Dalbavancin is increasingly being used for long-term treatment of subacute and chronic staphylococcal infections. In this study, a new Bayesian model was implemented and validated using MwPharm software for accurately forecasting the duration of pharmacodynamic target attainment above the efficacy thresholds of 4.02 mg/L or 8.04 mg/L against staphylococci. Forecasting accuracy improved substantially with the a posteriori approach compared with the a priori approach, particularly when two measured concentrations were used. This strategy may help clinicians to estimate the duration of optimal exposure with dalbavancin in the context of long-term treatment.

• MeSH
• antibakteriální látky * terapeutické užití   farmakologie   MeSH
• Bayesova věta MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• stafylokokové infekce * farmakoterapie   MeSH
• Staphylococcus MeSH
• teikoplanin terapeutické užití   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the synthesis and biological evaluation of seven derivatives of teicoplanin bearing hydrophobic or superbasic side chain. All but one teicoplanin derivatives were effective in inhibiting SARS-CoV-2 replication in VeroE6 cells. One lipophilic and three perfluoroalkyl conjugates showed activity against SARS-CoV-2 in human Calu-3 cells and against HCoV-229E, an endemic human coronavirus, in HEL cells. Pseudovirus entry and enzyme inhibition assays established that the teicoplanin derivatives efficiently prevent the cathepsin-mediated endosomal entry of SARS-CoV-2, with some compounds inhibiting also the TMPRSS2-mediated surface entry route. The teicoplanin derivatives showed good to excellent activity against Gram-positive bacteria resistant to all approved glycopeptide antibiotics, due to their ability to dually bind to the bacterial membrane and cell-wall. To conclude, we identified three perfluoralkyl and one monoguanidine analog of teicoplanin as dual inhibitors of Gram-positive bacteria and SARS-CoV-2.

• MeSH
• antibakteriální látky chemie   MeSH
• antivirové látky chemie   MeSH
• COVID-19 * MeSH
• fluorokarbony * farmakologie   MeSH
• glykopeptidy chemie   MeSH
• grampozitivní bakterie MeSH
• kathepsiny farmakologie   MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• teikoplanin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The study aimed to identify colonized patients as a possible source of eventual VRE (vancomycin-resistant enterococci) infection from stool samples positive for glutamate dehydrogenase antigen, as well as for Clostridioides difficile toxins A and B. The study was carried out from 7/2020 to 9/2021. Stool samples were grown in a brain heart infusion medium with a gram-positive non-spore-forming bacteria supplement under aerobic conditions. The samples for VRE identification were grown on CHROMID® VRE agar, and the MICs for vancomycin and teicoplanin were also estimated. The presence of the vanA/vanB genes was tested using the PCR method. The total number of 113 stool samples positive for Clostridioides difficile toxins was analyzed. Of these samples, 44 isolates with VRE characters were identified. The most prevalent isolates in our set of isolates were Enterococcus faecium (27 isolates, 62%), Enterococcus faecalis (9 isolates, 21%), Enterococcus solitarius (4 isolates, 9%), Enterococcus durans (2 isolates, 4%), 1 isolate Enterococcus sulfurous (2%), and Enterococcus raffinosus (2%). In total, 26 isolates were detected in the study in the presence of vanA genes (24 isolates E. faecium, 2 isolates E. faecalis) and 18 isolates detected in the presence of vanB genes (7 isolates E. faecalis, 4 isolates E. solitarius, 3 isolates E. faecium, 2 isolates E. durans, 1 isolate E. sulfurous, and E. raffinosus). The results of this study showed the local dominance character of the vanA gene of hospital VRE isolates that were carriers of genes associated with high resistance to vancomycin, teicoplanin, and occasionally linezolid.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• Clostridioides difficile * genetika   MeSH
• Enterococcus faecium * genetika   MeSH
• enterokoky rezistentní vůči vankomycinu * genetika   MeSH
• grampozitivní bakteriální infekce * mikrobiologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• teikoplanin farmakologie   MeSH
• vankomycin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin; however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of severe life-threatening infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, Enterococcus faecium and Clostridium difficile. The expression of vancomycin Z (vanZ), encoded either in the vancomycin A (vanA) glycopeptide antibiotic resistance gene cluster or in the genomes of E. faecium, as well as Streptococcus pneumoniae and C. difficile, was shown to specifically compromise the antibiotic efficiency through the inhibition of teicoplanin binding to the bacterial surface. However, the exact mechanisms of this action and protein structure remain unknown. In this study, the three-dimensional structure of VanZ from E. faecium EnGen0191 was predicted by using the I-TASSER web server. Based on the VanZ structure, a benzimidazole based ligand was predicted to bind to the VanZ by molecular docking. Importantly, this new ligand, named G3K, was further confirmed to specifically inhibit VanZ-mediated resistance to teicoplanin in vivo.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence účinky léků   MeSH
• bakteriální proteiny metabolismus   MeSH
• grampozitivní bakteriální infekce farmakoterapie   MeSH
• grampozitivní bakterie účinky léků   MeSH
• lidé MeSH
• lipoglykopeptidy farmakologie   MeSH
• mikrobiální testy citlivosti metody   MeSH
• simulace molekulového dockingu metody   MeSH
• teikoplanin farmakologie   MeSH
• vankomycin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Skin and soft tissue infections (SSTIs) are a large group of diseases with a wide range of clinically different conditions, some of which can be immediately life-threatening. A number of bacteria play an important role in the etiology of SSTIs, especially gram-positive cocci Staphylococcus aureus and Streptococcus pyogenes. In this case report, a young woman with skin defects after a fasciotomy was treated using a dermal substitute application. Multiple infectious complications in the skin and soft tissues with a high risk of development of phlebitis and with significant intolerance to a variety of antimicrobials were observed. The dramatic SSTI was treated using intravenous administration of dalbavancin, a very potent bactericidal antibio tic representing a rational option in the treatment of SSTIs caused by gram-positive bacteria.

