抗菌药物联用对耐甲氧西林金黄色葡萄球菌体外抗菌活性研究

目的了解万古霉素与头孢哌酮/舒巴坦、亚胺培南、左氧氟沙星联用对MRSA的体外抗菌活性,指导临床合理用药。方法常规方法培养分离细菌,用VITEK微生物自动分析仪或API系统鉴定到种。MRSA鉴定应用乳胶凝集试剂盒,药敏试验采用肉汤倍比稀释法和琼脂平板稀释法。结果万古霉素对40株MRSA的MIC90为4mg/L,而与头孢哌酮/舒巴坦、亚胺培南、左氧氟沙星联用MIC90降为0.25～1mg/L。结论万古霉素与上述三种药物联用以协同作用为主,抗菌活性提高4倍以上。临床上治疗由MRSA引起的重症感染应根据药敏试验结果采用万古霉素与亚胺培南或头孢哌酮/舒巴坦或其它抗菌药物联合应用。     

Antibacterial activity of hydroxychalcone against methicillin-resistant Staphylococcus aureus

Anti-candidal hydroxychalcone, 2,4,2′-trihydroxy-5′-methylchalcone (THMC), was investigated for its antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). THMC showed the minimum inhibitory concentrations of 25.0–50.0 μg/ml against tested 20 strains, at which the effect was based on a bacteriostatic action. THMC of 25.0 μg/ml completely inhibited the incorporation of radio-labelled thymidine and uridine into MRSA cells. In combination with antibiotics, the fractional inhibitory concentration indices were 0.47 for gentamicin and 0.79 for vancomycin, indicating that THMC acts synergistically with these agents. THMC would be a potent therapeutic agent for MRSA infections.     

Beta-lactams against methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) have developed resistance to virtually all non-experimental antibiotics. They are intrinsically resistant to beta-lactams by virtue of newly acquired low-affinity penicillin-binding protein 2A (PBP2A). Because PBP2A can build the wall when other PBPs are blocked by beta-lactams, designing beta-lactams capable of blocking this additional target should help solve the issue. Older molecules including penicillin G, amoxicillin and ampicillin had relatively good PBP2A affinities, and successfully treated experimental endocarditis caused by MRSA, provided that the bacterial penicillinase could be inhibited. Newer anti-PBP2A beta-lactams with over 10-fold greater PBP2A affinities and low minimal inhibitory concentrations were developed, primarily in the cephem and carbapenem classes. They are also very resistant to penicillinase. Most have demonstrated anti-MRSA activity in animal models of infection, and two--the carbapenem CS-023 and the cephalosporin ceftopibrole medocaril--have proceeded to Phase II and Phase III clinical evaluation. Thus, clinically useful anti-MRSA beta-lactams are imminent.     

溶葡萄球菌酶对耐甲氧西林金黄色葡萄球菌的体外抗菌活性

目的 :探讨溶葡萄球菌酶对万古霉素低敏耐甲氧西林金黄色葡萄球菌 (MRSA)的抗菌活性。方法 :琼脂稀释法测定万古霉素和溶葡萄球菌酶对MRSA的最低抑菌浓度 (MIC) ,棋盘法检测 2药联合抑菌作用。结果 :万古霉素对其敏感或低敏MR SA的MIC90 分别为 2mg·L- 1,8mg·L- 1;溶葡萄球菌酶对万古霉素敏感或低敏MRSA的MIC90 分别为 0 .2 5mg·L- 1,0 .5mg·L- 1;2药联合对其敏感株和低敏株的FIC90 (FIC为联合抑菌分数 )较万古霉素单独应用时MIC90 分别减少 4倍和 8倍 ,较溶葡萄球菌酶单独应用时均减少 4倍。FIC指数均小于0 .5。结论 :溶葡萄球菌酶对万古霉素敏感或低敏的MRSA均有良好的体外抗菌活性     

香叶醇体外抗MRSA活性研究

目的 通过体外抑菌实验,评价香叶醇单独使用以及与3种β-内酰胺类抗生素(阿莫西林、头孢氨苄及头孢吡肟)联合使用对耐甲氧西林金黄色葡萄球菌(methicillin resistant Staphylococcus aureus, MRSA)的抑制效果。方法 采用微量稀释法测定香叶醇与3种β-内酰胺类抗生素的最低抑菌浓度(minimum inhibitory concentration, MIC)及最低杀菌浓度(minimum bactericidal concentration, MBC);微量棋盘法测定香叶醇与3种β-内酰胺类抗生素的分级抑菌浓度指数(fractional inhibitory concentration, FIC)。结果与结论 香叶醇具有明显的体外抗MRSA活性,MIC和MBC分别为0.34~0.69mg/mL和0.69~10.76mg/mL。联合药敏试验发现香叶醇与3种β-内酰胺类抗生素联合使用FIC指数集中分布在≤0.5和0.5~1;能够增强β-内酰胺类抗生素的活性,降低其用量,使其MIC50和MIC90降低为单独用药的1/8~1/4和1/4~1/2。     

In-vitro activity of daptomycin against a worldwide collection of methicillin-resistant Staphylococcus aureus.

