Comparative in vitro activity of telavancin (TD-6424), a rapidly bactericidal, concentration-dependent anti-infective with multiple mechanisms of action against Gram-positive bacteria

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.     

Activity of dalbavancin against staphylococci and streptococci, assessed by BSAC and NCCLS agar dilution methods

BACKGROUND: Dalbavancin is a long-half-life (9-12 days) glycopeptide, now in Phase 3 development. Its pharmacokinetics may facilitate home intravenous therapy, early discharge and long prophylaxis. METHODS: Dalbavancin and comparators were tested in vitro against staphylococci and streptococci to determine (i) activity and (ii) the comparability of agar dilution MICs by the BSAC and the NCCLS methods. The test panels comprised 92-93 isolates each of Staphylococcus aureus, coagulase-negative staphylococci (CoNS) and 'viridans' streptococci, chosen for epidemiological diversity and to over-represent strains resistant to conventional agents, including teicoplanin. RESULTS: Dalbavancin MICs by the BSAC and NCCLS methods generally were identical, or else those by the BSAC method were two-fold lower. In both cases the MIC distributions of dalbavancin within species groups were unimodal, with peaks at 0.25, 0.12/0.25 and 0.12 mg/L for S. aureus, CoNS and viridans streptococci, respectively. MIC differences between the BSAC and NCCLS methods were similarly small for other glycopeptides and, generally, non-glycopeptides. Dalbavancin MICs were mostly two- to 16-fold below those of vancomycin and dalbavancin-like vancomycin-remained highly active against teicoplanin-non-susceptible staphylococci. CONCLUSIONS: Dalbavancin has good activity versus streptococci and staphylococci, including teicoplanin-resistant strains. MICs by BSAC and NCCLS agar dilution methods were comparable to each other; slightly lower MIC values, nevertheless, have been recorded by broth microdilution.     

Reduced susceptibility to vancomycin of nosocomial isolates of methicillin-resistant Staphylococcus aureus.

The MICs of vancomycin for 56 random nosocomial Staphylococcus aureus isolates homogeneously resistant to methicillin (homMRSA), 16 heterogeneously resistant isolates (hetMRSA) and 25 susceptible isolates (MSSA) were determined by a standard broth microdilution method. Representative isolates were also tested by an agar incorporation method, the Etest and population analysis. Although always in the susceptible range, MICs of vancomycin for homMRSA were significantly higher than those for hetMRSA or MSSA. Moreover, a homMRSA strain belonging to one of the major Greek MRSA clones contained a sub-population of cells that could grow in the presence of vancomycin 8 mg/L at a frequency of 6.7 x 10(-8).     

Decreased susceptibility to glycopeptides in methicillin-resistant Staphylococcus aureus: a 20 year study in a large French teaching hospital, 1983-2002

OBJECTIVES: To assess the evolution of glycopeptide susceptibility in methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in a large French teaching hospital from 1983 to 2002. METHODS: Determination of glycopeptide MICs by using the Etest method in Mueller-Hinton agar on a sample of randomly selected MRSA strains. RESULTS: A total of 1445 MRSA strains were tested, and one vancomycin-intermediate MRSA (VISA) and 31 teicoplanin-intermediate MRSA (TISA) strains were detected. The first strains were detected in 1985, and all strains were gentamicin resistant (GR). None of the gentamicin-susceptible strains had a glycopeptide MIC > 3 mg/L. In addition, there was a significant increase in glycopeptide MIC geometric means over the years, and this increase was higher for teicoplanin than for vancomycin. CONCLUSIONS: The higher increase in teicoplanin MICs, and the good correlation between vancomycin and teicoplanin MICs, suggests systematic determination of teicoplanin MIC to screen for abnormal glycopeptide susceptibility among GR-MRSA.     

耐甲氧西林金黄色葡萄球菌的SPA基因分型研究与耐药性分析

目的 探讨鄂尔多斯地区耐甲氧西林金黄色葡萄球菌(MRSA)分离株杀白细胞毒素(PVL)基因分布特点及药物敏感性。方法 收集2012年6月～2014年12月临床分离的SCCmecⅡ型和Ⅲ型MRSA菌株66株,应用聚合酶链反应对菌株进行PVL基因型检测,用琼脂稀释法测定PVL阳性菌株对常用抗菌药物的敏感性。结果 66例MRSA有6例PVL阳性,阳性率9.09%,其中Ⅱ型4株,Ⅲ型2株; 6株PVL阳性菌均对万古霉素、替考拉宁、利奈唑胺和对多种非β内酞胺类抗菌药敏感,对β内酞胺类、大环内酯类和克林霉素高度耐药。结论 在鄂尔多斯地区MRSA菌株中PVL阳性菌株较低,4株为CA-MRSA,2株为HA-MRSA,若以PVL阳性作为区分MRSA类型的标志有待进一步研究。     

Methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Canada

This study defines the characteristics of decreasing vancomycin susceptibility in multiple isolates of methicillin-resistant Staphylococcus aureus (MRSA) recovered from a hospitalized patient in Canada over a period of 6 months. The MICs of the isolates increased during therapy with vancomycin. The patient fractured her right hip while in the United States. She was started on treatment with vancomycin. The MICs of successive isolates increased from < or =1 to 4 mg/L over 6 months. Then, an isolate tested at 8 mg/L initially and 4 mg/L with confirmatory E-test (AB BIODISK, Solna, Sweden). One month later, MRSA was still present in her wound, and therapy was changed to linezolid with rifampin. Subsequent cultures were negative for MRSA. Susceptibility testing was performed on the BD Phoenix (Becton Dickinson Diagnostic Systems, Sparks, MD), Dade Microscan (Dade Behring Microscan, Sacramento, CA), Pasco MIC (Becton Dickinson, Sparks, MD), Vitek 2 (bioMerieux, St. Louis, MO), and Sensititre (Trek Diagnostic Systems, Cleveland, OH) systems, and by E-test. Molecular typing (pulsed-field gel electrophoresis [PFGE]) was used to verify the relatedness of the isolates. Transmission electron microscopy (TEM) was used to assess the cell wall thickness of isolates with differing MICs. Population analysis was performed to assess for vancomycin hetero-resistance. MICs of 4 mg/L were only obtained with BD Phoenix, E-test, and broth microdilution. All isolates were identical by PFGE. The most resistant isolate had a thicker cell wall on TEM. Vancomycin hetero-resistance was observed in the resistant isolates. This is the first strain of MRSA with reduced susceptibility to vancomycin reported in Canada. The breakpoints for vancomycin susceptibility have been revised in light of such observations.     

The in vitro activity of daptomycin against 514 Gram-positive aerobic clinical isolates

The in vitro activity of daptomycin was assessed in comparison with that of vancomycin and penicillin against a wide range of Gram-positive aerobic clinical isolates. MICs were determined by an agar dilution method on Mueller-Hinton agar (NCCLS/EUCAST) and on Isotonic agar adjusted to contain 50 mg/L free calcium (BSAC). Both media were enriched with 5% horse blood for fastidious organisms. Daptomycin MICs for all 172 staphylococci, including methicillin-susceptible and methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus, were 0.03-0.5 mg/L. For 99 of the 100 enterococci (Enterococcus faecalis, n = 50; Enterococcus faecium, n = 50), including 37 vancomycin-resistant isolates, they were 0.25-2 mg/L. For all 108 beta-haemolytic streptococci, including Streptococcus pyogenes and Streptococcus agalactiae, daptomycin MICs were 0.016- 0.25 mg/L; for 101 alpha-haemolytic streptococci, including Streptococcus pneumoniae and 'viridans' streptococci, they were 0.016-2 mg/L. For miscellaneous vancomycin-resistant isolates including Lactobacillus spp., Lactococcus spp., Leuconostoc spp., Pediococcus spp. and isolates of Enterococcus casseliflavus and Enterococcus gallinarum, daptomycin MICs were 0.03-2 mg/L; MICs for the seven isolates of Listeria monocytogenes were 0.25-4 mg/L. There was little difference between the results on Mueller-Hinton agar and on supplemented Isotonic agar The discrepant results occasionally obtained tended to be one dilution higher on supplemented Isotonic agar. Daptomycin was active (MICs < or = 2 mg/L) against all the isolates tested with the exception of one isolate each of E. faecium and L. monocytogenes (MICs = 4 mg/L). Our results indicate that daptomycin MICs are independent of methicillin and vancomycin MICs.     

