Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system

Titrated extract of Centella asiatica (TECA), a drug used in treating systemic scleroderma, is poorly water-soluble. A conventional dosage form for the intramuscular injection of TECA, propylene glycol (PG)-based TECA solution, causes severe pain after intramuscular injection. To improve the solubility of TECA and reduce pain after injection, mixed micellar systems composed of 10% surfactant mixture (Tween 20 and Tween 85) and 90% phosphate-buffered saline, pH 7.0 (PBS) were prepared. As the ratio of Tween 20 to Tween 85 increased from 0:10 to 10:0, the solubility of TECA in the mixed micellar systems increased from 7- to 26-fold compared to that in PBS (pH 7.0). The droplet size of micelles gradually decreased with the increasing ratio of Tween 20 to Tween 85 from 0:10 to 4:6, followed by an abrupt decrease in size above the ratio of 6:4. Furthermore, the micellar systems prepared with Tween 20 and Tween 85 at the ratio of 6:4, 8:2 or 10:0 could solubilize TECA more than 10 mg/ml and the resultant droplet sizes were less than 2 μm. No significant changes were observed in the droplet sizes and asiaticoside contents in these micellar formulations during storage, indicating these systems are stable for at least 60 days. Their osmotic pressures were remarkably lower than those of PG-based TECA solution and similar to that of saline solution, irrespective of dilution ratios. Most importantly, they markedly reduced the number of writhes compared with PG-based TECA solution after injection to mice. All of these results suggest that these three TECA micellar formulations prepared with Tween 20 and Tween 85 improved the solubility of TECA and reduced pain following injection, possibly due to the decrease in osmotic pressure. Thus, these micellar formulations composed of optimum ratios of Tween 20 and Tween 85 may have a potential as dosage forms for the intramuscular injection of a poorly water-soluble TECA.     

Antimicrobial and antifungal activities of a novel cationic antimicrobial peptide, omiganan, in experimental skin colonisation models

Omiganan pentahydrochloride is a novel, synthetic, cationic, antimicrobial peptide that is being developed for the prevention of catheter-related infections and the treatment of acne and rosacea. In this study, the efficacy of topical omiganan gel was evaluated in two skin colonisation models (ex vivo pig skin and in vivo guinea pig skin). When tested in the ex vivo pig skin colonisation model, omiganan 0.1–2% gels exhibited potent dose-dependent activity against Gram-positive and Gram-negative bacteria and yeasts; the maximum effect was observed at 1–2%. No significant difference was noted in activity toward meticillin-resistant and meticillin-sensitive Staphylococcus aureus, and drug activity was not affected by the inoculum size. The antimicrobial activity of omiganan 1% gel was rapid, with a 2.7 log₁₀ colony-forming unit (CFU)/site reduction in Staphylococcus epidermidis counts at 1 h post application and a 5.2 log₁₀ CFU/site reduction at 24 h. Additional studies in the guinea pig skin colonisation model confirmed the potent antimicrobial and antifungal activities of omiganan 1% gel. In conclusion, omiganan gels have been demonstrated to be rapidly bactericidal and fungicidal, with significant dose-dependent activity against a broad spectrum of infectious organisms. These results further confirm that the drug has the potential as a topical antimicrobial agent.     

