeneity amongst isolates from each of the medical centres varied considerably. Despite some intracentre and intercentre VRE dissemination, the present study found no evidence for the emergence of a dominant clonal strain. This suggests that the spread of VRE within North America is a complex process involving both the horizontal transfer of glycopeptide resistance determinants and polyclonal dissemination.     

In vitro activity of linezolid against Mycobacterium tuberculosis complex, including multidrug-resistant Mycobacterium bovis isolates

The activity of linezolid was studied against 55 Mycobacterium tuberculosis (42 susceptible, 3 isoniazid resistant and 10 isoniazid and rifampicin resistant), one Mycobacterium bovis and two multidrug-resistant M. bovis isolates using the standard 7H10 agar proportion and the ESP Culture System II methods. Both methods displayed similar MIC(90) values (minimum inhibitory concentrations for 90% of the organisms) of 0.5mg/L; however, the former method yielded slightly lower MIC(50) values (MICs for 50% of the organisms) (0.25mg/L) compared with the latter method (0.5mg/L). No differences were observed between susceptible and resistant isolates, including multidrug-resistant M. bovis isolates, with a MIC range of 0.12-0.5mg/L. The potential role of linezolid in tuberculosis patients requires further in vivo evaluation.     

利奈唑胺、替考拉宁和万古霉素等抗菌药物对常见需氧革兰阳性球菌的体外抗菌活性

目的评价利奈唑胺、替考拉宁和万古霉素等抗菌药物的体外抗菌活性。方法采用琼脂稀释法对临床收集的132株革兰阳性球菌进行抗菌活性测定,记录其各自的MIC并进行比较。结果利奈唑胺、替考拉宁及万古霉素3药对革兰阳性球菌均有较大抗菌活性,敏感率均为100%,包括其中的耐甲氧西林葡萄球菌和青霉素中介肺炎链球菌均有良好抗菌作用。3药在部分革兰阳性球菌的抗菌作用中与利福平相仿,但比氨基糖苷类抗生素和氟喹诺酮类抗菌药强。在对甲氧西林敏感金葡萄的抗菌活性中,替考拉宁的MIC90均为利奈唑胺和万古霉素的4倍;在对甲氧西林敏感凝固酶阴性葡萄球菌的抗菌活性中,替考拉宁的MIC90分别均为利奈唑胺和万古霉素的8倍;而在青霉素敏感和中介肺炎链球菌的抗菌活性中,替考拉宁的MIC90为利奈唑胺的1/16,为万古霉素的1/8;在肠球菌属的抗菌活性中,万古霉素的MIC90分别为利奈唑胺的2倍,是替考拉宁的4倍和8倍。结论利奈唑胺、替考拉宁以及万古霉素等三药对革兰阳性球菌有较大的抗菌作用,对部分革兰阳性菌的抗菌作用与利福平相仿,但比其他如氨基糖苷类抗生素和氟诺酮类抗菌药更优,是临床革兰阳性球菌严重感染的有效药物。     

In vitro activity of daptomycin against clinical isolates with reduced susceptibilities to linezolid and quinupristin/dalfopristin

An initiative was taken to determine the in vitro activity of daptomycin against 85 Gram-positive isolates with reduced susceptibilities to linezolid and quinupristin/dalfopristin. Daptomycin had potent activity against all strains, with a Staphylococcus spp. minimum inhibitory concentration (MIC) < or =2 microg/mL and an Enterococcus spp. MIC < or =8 microg/mL. Resistance to linezolid and quinupristin/dalfopristin appears to be independent of reduced susceptibility to daptomycin.     

In vitro activity of new fluoroquinolones and linezolid against non-tuberculous mycobacteria

The objective of the study was to determine the activity of new fluoroquinolones and linezolid against 108 clinical isolates of different species of non-tuberculous mycobacteria isolated in Spain. Gatifloxacin and moxifloxacin were found to be more effective than levofloxacin. Mycobacterium kansasii was more susceptible to the fluoroquinolones tested than M. avium complex and M. fortuitum was more susceptible than M. chelonae. Linezolid was more active against M. kansasii than against M. avium complex. A better understanding of the relationship between the in vitro activity of these compounds and their usefulness in the treatment of these infections is needed. The new fluoroquinolones exhibit good activity against M. kansasii and M. fortuitum and linezolid is active against M. kansasii.     

In vitro activity of fosfomycin against gram-negative urinary pathogens and the biological cost of fosfomycin resistance

The aim of this study was to reassess the activity of fosfomycin against recently isolated uropathogens circulating in Italy and to evaluate the effect of fosfomycin resistance on the expression of several virulence traits using the rare mutant strains. In vitro activity of fosfomycin was evaluated using 441 Gram-negative organisms isolated from patients with uncomplicated urinary tract infections (UTIs). Fosfomycin was the most active antibiotic against Escherichia coli (99% susceptibility). The activity against Proteus mirabilis was more potent than that of co-trimoxazole and nitrofurantoin (87.5, 67 and 0% susceptibility, respectively). The other microorganisms, accounting for about 7% of all pathogens tested, showed variable susceptibilities to fosfomycin. Compared with susceptible strains, fosfomycin-resistant mutants showed a reduced rate of growth and were impaired in their ability to adhere to uroepithelial cells and to urinary catheters. They were also more resistant to UV irradiation and to phage T7 and showed diminished rates of colicin synthesis and transfer of plasmids.     

