In vitro activity of vancomycin and teicoplanin against gram-positive cocci]

The activities of vancomycin and teicoplanin against 148 strains of Gram-positive cocci were tested using agar diffusion and liquid microdilution MIC determination. Tested strains included 84 staphylococci, 32 S. aureus, 52 coagulase-negative staphylococci (CNS), 52 enterococci, and 12 streptococci. Most strains (136) were susceptible to both agents, with inhibition diameters of 17 mm or more. MRSA strains exhibited lower geometric MIC means with teicoplanin (0.90 micrograms/ml) than with vancomycin (1.79 micrograms/ml); this difference was found for methicillin-susceptible S. aureus strains (1.07 and 1.38 micrograms/ml for teicoplanin and vancomycin, respectively). In contrast, methicillin-susceptible and methicillin-resistant strains of CNS exhibited similar MICs (1.60 micrograms/ml approximately). Enterococci were more susceptible to teicoplanin (MIC 0.25 micrograms/ml) than to vancomycin (MIC 1.35 micrograms/ml). Both vancomycin and teicoplanin were thus found to be consistently effective against Gram-positive cocci; however, teicoplanin proved more effective than vancomycin against enterococci and methicillin-resistant S. aureus strains and may therefore be a valuable therapeutic alternative for these multiresistant organisms.     

In vitro activity of six antibiotics against multiresistant staphylococci and other gram-positive cocci

Sixty-two strains ofStaphylococcus aureus and coagulase-negative staphylococci, 21Streptococcus faecalis and 17 other strains of streptococci isolated from cases of endocarditis were tested for sensitivity against rifampicin, teicoplanin, vancomycin, fusidic acid, erythromycin and novobiocin. Only rifampicin, novobiocin and teicoplanin were found to be active against the great majority of these strains. The microbial properties of these antibiotics suggest the necessity of combinations for effective therapy. The combinations rifampicin + novobiocin and rifampicin + teicoplanin were additive and suppressed the emergence of resistant mutants. Thus according to in vitro tests, either of these two combinations would be suitable for prophylactic use in high-risk patients, especially those scheduled to receive prosthetic implants.     

Antimicrobial activity of fusidic acid and disk diffusion susceptibility testing criteria for gram-positive cocci.

The in vitro activity of fusidic acid was assessed and was compared with those of cloxacillin, cefamandole, vancomycin, teicoplanin, ofloxacin, ciprofloxacin, pefloxacin, and fleroxacin against 500 gram-positive cocci: 151 Staphylococcus aureus, 197 coagulase-negative staphylococci, and 152 Enterococcus faecalis strains. All clinical isolates were concomitantly tested by disk diffusion and agar dilution procedures as outlined by the National Committee for Clinical Laboratory Standards. The results with fusidic acid were further analyzed by regression line and error rate-bounded methods. With control American Type Culture Collection organisms, the values were within the limits of the National Committee for Clinical Laboratory Standards or published limits. The incidence of resistance to fusidic acid was 0.7% for S. aureus, 2.5% for coagulase-negative staphylococci, and 99.3% for E. faecalis. The correlation coefficient between the results of disk diffusion and agar dilution tests with fusidic acid was 0.90. Current interpretive criteria for susceptibility to fusidic acid (i.e., MIC of < 2 micrograms/ml and inhibitory zone of 20 mm) gave 1% false susceptibility (all strains being E. faecalis). This error rate is practically eliminated if a zone diameter of 21 mm is considered the breakpoint for susceptibility.     

A comparative microbiological and pharmacokinetic activity of vancomycin and teicoplanin]

Vancomycin and teicoplanin are two commercially available glycopeptide antibiotics. They have identical spectra of activity and similar mechanisms of action, and both are complex molecules. In vitro, vancomycin is more active against coagulase-negative staphylococci, while teicoplanin is more active against enterococci and pneumococci. The activity of the two antibiotics against Staphylococcus aureus is similar. The serum pharmacokinetics of vancomycin and teicoplanin are highly different, teicoplanin having a longer elimination half-life (40 hours versus 6-8 hours for vancomycin), but a higher degree of protein binding (90% versus 55%). We compared the two antibiotics on the basis of their inhibitory quotient kinetics, using the MIC90 values for the above bacterial species as the microbiological parameters, and the total and free (non-protein bound) serum concentrations as the pharmacokinetic parameters. The inhibitory quotient kinetics of vancomycin were always more favorable in terms of the free concentrations, even against those bacteria for which the teicoplanin MIC was lower.     

