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.     

Antibacterial activity of oral Cephems against various clinically isolated strains

We determined the antibacterial activities of oral Cephems against isolated from the patients with the respiratory infections, the urinary tract infections, and infections in the obstetrics field of an adult and a child, during the period from 2002 to 2003; Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Klebsiella pneumoniae and Escherichia coli of 40 strains of each, and Peptostreptococcus spp. 22 strains. S. pneumoniae and H. influenzae strains that resistant is regarded were collected mainly, penicillin-intermediate S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase negative ampicillin-resistant H. influenzae (BLNAR) strains. The MICs of Cephems except cefaclor (CCL) were < or = 0.03 microgram/mL against all strains of S. pyogenes. The MICs of cefteram (CFTM) and cefditoren (CDTR) were < or = 0.0125 microgram/mL activity against 7 strains penicillin-susceptible S. pneumoniae (PSSP). However the MIC90s of cefditoren (CDTR) was 1 microgram/mL, cefteram (CFTM), and cefcapene (CFPN) were 2 micrograms/mL against PISP and PRSP, were higher than those of other drugs, but showed slightly higher than PSSP. The MIC90s of Cephems. were 0.5-4 micrograms/mL against strains of E. coli. The MIC90s of CFTM was 0.5 microgram/mL, and CDTR, CFPN were 1 microgram/mL against E. coli were higher than those of other drugs. The four strains of E. coli however were highly-resistant which MIC90s of CCL were more than 32 micrograms/mL were obtains. Furthermore it is necessary to pay much attention to the trend of resistant such as E. coli of Cephems. Although all strains showed resistant to AMPC, MIC90 of Cephems were 0.25-1 microgram/mL, good activities against K. pneumoniae. Against beta-lactamase negative ampicillin-susceptible H. influenzae (BLNAS) 23 strains the MIC90s of CCL and other Cephems were 64 micrograms/mL and 0.25-8 micrograms/mL. The MIC90s of CDTR and CFTM were < or = 1 microgram/mL of BLNAR (15 strains). However there of CFDN and CPDX were 8 micrograms/mL and CCL were > or = 16 micrograms/mL. Two strains which were produced beta-lactamase were highly--ABPC resistant. Although B. catarrhalis all strains were produced beta-lactamase and Cephems except for CCL showed better susceptibility than AMPC. The MIC90s of Cephems were 0.25-2 micrograms/mL against Peptostreptococcus spp.     

Activity of eight fluoroquinolones against methicillin-resistant Staphylococcus aureus isolated from cutaneous infections

The in vitro susceptibility of methicillin-resistant Staphylococcus aureus to eight fluoroquinolones, norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, sparfloxacin and nadifloxacin, was evaluated. Methicillin-resistant S. aureus strains were isolated from 64 cutaneous infections from 1991 to 1993. Nadifloxacin exhibited the lowest MIC among all of the fluoroquinolones. In addition, there was no resistance to nadifloxacin. The MIC(50) of these drugs has been increasing in the past 3 years.     

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.     

ε-聚赖氨酸对耐甲氧西林金黄色葡萄球菌USA300的作用机制

摘要：目的 研究ε-聚赖氨酸(ε-polylysine,ε-PL)对耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)标准菌株USA300的抑菌作用及其机制。方法 依据CLSI微量肉汤稀释法测定最低抑菌浓度(minimum inhibitory concentration, MIC)和最低杀菌浓度(minimum bactericidal concentration, MBC);绘制24 h内不同浓度ε-PL作用后USA300菌株时 间-抑菌曲线;SYBR Green I/PI检测ε-PL处理后USA300的生存情况;测定ε-PL处理后菌液电导率、胞外ATP含量、可溶性蛋白 含量的变化;利用扫描电镜(scanning electron microscopy,SEM)观察ε-PL对USA300形态的影响。结果 ε-PL对USA300的MIC、 MBC分别为5.12和10.24 mg/mL。ε-PL处理后细菌死/活比例,菌液电导率,胞外ATP含量,胞外可溶性蛋白含量均增加,表明菌 膜破损;经SEM进一步确证。结论 ε-PL对USA300生长有良好的抑制作用,且与ε-PL浓度呈正相关。ε-PL处理后细胞膜结构破 坏、通透性改变,导致细胞内容物大量渗出,其抑菌机制可能与破坏细菌菌体结构有关。     

Flavone markedly affects phenotypic expression of beta-lactam resistance in methicillin-resistant Staphylococcus aureus strains isolated clinically

Flavone and its derivatives had very weak antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus, but dramatically intensified MRSA's susceptibility to beta-lactams. We named these compounds "ILSMR (intensifier of beta-lactam-susceptibility in MRSA)." We also found discrepancies among MRSA strains in their responses to flavone; some strains showed phenotypic susceptibility to methicillin while others showed phenotypic resistance to it. To understand the mechanism underlying this discrepancy, we characterized 20 MRSA strains in detail, analyzed their conventional and molecular typings, and examined each strain's resistance to beta-lactams, with COL serving as a reference. Neither SCCmec typing nor coagulase typing explained the diverse effects of flavone on the beta-lactam MICs of these strains. Likewise, changes in pulsed-field gel electrophoresis (PFGE) type were not associated with the profiles of ILSMR effects. However, the present observations suggest that the ILSMR effects on MRSA is strain-specific, and that this effect depends on an as-yet unknown mechanism that is essential for the expression of the phenotype conferring beta-lactam resistance to MRSA strains, independently of an interaction with the mecA-encoded penicillin-binding protein 2a or with the beta-lactamase.     

Cross-resistance of clinical isolates of methicillin-resistant Staphylococcus aureus to aminoglycosides and fluoroquinolones.

Susceptibilities of 117 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to aminoglycosides and fluoroquinolones were investigated during 1987 and 1990. Gentamicin, tobramycin, sisomicin, micronomicin, and astromicin showed the bimodal antimicrobial activity pattern against MRSA, revealing cross-resistance to these antibiotics. However, amikacin, netilmicin, isepamicin and arbekacin (ABK) exhibited the monomodal antimicrobial activity pattern, suggesting the presence of less resistant strains. All 117 MRSA strains were susceptible to ABK with MICs less than 3 micrograms/ml. MRSA also showed the bimodal antimicrobial susceptibility pattern to fluoroquinolones such as ofloxacin (OFLX), ciprofloxacin (CPFX) and tosufloxacin (TFLX). Frequencies of TFLX susceptible MRSA isolates decreased progressively from 1987 to 1989 when this drug was not even in general clinical use. The cross-resistance of MRSA between TFLX and OFLX or CPFX persisted. Cross-resistance between aminoglycosides and fluoroquinolones, however, was less frequently observed.     

Antibacterial activities of new cephems against clinically isolated organisms (author's transl)

The antibacterial activities of cefotaxime (CTX), cefoperazone (CPZ), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), cefotiam (CTM), cefazolin (CEZ), gentamicin (GM) and cefsulodin (CFS) were investigated. All causative organisms were isolated from patients with urinary tract infections treated in Tokai University Hospital. The results were as follows. 1) The MICs of CMX, CTX, and CZX against most of clinically isolated strains of E. coli, K. pneumoniae, Indole (-) Proteus sp. were 0.1 microgram/ml and lower. And then CTM, LMOX and CPZ showed similar antibacterial activities. 2) LMOX and GM showed potent antibacterial activities against C. freundii which was considered to be causative organisms of infections in rare cases. 3) Against S. marcescens, CMX, CTX, CZX, and LMOX showed very potent antibacterial activities. 4) Against P. aeruginosa, CFS, GM and CPZ showed moderate antibacterial activities. 5) Against Enterobacter sp., GM and CMX showed potent antibacterial activities.     

Antibacterial effects of moxifloxacin and levofloxacin simulating epithelial lining fluid concentrations against community-acquired methicillin-resistant Staphylococcus aureus

BACKGROUND AND OBJECTIVE: Current North American guidelines advocate the use of respiratory fluoroquinolones for the empirical management of community-acquired pneumonia (CAP). While community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a pathogen frequently encountered in skin and skin structure infections, it has also now been recognised as a causative pathogen in CAP. Since fluoroquinolones may be used empirically to treat unsuspected CA-MRSA pneumonia, the objective of this study was to evaluate the antibacterial properties of levofloxacin and moxifloxacin using human simulated drug exposures in epithelial lining fluid (ELF). METHODS: An in vitro model was used to simulate the ELF concentrations, previously determined in older adults receiving multiple doses, of levofloxacin 500 mg once daily and moxifloxacin 400mg once daily. Four CA-MRSA isolates were studied at a starting inoculum of 10(6) colony-forming units (CFU)/mL; selected isolates were also studied at 10(8) CFU/mL. Bacterial density and resistance were quantitatively assessed over 48 hours. Drug exposure (area under the concentration-time curve [AUC]) was confirmed using validated drug assays. RESULTS: At a standard 10(6) starting inoculum, sustained bacterial kill (3.6-4.5 log) with both fluoroquinolones was noted for CA-MRSA isolates 27 and 44 (AUC/minimum inhibitory concentration [MIC] = 383-3923). Despite an MIC of 8 microg/mL (AUC/MIC = 25) for isolate 3, levofloxacin displayed a 2.8 log kill, while moxifloxacin (MIC 1 microg/mL) sustained a 4.5 log kill (AUC/MIC = 207) over 48 hours. Against isolate 59, levofloxacin displayed no antibacterial effect (AUC/MIC = 3), while moxifloxacin with an MIC of 8 microg/mL (AUC/MIC = 31) killed 4.6 log. At a high inoculum (10(8)), both fluoroquinolones showed 5.2-5.6 log kill for the susceptible isolate (44), while moxifloxacin showed no antibacterial activity against isolate 59. Drug exposure (AUC/MIC) appeared to correlate well (r(2) = 0.99) with the change in log CFU/mL. Maximal activity was observed for both drugs at an AUC/MIC of approximately 30. CONCLUSION: When evaluated at human simulated ELF concentrations, both levofloxacin and moxifloxacin appeared to demonstrate sustained antibacterial activity for CA-MRSA isolates with MICs 相似文献   

Antibacterial activities of macrolactin A and 7-O-succinyl macrolactin A from Bacillus polyfermenticus KJS-2 against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus

The principal objective of this study was to evaluate the antibacterial activities of macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA) generated from Bacillus polyfermenticus KJS-2 against vancomycin-resistant enterococci (VREs) and methicillin-resistant Staphylococcus aureus. The minimal inhibitory concentrations (MICs) of MA and SMA against VREs were 16 and 2∼1 μg/mL, respectively, and the MICs of MA and SMA against methicillin-resistant Staphylococcus aureus were 2 and < 0.25 μg/mL, respectively. Their MIC values were comparable or superior to those of teicoplanin. In evaluating the inhibitory effects of intestinal VRE colonization in mice, the oral MA and SMA effected a rapid inhibition of intestinal VRE colonization in mice, and the intraperitoneal SMA also inhibited VRE colonization, whereas intraperitoneal MA did not.     