金黄色葡菌萄球耐药性监测

目的：监测成都市4家三级甲等医院临床分离的金黄色葡萄球菌（金葡菌）耐药性。方法：用琼脂稀释法测定11种抗菌药物对282株金葡菌的最低抑菌浓度（MIC）修正，并对菌株来源及科室分布进行分析。结果：282株金葡菌共筛出耐甲氧西林金葡菌（MRSA）94株，检出率为33.3％；甲氧西林 敏感金葡菌（MSSA）共188株。MSSA对青霉素和克拉霉素的耐药率分别为71.3％和54.8％，而对其抗菌药物敏感。MRSA对万古霉素、阿米卡星和利福平敏感性高（最强为万古霉素），而对其余多种抗菌药物耐药。MRSA来源最多为痰，其次为各种分泌物；科室分布依次为烧伤科、重症监护病房（ICU）、感染科等。结论：青霉素、大环内酯类药物不宜用于金葡菌感染。MRSA具有多重耐药性。MRSA感染首选糖肽类抗生素治疗。金葡菌是一种重要的病原菌，应长期进行耐药性监测，病室需做好消毒隔离。     

Characteristics of French methicillin-resistant Staphylococcus aureus isolates with decreased susceptibility or resistance to glycopeptides

According to the French Society of Microbiology, Staphylococcus aureus isolates are suspected to have decreased susceptibility to glycopeptide(s) when at least one colony is able to grow from an inoculum of 10 microL of 2 McFarland bacterial suspension plated on Mueller-Hinton agar containing 5 mg/L teicoplanin and incubated for 48 h at 35-37 degrees C. We analysed 89 methicillin-resistant S. aureus isolates (MRSA), collected in 2000-2001 from 24 hospitals located in 18 French cities, which were able to grow on this selective medium. These isolates were distributed into six groups on the basis of their glycopeptide resistance phenotypes: (A) glycopeptide susceptible (GSSA, 21 isolates); (B) heterogeneous teicoplanin intermediately resistant (hetero-TISA, 24 isolates); (C) heterogeneous and intermediately resistant to both glycopeptides, teicoplanin and vancomycin (hetero-GISA, six isolates); (D) heterogeneous vancomycin intermediately resistant/teicoplanin intermediately resistant (hetero-VISA/TISA, 30 isolates); (E) GISA (four isolates); (F) TISA (four isolates). Despite the persistent decrease in gentamicin-resistant MRSA isolates in French hospitals since 1993, their prevalence is very high in groups D, E and F. Moreover, most of the group C, D and E isolates exhibiting decreased susceptibility to both glycopeptides belong to the same major SmaI genotype, which has been detected in Europe since at least 1989.     

Comparison of BSAC agar dilution and NCCLS broth microdilution MIC methods for in vitro susceptibility testing of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: the BSAC Respiratory Resistance Surveillance Programme

OBJECTIVE: The aim of this study was to establish the degree of comparability between the NCCLS broth microdilution and BSAC agar dilution MIC methods of antimicrobial susceptibility testing. METHODS: Six hundred and sixty-one clinical isolates of Streptococcus pneumoniae, 936 Haemophilus influenzae and 421 Moraxella catarrhalis, collected in the winter of 1999-2000 by 20 laboratories in the UK and Eire from patients with presumed community-acquired lower respiratory infections, were tested by the two methods. MIC agreement was defined as excellent (good) if results were within +/- 1 doubling dilution for > or =90% (> or =80%) of isolates and within +/- 2 doubling dilutions for > or =95%. Isolates were categorized as susceptible, intermediate or resistant using the breakpoints appropriate to the testing method. RESULTS: MIC agreement was good or excellent in 27 of 36 organism-agent combinations. Agreement was less for M. catarrhalis than for other species, and lower in all three species for cefaclor and trimethoprim than for other antimicrobials. Discrepancies in categorization occurred only occasionally, and were generally explained by differences in breakpoints rather than in measured MICs. One exception was S. pneumoniae with penicillin. Despite excellent MIC agreement and identical breakpoints, 9% of these had minor discrepancies, mainly because 7% of isolates were found intermediate by the BSAC method but resistant by the NCCLS method. CONCLUSION: There is generally very good agreement between the MICs obtained by the BSAC agar dilution and NCCLS broth microdilution methods in this population of isolates, comparable to the level of agreement achieved between different laboratories using a single method. Breakpoint differences contribute to most of the discrepancies in susceptibility categorization.     