European survey of glycopeptide susceptibility in Staphylococcus spp.

Objectives: To reassess the relative potencies of teicoplanin and vancomycin following several years of clinical usage.
Methods: The glycopeptide susceptibilities of clinical isolates of staphylococci collected from 70 hospitals in 1995 were determined using NCCLS (National Committee for Clinical Laboratory Standards) methods.
Results: In total, 2885 isolates of Staphylococcus aureus and 1480 isolates of coagulase-negative staphylococci were collected. S. aureus was significantly less susceptible to vancomycin (MIC₅₀ 1 mg/L) than teicoplanin (MIC₅₀ 0.5 mg/L), but the reverse was the case for S. haemolyticus and S. epidermidis . No S. aureus isolate was resistant (≥32 mg/L) to either glycopeptide, but nine isolates of coagulase-negative staphylococci had an MIC of teicoplanin of 32 mg/L. Respiratory isolates of S. aureus were less susceptible to glycopeptides than those from other sites. Staphylococci from Belgium and Italy were less susceptible to teicoplanin than isolates from other countries.
Conclusions: This European survey shows that in 10 years of clinical use there have been no major changes in the susceptibility of staphylococci to the glycopeptides.     

Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci collected from hospitals in Brazil.

Pharmacodynamic exposures, measured as the ratio of steady-state total drug area under the curve to MIC (AUC/MIC), were modelled using a 5000-patient Monte-Carlo simulation against 119 non-duplicate clinical isolates of Staphylococcus aureus and 82 coagulase-negative staphylococci (CNS) collected from hospitals in Brazil between 2003 and 2005. Pharmacodynamic targets included an AUC/MIC >82.9 for linezolid and >345 for teicoplanin and vancomycin, as well as a free drug AUC/MIC >180 for vancomycin. The cumulative fractions of response (CFRs) against all S. aureus isolates were 96.0%, 30.1%, 71.6%, 48.0% and 65.1% for linezolid 600 mg every 12 h, teicoplanin 400 mg every 24 h and 800 mg every 24 h, and vancomycin 1000 mg every 12 h and every 8 h, respectively. Using a free drug target for vancomycin improved the CFR to 94.6% for the high-dose regimen, but did not substantially alter results for the lower dose. CFRs against all CNS isolates were 97.8%, 13.4%, 34.6%, 10.9% and 31.3%, respectively, for the same antibiotic regimens. The CFR was reduced for all compounds among the methicillin-resistant isolates, except for linezolid against methicillin-resistant CNS. Sensitivity analyses did not alter the final order of pharmacodynamic potency against these isolates. Although higher doses of vancomycin and teicoplanin increased the CFR, the likelihood of achieving bactericidal targets was still lower than with linezolid. The results for the high-dose vancomycin regimen were highly dependent on the pharmacodynamic target utilised. These data suggest that linezolid has a greater probability of attaining its requisite pharmacodynamic target than teicoplanin and vancomycin against these staphylococci.     

Evaluation of the E test by using selected gram-positive bacteria.

The E test (AB Biodisk NA Inc.) was compared with standard reference methods using the National Committee for Clinical Laboratory Standards's recommendations for determining the MICs of four selected antibiotics against 208 clinical isolates of gram-positive bacteria. These bacteria included 32 strains of Streptococcus pneumoniae, 25 strains of Enterococcus faecium, 20 strains of oxacillin-sensitive Staphylococcus aureus (OSSA), 96 strains of oxacillin-resistant S. aureus (ORSA), and 35 strains of coagulase-negative staphylococci. Evaluation included MIC accuracy within 1 dilution, reproducibility testing, and cost analysis. There was 94% agreement between the E test and the reference method in testing S. pneumoniae and penicillin G. There was 92% agreement with ampicillin and 100% agreement with vancomycin in testing E. faecium isolates. Accuracy of the oxacillin E test with staphylococci was significantly improved by the use of salt-supplemented Mueller-Hinton agar, for an agreement of 100% with coagulase-negative staphylococci and oxacillin-sensitive S. aureus and that of 85% with oxacillin-resistant S. aureus, with no major discrepancies. The E test with American Type Culture Collection isolates and clinical strains gave excellent reproducibility and was less costly than microdilution panels when used to test fewer than three antibiotics. The E test is a simple, reliable, reproducible, and cost-effective method for MIC determination for gram-positive organisms.     