2015-2020年新郑市人民医院妇科肿瘤术后患者医院感染的病原菌分布和耐药情况分析

目的 探讨新郑市人民医院妇科肿瘤术后发生医院感染的病原菌情况。方法 选取2015年9月-2020年9月在新郑市人民医院接受妇科肿瘤手术的120例患者的治疗资料进行分析。结果 妇科肿瘤术120例患者总计检出病原菌208株,革兰阴性菌134株（64.42%）,革兰阳性菌60株（28.85%）,真菌14株（6.73%）。大肠埃希菌耐药性较高的药物依次为头孢曲松（59.09%）、复方新诺明（56.82%）、环丙沙星（54.55%）,对替加环素为0。肺炎克雷伯菌耐药性较高的药物依次为阿莫西林（71.42%）、头孢曲松（42.86%）、头孢噻肟（39.29%）,最低为替加环素（3.57%）。铜绿假单胞菌耐药性较高的药物依次为头孢曲松（81.25%）、复方新诺明（81.25%）、阿莫西林（68.75%）。鲍氏不动杆菌耐药性较高的药物依次为亚胺培南（100%）、哌拉西林（92.86%）、头孢吡肟（85.71%）。从主要革兰阳性菌对抗菌药物的耐药性来看,金黄色葡萄球菌对氨苄西林（90.00%）、复方新诺明（90.00%）耐药率较高。表皮葡萄球菌对青霉素（81.82%）、四环素（81.82%）耐药率较高。结论 妇科肿瘤手术后感染的发生与多种病原菌有关,主要为革兰阴性菌,不同病原菌的耐药性存在差异,临床治疗方案需要全面评估感染情况,保证用药方案的科学合理,并注重监测,结合病原学证据及时调整治疗方案。     

山奈酚对白假丝酵母生物被膜抑制作用的研究

目的 研究山奈酚抗白假丝酵母生物被膜的作用及其可能机制。方法 测定山奈酚对白假丝酵母处于形成过程中的生物被膜和成熟生物被膜代谢活性的影响;测定山奈酚对生物被膜基质产生水平的影响;显微镜下观察山奈酚对菌丝形成的抑制作用;水-烃两相分离法测定山奈酚对白假丝酵母细胞表面疏水性的影响;实时定量RT-PCR法测定山奈酚对生物被膜形成相关基因表达的影响。结果 山奈酚抑制白假丝酵母生物被膜形成,且呈剂量依赖性,同时具有抗成熟生物被膜作用,显著降低生物被膜基质含量;与对照组相比,山奈酚明显抑制白假丝酵母菌丝形成并降低其细胞表面疏水性;经山奈酚处理的白假丝酵母生物被膜形成相关基因BCR1、NRG1和TUP1的表达升高,同时HWP1、EFG1、CPH1、ALS1、ALS3和CSH1的表达下降。结论 山奈酚具有抗白假丝酵母生物被膜活性,其机制与抑制菌丝形成及降低其细胞表面疏水性相关。     

2018—2020年郑州市第七人民医院血流感染分离菌的分布及耐药性分析

目的 了解血流感染分离菌的分布及耐药特征,为临床防治血流感染提供指导和依据。方法 收集2018年1月—2020年12月郑州市第七人民医院血培养分离的非重复菌株,采用WHONET5.6软件统计菌株的分布及耐药特征。结果 共分离546株菌株,革兰阴性菌302株（55.31%）,革兰阳性菌220株（40.29%）,真菌24株（4.40%）。前6位分离菌依次为凝固酶阴性葡萄球菌（CNS,23.44%）、大肠埃希菌（18.68%）、肺炎克雷伯菌（14.84%）、金黄色葡萄球菌（6.04%）、鲍曼不动杆菌（4.21%）和铜绿假单胞菌（3.85%）。大肠埃希菌对碳青霉烯类最敏感,肺炎克雷菌碳对美罗培南和亚胺培南的耐药率分别为30.86%和35.80%,鲍曼不动杆菌耐药较严重,耐甲氧西林凝固酶阴性葡萄球菌（MRCNS）和耐甲氧西林金黄色葡萄球菌（MRSA）的检出率分别为72.66%、42.42%,未发现利奈唑胺和万古霉素耐药的葡萄球菌。结论 革兰阴性菌是医院血流感染的主要致病菌,细菌耐药情况复杂,临床要根据药敏结果合理选择抗菌药物。     

Evaluation of long-term co-administration of tobramycin and clarithromycin in a mature biofilm model of cystic fibrosis clinical isolates of Pseudomonas aeruginosa