Minimum inhibitory and minimum bactericidal concentrations (MIC and MBC) of daptomycin and of vancomycin have been compared against 80 strains of methicillin-resistant Staphylococcus aureus isolated from many parts of the world. In the presence of 30 mg/l of Ca++, daptomycin at 4 mg/l killed all the strains tested, and was only slightly less active than vancomycin.     

In vitro antimicrobial activity of telavancin against methicillin-resistant Staphylococcus aureus clinical isolates from Japan (2006)

In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 microg/ml to 0.5 microg/ml and a MIC90 value of 0.5 microg/ml. The MIC90s of vancomycin and linezolid were 1.0microg/ml and 2 microg/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.     

Flavonoids with activity against methicillin-resistant Staphylococcus aureus from Dalea scandens var. paucifolia

Bioassay-guided fractionation of the ethyl acetate extract of the roots of Dalea scandens (Miller) R. Clausen var. paucifolia led to the isolation of new flavonoids, 2( S)-5'-(-1"',1"'-dimethylallyl)-8-(3",3"-dimethylallyl)-2',4',5,7-tetrahydroxyflavanone, 2( S)-5'-(1"',1"'-dimethylallyl)-8-(3",3"-dimethylallyl)-2'-methoxy-4',5,7-trihydroxyflavanone and 5'-(1"',1"'-dimethylallyl)-8-(3",3"-dimethylallyl)-2',4',5,7-tetrahydroxyflavone. Structure elucidation was carried out by spectroscopic methods. All three compounds showed significant activity against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.     

Antibacterial activity of imipenem in combination with ampicillin against methicillin-resistant strains of Staphylococcus aureus

Imipenem (IPM) and beta-lactams have been reported to possess a synergistic relationship in their activities against methicillin (DMPPC)-resistant strains of Staphylococcus aureus (MRSA). The purpose of this study was to determine activities of IPM and ampicillin (ABPC) singly and in combination against MRSA. Activities of the 2 antibiotics against 19 strains of S. aureus resistant to DMPPC were investigated by means of the checkerboard method, the disk diffusion technique and the killing-curve method. MICs of DMPPC against these strains determined using the agar dilution method were greater than or equal to 100 micrograms/ml and MICs of IPM and ABPC ranged from 12.5 to 100 micrograms/ml and from 12.5 to 50 micrograms/ml, respectively, when used singly. The following results were obtained with the checkerboard method: Synergistic effects and additive effects were found against 13/19 and against 6/19 strains, respectively, and no antagonistic effect was found according to the FIC (fractionary inhibitory concentration) index. The disk diffusion technique indicated synergistic results. Killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth against 5 fosfomycin(FOM)-resistant and 5 FOM-susceptible stains: (1) IPM 12.5 micrograms/ml, (2) ABPC 25 micrograms/ml, (3) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml, (4) IPM 6.25 micrograms/ml + ABPC 25 micrograms/ml, (5) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml, (6) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml + FOM (fosfomycin) 25 micrograms/ml, (7) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml + FOM 50 micrograms/ml, (8) FOM 50 micrograms/ml. The following results were obtained with the killing-curve method; (1) Synergistic effects were found against 8/10 strains and no antagonistic effect was found with the combinations of IPM and ABPC. (2) Synergistic effects were found against 3/5 strains and no antagonistic effect was found with the combinations of IPM, ABPC and FOM against 5 FOM-susceptible strains. Conclusions: IPM in combination with ABPC produced synergistic effects against MRSA. This combination therapy should be evaluated in treating MRSA infections.     

利奈唑胺与万古霉素对耐甲氧西林金黄色葡萄球菌体外抗菌活性

目的 评价利奈唑胺(嗯唑烷酮类抗菌药)、万古霉素(胺基糖苷类抗生素)2种抗菌药物对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性.方法 用琼脂二倍稀释法,测定抗菌药物的最低抑菌浓度(MIC);用肉汤稀释法,测定抗菌药物的最低杀菌浓度(MBC),绘制杀菌曲线(KCs).结果 利奈唑胺对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为2 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%;万古霉素对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为1 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%.随着抗菌药物浓度的升高,其杀菌时间缩短不甚明显,呈现非浓度依赖性的特点.结论 利奈唑胺对MRSA的体外抗菌活性与万古霉素相当,均显示非浓度依赖性的杀菌曲线.     