In vivo emergence of subpopulations expressing teicoplanin or vancomycin resistance phenotypes in a glycopeptide-susceptible, methicillin-resistant strain of Staphylococcus aureus

Several reports indicate the emergence of subpopulations resistant to glycopeptides in some clinical isolates of Staphylococcus aureus. While the development of glycopeptide resistance in S. aureus is easily observed in vitro, the in vivo conditions promoting emergence of glycopeptide-resistant subpopulations are unknown. Using a rat model, subcutaneous implants were chronically infected with a methicillin-resistant strain of S. aureus, MRGR3, devoid of a significant (>10(-7)) glycopeptide-resistant subpopulation at 2 mg/L of either teicoplanin or vancomycin. After 3 weeks of infection in antibiotic-untreated animals, subpopulations emerged, growing on agar containing 10 mg/L of either glycopeptide. These subpopulations were detected in all tissue cage fluids containing >7 log cfu/mL at average frequencies of 4 x 10(-5) and 2 x 10(-5) on teicoplanin- and vancomycin-containing agar, respectively. While teicoplanin MICs increased two- to 16-fold, vancomycin MICs increased by less than two-fold. Population analysis and survival kinetic studies of three teicoplanin-selected subclones indicated that transfer from solid to liquid medium conditions decreased expression of teicoplanin resistance in the bacterial population. In Mueller-Hinton broth, >90% of cells remained fully resistant to antibiotic, but did not grow in the presence of teicoplanin for an initial period of at least 6 h. All three teicoplanin-resistant subclones expressed stable teicoplanin resistance with slight cross-resistance to vancomycin after a few transfers on teicoplanin-supplemented agar. These data suggest that some in vivo conditions may lead to selection of S. aureus subpopulations exhibiting decreased glycopeptide susceptibility and growing in the presence of otherwise inhibitory concentrations of these antimicrobial agents.     

High prevalence of isolates with reduced glycopeptide susceptibility in persistent or recurrent bloodstream infections due to methicillin-resistant Staphylococcus aureus

Reduced susceptibility to glycopeptides in methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates is considered a risk factor for failure of glycopeptide therapy. We compared the prevalences of MRSA isolates with reduced glycopeptide susceptibility in patients with versus without persistent or recurrent MRSA bloodstream infections. A retrospective cohort study at the University Hospital of Geneva identified 27 patients with persistent or recurrent clonally related MRSA bacteremic episodes over an 8-year period, which included 208 consecutive nosocomial MRSA bacteremic episodes. Vancomycin and teicoplanin MICs were determined by a modified macrodilution assay allowing improved detection of glycopeptide-intermediate MRSA isolates (GISA), characterized by elevated teicoplanin or/and vancomycin MICs (≥ 4 μg/ml). For 16 patients (59%), their pretherapy and/or posttherapy MRSA isolates showed elevated teicoplanin MICs, among which 10 (37%) concomitantly displayed elevated vancomycin MICs. In contrast, 11 other patients (41%) were persistently or recurrently infected with non-GISA isolates. In comparison, only 39 (22%) of 181 single isolates from patients with no microbiological evidence of persistent or recurrent infections showed elevated teicoplanin MICs, among which 14 (8%) concomitantly displayed elevated vancomycin MICs. Clinical, microbiological, and pharmacokinetic variables for patients persistently or recurrently infected with GISA or non-GISA isolates were similar. Bacteremic patients with a poor response to glycopeptide therapy had a 2.8-fold- and 4.8-fold-higher rates of MRSA isolates displaying elevated teicoplanin and vancomycin MICs, respectively, than patients with single isolates (P < 0.0001). Detection of elevated teicoplanin MICs may help to predict a poor response to glycopeptide therapy in MRSA bacteremic patients.     

Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems.

Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.     

Glycopeptide susceptibility profiles of Staphylococcus haemolyticus bloodstream isolates

Twelve clinical strains of Staphylococcus haemolyticus (eight methicillin resistant and three methicillin susceptible), isolated from blood cultures between 1982 and 1997, were investigated for teicoplanin and vancomycin susceptibility profiles. On the basis of conventional MIC tests and breakpoints, four isolates were susceptible (MICs, 1 to 8 microgram/ml) and eight were resistant (MICs, 32 to 64 microgram/ml) to teicoplanin while all were susceptible to vancomycin (MICs, 1 to 2 microgram/ml). All four strains for which the conventional teicoplanin MICs were within the range of susceptibility expressed heterogeneous resistance to teicoplanin and homogeneous vancomycin susceptibility. Of the eight strains for which the conventional teicoplanin MICs were within the range of resistance, six expressed heterogeneous and two expressed homogeneous teicoplanin resistance while seven showed heterogeneous vancomycin resistance profiles (with subpopulations growing on 8 microgram of the drug per ml at frequencies of >/=10(-6) for six strains and 10(-7) for one) and one demonstrated homogeneous vancomycin susceptibility. Of six bloodstream isolates of other staphylococcal species (S. aureus, S. epidermidis, and S. simulans), for all of which the conventional teicoplanin MICs were >/=4 microgram/ml and the vancomycin MICs were 相似文献   

Clinical isolates of Staphylococcus aureus from 1987 and 1989 demonstrating heterogeneous resistance to vancomycin and teicoplanin

Fifty isolates of Staphylococcus aureus, obtained during a multicenter clinical trial evaluating the efficacy of teicoplanin that was performed between 1987 and 1992, underwent glycopeptide susceptibility testing, and 2 isolates were found to be capable of growth on agar containing 4 or 8 mg/L of vancomycin. Both of these isolates were from patients that had received prolonged teicoplanin therapy and were deemed clinical failures. Extended susceptibility testing combined with mecA gene probing revealed that one isolate was susceptible to oxacillin, the other was resistant, and both were susceptible to a variety of nonglycopeptide agents. Population analyses revealed heterogeneous vancomycin- and teicoplanin-susceptibility profiles. Both strains were differentiated from recent glycopeptide intermediately resistant Staphylococcus aureus isolates by pulse-field analysis and by the fact that the resistance phenotype was stable to multiple serial passages. To our knowledge, this is the earliest report of S. aureus clinical isolates having reduced vancomycin and teicoplanin susceptibility.     

Effect of human plasma on the antimicrobial activity of iclaprim in vitro

OBJECTIVES: Iclaprim is a novel diaminopyrimidine for which a human plasma binding level of approximately 93% has been reported. The purpose of this study was to evaluate the effect of human plasma on the in vitro activity of iclaprim and to compare it with that of fusidic acid, teicoplanin and vancomycin, antibiotics with protein binding to human plasma of 97%, >90% and 55%, respectively. METHODS: MICs were determined using 40 methicillin-susceptible Staphylococcus aureus (MSSA) and 38 methicillin-resistant S. aureus (MRSA) isolates in Mueller-Hinton broth (MHB) alone or in the presence of 50% human plasma. RESULTS: MICs of iclaprim were not affected by the addition of human plasma. MIC ranges (MIC(90)) for iclaprim against MSSA and MRSA were < or =0.016-0.06 mg/L (MIC(90) 0.06 mg/L) and < or =0.016-0.5 mg/L (MIC(90) 0.06 mg/L), respectively, in MHB and < or =0.016-0.125 mg/L (MIC(90) 0.06 mg/L) and < or =0.016-0.25 mg/L (MIC(90) 0.125 mg/L), respectively, in the presence of human plasma. As expected, the antimicrobial activity of fusidic acid was greatly affected by the presence of human plasma (MIC elevations of 4- to >128-fold), whereas MICs of vancomycin remained unchanged. By contrast, despite the high protein binding, MICs of teicoplanin were only marginally affected by the presence of plasma with an MIC elevation of maximum 8-fold for two strains. CONCLUSIONS: This study demonstrates that human plasma does not affect the MIC of iclaprim in vitro.     

耐万古霉素肠球菌的基因检测

目的 调查上海华山医院2007-2009年间VRE的分离率,并对耐药菌株的分子特性进行研究,为本地区VRE的预防和控制提供有价值的信息.方法 通过琼脂平板稀释法(ADSP)从临床鉴定的890株肠球菌中筛选VRE菌株,并通过微量肉汤稀释实验测其对万古霉素及替考拉宁的MIC;采用PCR及测序方法检测万古霉素耐药基因以及可能毒力基因esp,hyl;运用MLST对VRE进行克隆分型并通过PFGE分型技术进行验证.结果 ADSP法及微量肉汤稀释实验共筛选出13株VRE菌株.其中6株VRE(2007-2008年)只对万古霉素耐药,但对于替考拉宁敏感(万古霉素MIC64～256μg/ml);耐药基因PCR产物测序结果提示这6株VRE均携带同一种可能导致万古霉素耐药的新型基因,该基因序列与已报道的耐药基因均不同;MLST及PFGE分型提示其属于不同型别.另外7株VRE(2009年1-7月)对万古霉素和替考拉宁的MIC结果分别为32～64μg/ml和16～32 μg/ml,耐药基因检测均为vanA.MLST分型结果提示13株VRE共分为4个不同的ST型,其中11株均属克隆复合型CC-17.13株VRE毒力基因esp和hyl的阳性率分别为69.2%和30.8%.结论 上海华山医院VRE克隆分型以CC17为主,同时发现上海华山医院存在一种可能导致万古霉素耐药的新型基因介导的VRE,该新基因的功能和定位尚待进一步研究.     