Pseudomonas aeruginosa colonisation and chronic lung infection associated with biofilm formation is a major cause of morbidity and mortality in cystic fibrosis (CF) patients. There is thus an urgent need to develop alternative ways to treat biofilm-associated clinical infections. A kinetic study of twice-daily co-administration of the antibiotics tobramycin and clarithromycin was performed over 28 days on 12-day-old mature P. aeruginosa biofilms formed on microplate pegs for 23 clinical isolates of various phenotypes and genotypes to simulate the treatment of CF patients with inhaled tobramycin through aerosolisation (TOBI^®). Drug activity was assessed by enumeration of persistent bacteria before, during and after treatment. A mature (12-day-old) biofilm model was chosen because a previous study suggested that such a biofilm was a more realistic in vitro model than a 24-h-old biofilm. Synergistic activity of the drug combination was confirmed on biofilms of 9/23 P. aeruginosa isolates. Of these nine isolates, total destruction of the biofilm was observed for five of them. Combination treatment was superior or equivalent to treatment with tobramycin alone, as activity was observed on 47.8% of the isolates with the combination versus 26.1% with tobramycin alone. No correlation was observed between drug susceptibility profiles and the phenotype or genotype of the isolates.     

Synergistic encapsulation of the anti-HIV agent efavirenz within mixed poloxamine/poloxamer polymeric micelles

This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly(ethylene oxide)-poly(propylene oxide) for the more effective encapsulation of the anti-HIV drug efavirenz. The co-micellization process of 10% binary systems combining different weight ratios of a highly hydrophilic poloxamer (Pluronic F127) and a more hydrophobic poloxamine counterpart (Tetronic T304 and T904) was investigated by means of dynamic light scattering, cloud point and electronic spin resonance experiments. Then, the synergistic solubilization capacity of the micelles was shown. Findings revealed a sharp solubility increase from 4 μg/ml up to more than 33 mg/ml, representing a 8430-fold increase. Moreover, the drug-loaded mixed micelles displayed increased physical stability over time in comparison with pure poloxamine ones. Overall findings confirmed the enormous versatility of the poloxamer/poloxamine systems as Trojan nanocarriers for drug encapsulation and release by the oral route and they entail a relevant enhancement of the previous art towards a more compliant pediatric HIV pharmacotherapy.

From the Clinical Editor

In this study, the authors demonstrate the versatility of poloxamer/poloxamine systems as Trojan nanocarriers for anti-HIV drug encapsulation and release by the oral route. A highly relevant stability and solubility enhancement is shown, which may ultimately lead to more compliant anti-HIV pharmacotherapy.     

2012—2020年泰达国际心血管病医院心血管疾病患者血流感染病原菌分布和耐药性分析

目的 分析泰达国际心血管病医院心血管疾病患者发生血流感染的病原菌分布及耐药特征,为临床合理应用抗菌药物提供依据.方法 对2012年1月—2020年12月泰达国际心血管病医院血流感染病原菌的分布及耐药性进行回顾性分析.结果 共检出病原菌234株,其中革兰阴性菌133株,构成比为56.8％,主要为大肠埃希菌、肺炎克雷伯菌和...     

Serum and lung levels of thiamphenicol after administration of its glycinate N-acetylcysteinate ester in experimentally infected guinea pigs

Thiamphenicol is an analogue of chloramphenicol and is characterised by a broad spectrum of action. In this study, serum and lung levels of thiamphenicol (TAP) were studied in infected guinea pigs after the administration of thiamphenicol glycinate N-acetylcysteinate (TGA). Animals received a single dose of TGA (15 mg/kg, subcutaneously) immediately after intra-tracheal infection with Haemophilus influenzae (about 10⁷ CFU/animal). Serum and lung concentrations of TAP were determined at 0, 1, 3, 6, 12 and 24 h after drug administration by means of HPLC. TAP serum levels were elevated at 1 h and remained detectable for 24 h after drug administration. Tissue lung levels were comparable to peak serum concentrations but remained higher and decreased more slowly than serum concentrations.     

The hydrophobic fragmental constant approach forcalculating log P in octanol/water and aliphatic hydrocarbon/water systems

We have investigated the relationship between drug retention in immobilized liposome partitioning chromatography and liposome partitioning and found a strong linear correlation. Separate linear relationships were found depending on the charge of the compound when liposome chromatographic measurements were related to the octanol/water partition coefficients. We have also investigated the importance of the water/octanol partition coefficient in quantitative structure–property relationships related to drug transport properties. The studies show that the inclusion of a parameter related to lipophilicity causes only, at best, a marginal increase in internal predictivity and, at worst, a decrease in external predictivity. The studies also show that parameters related to hydrogen bonding, polarizability and size are important properties that need to be included in quantitative models for drug transport processes. We believe that the use of multivariate characterizations of compounds based on non-composite parameters may result in better and more predictive models compared with models based on parameters of a more composite nature when investigating the possibilities to establish quantitative structure–property relationships. This revised version was published online in August 2006 with corrections to the Cover Date.     

The effect of Nepeta cataria extract on adherence and enzyme production of Staphylococcus aureus

Nepeta cataria L., commonly known as catnip, is a perennial herb with a considerable folkloric reputation. A diethyl ether extract of this plant has been shown to have antimicrobial activity against fungi and Gram-positive bacteria. The aim of this work was to study the activity of N. cataria extract on 44 Staphylococcus aureus strains, some resistant to methicillin, and S. aureus 6538P (American Type Culture Collection) by evaluating the effect of subminimum inhibitory concentrations on coagulase, DNAse, thermonuclease and lipase production, and on in-vitro adherence. DNAse, thermonuclease and lipase were inhibited by concentrations equal to 1/2 and 1/4 MIC. A reduction of adherence was also observed.     

Activity of finafloxacin, a novel fluoroquinolone with increased activity at acid pH, towards extracellular and intracellular Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila

Finafloxacin, an 8-cyano-substituted fluoroquinolone, expresses enhanced activity at acidic pH and is less susceptible to several fluoroquinolone resistance determinants. In this study, we compared finafloxacin and ciprofloxacin for (i) activity against ciprofloxacin-susceptible and -resistant Staphylococcus aureus as well as wild-type and Lde efflux-positive (Lde+) Listeria monocytogenes, (ii) accumulation in THP-1 macrophages and (iii) intracellular activity towards phagocytised S. aureus, L. monocytogenes and Legionella pneumophila (developing in acidic, neutral and mildly acidic environments, respectively), using a pharmacological approach assessing drug potencies and maximal relative efficacies (E_max). Finafloxacin minimum inhibitory concentrations (MICs) were two-fold lower than those of ciprofloxacin against meticillin-susceptible S. aureus ATCC 25923, were only modestly increased in an isogenic strain overexpressing NorA and were ≤0.25 mg/L for community-acquired meticillin-resistant S. aureus. No loss of activity was seen in Lde+ L. monocytogenes. An acidic pH decreased the MIC of finafloxacin and increased that of ciprofloxacin both for S. aureus and L. monocytogenes, in parallel with corresponding changes in drug accumulation (tested with S. aureus ATCC 25923 only). Finafloxacin accumulated less than ciprofloxacin in THP-1 cells, but the situation was reversed by exposure of cells to acid pH. In S. aureus-infected cells, acid pH increased the potency of finafloxacin without change of E_max, whilst decreasing the potency and the maximal relative efficacy of ciprofloxacin (less negative E_max). Finafloxacin was more potent and showed larger E_max than ciprofloxacin against phagocytised L. pneumophila, but was less potent against phagocytised L. monocytogenes. Finafloxacin appears to be an acid-pH-favoured antibiotic that may find useful applications in infections where the local pH is low.     

Influence of the surface properties of low contact angle surfactants on the body distribution of 14C-poly(methyl methacrylate) nanoparticles.

The body distribution of surfactant-coated and non-coated poly(methyl methacrylate) nanoparticles with a size of 131 +/- 30 nm after intravenous injection into rats was investigated. The coating materials were poloxamine 904, poloxamine 908, poloxamine 1508, poloxamer 338, and Brij 35. These materials were preselected by the method of contact angle measurement. No overall valid relation between contact angles and the modification of body distribution could be found. However, the classification of surfactants by determination of the contact angles of the surfactant solution on the polymer material seems to be a very helpful method for preselection of poloxamers and poloxamines. Another parameter for preselection could be molecular weights of the poloxamines. Poloxamine 1508 was the most efficient coating material in reducing the liver uptake and increasing the blood levels of poly(methyl methacrylate) nanoparticles.     

Isolation and characterisation of a new antimicrobial peptide from the skin of Xenopus laevis

A new antimicrobial peptide (AMP) named PGLa-H has been isolated from the skin of the African clawed frog (Xenopus laevis) using gel filtration and reverse-phase high-performance liquid chromatography (RP-HPLC). Its amino acid sequence was determined as KIAKVALKAL by Edman degradation, with a molecular weight of 1053.727 Da as analysed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). No similar AMP was found by BLAST search. Purified PGLa-H demonstrated antimicrobial ability against the reference bacteria Escherichia coli ATCC 25922 [minimum inhibitory concentration (MIC) = 23.6 μg/mL], Staphylococcus aureus ATCC 25923 (MIC = 8.7 μg/mL) and Bacillus subtilis (MIC = 14.4 μg/mL) and was active against multidrug-resistant meticillin-resistant S. aureus (MRSA) (MIC = 67.8 μg/mL). The antimicrobial mechanism for this new peptide was further investigated by transmission electron microscopy. PGLa-H killed cells by destroying the cell membrane.     

In vitro activity of terpenes against Candida biofilms

The antibiofilm activity of 10 terpenes was tested in vitro against three Candida species by 24-h treatment of biofilms aged 1-5 days. Treatment of 24-h-old Candida albicans biofilms with carvacrol, geraniol or thymol (0.06%) resulted in >80% inhibition. Carvacrol (0.03%) inhibition was > or =75% independent of the age of the C. albicans biofilm. Carvacrol (0.125%) inhibition was >75% against Candida glabrata and Candida parapsilosis biofilms. Geraniol (> or =0.125%) and thymol (0.06% or 0.125%) inhibition was >75% against C. parapsilosis biofilms whatever their age. This study demonstrates the antibiofilm activity of terpenes and points out the exceptional efficiency of carvacrol, geraniol and thymol, which could represent candidates in the treatment of candidiasis associated with medical devices.     

Ionotropic cross-linked chitosan microspheres for controlled release of ampicillin

The solubility of non cross-linked chitosan in weak acid solutions restricts its utility in microspheres for drug delivery. The primary aim of this study was to produce pentasodium tripolyphosphate cross-linked chitosan microspheres with higher acid resistance for controlled release of ampicillin. The microspheres were prepared by two different microencapsulation procedures (by emulsification and by spray-drying) and characterized by their particle size, surface morphology, stability, drug entrapment efficiency and drug release. The size of the microspheres was <10 microm with a narrow size distribution. The entrapment of ampicillin in the microspheres was more than 80%. Stability of uncross-linked and cross-linked microspheres was affected by the pH of simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5). The inclusion of the enzymes pepsin and pancreatin did not affect the stability of the microspheres. The inclusion of lysozyme in phosphate buffer saline resulted in increased solubilization. The release of the drug was affected by cross-linking of microspheres with tripolyphosphate (TPP). The cross-linked microspheres were more stable in simulated gastric fluid and showed slower but sustained release of ampicillin. The antimicrobial activity of the released ampicillin was confirmed by Staphylococcus aureus bioassay.     