绿茶对耐甲氧西林金黄色葡萄球菌的抗菌作用及机制研究进展

泛耐药的出现,使得耐甲氧西林金黄色葡萄球菌(MRSA)感染的治疗成为临床棘手的问题。绿茶提取物对MRSA有一定的抗菌作用。本文就绿茶对MRSA感染的临床试验、与抗生素的协同抗MRSA作用、有效成分的分离分析及作用机制作一综述。     

In vitro activity of lauric acid or myristylamine in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA)

The objective of this study was to investigate the in vitro activities of lauric acid and myristylamine in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA). The combination effect of lipids and antimicrobial agents was evaluated by the checkerboard method to obtain a fractional inhibitory concentration (FIC) index. The effects of lauric acid + gentamicin (GM) and lauric acid + imipenem (IPM) combinations were synergistic against the clinical isolates in 12 combinations. An antagonistic FIC index was observed only with the myristylamine + GM combination. We investigated in detail the antimicrobial activity for two combinations that showed a synergistic effect. The cytotoxicity of lauric acid was not enhanced by the addition of GM and IPM. In time-kill studies, lauric acid + GM and lauric acid + IPM combinations at one-eighth of the minimum inhibitory concentration produced a bacteriostatic effect.     

Community-associated methicillin-resistant Staphylococcus aureus: a review

Methicillin-resistant Staphylococcus aureus (MRSA) is a common bacterial pathogen responsible for a variety of infections in both children and adults. Treatment of infections caused by this organism is problematic due to its resistance to many drugs. Recent reports of community-associated MRSA (CA-MRSA) infections in patients with no known risk factors have serious public health implications. Therapeutic options for these infections are untested; therefore, the potential exists for high morbidity and mortality. Recently, clinical definitions have been established, and new molecular approaches have allowed investigators to distinguish CA-MRSA more easily from traditional nosocomial-derived MRSA strains. Identifying potential risk factors for CA-MRSA acquisition and fully characterizing the epidemiologic, clinical, and molecular properties of these strains are necessary to provide effective therapeutic guidelines.     

Database screening and in vivo efficacy of antimicrobial peptides against methicillin-resistant Staphylococcus aureus USA300

Natural antimicrobial peptides (AMPs) are promising candidates for developing a generation of new antimicrobials to meet the challenge of antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the search for new candidates, we have utilised the Antimicrobial Peptide Database (APD), which contains natural AMPs from bacteria, fungi, plants and animals. This study demonstrates the identification of novel templates against MRSA by screening 30 peptides selected from the APD. These peptides are short (<25 residues), cysteine-free, cationic and represent candidates from different biological sources such as bacteria, insects, arachnids, tunicates, amphibians, fish and mammals. Six peptides, including ascaphin-8, database-screened antimicrobial peptide 1 (DASamP1), DASamP2, lycotoxin I, maculatin 1.3 and piscidin 1, were found to exert potent antimicrobial activity against an MRSA USA300 isolate. Although five of the six peptides showed broad-spectrum antibacterial activity, DASamP1 displayed killing of MRSA in vitro but not of Escherichia coli, Bacillus subtilis or Pseudomonas aeruginosa. In addition, DASamP1 suppressed early biofilm formation in a mouse model of catheter-associated MRSA infection. DASamP1 is a novel, short and potent peptide that will be a useful starting template for further developing novel anti-MRSA peptides.     

Efficacy of newly generated short antimicrobial cationic lipopeptides against methicillin-resistant Staphylococcus aureus (MRSA)

IntroductionInfection caused by methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) is a serious clinical challenge and research to develop new antimicrobials is imperative.MethodsThis study investigated the in vitro and in vivo efficacy of the short cationic dialkyl lipopeptides (C₁₀)₂-KKKK-NH₂ and (C₁₂)₂-KKKK-NH₂. The antibacterial efficacy of (C₁₀)₂-KKKK-NH₂ and (C₁₂)₂-KKKK-NH₂ was evaluated in representative clinical methicillin-susceptible S. aureus and MRSA strains by both in vitro (MIC, time-kill curve) and in vivo (wax worms model) approaches.ResultsThese studies revealed that both (C₁₀)₂-KKKK-NH₂ and (C₁₂)₂-KKKK-NH₂ have rapid bactericidal activity, with a decrease of > 3 log₁₀ colony forming units (CFU)/mL achieved in the first 6 hours of treatment. Furthermore, (C₁₀)₂-KKKK-NH₂ performed similarly to daptomycin, with a sustained bacterial killing after 24 hours. Wax worms infected and treated with these lipopeptides showed a decreased survival rate of 90% to 50% within the first day of treatment. Scanning electron microscopy determined that the effect of the short lipopeptides in S. aureus was associated with important morphological structural changes that may suggest cell membrane perturbation.ConclusionThese findings suggest that the short lipopeptides (C₁₀)₂-KKKK-NH₂ and (C₁₂)₂-KKKK-NH₂ may be potential new options for treating MRSA infections.     

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