Multilocus sequence typing (MLST) shows that the 'Iberian' clone of methicillin-resistant Staphylococcus aureus has spread to France and acquired reduced susceptibility to teicoplanin

Infection by methicillin-resistant Staphylococcus aureus (MRSA) presents a serious problem, as these organisms are resistant to a wide range of antibiotics. Moreover, MRSA with reduced susceptibility to glycopeptides (GISA) have emerged in recent years. In our hospital we were faced with an outbreak of GISA between January and March 2000, involving six patients who were free of MRSA when the GISA isolate emerged, and five of whom had not been given glycopeptides. The initial GISA isolate from the six patients was compared with six 'historical' multiple-resistant MRSA isolates (1996-1999), which had not been found to be GISA by the routinely used method. Antibiotic susceptibility was studied through the disc diffusion method, and MICs of glycopeptides were determined by Etest, agar and broth dilution techniques. Molecular strain typing was done by PFGE and multilocus sequence typing (MLST). All 12 isolates that belonged to the gentamicin-resistant group of MRSA were susceptible to vancomycin, but showed reduced susceptibility to teicoplanin through at least one MIC method. PFGE typing yielded five different but closely related profiles, and eight of the 12 clinical isolates were classified into a single PFGE type. MLST yielded an identical allelic profile for all 12 isolates, corresponding to the profile (3-3-1-12-4-4-16) of the 'Iberian' clone HPV107 of MRSA. MLST allowed us to confirm the presence of the 'Iberian' MRSA clone HPV107 with the same allelic profile in our hospital for several years. We can now note that strains of this clone have acquired reduced susceptibility to teicoplanin.     

Detection and expression of methicillin/oxacillin resistance in multidrug-resistant and non-multidrug-resistant Staphylococcus aureus in Central Sydney,Australia

Ninety clinical Staphylococcus aureus isolates from separate patients were examined phenotypically and genotypically for susceptibility to methicillin/oxacillin. Thirty were methicillin/oxacillin susceptible and 60 were methicillin and oxacillin resistant (MRSA). The 60 MRSA isolates examined were subdivided into two groups according to their antibiotic profiles and comprised 30 non-multidrug-resistant (NMDR) isolates, resistant to less than two non-beta-lactam antibiotics, and 30 multidrug-resistant (MDR) isolates, resistant to three or more non-beta-lactam antibiotics. Phenotypic and genotypic analysis of methicillin/oxacillin showed that despite use of the guidelines published by the NCCLS for the testing of S. aureus susceptibility to methicillin/oxacillin, MIC values of some NMDR MRSA isolates fell below the NCCLS-recommended breakpoints. Etest strips failed to detect two NMDR MRSA isolates tested with oxacillin and four tested with methicillin. Lowering the NCCLS-recommended oxacillin screen agar concentration from 6 to 2 mg/L and temperature of incubation to 30 degrees C, improved the specificity and sensitivity of NMDR MRSA detection from 87% to 100%. On PFGE analysis these NMDR MRSA strains were genotypically different. Genotypic tests, such as multiplex PCR for the mecA/nuc genes and DNA hybridization for the mecA gene, or phenotypic monoclonal antibody-based tests to detect penicillin-binding protein 2a (PBP2a) offer advantages for problematic isolates in detecting or confirming low-level phenotypic heterogeneous mecA expression of oxacillin and methicillin resistance in NMDR MRSA.     

Methicillin-resistant Staphylococcus aureus heterogeneously resistant to vancomycin in a Turkish university hospital

OBJECTIVES: We investigated vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneously vancomycin-intermediate S. aureus (hetero-VISA) isolates from clinical specimens of hospitalized patients at Hacettepe University over a 4 year period. METHODS: Strains were screened for VISA and hetero-VISA by using brain heart infusion agar containing 4 mg/L vancomycin (BHI-V4) and macro Etest. Confirmation of the isolates that were found to have intermediate susceptibility to vancomycin with either of the methods was done by population analysis of subpopulations with reduced susceptibility to vancomycin. The MIC of vancomycin for the isolates grown on BHI-V4 was determined by the microdilution method. RESULTS: Among 256 methicillin-resistant S. aureus (MRSA) isolates, 145 grew on BHI-V4. Forty-six of these were also found to be heterogeneously vancomycin-intermediate strains when screened with the macro Etest. There were no VISA among 256 MRSA tested but 46 (17.97%) S. aureus strains with reduced susceptibility to vancomycin were identified by population analysis. Vancomycin MIC values for all isolates with reduced susceptibility were between 相似文献