Infekce kůže a měkkých tkání jsou rozsáhlou skupinou onemocnění s širokým spektrem klinických projevů. Některé z těchto infekcí mohou bezprostředně ohrožovat život. V rámci etiologie se uplatňuje celá řada bakterií, mezi epidemiologicky privilegované patogeny patří bezesporu gram-pozitivní koky Staphylococcus aureus a Streptococcus pyogenes. V kazuistice prezentujeme komplikovaný případ mladé ženy s kožními defekty po fasciotomii řešenými aplikací dermální náhrady. U pacientky s výraznou nesnášenlivostí k celé řadě antimikrobiálních preparátů došlo k rozvoji mnohočetných infekčních komplikací v oblasti kůže a měkkých tkání s vysokým rizikem rozvoje flebitid. Dramatický obraz se podařilo zvládnout za pomoci intravenózního podání dalbavancinu, potentního baktericidního antibiotika reprezentujícího racionální možnost v léčbě SSTIs způsobených gram-pozitivními bakteriemi.

• Klíčová slova
• dalbavancin,
• MeSH
• antibakteriální látky terapeutické užití   MeSH
• dospělí MeSH
• grampozitivní bakterie účinky léků   MeSH
• infekce měkkých tkání * etnologie   farmakoterapie   MeSH
• lidé MeSH
• teikoplanin * analogy a deriváty   farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Application of the superficially porous particles (SPPs) grafted with chiral selectors can substantially improve resolution in chromatographic techniques. In this work, we carried out a deeper study on supercritical fluid chromatography systems with 2.7 µm SPPs bonded with teicoplanin and vancomycin. Fast separations of the majority of enantiomers of phytoalexins, substituted tryptophans, and ketamine derivatives, as representatives of important biologically active and structurally diverse chiral compounds have been achieved. The chromatographic behavior of the structurally different analytes served to characterize these separation systems. The influence of separation conditions, namely mobile phase composition, i.e. type of co-solvent and additive on retention, enantioselective resolution and enantioselectivity was examined. The success rate of baseline and partial separations in individual groups of compounds differed with the chiral stationary phase and also with mobile phase composition. The best, baseline separations for the phytoalexins were achieved on the TeicoShell column using methanol as a co-solvent and trifluoroacetic acid as an additive if used. Mostly partial separations were achieved on the vancomycin-based column for all groups of analytes. Complementary separation behavior of these CSPs was confirmed for the majority of the chiral compounds examined in this work.