In vitro activity of linezolid and 12 other antimicrobials against coryneform bacteria

OBJECTIVES: To compare the in vitro activity of linezolid with 12 other antimicrobials against 190 strains of the coryneform bacteria, including 60 strains of C. amycolatum, 30 of C. striatum, 30 of C. jeikeium, 10 of C. urealyticum, 20 of B. casei, 20 of D. hominis and 20 of T. otitidis. METHODS: Minimum inhibitory concentrations (MICs) and time-death curves were carried out according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Linezolid was very active against the 130 strains of the Corynebacterium species studied. Only the glycopeptides showed similar efficacy. In contrast, penicillin G, ampicillin, macrolides, lincosamides, fluoroquinolones and aminoglycosides showed generally high MICs. Among the beta-lactams, only imipenem was active against the majority of strains of C. striatum and C. amycolatum, and, approximately half of the C. jeikeium and C. urealyticum isolates. Both Dermabacter hominis and Brevibacterium casei showed marked resistance against most of the antimicrobials tested, while Turicella otitidis only showed high MICs against macrolides and clindamycin. For all of them, linezolid, vancomycin and teicoplanin proved effective. The time-death curves showed linezolid to behave as a bacteriostatic agent (approximately 90% death rate). Such activity was more accentuated for C. amycolatum and C. striatum (reduction of 1.3 and 1.7log(10)CFU/mL, respectively) than for C. jeikeium and C. urealyticum (reduction of 1.0 and 0.8log(10), respectively). CONCLUSIONS: Our results indicate that linezolid is active against coryneform bacteria. The efficacy of linezolid is equal to or even superior to that of the glycopeptides.     

In vitro activity of meropenem/piperacillin/tazobactam triple combination therapy against clinical isolates of Staphylococcus aureus,Staphylococcus epidermidis,Staphylococcus pseudintermedius and vancomycin-resistant Enterococcus spp

ObjectivesTo evaluate the activity of the reported synergistic and collaterally sensitive antibiotic combination, meropenem/piperacillin/tazobactam (ME/PI/TZ), against a panel of methicillin-resistant Staphylococcus aureus (MRSA) and other methicillin-resistant Staphylococcus species; and to investigate the relationship between ME/PI/TZ susceptibility and the genomic background of clinical isolates of MRSA.MethodsME/PI/TZ combination and single drug minimum inhibitory concentrations (MICs) were determined for 207 strains (including 121 MRSA, 4 methicillin-sensitive S. aureus [MSSA], 37 vancomycin-intermediate S. aureus [VISA], 6 ceftaroline non-susceptible MRSA, 29 coagulase-negative staphylococci [CoNS], 5 S. pseudointermedius and 5 vancomycin-resistant Enterococci [VRE]) by broth microdilution. Whole genomes of 168 S. aureus strains were sequenced, assembled, and comparatively analysed.ResultsUSA300-SCCmec type IV isolates, clonal complex 8 (CC8)-MRSA isolates, including some VISA and ceftaroline (CPT)-intermediate strains, and all tested methicillin-resistant S. epidermidis isolates were highly susceptible to ME/PI/TZ. Isolates with elevated MICs (MICs of >16/16/16 mg/L) clustered with the USA100-SCCmec type II strain. Susceptibility of MRSA to ME/PI/TZ was correlated with susceptibility to ME. No obvious cross-resistance to CPT was observed among high-ME/PI/TZ MIC isolates.ConclusionsThe ME/PI/TZ combination is effective against a variety of clinical MRSA isolates, particularly of the USA300 lineage, which is expanding worldwide. ME/PI/TZ is also effective against drug-resistant CoNS and S. pseudintermedius clinical isolates.     

帕珠沙星对临床分离致病菌的体外抗菌活性研究

目的评价帕珠沙星的体外抗菌活性。方法采用琼脂二倍稀释法，测定帕珠沙星与左氧氟沙星对342株临床分离菌株的最低抑菌浓度（MIC）。结果帕珠沙星对革兰阴性菌和革兰阳性菌的MIC90分别为0．06～4和1～16μg／ml。对大肠埃希菌、阴沟肠杆菌、变形菌、铜绿假单胞菌、不动杆菌和链球菌的MIC90为0．06～4μg／ml，是左氧氟沙星的1／2～1／8;对肺炎克雷伯菌、金葡菌和表葡菌与左氧氟沙星抗菌作用相当，MIC90分别为0．5、1、1μg／ml；对流感嗜血杆菌、黏膜炎莫拉菌和粪肠球菌的MIC90为0．5、1、16μg／ml，高于左氧氟沙星（0．25、0．5、8μg／ml）。结论帕珠沙星对革兰阴性菌和革兰阳性菌均具有广谱的抗菌作用，对革兰阴性菌的抗菌活性优于革兰阳性菌。     

Bactericidal activity of daptomycin, vancomycin, teicoplanin and linezolid against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium using human peak free serum drug concentrations

The bactericidal activities of daptomycin, vancomycin, teicoplanin and linezolid at human peak free serum concentrations (C(max,free)) were determined against Staphylococcus aureus (one methicillin-susceptible and two methicillin-resistant strains), Enterococcus faecalis and Enterococcus faecium (one vancomycin-susceptible and one vancomycin-resistant strain of each). Daptomycin was rapidly bactericidal against 7/7 strains at C(max,free) of 22.0 mg/L (corresponding to 63% protein binding) and against 3/7 strains at 4.8 mg/L (corresponding to 92% protein binding). Vancomycin (18.0 mg/L) was bactericidal against only two strains. Both teicoplanin (4.5 mg/L) and linezolid (10.4 mg/L) were consistently bacteriostatic. Daptomycin is a useful option for the treatment of Gram-positive infections owing to its strong bactericidal activity.