Molecular Epidemiology of Oxacillin-resistant Staphylococcus aureus and in vitro Activity of Glycopeptides against Staphylococcus species

Oxacillin resistant Staphylococcus aureus and coagulase negative Staphylococcus species (MRSA and MRSCoN)have become major pathogens in nosocomial infections.The first MRSA isolate in the world was identified in En gland in 1961 [1]. Since that tim…     

Accuracy of the VITEK 2 system to detect glycopeptide resistance in enterococci

We evaluated the accuracy of the VITEK 2 fully automated system to detect and identify glycopeptide-resistant enterococci (GRE) compared to a reference agar dilution method. The sensitivity of vancomycin susceptibility testing with VITEK 2 for the detection of vanA, vanB, and vanC1 strains was 100%. The sensitivity of vancomycin susceptibility testing of vanC2 strains was 77%. The sensitivity of teicoplanin susceptibility testing of vanA strains was 90%. Of 80 vanC enterococci, 78 (98%) were correctly identified by VITEK 2 as Enterococcus gallinarum/Enterococcus casseliflavus. Since the identification and susceptibility data are produced within 3 and 8 h, respectively, VITEK 2 appears a fast and reliable method for detection of GRE in microbiology laboratories.     

In vitro activity of teicoplanin against gram-positive cocci

The glycopeptide susceptibility of 443 clinical isolates of gram-positive cocci collected from nine general hospitals in 1996 was determined according to the recommendations of the CA-SFM (the Antibiogram Committee of the French Society for Microbiology). In total, 234 isolates of Staphylococcus aureus, 84 isolates of coagulase-negative staphylococci (CNS), 98 enterococci and 27 streptococci were collected. The mecA gene confirming resistance to methicillin was found in 42.7% of S. aureus isolates and 51.2% of CNS isolates. No resistance to teicoplanin and vancomycin was found in S. aureus but four isolates of CNS had an MIC of teicoplanin > or = 8 mg/L. All isolates of Enterococcus faecalis tested were susceptible to both glycopeptides. This study confirms that teicoplanin has a very good in vitro activity against gram-positive cocci, isolated in France from nosocomial infections.     

Validation of VITEK 2 version 4.01 software for detection, identification, and classification of glycopeptide-resistant enterococci

We evaluated the ability of the new VITEK 2 version 4.01 software to identify and detect glycopeptide-resistant enterococci compared to that of the reference broth microdilution method and to classify them into the vanA, vanB, vanC1, and vanC2 genotypes. Moreover, the accuracy of antimicrobial susceptibility testing with agents with improved potencies against glycopeptide-resistant enterococci was determined. A total of 121 enterococci were investigated. The new VITEK 2 software was able to identify 114 (94.2%) enterococcal strains correctly to the species level and to classify 119 (98.3%) enterococci correctly to the glycopeptide resistance genotype level. One Enterococcus casseliflavus strain and six Enterococcus faecium vanA strains with low-level resistance to vancomycin were identified with low discrimination, requiring additional tests. One of the vanA strains was misclassified as the vanB type, and one glycopeptide-susceptible E. facium wild type was misclassified as the vanA type. The overall essential agreements for antimicrobial susceptibility testing results were 94.2% for vancomycin, 95.9% for teicoplanin, 100% for quinupristin-dalfopristin and moxifloxacin, and 97.5% for linezolid. The rates of minor errors were 9% for teicoplanin and 5% for the other antibiotic agents. The identification and susceptibility data were produced within 4 h to 6 h 30 min and 8 h 15 min to 12 h 15 min. In conclusion, use of VITEK 2 version 4.01 software appears to be a reliable method for the identification and detection of glycopeptide-resistant enterococci as well as an improvement over the use of the former VITEK 2 database. However, a significant reduction in the detection time would be desirable.     