• MeSH
• alkaloidy chemie   MeSH
• ketamin chemie   MeSH
• kyselina trifluoroctová chemie   MeSH
• poréznost MeSH
• rozpouštědla chemie   MeSH
• seskviterpeny chemie   MeSH
• stereoizomerie MeSH
• superkritická fluidní chromatografie metody   MeSH
• teikoplanin chemie   MeSH
• vankomycin chemie   MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH

Článok pojednáva o pomerne novom lipoglykopeptidovom antibiotiku na trhu s názvom dalbavancín. Stručne popisuje spektrum a mechanizmus jeho antibakteriálneho účinku a dávkovacie schémy, ktoré je možné použiť v liečbe infekcií kože a mäkkých tkanív. V predloženej kazuistike autori popisujú prípad flegmóny ramena u pacientky, ktorej vyvolávateľom bol MRSA a na jej liečbu bolo -úspešne použité toto antibiotikum.

The article discusses dalbavancin, a relatively new lipoglycopeptide antibiotic brought to market. It briefly describes the spectrum and mechanism of its antibacterial effect and dosing regimens that can be used in the treatment of skin and soft tissue infections. The authors present a case of a patient with shoulder phlegmon caused by MRSA who was successfully treated with this antibiotic.

• Klíčová slova
• Dalbavalcín, Teicoplanin,
• MeSH
• antibakteriální látky aplikace a dávkování   MeSH
• celulitis farmakoterapie   mikrobiologie   MeSH
• diferenciální diagnóza MeSH
• horní končetina MeSH
• infekční nemoci kůže farmakoterapie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus izolace a purifikace   účinky léků   MeSH
• teikoplanin analogy a deriváty   aplikace a dávkování   farmakologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

PURPOSE OF THE STUDY Septic arthritis is an infection of joints caused by a pathogenic microorganism. Septic arthritis has a mortality rate of 11-40% when it's not treated properly. The mortality rate with methicillin-sensitive Staphylococcus aureus (MSSA)is 5-7%, while the rate with methicillin-resistant Staphylococcus aureus (MRSA)is 13-20%. The aim of this study is to evaluate the effects of intraarticular vancomycin and teicoplanin on joint cartilage in in vivo settings and its utility in routine MRSA treatment. MATERIALS AND METHODS In our study, 35 male Sprague-Dawley rats aged 28 days were used. Rats were obtained from the Regenerative and Restorative Medicine Research Center (REMER) of Istanbul Medipol University. Rats were randomly divided into 5 groups each containing 7 rats. Joint injections were administered with isoflurane analgesia every day at 6 am. Three rats (15 rats) from each group were sacrified in seventh day and evaluated immunohistologically to evaluate acute healing in articular cartilage. All remaining rats were sacrificed on day 28 and their knees were evaluated by immunohistochemical examination. RESULTS In our study, there were no complications in any rat during injection and the study period. Hematoxylin eosin (H & E) histological staining for evaluating cartilage healing and healing levels did not show statistically significant differences between the groups at first week (p > 0.05). Matrix metalloproteinase-13 (MMP-13) staining did not show any statistically significant difference between the groups. (p > 0.05). DISCUSSION MRSAseptic arthritis, diagnosed for the first time in 1960, has recently been responsible for 6-22% of all septic arthritis and is increasing day by day. The use of systemic vancomycin or teicoplanin is the first-line treatment method in MRSA septic arthritis. Serum levels reach the desired level, especially with intravenous infusion dose. On the other hand, it has been shown that intraarticular concentration does not reach a sufficient level in studies conducted. The use of intraarticular antibiotics during treatment can lead to more effective and early disease control by turning this negative situation into favor of the patient. As a result, intraarticular vancomycin and teicoplanin maximale tolerable and maintenance doses can be safely used beside surgery and intravenous antibiotics to increase efficacy of treatment, reduction of recurrence rates and reduction of mortality in MRSAseptic arthritis. CONCLUSIONS Intraarticular vancomycin and teicoplanin maximale tolerable and maintenance doses can be safely used beside surgery and intravenous antibiotics to increase efficacy of treatment, reduction of recurrence rates and reduction of mortality in MRSA septic arthritis. Key words:arthritis, infectious; methicillin-resistant Staphylococcus aureus; mortality.