Antibacterial activities of arbekacin, a new aminoglycoside antibiotic, against methicillin-cephem-resistant Staphylococcus aureus

The in vitro and in vivo antibacterial activities of a new aminoglycoside antibiotic, arbekacin (HBK), against methicillin-cephem-resistant Staphylococcus aureus (MRSA) were compared with those of gentamicin (GM), netilmicin (NTL) and amikacin (AMK). The results obtained were summarized as follows: Compared to other aminoglycoside antibiotics, HBK had the highest antibacterial activities against clinically isolated MRSA (46 strains). Therapeutic effects of HBK against experimental systemic infections with MRSA in mice, were superior to those of GM, NTL and AMK. The ED50's of GM, NTL and AMK were more than 2 mg/mouse. Therapeutic effects of HBK against experimental subcutaneous infections with MRSA in mice were also superior to those of GM, NTL and AMK.     

The mechanism of action of sanguinarine against methicillin-resistant Staphylococcus aureus

Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis. It is known to perform a wide spectrum of biological activities. The aim of this study is to examine the antimicrobial actions of sanguinarine against methicillin-resistant Staphylococcus aureus (MRSA). Sanguinarine antimicrobial activity was assessed by broth dilution method; its mechanism of action was investigated by bacteriolysis, detergent or ATPase inhibitors and transmission electron microscopy were used to monitor the survival characteristics and the changes in bacteria morphology. The activity of sanguinarine against MRSA strains ranged from 3.12 to 6.25 μg/ml, while the minimum inhibitory concentrations of the two reference strains are 3.12 μg/ml and 1.56 μg/ml. The treatment of the cells with sanguinarine induced the release of membrane-bound cell wall autolytic enzymes, which eventually resulted in lysis of the cell. The OD(600s) of the suspensions treated with the combination of Tris-(hydroxymethyl) aminomethane and Triton X-100 with sanguinarine were reduced to 40% and 8%, respectively. Transmission electron microsco-py of MRSA treated with sanguinarine showed alterations in septa formation. The predisposition of lysis and the altered morphology seen by transmission electron microscopy suggest that sanguinarine compromises the cytoplasmic membrane.     

In vitro combination effect of pazufloxacin with various antibiotics against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

The in vitro combination effects of pazufloxacin (PZFX) with various antibiotics were investigated by the checkerboard dilution method using piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), cefozoprane (CZOP), imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP), amikacin (AMK) and isepamicin (ISP) for clinical isolates of 27 Pseudomonas aeruginosa strains, vancomycin (VCM), teicoplanin (TEIC) and arbekacin (ABK) for clinical isolates of methicillin-resistant 26 Staphylococcus aureus (MRSA) strains, respectively. The following results were obtained. 1. For 27 P. aeruginosa strains, the synergistic effects were observed with the combination of PZFX and CAZ or MEPM (11.1%: 3 strains), and PZFX and CZOP or PAPM/BP (3.7%: 1 strain), respectively. The additive and synergistic effects of PZFX were observed with the combination in all beta-lactams tested in the strains more than 50%. No antagonistic effect was observed. The additive effects were also observed with the combination of PZFX and AMK or ISP in the strains more than 50% of the test strains and no antagonistic effect was observed. 2. For 26 MRSA strains, no antagonistic effect was observed with the combination of all antibiotics tested. The indifference was observed with the combination of PZFX and VCM or ABK in the strains more than 60%, and the additive effects were observed with the combination of TEIC in the strains more than 80%. In conclusion, no antagonistic effect was observed in PZFX with the combination of beta-lactams and anti-MRSA agents, suggesting that the combination therapy of PZFX with these antibiotics would be possible to use for the infections caused by P. aeruginosa and MRSA.     

Antimicrobial activities of hydrophobic 2-arylbenzofurans and an isoflavone against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus

Eight 2-arylbenzofurans and an isoflavone isolated from medicinal plants were tested for their antimicrobial activities against vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, six hydrophobic 2-arylbenzofurans (log P = 4.4-8.7) exhibited considerable antibacterial activity against five VRE strains(VanA-, VanB-, and VanC-phenotypes) (MICs = 3.13-6.25 microg/mL). Five compounds also showed antibacterial activity against ten MRSA strains (MIC80 = 3.13 microg/mL).     

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。