Prevalence of antibiotic resistance among clinical isolates of methicillin-resistant staphylococci

The prevalence of methicillin-resistant and multiply antibiotic-resistant staphylococci causing infections in hospitalized patients was studied over a two-year period. Among 122 clinically significant staphylococci, the prevalence of methicillin resistance was 66 %, with a higher prevalence ofStaphyloccus haemolyticus (85 %) andStaphylococcus epidermidis (83 %) observed than ofStaphylococcus aureus (49 %). Multiple antibiotic resistance was observed more frequently among coagulase-negative staphylococci (52 to 70 %) than amongStaphylococcus aureus (17 %). All strains of methicillin-resistantStaphylococcus aureus were susceptible to glycopeptide antibiotics and to trimethoprim-sulfamethoxazole, whereas approximately 50 % of coagulase-negative staphylococci exhibited either moderate susceptibility or resistance to teicoplanin. For these latter strains, vancomycin remains the agent of choice, whereas teicoplanin cannot be recommended unless its efficacy is established by MIC determination.     

新生儿败血症致病菌分布及耐药性分析

目的 研究新生儿败血症感染致病菌分布及耐药性情况,为临床合理用药提供理论依据。方法 通过医院信息管理系统对我院2015年4月~2018年4月在围产儿科住院的共111例新生儿败血症的临床资料进行回顾性分析,对其所采血培养结果进行分析。结果 111例新生儿败血症患儿共检出菌株113株,其中革兰氏阳性菌103株（91.15%）,革兰氏阴性菌10株（8.85%）,真菌检出（0%）。革兰氏阳性菌以凝固酶阴性葡萄球菌（表皮葡萄球菌58株、溶血性葡萄球菌12株、人葡萄球菌9株、沃氏葡萄球菌3株）、粪肠球菌、金黄色葡萄球菌为主,分别为82株（72.57%）、10株（8.85%）、7株（6.19%）;革兰氏阴性菌以大肠埃希菌为主,共7株（6.19%）。革兰氏阳性球菌是新生儿败血症的主要病原菌,其对青霉素、红霉素及苯唑西林耐药率高,对万古霉素、替考拉宁100.00%敏感。革兰氏阴性菌对氨苄青霉素舒巴坦、氨苄西林、复方新诺明耐药率高,对亚胺培南、美洛培南敏感。结论 根据血培养药敏结果,选择敏感抗菌药物,合理使用抗生素,可减少细菌耐药的发生,提高临床治疗效果。     

1999-2006年北京朝阳医院革兰阳性球菌耐药性分析

目的 探讨北京朝阳医院1999-2006年临床分离的革兰阳性球菌的耐药变迁,以指导临床合理使用抗菌药物.方法 采用MIC法进行抗菌药物敏感性试验,以WHONET5.3软件分析数据.结果 6192株临床分离的革兰阳性球菌中,前4位病原菌依次为凝同酶阴性葡萄球菌、金黄葡萄球菌、粪肠球菌、屎肠球菌.耐甲氧西林金黄葡萄球菌(MRSA)、耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)平均检出率分别为88.4%、86.9%,金黄葡萄球菌对青霉素、氨苄西林耐药率最高,8年间始终保持在90.0%以上.未发现对万古霉素耐药或中介的金黄葡萄球菌或凝固酶阴性葡萄球菌.2003年首次分离耐万古霉素肠球菌(VRE),至2006年共发现30株VRE,其中13株为耐万古霉索粪肠球菌,均为VanB基因型;17株为耐万古霉素屎肠球菌,均为VanA基因型,耐万古霉素屎肠球菌分离率呈上升趋势.对于粪肠球菌活性最高的是万古霉素、氨苄西林、青霉素,敏感率分别为98.7%、95.7%、85.6%.但是青霉素敏感性略有下降,从94.3%降至84.6%.克林霉素的耐药率8年中始终维持在99.0%以上.屎肠球菌对红霉素、克林霉素的耐药率均达95.0%以上,对青霉素、氨苄西林、环丙沙星的耐药率均大于90.0%.屎肠球菌最为敏感的药物是万古霉素,对四环素敏感性出现上升的趋势,从27.8%升到82.6%.结论 万古霉素对临床常见的革兰阳性菌保持很高的活性,发现30株耐万古霉素的肠球菌.     