• MeSH
• antibakteriální látky aplikace a dávkování   MeSH
• hojení ran účinky léků   MeSH
• infekční artritida farmakoterapie   patologie   MeSH
• injekce intraartikulární MeSH
• kloubní chrupavka účinky léků   patologie   MeSH
• krysa rodu rattus MeSH
• methicilin rezistentní Staphylococcus aureus izolace a purifikace   MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• potkani Sprague-Dawley MeSH
• stafylokokové infekce farmakoterapie   patologie   MeSH
• teikoplanin aplikace a dávkování   MeSH
• vankomycin aplikace a dávkování   MeSH
• zadní končetina účinky léků   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

Here, we describe a fluorescent assay developed to study competitive binding of the glycopeptide antibiotics to live bacteria cells. This assay demonstrated that the mechanism of action of the lipoglycopeptide antibiotics strongly depends on the hydrophobicity of the substitutes, with the best antibacterial activity of the glycopeptide antibiotics equally sharing properties of binding to D-Ala-D-Ala residues of the nascent peptidoglycan and to the membrane.

• MeSH
• antibakteriální látky metabolismus   MeSH
• barvení a značení MeSH
• buněčná stěna mikrobiologie   MeSH
• Enterococcus faecium metabolismus   MeSH
• enterokoky rezistentní vůči vankomycinu metabolismus   MeSH
• fluorescence MeSH
• glykopeptidy metabolismus   MeSH
• lipoglykopeptidy chemie   metabolismus   MeSH
• mikrobiální testy citlivosti MeSH
• peptidoglykan metabolismus   MeSH
• rhodaminy chemie   MeSH
• Staphylococcus aureus metabolismus   MeSH
• teikoplanin analogy a deriváty   chemie   metabolismus   MeSH
• vankomycin chemie   metabolismus   MeSH
• vazba proteinů fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: The aim of this study was to analyse the DNA sequences of three teicoplanin-resistant Staphylococcus epidermidis isolates collected from patients not previously treated with glycopeptide antibiotics. METHODS: The minimum inhibitory concentrations (MICs) of 12 antibiotics, including teicoplanin and vancomycin, were determined by the broth microdilution method. Genomic DNA was isolated, was sequenced by HiSeqX paired-end sequencing and was assembled into draft genome sequences using MyPro pipeline. RESULTS: Analysis of the draft genome sequences demonstrated that the teicoplanin-resistant S. epidermidis isolates belonged to multilocus sequence typing (MLST) sequence types ST5 and ST87 and encoded multiple antimicrobial resistance genes, including the methicillin resistance gene mecA. CONCLUSIONS: This report highlights the risk of dissemination of S. epidermidis strains resistant to a wide range of clinically important antibiotics.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence * MeSH
• genom bakteriální * MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• multilokusová sekvenční typizace MeSH
• sekvenování celého genomu MeSH
• stafylokokové infekce mikrobiologie   MeSH
• Staphylococcus epidermidis klasifikace   účinky léků   MeSH
• techniky typizace bakterií MeSH
• teikoplanin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH