替考拉宁(Teicoplanin)一种可治疗甲氧西林耐药菌感染的新的糖肽类抗生素

1991年由Marion Merrell Dow—Lepetit公司首先在意大利上市的Teicoplanin,由于在临床上可治疗甲氧西林耐药菌以及多剂耐药菌引起的子种感染,故引起人们的关注。

替考拉宁中主要组分的LC-MS法测定

LC-MS and LC-MS/MS methods were established to identify the main components of teicoplanin.By using electrospray ionization and positive ion monitoring,mass spectrometric detection were operated on a sigle quadrupole mass spectrometer and a triple quadrupole tandem mass spectrometer.Six components of teicoplanin were identified and determined.The established methods can be used to analyze teicoplanin qualitatively and quantitatively in the new drug development for quality control and stability study.

Teicoplanin combined with conventional vancomycin therapy for the treatment of pulmonary methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis infections

BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections.METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections,treated in our hospital between January 2018 and February 2020,were assigned to the study and control groups using a random number table method,with 43 patients in each group.The control group received conventional treatment(vancomycin),and the study group received both teicoplanin and conventional treatment.The following indicators were assessed in both groups:the time required for symptom relief,treatment effectiveness,serum levels of inflammatory factors(procalcitonin,interleukin-1β,tumor necrosis factor-α,C-reactive protein),clinical pulmonary infection scores before and after treatment,and the incidence of adverse reactions.RESULTS Patients in the study group were observed to have faster cough and expectoration resolution,white blood cell count normalization,body temperature normalization,and rales disappearance than patients in the control group(all P<0.05);the total rate of effectiveness was 93.02%in the study group,higher than the 76.74%in the control group(P<0.05).The pre-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups.However,the post-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the groups.CONCLUSION Compared with conventional(vancomycin only)therapy,teicoplanin and vancomycin combination therapy for patients with pulmonary methicillinresistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms,modulate serum inflammatory factor levels,and improve treatment efficacy,without increasing the risk of adverse reactions.

Determination of Teicoplanin A2's Partition Coefficient in Different Liquid-Liquid Extraction Systems

Teicoplanin is one of the macrocyclic glycopeptide antibiotics, which is active against Gram-positive bacteria, and has attracted a lot of attention in the field of chiral separation recently. In this work, the partition coefficients and extraction ratio of teicoplanin in three different solvent systems were studied: conventional extraction, reactive extraction and reverse micelle extraction. With conventional solvent extraction, n-butanol demonstrated high partition coefficient for teicoplanin, but low extraction ratio because of its high solubility in water. Reactive extraction of teicoplanin showed the highest partition coefficient with almost 100% recovery in organic phase when tri-n-octylmethyl ammonium chloride (TOMAC) was used as extractant and pH value was above 5.0. A reverse micelle system, consisted of isooctane +10mmol-L-1 TOMAC +1% n-octanol, also offered high separation factor for teicoplanin. The results are beneficial for the design of teicoplanin separation and purification process.

TEICOPLANIN体外抗菌活性研究

Ｔｅｉｃｏｐｌａｍｉｎ为一种新的糖肽类抗生素。本文报道ｔｅｉｃｏｐｌａｎｉｎ对临床检验的１６５株革兰氏阳性球菌，包括甲氧西林敏感及耐药金黄色葡萄球菌（ＭＳＳＡ、ＭＲＳＡ）、肺炎球菌、粪链球菌和草绿色链球菌的体外抗菌活性，并与去甲万古霉素等抗菌剂比较。结果显示，ｔｅｉｃｏｐｌａｎｉｎ对ＭＲＳＡＭＳＳＡ、肺炎球菌和草绿色链球菌有强的抗菌活性，ＭＩＣ＿（９０）≤２ｍｇ／Ｌ，抑菌率为９５～１００％，对ＭＲＳＥ和ＭＳＳＥ的抗菌率为７１．４％和８２．６％。但对粪链球菌的ＭＩＣ＿（９０）为６４ｍｇ／Ｌ，抑菌率为５８．３％。

Wavelength Selection for Near-Infrared Spectroscopic Analysis of Teicoplanin

Teicoplanin (TCP) is a multiple drug-resistant lipoglycopeptide antibiotic produced by fermenting Actinoplanes teichomyceticus. In this study, a mixture of TCP with the Tris-HCl buffer (TCP-Tris- HCl) was used to simulate TCP fermentation broth. The reagent-free, rapid and simultaneous quantitative analysis models for TCP and Tris in the TCP-Tris-HCl mixtures were established by near-infrared (NIR) spectroscopy. The equidistant combination partial least squares (EC-PLS) method and the equivalent model sets were proposed, the simplest equivalent model with the smallest number of wavelengths were further selected. The initial wavelength, number of wavelengths, number of wavelength gaps, number of PLS factors were 1520 nm, 28, 5, 5 for TCP and 1084 nm, 13, 6, 4 for Tris, respectively. Compared with the optimal EC-PLS models, the simplest equivalent models adopted fewer wavelengths. Thus, the redundant wavelengths were removed, the models were further simplified. The root-mean-square errors (SEP) and correlation coefficients (RP) for prediction were 0.043 mg·mL-1 and 0.9998 for TCP, and 0.222 mg·mL-1 and 0.9989 for Tris, respectively. The results indicate that NIR method can be applied to highly accurate quantitative analysis for TCP and provide valuable references for further application to TCP fermentation broth.

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

The purpose of this subject was to investigate molecular epidemiology of oxacillin-resistant Staphylococcus aureus (MRSA) isolated from hospitalized patients, and to survey the in vitro activity of teicoplanin, vancomycin and other 9 antibiotics against Staphylococcus species . MRSA were detected by oxacillin-NaCl-containing screen agar. The homology of nosocomial MRSA from ICU and RCU was determined by pulse-field gel electrophoresis. Agar diffusion, E test and agar dilution were used to compare the in vitro activity of teicoplanin and vancomycin against Staphylococcus spp from 2001 to 2003 at Peking Union Medical College Hospital. WHONET-5.3 software was used to analyze the antimicrobial susceptibility data. From 2001 to 2003, the prevalences of MRSA were 56.5%, 65.3%, 64.7%, respectively. PFGE found most of MRSA from ICU and RCU were closely related. All of S.aureus and S.epidimidis isolates were susceptible to teicoplanin and vancomycin from 2001 to 2003. However, 1 isolate of S.haemolyticus was resistant and 9 isolates intermediate to teicoplanin. The minimal inhibitory concentration of teicoplanin did not correlate well with zone diameter, when inoculum increased by 100 folds, the zone diameters of teicoplanin decreased more greatly than those of vancomycin. In 2002, severe outbreaks caused by MRSA strains had been found in ICU and RCU wards. Teicoplanin and vancomycin had good activity against clinical isolates of Staphylococci spp . Teicoplanin was less active than vancomycin against S.haemolyticus . Most of S.haemolyticus isolates were intermediate to teicoplanin. Antimicrobial susceptibility testing of teicoplanin was influenced by the diffusion speed in the agar and inoculum size.

AO-MW-PLS method applied to rapid quantification of teicoplanin with near-infrared spectroscopy

Teicoplanin(TCP)is an important lipoglycopeptide antibiotic produced by fermenting Acti-noplanes teichomyceticus.The change in TCP concentration is important to measure in the fermentation process.In this study,a reagent-free and rapid quantification method for TCP in the TCP-Tris-HCl mixture samples was developed using near infrared(NIR)spectroscopy by focusing our attention on the fermentation process for TCP.The absorbance optimization(AO)partial least squares(PLS)was proposed and integrated with the moving window(MW)PLS,which is called AO-MW-PLS method,to select appropriate wavebands.Amodel set that includes various wavebands that were equivalent to the optimal AO-MW-PLS waveband was,proposed based on statistical considerations.The public region of all equivalent wavebands was just one of the equivalent wavebands.The obtained public regions were 1540-1868 nm for TCP and 1114-1310 nm for Tris.The root-mean-square error and correlation coeficient for leave-one-out cross validation were 0.046 mg mL^(-1)and 0.9998 mg mL^(-1)for TCP,and 0.235 mg mL^(-1)and 0.9986 mg mL^(-1)for Tris,respectively.All the models achieved highly accurate prediction effects,and the selected wavebands provided valuable references for designing specialized spectrometers.This study provided a valuable reference for further application of the proposed methods to TCP fermentation broth and to other spectroscopic analysis fields.

糖肽类抗生素Teicoplanin

Teicoplanin系由游动放线菌(Actino-planes teichomyceticus)产生的一种糖肽类抗生素,原名teichomycinA_2。它是有5种密切相关的糖肽抗生素的复合物,每种糖肽抗生素有类似三环结构万古霉素的四环分子结构(附图)。本品由意大利开发上市,商品名为Targocid。

万古霉素和Teicoplanin的体外抗生素后效作用的比较

万古霉素被确定用来作为治疗革兰氏阳性菌感染的抗生素,尤其是当菌类对多种抗生素产生耐药性造成治疗上的困难时。Tei-coplanin是由5个结构很相似的糖肽抗生素组成,其基本结构与万古霉素类似,并有类似的抗菌谱和作用方式,但药代动力学不同。Teicoplanin有很长的半衰期和较好的组织渗透力以及可能毒性较低,而且与万古霉素形成对照。

Coagulase Negative Staphylococcus Causes Catheter Associated Bacteriemia in a Patient with Esophagus Adenocarcinome

We report a case of a man suffering esophagus adenocarcinome who acquired catheter associated bacteriemia caused by a coagulase negative Staphylococcus. This CoNS was sensible to linezolid, teicoplanine, vancomycin and rifampicin. This information was relevant for antibiotherapy planning. The patient was successfully treated with teicoplanin together with the catheter exchange. In conclusion, infections should be treated with adequate doses and duration of antibiotics together with catheter exchange. Pre-emptive measurements in the cancer patient and establishing the most adequate treatment are imperative for obtaining good results.

Accelerated Cutaneous Wound Healing Using an Injectable Teicoplanin-loaded PLGA-PEG-PLGA Thermogel Dressing

Bacterial infection is a very troublesome issue in wound treatment, which stimulates exudate formation and severely delays the healing process. Herein, a thermogelling dressing system composed of two triblock copolymers of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid)(PLGA-PEG-PLGA) with different block lengths was developed to deliver teicoplanin(TPN), a glycopeptide antibiotic, for cutaneous wound repair. The TPN-loaded thermogel was a free-flowing sol at room temperature and formed a semi-solid gel at physiological temperature. In vitro studies demonstrated that the TPN-loaded thermogel system exhibited desired tissue adhesiveness and realized the sustained release of TPN in a fast-followed-slow manner for over three weeks. Furthermore, a full-thickness excision wound model in Sprague-Dawley(SD) rats was constructed to assess the efficacy of TPNloaded thermogel formulation. Gross and histopathologic observations implied that treatment with the thermogel formulation reduced inflammation response, promoted disposition of collagen, enhanced angiogenesis, and accelerated wound closure and maturity of SD rats.The combination of the bioactivity of TPN and the acidic nature of the thermogel matrix was responsible for such an enhanced wound healing process. Consequently, the TPN-loaded PLGA-PEG-PLGA thermogel is a good candidate of wound dressing for full-thickness excision wound healing.

Aptamer-quantum dots and teicoplanin-gold nanoparticles constructed FRET sensor for sensitive detection of Staphylococcus aureus

The detection of bacterial pathogen such as Staphylococcus aureus(S.aureus) is essential for the regulation of food hygiene and disease diagnosis.Herein,we developed a simple one-step fluorescence resonance energy transfer(FRET)-based sensor for specific and sensitive detection of S.aureus in food and serum samples,in which aptamer-modified quantum dots(aptamer-QDs) was employed as the energy donor and antibiotic of teicoplanin functionalized-gold nanoparticles(Teico-AuNPs) was chosen as the energy acceptor.Within 1 h,the FRET-based sensor showed a linear range of from 10 cfu/mL to 5 × 10^(8) cfu/mL,with the low limit of detection(LOD,2 cfu/mL) for S.aureus in buffer.When further applied to assay S.aureus in real samples,the FRET-based sensor showed good recoveries ranging from 84.5% to 110.0%,with relative standard derivations(RSDs) of 0.01%-0.44% and a LOD of 100 cfu/mL in milk,orange juice and human serum.

Evaluation and Comparison of a 3,5-Dimethylphenyl Isocyanate Teicoplanin with Phenyl Isocyanate Teicoplanin Chiral Stationary Phase Using RP-HPLC

HPLC enantiomeric separations of 8 a-amino acids were achieved using two self-made chiral stationary phases （CSP）-henyl isocyanate teicoplanin （Phe-TE） and 3,5-dimethylphenyl isocyanate teicoplanin （DMP-TE）, using reversed phase mobile phases. The Phe-TE or the DMP-TE CSP was prepared from the TE using derivative agents, phenyl isocyanate or 3,5-dimethylphenyl isocyanate, respectively. The chromatographic results were given as the retention, selectivity, resolution factor and the enantioselective free energy difference corresponding to the separation of the two enantiomers. The effect of pH, organic modifier type and amount were discussed, and the stereose- lectivities for two TE-based CSPs were compared. The chiral selectivity factor for six a-amino acids on DMP-TE is somewhat bigger than that on Phe-TE CSP under reversed phase （RP） mode. Comparison of the enantiomeric separations using self-made Phe-TE and DMP-TE was conducted to gain a better understanding of the chiral recognition mechanism of the macrocyclic glycopeptide CSP.

Granulicatella adiacens Infective Endocarditis Treated With Teicoplanin and Ceftriaxone:A Case Report

We describe a case of infective endocarditis(IE)caused by Granulicatella adiacens in a patient who had fever for 4months before admission.He had a complex medical history of active hyperthyroidism and schizophrenia,which might have misled the clinician in ignoring the existence of a serious infection like IE.A history of splenectomy and the likelihood of congenital cardiac valve deficiency were the possible underlying risk factors.His persistent leukocytosis perplexed our judgement in terms of resolution of infection and treatment efficacy,which was probably due to his splenectomy.C-reactive protein was the alternative laboratory indicator.Clinical and Laboratory Standards Institute criteria have not been established for the fastidious G.adiacens.Therefore,we referred to the viridans group streptococci and literature to evaluate antimicrobial susceptibility testing.We suggest that teicoplanin combined with ceftriaxone could serve as an effective therapy for IE caused by G.adiacens.