Comparative in vitro activity of glycopeptides against coagulase negative staphylococci isolated in pediatric hospital units]

The minimum inhibitory concentrations (MICs) of vancomycin and teicoplanin were determined for 32 coagulase-negative staphylococci strains recovered from blood specimens from pediatric intensive care patients. All the strains were susceptible to vancomycin (MIC less than 4 mg/l). Sixteen strains were susceptible to teicoplanin (MIC less than 4 mg/l) and the sixteen remaining strains exhibited intermediate susceptibility, with MICs of 8 mg/l (10 strains) or 16 mg/l (6 strains). Inhibition zone diameters seen with vancomycin during agar diffusion susceptibility testing were consistently greater than 17 mm. Inhibition zones obtained with teicoplanin were 17 mm or more in diameter for 30 strains and under 17 mm in diameter for 2 strains. For 14 strains (44%), agar diffusion testing failed to detect the decreased susceptibility to teicoplanin revealed by MIC determinations. The agar diffusion method does not seem reliable for the determination of in vitro susceptibility to teicoplanin.     

In vitro activity of evernimicin and selected antibiotics against methicillin-resistant staphylococci: a 24-country study

Objective   To collect and analyze data on susceptibility of methicillin-resistant staphylococci to evernimicin and other antimicrobial agents.
Methods   Recent clinical isolates of methicillin-resistant staphylococci from 33 laboratories in North America, Europe and South Africa were investigated.
Results   Of the antimicrobial agents tested, evernimicin had the lowest MIC₉₀s for methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci (0.75 and 1.0 mg/L, respectively). Resistance to ciprofloxacin and erythromycin was widespread, with higher levels of resistance in North America than in other regions.
Conclusions   Susceptibility surveys help to determine the antimicrobial activity of new agents. Ciprofloxacin- and erythromycin-resistant staphylococci were prevalent throughout all regions.     

Evaluation of the VITEK 2 system for identification and antimicrobial susceptibility testing of medically relevant gram-positive cocci

A study was conducted to evaluate the new VITEK 2 system (bioMérieux) for identification and antibiotic susceptibility testing of gram-positive cocci. Clinical isolates of Staphylococcus aureus (n = 100), coagulase-negative staphylococci (CNS) (n = 100), Enterococcus spp. (n = 89), Streptococcus agalactiae (n = 29), and Streptococcus pneumoniae (n = 66) were examined with the ID-GPC identification card and with the AST-P515 (for staphylococci), AST-P516 (for enterococci and S. agalactiae) and AST-P506 (for pneumococci) susceptibility cards. The identification comparison methods were the API Staph for staphylococci and the API 20 Strep for streptococci and enterococci; for antimicrobial susceptibility testing, the agar dilution method according to the procedure of the National Committee for Clinical Laboratory Standards (NCCLS) was used. The VITEK 2 system correctly identified to the species level (only one choice or after simple supplementary tests) 99% of S. aureus, 96.5% of S. agalactiae, 96.9% of S. pneumoniae, 92.7% of Enterococcus faecalis, 91.3% of Staphylococcus haemolyticus, and 88% of Staphylococcus epidermidis but was least able to identify Enterococcus faecium (71.4% correct). More than 90% of gram-positive cocci were identified within 3 h. According to the NCCLS breakpoints, antimicrobial susceptibility testing with the VITEK 2 system gave 96% correct category agreement, 0.82% very major errors, 0.17% major errors, and 2.7% minor errors. Antimicrobial susceptibility testing showed category agreement from 94 to 100% for S. aureus, from 90 to 100% for CNS, from 91 to 100% for enterococci, from 96 to 100% for S. agalactiae, and from 91 to 100% for S. pneumoniae. Microorganism-antibiotic combinations that gave very major errors were CNS-erythromycin, CNS-oxacillin, enterococci-teicoplanin, and enterococci-high-concentration gentamicin. Major errors were observed for CNS-oxacillin and S. agalactiae-tetracycline combinations. In conclusion the results of this study indicate that the VITEK 2 system represents an accurate and acceptable means for performing identification and antibiotic susceptibility tests with medically relevant gram-positive cocci.     

New antimicrobial cystatin C-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus and multiresistant coagulase-negative staphylococci

We describe the synthesis and antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)-2-(Nalpha-benzyloxycarbonyl-arginyl-leucylamido-1-[(E)-cinnamoylamido]-3-methylbutane, structurally based upon the inhibitory centre of the human cysteine protease inhibitor, cystatin C. The derivative, here called Cystapep 1, displayed antibacterial activity against several clinically important gram-positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 microg/ml for both Staphylococcus aureus and Streptococcus pyogenes. In radial agar diffusion assays, groups A, B, C and G streptococci as well as staphylococci were generally susceptible to the action of Cystapep 1, whereas pneumococci and enterococci were less susceptible. No activity against gram-negative bacteria was observed. Cystapep 1 also showed high activity against methicillin-resistant S. aureus (MRSA) and multiantibiotic-resistant coagulase-negative staphylococci (CNS), suggesting that its mechanism of action differs from those of most currently used antibiotics.     

In vitro activity of quinupristin/dalfopristin against selected bacterial pathogens isolated in Italy

Objectives: To evaluate the activity of quinupristin/dalfopristin, a new injectable streptogramin, against 732 clinical strains recently isolated in Italy.
Methods: Susceptibility tests were performed according to NCCLS-guided MIC methodology. Pathogens included in the evaluation included 108 Staphylococcus aureus isolates, 124 coagulase-negative staphylococcal isolates, 158 Streptococcus pyogenes isolates, 30 Streptococcus agalactiae isolates, 30 β-hemolytic streptococcal isolates, 18 Streptococcus sanguis isolates, 80 Streptococcus pneumoniae isolates, 69 Enterococcal isolates, 40 Haemophilus influenzae isolates, 30 Moraxella catarrhalis isolates and, finally, 30 Gram-positive and 25 Gram-negative anaerobes.
Results: Quinupristin/dalfopristin inhibited Staphylococcus aureus and other Staphylococcus spp., irrespective of their oxacillin or erythromycin resistance phenotypes. Similarly, streptococci were fully inhibited by quinupristin/dalfopristin. Enterococcus faecalis was not included in the spectrum of this streptogramin, while isolates of Enterococcus faecium were inhibited by the new compound. Respiratory pathogens such as H. influenzae and M. catarrhalis were inhibited by quinupristin/dalfopristin as well as all Gram-negative anaerobes tested.
Conclusions: These findings suggest a putative role for quinupristin/dalfopristin in the empirical treatment of severe nosocomial and community-acquired infections caused by pathogens often displaying resistance to multiple antibiotics. This drug may provide an alternative to glycopeptide compounds.     

Resistance to vancomycin and teicoplanin: an emerging clinical problem.

Vancomycin and teicoplanin are glycopeptides active against a wide range of gram-positive bacteria. For 30 years following the discovery of vancomycin in 1956, vancomycin resistance was not detected among normally susceptible bacteria recovered from human specimens. Since 1986, however, bacteria resistant to vancomycin or teicoplanin or both have been described. Strains of the genera Leuconostoc, Lactobacillus, Pediococcus, and Erysipelothrix seem inherently resistant to glycopeptides. Species and strains of enterococci and coagulase-negative staphylococci appear to have acquired or developed resistance. There are at least two categories of glycopeptide resistance among enterococci, characterized by either high-level resistance to vancomycin (MIC, greater than or equal to 64 mg/liter) and teicoplanin (MIC, greater than or equal to 8 mg/liter) or lower-level vancomycin resistance (MIC, 32 to 64 mg/liter) and teicoplanin susceptibility (MIC, less than or equal to 1 mg/liter). The two categories appear to have similar resistance mechanisms, although genetic and biochemical studies indicate that they have arisen independently. Among coagulase-negative staphylococci, strains for which vancomycin MICs are up to 20 mg/liter or teicoplanin MICs are 16 to 32 mg/liter have been reported, but cross-resistance between these glycopeptides varies. The selective advantage accorded to glycopeptide-resistant bacteria and the observation that high-level resistance in enterococci is transferable suggest that such resistance may be expected to increase in incidence. Clinicians and microbiologists need to be aware of this emerging problem.