The Effect of Formulation on the Antimicrobial Activity of Cetylpyridinium Chloride in Candy Based Lozenges

Purpose. The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges. Methods. In vivo activity was investigated using six volunteers by determining the reduction in colony forming units recoverable from the oropharynx after sucking each lozenge separately on different days. In vitro determinations investigated the relative activity of aqueous solutions of the lozenges, the effect on activity of additional active ingredients, pH and lozenge base ingredients against separate inocula of each of the test organisms Staphylococcus aureus, Streptococcus pyogenes and Candida albicans. Results. Both in vivo and in vitro results showed that the pH of the dissolved lozenge solution was the single most influential readily adjustable formulation parameter which significantly influenced the activity of cetylpyridinium chloride activity in candy based lozenges. Conclusions. Lozenges containing cetylpyridinium chloride as the active ingredient should be formulated at a pH greater than 5.5.     

线性回归模型在预测信阳市中心医院金黄色葡萄球菌耐药率中的应用

目的 考察金黄色葡萄球菌耐药率与抗菌药物使用强度(AUD)的相关性,建立可用于预测金黄色葡萄球菌耐药率的回归模型.方法 回顾性分析2014年第1季度至2020年第4季度信阳市中心医院金黄色葡萄球菌耐药率监测数据以及同期抗菌药物AUD数据.采用2014年第1季度至2019年第4季度数据作为试验样本数据,采用线性相关性分析法分析两者的相关性.以耐药率为因变量,抗菌药物AUD为自变量,对相关性显著的变量建立线性回归模型.以2020年第1季度至2020年第4季度数据为考核样本,应用所建立的回归模型预测金黄色葡萄球菌耐药率,并与同期耐药率实际值对比以验证模型预测的有效性.结果 金黄色葡萄球菌对大部分抗菌药物耐药率随时间呈下降趋势(P<0.05),对红霉素和阿奇霉素耐药率随时间无显著变化趋势.金黄色葡萄球菌对庆大霉素耐药率与头孢唑林AUD呈正相关(r=0.431,P=0.036),与阿奇霉素AUD呈正相关(r=0.523,P=0.009),与左氧氟沙星AUD呈正相关(r=0.606,P=0.002).对左氧氟沙星耐药率与头孢唑林AUD呈正相关(r=0.447,P=0.029),与左氧氟沙星AUD呈正相关(r=0.482,P=0.017).耐甲氧西林金黄色葡萄球菌(MRSA)检出率与左氧氟沙星AUD呈正相关(r=0.639,P=0.001).分别对庆大霉素耐药率、左氧氟沙星耐药率、MRSA检出率建立一元或多元线性回归模型,结果显示模型均通过显著性检验(F1=7.416,P1=0.004;F2=6.317,P2=0.007;F3=11.65,P3=0.002).将2020年第1季度至2020年第4季度抗菌药物AUD数据代入相应的回归模型,得到的耐药率预测值在实际值上下浮动,耐药率实际值均处于95％预测区间以内.结论 信阳市中心医院金黄色葡萄球菌耐药率与抗菌药物AUD存在相关性,所建立的线性回归模型可初步反映两者的量化关系,可对耐药率进行有效预测.     

Antibacterial and membrane damaging activity of Livistona chinensis fruit extract

Livistona chinensis is used in traditional Chinese medicine as an anticancer agent. Experimental studies have shown the antiproliferative and antiangiogenic properties of extracts of L. chinensis fruits and seeds. In the present study, qualitative phytochemical composition of L. chinensis fruits was investigated. We hypothesized that the presence of high concentration of phenolic compounds with astringent properties may result in bacterial cell death. Hence, antibacterial activity of an aqueous extract of L. chinensis fruits was investigated against Staphylococcus aureus. The antibacterial activity was attributed to DNA, enzyme and protein denaturing properties of the phenolic compounds present in the extract. The extract also resulted in increased membrane permeability. The antibacterial, DNA and enzyme denaturing and membrane damaging activity was limited to an acid-precipitable fraction of the extract and these effects were abrogated in presence of proteins. The membrane damaging activity of phenolic compounds was also observed in leucocytes. In conclusion, this study reported the antibacterial activity of the fruits of L. chinensis due to their high content of phenolic compounds.